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Hypertensive Agents

Introduction   

Hypertension, or high blood pressure, is a common medical condition diagnosed and treated by healthcare professionals. According to the Centers for Disease Control and Prevention, around 34 million Americans are prescribed antihypertensive medications. Additionally, hypertension was a primary or contributing cause of more than 690,000 deaths in the United States in 2021 [6].  

Healthcare providers must be knowledgeable of and follow current hypertension clinical practice guidelines. Understanding the different pharmacokinetics of antihypertensive medications is essential. This course outlines antihypertensive pharmacology and addresses pharmacokinetics, including mechanism of action, side effects, usage, and contraindications. 

Definitions 

Hypertension – high blood pressure above normal. Normal is considered anything less than 120/80 mmHg [7]. 

Antihypertensives – medications used to control hypertension and lower blood pressure [7]. 

Hypertensive crisis – severely elevated blood pressure of either: 

1. Systolic greater than 180 mmHg 

1. Diastolic greater than 120 mmHg [19]. 

Hypertensive emergency – acutely elevated blood pressure with signs of target organ damage [2]. 

Medications Overview 

Antihypertensive medications are used for the treatment of hypertension and are used in both inpatient, outpatient, and emergency settings.  

Some of the major antihypertensive medication classes include: 

• Diuretics 
• Beta-blockers 
• Angiotensin-converting enzyme inhibitors 
• Angiotensin II receptor blockers 
• Calcium channel blockers 
• Selective alpha-1 blockers 
• Alpha-2 Receptor Agonists 
• Vasodilators [3]. 

Different medical organizations have varying recommendations and hypertension treatment guidelines. Hypertension treatment clinical practice guidelines are available from organizations like the American Heart Association, the American College of Cardiology, and the European Society of Cardiology to name a few [21]. Healthcare providers should be aware of their healthcare institution’s recommendations for clinical practice guidelines and organizations.  

All organizational guidelines share the same recommended treatment of starting antihypertensives immediately when: 

1. Blood pressure is greater than 140/90 mmHg for patients with a history of ischemic heart disease, heart failure, or cerebrovascular disease. 
2. Blood pressure is greater than 160/100 mmHg regardless of underlying medical conditions [21]. 

Again, healthcare providers should follow current and evidence-based clinical guidelines for initiating or titrating antihypertensive medications. 

While most antihypertensives are prescribed in an outpatient setting, certain antihypertensives are indicated during hypertensive or medical emergencies. For example, intravenous (IV) vasodilators, like nitroprusside and nitroglycerin, and calcium channel blockers, like nicardipine, are used during hypertensive emergencies and crises. 

Pharmacokinetics 

Diuretics 

Diuretics are a class of drugs that help control blood pressure by removing excess sodium and water from the body through the kidneys. There are several varying types of diuretics, some including thiazide, potassium-sparing, and loop, and all work to lower blood pressure differently [3]. 

Thiazide Diuretics 

Thiazide diuretics remove excess sodium and water from the body by blocking the sodium-chloride (Na-Cl) channels in the kidneys’ distal convoluted tubule. As the Na-Cl channel becomes blocked, this inhibits the reabsorption of sodium and water into the kidneys. Concurrently, this causes a loss of potassium and calcium ions through the sodium-calcium channels and sodium-potassium pump [1]. 

Thiazide diuretics are approved by the Food and Drug Administration (FDA) for controlling primary hypertension and are available via oral route. Some common thiazide diuretics are hydrochlorothiazide, chlorthalidone, and metolazone [3].  

When initiating this medication, the healthcare provider should start with the lowest dose, which is usually 25mg daily, and then increase accordingly to aid with blood pressure control or if the patient has excess fluid retention, usually as evidenced by leg swelling or edema [1].  

Common side effects of thiazide diuretics include: 

• Increased urination 
• Diarrhea 
• Headache 
• Stomach and muscle aches [16]. 

As thiazide diuretics interfere with Na-Cl, Na-Ca, and Na-K channels, there is an increased potential for adverse effects, including: 

• Hypotension 
• Hypokalemia 
• Hyponatremia 
• Hypercalcemia 
• Hyperglycemia 
• Hyperlipidemia 
• Hyperuricemia 
• Acute pancreatitis 

When prescribing thiazide diuretics, healthcare providers should avoid prescribing thiazide diuretics to patients with a sulfonamide allergy, since thiazides are sulfa-containing medications. Also, they should avoid prescribing these to patients with a history of gout [1].  

Additionally, patients can experience a thiazide overdose if they take more than the amount prescribed. Patients with a suspected overdose may experience confusion, dizziness, hypotension, and other symptoms. These patients must seek emergency care and poison control must be alerted [16]. 

Potassium-Sparing Diuretics 

Potassium-sparing diuretics remove excess sodium and water from the body without causing loss of potassium. Depending on the type, they interrupt sodium reabsorption by either binding to epithelial sodium channels or inhibiting aldosterone receptors. When catatonic sodium is reabsorbed, this creates a negative gradient causing the reabsorption of potassium ions through the mineralocorticoid receptor [5]. 

Potassium-sparing diuretics are approved for controlling hypertension and are usually combined with other diuretics, like thiazide or loop diuretics since they have a weak antihypertensive effect.  

Common names of potassium-sparing diuretics are amiloride, triamterene, and spironolactone. These medications are available by either intravenous or oral routes. Spironolactone is commonly used for treating primary aldosteronism and heart failure [5]. Patients should be started on the lowest dose when first prescribing this class of medications.  

Common side effects can include: 

• Increased urination 
• Hyperkalemia 
• Metabolic acidosis 
• Nausea  

[4] 

Healthcare providers should avoid prescribing this class of medications to patients with hyperkalemia or chronic kidney disease. They should also be avoided during pregnancy or in patients who are taking digoxin. Since potassium-sparing medications can cause hyperkalemia, periodic monitoring for electrolyte imbalances and potassium levels is necessary [4]. 

Loop Diuretics 

Loop diuretics inhibit sodium and chloride reabsorption by competing with chloride binding in the Na-K-2Cl (NKCC2) cotransporter. Potassium is not reabsorbed by the kidney, which causes additional calcium and magnesium ion loss.  

Loop diuretics are FDA-approved for the treatment of hypertension but are not considered first-line treatment. They can also be used for treating fluid overload in conditions like heart failure or nephrotic syndrome [12]. 

Loop diuretics are available via oral or IV routes and furosemide, torsemide, and bumetanide are common forms [3].  

Bioavailability and dosage differ for each type and route of loop diuretics. The bioavailability of furosemide is 50%, with a half-life of around 2 hours for patients with normal kidney function, and dosages start at 8mg for oral medication. Torsemide has a bioavailability of about 80%, a half-life of about 3 to 4 hours, and oral dosages start at 5mg [12].  

Common side effects can include: 

• Dizziness 
• Increased urination 
• Headache 
• Stomach upset 
• Hyponatremia 
• Hypokalemia [13]. 

Loop diuretics can lead to several adverse effects, including toxicity, electrolyte imbalances, hyperglycemia, and ototoxicity. They have a black box warning stating that high dosages can cause severe diuresis. Therefore, electrolytes, BUN, and creatinine values should be monitored closely by a healthcare provider.  

People with a sulfonamide allergy may also be allergic to loop diuretics, so this should be avoided if the patient is allergic. Loop diuretics also interfere with digoxin and therefore should be avoided. Other contraindications include anuria, hepatic impairments, and use during severe electrolyte disturbances [12]. 

Beta-Blockers 

Beta-blockers work by reducing the body’s heart rate and thus, lowering cardiac output resulting in lowered blood pressure [3]. The mechanism of action for beta-blockers varies, depending on the receptor type it blocks, and are classified as either non-selective or beta-1 (B1) selective.  

Non-selective beta-blockers bind to the B1 and B2 receptors, blocking epinephrine and norepinephrine, causing a slowed heart rate. Propranolol, labetalol, and carvedilol are common non-selective beta-blockers.  

Alternatively, beta-1 selective blockers only bind to the B1 receptors of the heart, so they are considered cardio-selective. Some examples include atenolol, metoprolol, and bisoprolol. Sotalol is a type of beta-blocker that also blocks potassium channels and is, therefore, a class III antiarrhythmic [8]. 

Beta-blockers are not primarily used for the initial treatment of hypertension but can be prescribed for conditions like tachycardia, myocardial infarction, congestive heart failure, and cardiac arrhythmias. It’s also approved for use in conditions such as essential tremors, hyperthyroidism, glaucoma, and prevention of migraines.  

Beta-blockers are available in many forms, including oral, IV, intramuscular injection, and ophthalmic drops. Starting dosage and route are determined by the health condition being treated [8]. 

Common side effects of beta-blockers include: 

• Bradycardia 
• Hypotension 
• Dizziness 
• Feeling tired 
• Nausea 
• Dry mouth 
• Sexual Dysfunction  

[17] 

This class of medications can also lead to more severe adverse effects such as orthostatic hypotension, bronchospasm, shortness of breath, hyperglycemia, and increased risk of QT prolongation, torsades de pointes, and heart block [8]. Healthcare providers should avoid prescribing non-selective beta-blockers to patients with asthma. Instead, they can prescribe cardio-selective beta-blockers for patients with asthma.  

Additionally, the use of beta-blockers is contraindicated in patients with a history of bradycardia, hypotension, Raynaud disease, QT prolongation, or torsades de pointes. Healthcare providers must encourage patients to monitor their heart rate and blood pressure and follow administration parameters before taking beta-blockers daily since it decreases their heart rate.  

Overdose of beta-blockers is life-threatening and healthcare providers must discuss the symptoms of an overdose and the need for emergency care [8]. 

Angiotensin-converting Enzyme Inhibitors 

Angiotensin-converting enzyme (ACE) inhibitors prevent the body from producing angiotensin, a hormone that causes vasoconstriction. As angiotensin production is reduced, this allows the blood vessels to dilate and therefore lowers blood pressure [3].  

Moreover, ACE inhibitors act specifically on the renin-angiotensin-aldosterone system (RAAS) by preventing the conversion of angiotensin I to angiotensin II. It also works to decrease aldosterone, which in turn, decreases sodium and water reabsorption [9]. 

ACE inhibitors usually end in the suffix -pril and some common examples include lisinopril, benazepril, enalapril, and captopril, and they usually end in the suffix [3].  

While ACE inhibitors are approved for treating hypertension, they are also FDA-approved for other uses or combination therapies for medical conditions such as: 

• Systolic heart failure 
• Chronic kidney disease 
• ST-elevated myocardial infarction 

One non-approved FDA use is treatment of diabetic nephropathy [9]. This class of medication is available in oral, and IV forms, and dosages are dependent on clinical guidelines, underlying medical conditions, and route.  

ACE inhibitors have common side effects, with some including: 

• Dry cough 
• Dizziness 
• Hypotension [9]. 

This medication can also lead to adverse effects, such as syncope, angioedema, and hyperkalemia [9]. As angioedema is an adverse effect, healthcare providers should understand this class of medications is contraindicated in patients with a history of hypersensitivity to ACE inhibitors.  

Additionally, ACE inhibitors are contraindicated in patients with aortic valve stenosis, hypovolemia, and during pregnancy. Individuals with abnormal kidney function should have renal function and electrolyte values monitored. If a patient develops a chronic dry cough, then the healthcare provider should consider another antihypertensive medication class by following current guidelines [9]. 

Angiotensin II Receptor Blockers 

Similar to ACE inhibitors, Angiotensin II Receptor Blockers (ARBs) act on the RAAS by binding to angiotensin II receptors and thus block and reduce the action of angiotensin II. Again, this reduces blood pressure by causing blood vessel dilation and decreasing sodium and water reabsorption [11]. ARBs typically end in the suffix -artan and common names are losartan, valsartan, and Olmesartan [3]. Oral and IV routes of the medication are available and again, dosages are dependent on the medication specifically and form [11]. 

All ARBs are FDA-approved for the treatment of hypertension, but a select few are approved for treating other medical conditions, such as: 

• Candesartan for heart failure 
• Irbesartan for diabetic nephropathy 
• Losartan for proteinuria and diabetic nephropathy 
• Telmisartan for stroke and myocardial infarction prevention 
• Valsartan for heart failure and reduction of mortality in patients with left ventricular dysfunction [11]. 

Although not as common as ACE inhibitors, two side effects of ARBs are dry cough and angioedema.  

Other common side effects include: 

• Dizziness 
• Hypotension 
• Hyperkalemia  

[11] 

Contraindications for use are if the patient is pregnant or has renal impairment or failure. If a patient is on an ARB, the healthcare provider should closely monitor lab values for electrolyte imbalances and kidney function.  

Additionally, if a patient is taking lithium, ARBs can increase lithium concentration and therefore, lithium blood concentration should be frequently checked [11]. 

Calcium Channel Blockers 

Calcium channel blockers (CCBs), also known as calcium channel antagonists, act by preventing calcium from entering the smooth vascular and heart muscles. In turn, this reduces heart rate and causes vasodilation [3].  

They are further divided into two major categories, non-dihydropyridines and dihydropyridines, where there are differences in the mechanism of action. Non-dihydropyridines inhibit calcium from entering the heart’s sinoatrial and atrioventricular nodes and thus cause a cardiac conduction delay and reduce cardiac contractility.  

Alternatively, dihydropyridines do not directly affect the heart but do act as a peripheral vasodilator leading to lowered blood pressure. Both categories are metabolized by the CYP3A4 pathway [15]. 

Names of non-dihydropyridine CCBs are verapamil and diltiazem. Dihydropyridine CCBs typically end in the suffix  -pine and common names are amlodipine and nicardipine. Both categories are available via oral and IV routes for administration. Oral dosages of non-dihydropyridine CCBs start at 30mg daily and dihydropyridine CCBs start at 30mg daily for immediate release [15].  

Calcium channel blockers can be used to treat other medical conditions in addition to hypertension and include: 

• Coronary spasm 
• Angina pectoris 
• Supraventricular dysrhythmias 
• Pulmonary hypertension 
• Hypertrophic cardiomyopathy 

Non-dihydropyridine CCBs can cause side effects like bradycardia, and constipation, while dihydropyridine CCBs can cause: 

• Headaches 
• Feeling lightheaded 
• Leg swelling [15]. 

Both categories pose the risk of potential hypotension and bradycardia, so healthcare providers should closely monitor the patient’s blood pressure and heart rate when initiating or titrating the dosage.  

Also, an overdose of this medication can lead to cardiac conduction delays, complete heart block, and cardiovascular collapse. Patients with possible symptoms of overdose should be sent to the emergency room immediately.  

Additionally, healthcare providers should avoid prescribing CCBs to people with heart failure and sick sinus syndrome [15]. 

Selective Alpha-1 Blockers 

Selective alpha-1 blockers act on the body’s sympathetic nervous system to lower blood pressure. They prevent norepinephrine from binding to the alpha-1 receptors of the sympathetic nervous system, causing smooth muscle relaxation and vasodilation which leads to lowered blood pressure [18]. 

Selective alpha-1 blockers are available via the oral route, end in the suffix -osin and examples are doxazosin, terazosin, and prazosin [3]. They are FDA-approved for the treatment of hypertension but are not considered first-line therapy. Additionally, this class of medications may be used to treat benign prostatic hyperplasia. Dosages can start as low as 1mg daily depending on the drug selected. 

Common side effects include: 

• Hypotension 
• Tachycardia 
• Dizziness 
• Headache 
• Weakness [18]. 

As selective alpha-1 blockers can lead to orthostatic hypotension, the healthcare provider should instruct the patient to take this medication at night. They should also avoid prescribing to the elderly population when able because of hypotension and increased fall risk [18]. 

Alpha-2 Receptor Agonists 

Alpha-2 receptor agonists work by decreasing the activity of the sympathetic nervous system to lower blood pressure. It inhibits adenylyl cyclase and decreases the formation of cyclic adenosine monophosphate (cAMP). Alpha-2 agonists also cause vasodilation by reducing the amount of available cytoplasmic calcium [20].  

This class of medications is typically administered via oral route but is also available in intravenous and transdermal forms. Two FDA-approved alpha-2 agonists for hypertension treatment are methyldopa and clonidine and dosages are dependent on the name and route.  

Methyldopa is commonly prescribed to patients with hypertension and who are pregnant since it’s safe [20]. 

Common side effects of alpha-2 receptor agonists are: 

• Dry mouth 
• Drowsiness 
• Fatigue 
• Headache 
• Sexual dysfunction [3]. 

Contraindications for use are orthostatic hypotension and autonomic disorders. Healthcare providers must avoid prescribing alpha-2 receptor agonists to individuals taking phosphodiesterase inhibitors [20]. 

Vasodilators 

Vasodilators lower blood pressure by dilating the body’s blood vessels. It binds to the receptors of the blood vessel’s endothelial cells, releasing calcium. Calcium stimulates nitric oxide synthase (NO synthase), eventually converting to L-arginine to nitric oxide. As nitric oxide is available, this allows for GTP to convert to cGMP, and causes dephosphorylation of the myosin and actin filaments. As this occurs, the blood vessels’ smooth muscles relax, leading to vasodilation and lowered blood pressure.  

Common vasodilators that act via this pathway are nitrates and minoxidil. Hydralazine is another vasodilator, but the mechanism of action is unknown [10]. 

Available forms of vasodilators are sublingual, oral, and intravenous. Similar to other classes of antihypertensives, vasodilator dosages depend on the form and treatment setting [10].  

Nitrovasodilators like nitroprusside and nitroglycerin are used during hypertensive emergencies. Hydralazine is used for severe hypertension for the prevention of eclampsia or intracranial hemorrhage and minoxidil for resistant hypertension [10] [3]. 

Side effects for each will vary, but nitrates commonly cause: 

• Reflex tachycardia 
• Headache 
• Orthostatic hypotension  

[10] 

Common side effects of hydralazine are headaches, heart palpitations, and myalgias. Minoxidil causes excessive hair growth, weight gain, and fluid retention [3]. Additionally, nitroprusside can potentially cause cyanide toxicity.  

Vasodilators have varying degrees of contraindications, such as nitrates are avoided in patients with an inferior myocardial infarction. Hydralazine should not be given to patients with coronary artery disease, angina, or rheumatic heart disease. Healthcare providers should be aware of contraindications and monitor patients’ blood pressure and potential side effects [10]. 

Combination Antihypertensives 

Many antihypertensive medications come in combined forms, such as ACE inhibitors and thiazide diuretics, beta-blockers and diuretics, or calcium channel blockers and ACE inhibitors. The mechanism of action for combination antihypertensives depends on the blend of medications [3]. 

Considerations for Prescribers 

This section reviews potential considerations when prescribing antihypertensives. 

When prescribing antihypertensive medications, there are several factors that healthcare providers must consider. The route is typically determined by the healthcare setting and dosage by the underlying treatment goals. Again, healthcare providers should follow current guidelines when initiating or titrating antihypertensive medications.  

Healthcare providers must complete a thorough health history, and review lab values, and contraindications as mentioned above. Monitoring kidney function and electrolyte values is imperative while any patient is taking antihypertensive medications.  

While a single antihypertensive medication is recommended for initial treatment, there are some scenarios where combination therapy or combination antihypertensives are recommended [14]. 

Healthcare providers should also discuss the potential side effects of antihypertensives with patients and what to do if they are experiencing symptoms. For instance, if a patient reports syncope, they should be advised to go to the emergency room or be seen immediately for further evaluation. Also, healthcare providers must encourage patients to monitor their heart rate and blood pressure at home and abide by administration parameters.  

For example, instruct patients who are taking beta-blockers to measure their blood pressure and heart rate before taking their medication. If their heart rate is below 60 beats per minute, then they should not take the medication [14].  

If a patient is experiencing side effects from an antihypertensive medication, then another alternative should be selected. 

Upcoming Research 

This section reviews upcoming research and medications for hypertension treatment. 

Research on antihypertensive medications has slowed throughout the years. Some clinical trials were performed on the potential of endothelin receptor antagonists to reduce hypertension. However, some studies found several unwanted side effects, and thus clinical use was stopped for safety reasons.  

An endothelin-A and endothelin-B receptor blocker, called aprocinentan, has shown promise for the treatment of resistant hypertension by lowering blood pressure and decreasing vascular resistance.  

Research on sodium-glucose transport protein (SGLT2) inhibitors, which are typically used for the treatment of type II diabetes mellitus, is also ongoing. SGLT2 inhibitors may promote blood pressure reduction through diuresis and reduce sympathetic tone [21]. 

Conclusion

If hypertension is left untreated, it can lead to serious health complications, including death. When selecting antihypertensive treatment, healthcare providers should understand the pharmacokinetics of each drug class along with potential side effects and contraindications. They should also follow current clinical guidelines for an evidence-based approach. 

Final Reflection Questions 

• Which antihypertensive medication is often prescribed during pregnancy? 
• Which lab values are important when monitoring patients on each antihypertensive medication? 
• Which antihypertensive medications cause hypokalemia? 
• Which antihypertensive medications cause hyperkalemia? 

Controlled Substances: A comprehensive review

Introduction   

Pain is complex and subjective. The experience of pain can significantly impact an individual’s quality of life. According to the National Institute of Health (NIH) (40), pain is the most common complaint in a primary care office, with 20% of all patients reporting pain. Chronic pain is the leading cause of disability, and effective pain management is crucial to health and well-being, particularly when it improves functional ability. Effective pain treatment starts with a comprehensive, empathic assessment and a desire to listen and understand. Nurse Practitioners are well-positioned to fill a vital role in providing comprehensive and empathic patient care, including pain management (23).

While the incidence of chronic pain has remained a significant problem, how clinicians manage pain has significantly changed in the last decade, primarily due to the opioid epidemic. This education aims to discuss pain and the assessment of pain, federal guidelines for prescribing, the opioid epidemic, addiction and diversion, and recommendations for managing pain.

Definition of Pain

Understanding the definition of pain, differentiating between various types of pain, and recognizing the descriptors patients use to communicate their pain experiences are essential for Nurse practitioners involved in pain management. By understanding the medical definition of pain and how individuals may communicate it, nurse practitioners can differentiate varying types of pain to target assessment.

According to the International Association for the Study of Pain (27), pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or terms of described such in damage.” The IASP, in July 2020, expanded its definition of pain to include context further.

Their expansion is summarized below:

• Pain is a personal experience influenced by biological, psychological, and social factors.
• Pain cannot be inferred solely from activity in sensory neurons.
• Individuals learn the concept of pain through their life experiences.
• A person’s report of an experience in pain should be respected.
• Pain usually serves an adaptive role but may adversely affect function and social and psychological well-being.
• The inability to communicate does not negate the possibility of the experience of pain.

Types of Pain

Pain originates from different mechanisms, causes, and areas of the body. As a nurse practitioner, understanding the type of pain a patient is experiencing is essential for several reasons (23).

• Determining an accurate diagnosis. This kind of pain can provide valuable clues to the underlying cause or condition.
• Creating a treatment plan. Different types of pain respond better to specific treatments or interventions.
• Developing patient education. A nurse practitioner can provide targeted education to patients about their condition, why they may experience the pain as they do, its causes, and treatment options. Improving the patient's knowledge and control over their condition improves outcomes.

Acute Pain

Acute pain is typically short-lived and is a protective response to an injury or illness. Patients are usually able to identify the cause. This type of pain resolves as the underlying condition improves or heals (12).

Chronic Pain

Chronic pain is diagnosed when it continues beyond the expected healing time. Pain is defined as chronic when it persists for longer than three months. It may result from an underlying disease or injury or develop without a clear cause. Chronic pain often significantly impacts a person's physical and emotional well-being, requiring long-term management strategies. The prolonged experience of chronic pain usually indicates a central nervous system component of pain that may require additional treatment. Patients with centralized pain often experience allodynia or hyperalgesia (12).

Allodynia is pain evoked by a stimulus that usually does not cause pain, such as a light touch. Hyperalgesia is the effect of a heightened pain response to a stimulus that usually evokes pain (12).

Nociceptive Pain

Nociceptive pain arises from activating peripheral nociceptors, specialized nerve endings that respond to noxious stimuli. This type of pain is typically associated with tissue damage or inflammation and is further classified into somatic and visceral pain subtypes.

Somatic pain is most common and occurs in muscles, skin, or bones; patients may describe it as sharp, aching, stiffness, or throbbing.

Visceral pain occurs in the internal organs, such as indigestion or bowel spasms. It is more vague than somatic pain; patients may describe it as deep, gnawing, twisting, or dull (12).

Neuropathic pain

Neuropathic pain is a lesion or disease of the somatosensory nervous system. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia, and central poststroke pain (10).

Neuropathic pain may be ongoing, intermittent, or spontaneous pain. Patients often describe neuropathic pain as burning, prickling, or squeezing quality. Neuropathic pain is a common chronic pain. Patients commonly describe allodynia and hyperalgesia as part of their chronic pain experience (10).

Affective pain

Affective descriptors reflect the emotional aspects of pain and include terms like distressing, unbearable, depressing, or frightening. These descriptors provide insights into the emotional impact of pain on an individual's well-being (12).

Case Study

Mary Adams is a licensed practical nurse who has just relocated to town. Mary will be the utilization review nurse at a local long-term care facility. Mary was diagnosed with Postherpetic Neuralgia last year, and she is happy that her new job will have her mostly doing desk work and not providing direct patient care as she had been before the relocation. Mary was having difficulty at work at her previous employer due to pain. She called into work several times, and before leaving, Mary's supervisor had counseled her because of her absences.

Mary wants to establish primary care immediately because she needs ongoing pain treatment. She is hopeful that, with her new job and pain under control, she will be able to continue a successful career in nursing. When Mary called the primary care office, she specifically requested a nurse practitioner as her primary care provider because she believes that nurse practitioners tend to spend more time with their patients.

Assessment

The assessment effectively determines the type of treatment needed, the options for treatment, and whether the patient may be at risk for opioid dependence. Since we know that chronic pain can lead to disability and pain has a high potential to negatively affect the patient's ability to work or otherwise, be productive, perform self-care, and potentially impact family or caregivers, it is imperative to approach the assessment with curiosity and empathy. This approach will ensure a thorough review of pain and research on pain management options. Compassion and support alone can improve patient outcomes related to pain management (23).

Record Review

Regardless of familiarity with the patient, reviewing the patient's treatment records is essential, as the ability to recall details is unreliable. Reviewing the records can help identify subtle changes in pain description and site, the patient's story around pain, failed modalities, side effects, and the need for education, all impacting further treatment (23).

Research beforehand the patient's current prescription and whether or not the patient has achieved the maximum dosage of the medication. Analysis of the patient's past prescription could reveal a documented failed therapy even though the patient did not receive the maximum dose (23).

A review of documented allergens may indicate an allergy to pain medication. Discuss with the patient the specific response to the drug to determine if it is a true allergy, such as hives or anaphylaxis, or if the response may have been a side effect, such as nausea and vomiting.

Research whether the patient tried any non-medication modalities for pain, such as physical therapy (PT), occupational therapy (OT), or Cognitive Behavioral Therapy (CBT). Note any non-medication modalities documented as failed therapies. The presence of any failed therapies should prompt further discussion with the patient, family, or caregiver about the experience. The incompletion of therapy should not be considered failed therapy. Explore further if the patient abandoned appointments.

Case Study

You review the schedule for the week, and there are three new patient appointments. One is Mary Adams. The interdisciplinary team requested and received Mary's treatment records from her previous primary care provider. You make 15 minutes available to review Mary's records and the questionnaire Mary filled out for her upcoming appointment. You see that Mary has been diagnosed with Postherpetic Neuralgia and note her current treatment regimen, which she stated was ineffective. You write down questions you will want to ask Mary. You do not see evidence of non-medication modalities or allergies to pain medication.

Pain Assessment

To physically assess pain, several acronyms help explore all the aspects of the patient's experience. Acronyms commonly used to assess pain are SOCRATES, OLDCARTS, and COLDERAS. These pain assessment acronyms are also helpful in determining treatment since they include a character and duration of pain assessment (23).

Inquire where the patient is feeling pain. The patient may have multiple areas and types of pain. Each type and location must be explored and assessed. Unless the pain is from a localized injury, a body diagram map, as seen below, is helpful to document, inform, and communicate locations and types of pain. In cases of Fibromyalgia, rheumatoid arthritis, or other centralized or widespread pain, it is vital to inquire about radiating pain. The patient with chronic pain could be experiencing acute pain or a new pain site, such as osteoarthritis, that may need further evaluation and treatment (23).

Inquire with the patient how long their pain has been present and any associated or known causative factors. Pain experienced longer than three months defines chronic versus acute pain. Chronic pain means that the pain is centralized or a function of the Central Nervous system, which should guide treatment decisions.

To help guide treatment, ask the patient to describe their pain. The description helps identify what type of pain the patient is experiencing: Allodynia and hyperalgesia indicate centralized pain; sharp, shooting pain could indicate neuropathic pain. Have the patient rate their pain. There are various tools, as shown below, for pain rating depending on the patient's ability to communicate. Not using the pain rating number alone is imperative. Ask the patient to compare the severity of pain to a previous experience. For example, a 1/10 may be experienced as a bumped knee or bruise, whereas a 10/10 is experienced on the level of a kidney stone or childbirth (23).

Besides the 0-10 rating scale and depending on the patient's needs, several pain rating scales are appropriate. They are listed below.

The 0-5 and Faces scales may be used for all adult patients and are especially effective for patients experiencing confusion.

The Defense and Veterans Pain Rating Scale (DVPRS) is a five-item tool that assesses the impact of pain on sleep, mood, stress, and activity levels (20).

For patients unable to self-report pain, such as those intubated in the ICU or late-stage neurological diseases, the FLACC scale is practical. The FLACC scale was initially created to assess pain in infants. Note: The patient need not cry to be rated 10/10.

(21).

Assess contributors to pain such as insomnia, stress, exercise, diet, and any comorbid conditions. Limited access to care, socioeconomic status, and local culture also contribute to the patient's experience of pain (23). Most patients have limited opportunity to discuss these issues, and though challenging to bring up, it is compassionate and supportive care. A referral to social work or another agency may be helpful if you cannot explore it fully.

Assess for substance abuse disorders, especially among male, younger, less educated, or unemployed adults. Substance abuse disorders increase the likelihood of misuse disorder and include alcohol, tobacco, cannabis, cocaine, and heroin (29).

Inquire as to what changes in function the pain has caused. One question to ask is, "Were it not for pain, what would you be doing?" As seen below, a Pain, Enjoyment, and General Activity (PEG) three-question scale, which focuses on function and quality of life, may help determine the severity of pain and the effect of treatment over time.

(21).

Assess family history, mental health disorders, chronic pain, or substance abuse disorders. Each familial aspect puts patients at higher risk for developing chronic pain (23).

Evaluate for mental health disorders the patient may be experiencing, particularly anxiety and depression. The Patient Health Questionnaire (PHQ4) is a four-question tool for assessing depression and anxiety.

In some cases, functional MRI or imaging studies effectively determine the cause of pain and the treatment. If further assessment is needed to diagnose and treat pain, consult Neurology, Orthopedics, Palliative care, and pain specialists (23).

Case Study

You used OLDCARTS to evaluate Mary's pain and completed a body diagram. Mary is experiencing allodynia in her back and shoulders, described as burning and tingling. It is exacerbated when she lifts, such as moving patients at the long-term care facility and, more recently, boxes from her move to the new house. Mary has also been experiencing anxiety due to fear of losing her job, the move, and her new role. She has moved closer to her family to help care for her children since she often experiences fatigue. Mary has experienced a tumultuous divorce in the last five years and feels she is still undergoing some trauma.

You saw in the chart that Mary had tried Gabapentin 300 mg BID for her pain and inquired what happened. Mary explained that her pain improved from 8/10 to 7/10 and had no side effects. Her previous care provider discontinued the medication and documented it as a failed therapy. You reviewed the minimum and maximum dosages of Gabapentin and know Mary can take up to 1800mg/day.

During the assessment, Mary also described stiffness and aching in her left knee. She gets a sharp pain when she walks more than 500 steps, and her knee is throbbing by the end of the day. Mary rated the pain a 10/10, but when she compared 10/10 to childbirth, Mary said her pain was closer to 6/10. Her moderate knee pain has reduced Mary's ability to exercise. She used to like to take walks. Mary stated she has had knee pain for six months and has been taking Ibuprofen 3 – 4 times daily.

Since Mary's pain is moderate, you evaluate your options of drugs for moderate to severe pain.

Opioid Classifications and Drug Schedules

A comprehensive understanding of drug schedules and opioid classifications is essential for nurse practitioners to ensure patient safety, prevent drug misuse, and adhere to legal and regulatory requirements. Nurse practitioners with a comprehensive understanding of drug schedules and opioid classifications can effectively communicate with colleagues, ensuring accurate medication reconciliation and facilitating interdisciplinary care. Nurse practitioners’ knowledge in facilitating discussions with pharmacists regarding opioid dosing, potential interactions, and patient education is essential (49).

Drug scheduling became mandated under the Controlled Substance Act. The Drug Enforcement Agency (DEA) Schedule of Controlled Drugs and the criteria and common drugs are listed below.

(Pain Physician, 2008)

Listed below are drugs classified by their schedule and mechanism of action. "Agonist" indicates a drug that binds to the opioid receptor, causing pain relief and also euphoria. An agonist-antagonist indicates the drug binds to some opioid receptors but blocks others. Mixed antagonist-agonist drugs control pain but have a lower potential for abuse and dependence than agonists (7).

(41).

Commonly Prescribed Opioids, Indications for Use, and Typical Side Effects

Opioid medications are widely used for managing moderate to severe pain. Referencing NIDA (2023), this section aims to give healthcare professionals an overview of the indications and typical side effects of commonly prescribed Schedule II opioid medications, including hydrocodone, oxycodone, morphine, Fentanyl, and hydromorphone.

Opioids are derived and manufactured in several ways. Naturally occurring opioids come directly from the opium poppy plant. Synthetic opioids are manufactured by chemically synthesizing compounds that mimic the effects of a natural opioid. Semi-synthetic is a mix of naturally occurring and man-made (35).

Understanding the variations in how an opioid is derived and manufactured is crucial in deciding the type of opioid prescribed, as potency and analgesic effects differ. Synthetic opioids are often more potent than naturally occurring opioids. Synthetic opioids have a longer half-life and slower elimination, affecting the duration of action and timing for dose adjustments. They are also associated with a higher risk of abuse and addiction (38).

Hydrocodone

Mechanism of Action and Metabolism

Hydrocodone is a Schedule II medication. It is an opioid agonist and works as an analgesic by activating mu and kappa opioid receptors located in the central nervous system and the enteric plexus of the bowel. Agonist stimulation of the opioid receptors inhibits nociceptive neurotransmitters' release and reduces neuronal excitability (17).

• Produces analgesia.
• Suppresses the cough reflex at the medulla.
• Causes respiratory depression at higher doses.

Hydrocodone is indicated for treating severe pain after nonopioid therapy has failed. It is also indicated as an antitussive for nonproductive cough in adults over 18.

Available Forms

Hydrocodone immediate release (IR) reaches maximum serum concentrations in one hour with a half-life of 4 hours.  Extended-release (ER) Hydrocodone reaches peak concentration at 14-16 hours and a half-life of 7 to 9 hours. Hydrocodone is metabolized to an inactive metabolite in the liver by cytochrome P450 enzymes CYP2D6 and CYP3A4. Hydrocodone is converted to hydromorphone and is excreted renally. Plasma concentrations of hydromorphone are correlated with analgesic effects rather than hydrocodone.

Hydrocodone is formulated for oral administration into tablets, capsules, and oral solutions. Capsules and tablets should never be crushed, chewed, or dissolved. These actions convert the extended-release dose into immediate release, resulting in uncontrolled and rapid release of opioids and possible overdose.

Dosing and Monitoring

Hydrocodone IR is combined with acetaminophen or ibuprofen. The dosage range is 2.5mg to 10mg every 4 to 6 hours. If formulated with acetaminophen, the dosage is limited to 4gm/day.

Hydrocodone ER is available as tablets and capsules. Depending on the product, the dose of hydrocodone ER formulations in opioid-naïve patients is 10 to 20 mg every 12 to 24 hours.

Nurse practitioners should ensure patients discontinue all other opioids when starting the extended-release formula.

Side Effects and Contraindications

Because mu and kappa opioid receptors are in the central nervous system and enteric plexus of the bowel, the most common side effects of hydrocodone are constipation and nausea (>10%).

Other adverse effects of hydrocodone include:

• Respiratory: severe respiratory depression, shortness of breath
• Cardiovascular: hypotension, bradycardia, peripheral edema
• Neurologic: Headache, chills, anxiety, sedation, insomnia, dizziness, drowsiness, fatigue
• Dermatologic: Pruritus, diaphoresis, rash
• Gastrointestinal: Vomiting, dyspepsia, gastroenteritis, abdominal pain
• Genitourinary: Urinary tract infection, urinary retention
• Otic: Tinnitus, sensorineural hearing loss
• Endocrine: Secondary adrenal insufficiency (17)

Hydrocodone, being an agonist, must not be taken with other central nervous system depressants as sedation and respiratory depression can result. In formulations combined with acetaminophen, hydrocodone can increase the international normalized ratio (INR) and cause bleeding.  Medications that induce or inhibit cytochrome enzymes can lead to wide variations in absorption.

The most common drug interactions are listed below:

• Alcohol
• Benzodiazepines
• Barbiturates
• other opioids
• rifampin
• phenytoin
• carbamazepine
• cimetidine,
• fluoxetine
• ritonavir
• erythromycin
• diltiazem
• ketoconazole
• verapamil
• Phenytoin
• John’s Wort
• Glucocorticoids

Considerations

Use with caution in the following:

• Patients with Hepatic Impairment: Initiate 50% of the usual dose
• Patients with Renal Impairment: Initiate 50% of the usual dose
• Pregnancy: While not contraindicated, the FDA issued a black-boxed warning since opioids cross the placenta, and prolonged use during pregnancy may cause neonatal opioid withdrawal syndrome (NOWS).
• Breastfeeding: Infants are susceptible to low dosages of opioids. Non-opioid analgesics are preferred.

Pharmacogenomic: Genetic variants in hydrocodone metabolism include ultra-rapid, extensive, and poor metabolizer phenotypes. After administration of hydrocodone, hydromorphone levels in rapid metabolizers are significantly higher than in poor metabolizers.

Oxycodone

Mechanism of Action and Metabolism

Oxycodone has been in use since 1917 and is derived from Thebaine. It is a semi-synthetic opioid analgesic that works by binding to mu-opioid receptors in the central nervous system. It primarily acts as an agonist, producing analgesic effects by inhibiting the transmission of pain signals (Altman, Clark, Huddart, & Klein, 2018).

Oxycodone is primarily metabolized in the liver by CYP3A4/5. It is metabolized in the liver to noroxycodone and oxymorphone.  The metabolite oxymorphone also has an analgesic effect and does not inhibit CYP3A4/5. Because of this metabolite, oxycodone is more potent than morphine, with fewer side effects and less drug interactions. Approximately 72% of oxycodone is excreted in urine (Altman, Clark, Huddart, & Klein, 2018).

Available Forms

Oxycodone can be administered orally, rectally, intravenously, and as an epidural. For this sake, we will focus on immediate-release and extended-release oral formulations.

• Immediate-release (IR) tablets
• IR capsules
• IR oral solutions
• Extended-release (ER) tablets

Dosing and Monitoring

The dosing of oxycodone should be individualized based on the patient's pain severity, previous opioid exposure, and response. Initial dosages for opioid naïve patients range from 5-15 mg for immediate-release formulations, while extended-release formulations are usually initiated at 10-20 mg. Dosage adjustments may be necessary based on the patient's response, but caution should be exercised. IR and ER formulations reach a steady state at 24 hours and titrating before 24 hours may lead to overdose.

Regular monitoring is essential to assess the patient's response to treatment, including pain relief, side effects, and signs of opioid misuse or addiction. Monitoring should include periodic reassessment of pain intensity, functional status, and adverse effects (Altman, Clark, Huddart, & Klein, 2018).

Side Effects and Contraindications

Common side effects of oxycodone include:

• constipation
• nausea
• sedation
• dizziness
• respiratory depression
• respiratory arrest
• hypotension
• fatal overdose

Oxycodone is contraindicated in patients with known hypersensitivity to opioids, severe respiratory depression, paralytic ileus, or acute or severe bronchial asthma. It should be used cautiously in patients with a history of substance abuse, respiratory conditions, liver or kidney impairment, and those taking other medications that may interact with opioids, such as alcohol (4).

It is also contraindicated with the following medications and classes:

• Antifungal agents
• Antibiotics
• Rifampin
• Carbamazepine
• Fluoxetine
• Paroxetine

Considerations

• Nurse practitioners should consider the variations in the mechanism of action for the following:
• Metabolism differs between males and females: females have been shown to have less concentration of oxymorphone and more CYP3A4/5 metabolites.
• Infants have reduced clearance of oxycodone, increasing side effects.
• Pediatrics have 20-40% increased clearance over adults.
• Reduced clearance with age increases the half-life of oxycodone.
• Pregnant women have a greater clearance and reduced half-life.
• Impairment of the liver reduces clearance.
• Cancer patients with cachexia have increased exposure to oxycodone and its metabolite.
• Maternal and neonate concentrations are similar, indicating placenta crossing (4)

Morphine

Mechanism of Action and Metabolism

Morphine is a naturally occurring opioid alkaloid extracted from the opium poppy. It was isolated in 1805 and is the opioid against which all others are compared. Morphine binds to mu-opioid receptors in the brain and spinal cord, inhibiting the transmission of pain signals and producing analgesia. It is a first-line choice of opioid for moderate to severe acute, postoperative, and cancer-related pain (8).

Morphine undergoes first-pass metabolism in the liver and gut. It is well absorbed and distributed throughout the body. Its main metabolites are morphine-3-glucuronide and morphine-6-glucuronide. Its mean plasma elimination half-life after intravenous administration is about 2 hours. Approximately 90% of morphine is excreted in the urine within 24 hours (8).

Available Forms

Morphine is available in various forms, including.

• immediate-release tablets
• extended release tablets
• oral IR solutions
• injectable solutions
• transdermal patches

Dosing and Monitoring

Morphine is hydrophilic and, as such, has a slow onset time. The advantage of this is that it is unlikely to cause acute respiratory depression even when injected. However, because of the slow onset time, there is more likelihood of morphine overdose due to the ability to “stack” doses in patients experiencing severe pain (Bistas, Lopez-Ojeda, & Ramos-Matos, 2023).

The dosing of morphine depends on the patient's pain severity, previous opioid exposure, and other factors. It is usually initiated at a low dose and titrated upwards as needed. Monitoring pain relief, adverse effects, and signs of opioid toxicity is crucial. Reevaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy or of dose escalation. General recommendations for initiating morphine (Bistas, Lopez-Ojeda, & Ramos-Matos, 2023).

Prescribe IR opioids instead of ER opioids.

Prescribe the lowest effective dosage, below 50 Morphine Milligram Equivalents (MME) /day.

Side Effects and Contraindications

Because morphine binds to opioid receptors in the brain and spinal cord, is metabolized in the liver and gut, and has a slow onset, the following side effects are common:

• Constipation
• Nausea
• Vomiting
• Sedation
• Dizziness
• Respiratory depression
• Pruritis
• Sweating
• Dysphoria/Euphoria
• Dry mouth
• Anorexia
• Spasms of urinary and biliary tract

Contraindications of morphine are:

• Known hypersensitivity or allergy to morphine.
• Bronchial asthma or upper airway obstruction
• Respiratory depression in the absence of resuscitative equipment
• Paralytic ileus
• Risk of choking in patients with dysphagia, including infants, children, and the elderly (8)

Concurrent use with other sedating medications: Amitriptyline, diazepam, haloperidol, chlorpromazine

Morphine interacts with the following medications:

• Ciprofloxacin
• Metoclopramide
• Ritonavir

Considerations for Nurse Practitioners

Assess for medical conditions that may pose serious and life-threatening risks with opioid use, such as the following:

• Sleep-disordered breathing, such as sleep apnea.
• Pregnancy
• Renal or hepatic insufficiency
• Age >= 65
• Certain mental health conditions
• Substance use disorder
• Previous nonfatal overdose

Fentanyl

Mechanism of Action and Metabolism

Fentanyl is a synthetic opioid more potent than morphine and was approved in 1968. Fentanyl is an agonist that works by binding to the mu-opioid receptors in the central nervous system. This binding inhibits the transmission of pain signals, resulting in analgesia. Fentanyl is often used for severe pain management, particularly in the perioperative and palliative care settings, or for severe pain in patients with Hepatic failure (8).

It is a mu-selective opioid agonist. However, it can activate other opioid receptors in the body, such as the delta and kappa receptors, producing analgesia. It also activates the Dopamine center of the brain, stimulating relaxation and exhilaration, which is responsible for its high potential for addiction (8).

Indications for fentanyl are as follows:

• Preoperative analgesia
• Anesthesia adjunct
• Regional anesthesia adjunct
• General anesthesia
• Postoperative pain control
• Moderate to severe acute pain (off-label)

Available Forms

• Fentanyl is available in various forms, including:
• transdermal patches
• injectable solutions
• lozenges
• nasal sprays
• oral tablets (8)

Dosing and Monitoring

Fentanyl is metabolized via the CYP3A4 enzyme in the liver. It has a half-life of 3 to 7 hours, and 75% of Fentanyl is excreted in the urine and 9% in feces.

The dosing of fentanyl depends on the route of administration and the patient's needs. For example, transdermal patches are typically applied every 72 hours, while injectable solutions are titrated to achieve the desired analgesic effect. Monitoring should include assessing pain levels, respiratory rate, blood pressure, and sedation scores (8).

Fentanyl is most dosed as follows:

• Post-operative pain control
• 50 to 100 mcg IV/IM every 1 to 2 hours as needed; alternately 0.5 to 1.5 mcg/kg/hour IV as needed. Consider lower dosing in patients 65 and older.

PCA (patient-controlled analgesia): 10 to 20 mcg IV every 6 to 20 minutes as needed; start at the lowest effective dose for the shortest effective duration - refer to institutional protocols (8).

Moderate to severe acute pain (off-label) 1 to 2 mcg/kg/dose intranasally each hour as needed; the maximum dose is 100 mcg. Use the lowest effective dose for the shortest effective duration (8).

Side Effects and Contraindications

Common side effects of fentanyl include:

• respiratory depression
• sedation
• constipation
• nausea
• vomiting
• euphoria
• confusion
• respiratory depression/arrest
• visual disturbances
• dyskinesia
• hallucinations
• delirium
• narcotic ileus
• muscle rigidity
• addiction
• loss of consciousness
• hypotension
• coma
• death (8).

The use of fentanyl is contraindicated in patients in the following situations:

• After operative interventions in the biliary tract, these may slow hepatic elimination of the drug.
• With respiratory depression or obstructive airway diseases (i.e., asthma, COPD, obstructive sleep apnea, obesity hyperventilation, also known as Pickwickian syndrome)
• With liver failure
• With known intolerance to fentanyl or other morphine-like drugs, including codeine or any components in the formulation.
• With known hypersensitivity (i.e., anaphylaxis) or any common drug delivery excipients (i.e., sodium chloride, sodium hydroxide) (8).

Considerations for Nurse Practitioners

Nurse practitioners prescribing fentanyl should thoroughly assess the patient's pain, medical history, and potential risk factors for opioid misuse. They should also educate patients about the proper use, storage, and disposal of fentanyl. It should be used cautiously in patients with respiratory disorders, liver or kidney impairment, or a history of substance abuse. Fentanyl is contraindicated in patients with known hypersensitivity to opioids and those without exposure to opioids.

Alcohol and other drugs, legal or illegal, can exacerbate fentanyl's side effects, creating multi-layered clinical scenarios that can be complex to manage. These substances, taken together, generate undesirable conditions that complicate the patient's prognosis (8).

Hydromorphone

Mechanism of Action and Metabolism

Hydromorphone is a semi-synthetic opioid derived from morphine. It binds to the mu-opioid receptors in the central nervous system. It primarily exerts its analgesic effects by inhibiting the release of neurotransmitters involved in pain transmission, thereby reducing pain perception. Hydromorphone also exerts its effects centrally at the medulla level, leading to respiratory depression and cough suppression (1).

Hydromorphone is indicated for:

• moderate to severe acute pain
• severe chronic pain
• refractory cough suppression (off-label) (1)

Available Forms

Hydromorphone is available in various forms, depending on the patient’s needs and severity of pain.

• immediate-release tablet
• extended release tablets
• oral liquid
• injectable solution
• rectal suppositories

Dosing and Monitoring

The immediate-release oral formulations of hydromorphone have an onset of action within 15 to 30 minutes. Peak levels are typically between 30 and 60 minutes with a half-life of 2 to 3 hours. Hydromorphone is primarily excreted through the urine.

The dosing of hydromorphone should be individualized based on the patient's pain intensity, initiated at the lowest effective dose, and adjusted gradually as needed. Close monitoring of pain relief, adverse effects, and signs of opioid toxicity is essential. Patients should be assessed regularly to ensure they receive adequate pain control without experiencing excessive sedation or respiratory depression.

The following are standard dosages that should only be administered when other opioid and non-opioid options fail.

• Immediate-release oral solutions dosage: 1 mg/1 mLoral tablets are available in 2 mg, 4 mg, and 8 mg.
• Extended-release oral tablets are available in dosages of 8 mg, 12 mg, 16 mg, and 32 mg.
• Injection solutions are available in concentrations of 1 mg/mL, 2 mg/mL, 4 mg/mL, and 10 mg/mL.
• Intravenous solutions are available in strengths of 2 mg/1 mL, 2500 mg/250 mL, ten mg/1 mL, and 500 mg/50 mL.
• Suppositories are formulated at a strength of 3 mg (1).

Side Effects and Contraindications

Hydromorphone has potential adverse effects on several organ systems, including the integumentary, gastrointestinal, neurologic, cardiovascular, endocrine, and respiratory.

Common side effects of hydromorphone include:

• Constipation
• Nausea
• Vomiting
• Dizziness
• Sedation
• respiratory depression
• pruritus
• headache
• Somnolence
• Severe adverse effects of hydromorphone include:
• Hypotension
• Syncope
• adrenal insufficiency
• coma
• raised intracranial pressure.
• seizure
• suicidal thoughts
• apnea
• respiratory depression or arrest
• drug dependence or withdrawal
• neonatal drug withdrawal syndrome
• Hydromorphone is contraindicated in patients with:
• known allergies to the drug, sulfites, or other components of the formulation.
• known hypersensitivity to opioids.
• severe respiratory depression
• paralytic ileus
• acute or severe bronchial asthma (1).

Caution should be exercised in patients with:

• respiratory insufficiency
• head injuries
• increased intracranial pressure.
• liver or kidney impairment.

Considerations for Nurse Practitioners

As nurse practitioners, it is crucial to assess the patient's pain intensity and overall health status before initiating Hydromorphone. Start with the lowest effective dose and titrate carefully for optimal pain control. Regular monitoring for adverse effects, signs of opioid toxicity, and therapeutic response is essential. Educate patients about the potential side effects, proper dosing, and the importance of not exceeding prescribed doses. Additionally, nurse practitioners should be familiar with local regulations and guidelines regarding opioid prescribing and follow appropriate documentation and monitoring practices.

Additional Considerations

In terminal cancer patients, clinicians should not restrain opioid therapy even if signs of respiratory depression become apparent.

Hydromorphone requires careful administration in cases of concurrent psychiatric illness.

Specific Patient Considerations:

• Hepatic impairment and Renal Impairment: Initiate hydromorphone treatment at one-fourth to one-half of the standard starting dosage, depending on the degree of impairment.
• Pregnancy considerations: Hydromorphone can traverse the placental barrier and induce NOWS.
• Breastfeeding considerations: Nonopioid analgesic agents are preferable for breastfeeding women.
• Older patients: hydromorphone is categorized as a potentially inappropriate medication for older adults (1).

Tramadol

Mechanism of Action and Metabolism

Tramadol is a Schedule IV opioid medication with a higher potential for dependency and misuse than non-opioid medications. It binds to opioid receptors in the central nervous system, inhibiting the reuptake of norepinephrine and serotonin. It also has weak mu-opioid receptor agonist activity.

The liver metabolizes tramadol mediated by the cytochrome P450 pathways (particularly CYP2D6) and is mainly excreted through the kidneys.

Tramadol is used for moderate to severe pain.

Available Forms of Tramadol include:

• Immediate-release-typically used for acute pain management.
• Extended-release-used for chronic pain.

Dosing and Monitoring

Tramadol has an oral bioavailability of 68% after a single dose and 90–100% after multiple doses and reaches peak concentrations within 2 hours. Approximately 75% of an oral dose is absorbed, and the half-life of tramadol is 9 hours (18).

Tramadol dosing should be individualized based on the patient's pain severity and response.

The initial dose for adults is usually 50-100 mg orally every 4-6 hours for pain relief. The maximum daily dose is 400 mg for immediate-release formulations and 300 mg for extended-release formulations (18).

It is essential to monitor the patient's pain intensity, response to treatment, and any adverse effects. Regular reassessment and adjustment of the dosage may be necessary.

Side Effects and Contraindications

Tramadol is responsible for severe intoxications leading to consciousness disorder (30%), seizures (15%), agitation (10%), and respiratory depression (5%). The reactions to Tramadol suggest that the decision to prescribe should be carefully considered.

Common Side Effects of Tramadol Include:

• Nausea
• Vomiting
• Dizziness
• Constipation
• Sedation
• Headache
• CNS depression
• Seizure
• Agitation
• Tachycardia
• Hypertension
• reduced appetite
• pruritus and rash
• gastric irritation

Serious side effects include:

• respiratory depression
• serotonin syndrome
• seizures

Contraindications

Tramadol is contraindicated in patients with:

• history of hypersensitivity to opioids
• acute intoxication with alcohol
• opioids, or other psychoactive substances
• Patients who have recently received monoamine oxidase inhibitors (MAOIs)

Additionally, the following can be observed in tramadol intoxication:

• miosis
• respiratory depression
• decreased level of consciousness
• hypertension
• tremor
• irritability
• increased deep tendon reflexes

Poisoning leads to:

• multiple organ failure
• coma
• cardiopulmonary arrest
• death

Considerations for Nurse Practitioners

Tramadol has been increasingly misused with intentional overdoses or intoxications. Suicide attempts were the most common cause of intoxication (52–80%), followed by abuse (18–31%), and unintentional intoxication (1–11%). Chronic tramadol or opioid abuse was reported in 20% of tramadol poisoning cases. Fatal tramadol intoxications are uncommon except when ingested concurrent with depressants, most commonly benzodiazepines and alcohol (18).

Tramadol poisoning can affect multiple organ systems:

• gastrointestinal
• central nervous system: seizure, CNS depression, low-grade coma, anxiety, and over time anoxic brain damage
• Cardiovascular system: palpitation, mild hypertension to life-threatening complications such as cardiopulmonary arrest
• respiratory system
• renal system: renal failure with higher doses of tramadol intoxication
• musculoskeletal system: rhabdomyolysis
• endocrine system: hypoglycemia, serotonin syndrome (18)

Cannabis

Mechanism of Action and Metabolism

Cannabis is classified as a Schedule I status. It contains various cannabinoids, with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most studied. THC primarily acts on cannabinoid receptors in the brain, producing psychoactive effects, while CBD has more diverse effects on the nervous system. These cannabinoids interact with the endocannabinoid system, modulating neurotransmitter release and influencing various physiological processes (32).

Similar to opioids, cannabinoids are synthesized and released in the body by synapses that act on the cannabinoid receptors present in presynaptic endings (32). They perform the following actions related to analgesia:

• Decrease the release of neurotransmitters.
• Activate descending inhibitory pain pathways.
• Reduce postsynaptic sensitivity and alleviate neural inflammation.
• Modulate CB1 receptors within central nociception processing areas and the spinal cord, resulting in analgesic effects.
• Attenuate inflammation by activating CB2 receptors (32).
• Emerging research shows cannabis is indicated for:
• Migraines
• chronic pain
• back pain
• arthritic pain
• pain associated with cancer and surgery.
• neuropathic pain
• diabetic neuropathic pain when administered early in the disease progression.
• sickle cell disease
• cancer
• inflammatory bowel disease (32)

Available Forms

Cannabis refers to products sourced from the Cannabis sativa plant. There are differences between cannabis, cannabinoids, and cannabidiol (CBD). Cannabinoids are extracted from the cannabis plants. Cannabinoid-based treatments, such as dronabinol and CBD, are typically approved medical interventions for specific indications. THC (9-tetrahydrocannabinol) is the psychoactive component of the cannabis plant. CBD is a non-psychoactive component (32).

Cannabis can be consumed in different forms, each with a different onset and duration. Patients may have individual preferences, including:

• smoking/vaporizing dried flowers.
• consuming edibles
• tinctures or oils
• applying topicals (32)

Dosing and Monitoring

Inhaling marijuana via the lungs by smoking or vaping causes maximum plasma concentration within minutes. Psychiatric effects begin within seconds to a few minutes after inhalation and peak after 15 to 30 minutes. The effect diminishes throughout 2 to 3 hours (32).

Oral ingestion of marijuana causes psychiatric effects that typically occur between 30 and 90 minutes and reach maximum effect after 2 to 3 hours. Ingested marijuana effects last about 4 to 12 hours (32).

Dosing cannabis is challenging due to variations in potency and individual responses. Start with low doses and titrate slowly to achieve the desired effect while minimizing side effects. Regular monitoring is crucial, including assessing symptom relief, adverse effects, and potential drug interactions. Encourage patients to keep a diary to track their cannabis use and its effects (32).

Side Effects and Contraindications

Cannabis can exacerbate mental health conditions such as anxiety and psychosis. Common side effects of cannabis include (32):

• Dizziness
• dry mouth
• increased heart rate
• impaired memory
• psychoactive effects

Contraindications include:

• Pregnancy
• Breastfeeding
• heart disease
• respiratory conditions
• history of substance abuse
• mental health disorders

Case Study

Mary is agreeable to trying an increased dose of Gabapentin. Mary would also like to see a counselor to discuss her past and get help with her anxiety. You made an appointment for Mary to see a Licensed Clinical Social Worker in your clinic.

You read the side effects and warnings for Gabapentin, and it is unsafe to use Gabapentin and Tramadol together since they are both depressants. You order a non-steroidal drug for Mary's somatic knee pain and make a consult for imaging studies on her left knee. You also make a referral to Orthopedics.

You educated Mary about the side effects of Gabapentin and scheduled a follow-up appointment. The day after Mary began her treatment with the increased Gabapentin, you called Mary to follow up on its effect. Mary still has pain, but she is not having any untoward side effects. Gabapentin may not work immediately so you will schedule a follow-up call in 3 days.

Opioid Use, the Opioid Epidemic, and Statistics

The use and misuse of opioids has become a pressing public health concern, leading to a global epidemic. The history of opioid use, the opioid epidemic, and associated statistics provide essential context for healthcare professionals in addressing this public health crisis. More importantly, it is estimated that 1 in 4 patients receiving prescription opioids in primary care settings will misuse them. In addition, 50% of opioid prescriptions are written by primary care providers, including nurse practitioners (22). Understanding the factors contributing to the epidemic and the magnitude of its impact is crucial for effective prevention, intervention, and treatment strategies.

History of Opioid Use

Opioids have a long history of medicinal use, dating back to ancient civilizations. They have been a drug of choice for pain relief for thousands of years. The introduction of synthetic opioids in the 19^th century, such as morphine and later heroin, revolutionized pain management. However, their potential for addiction and misuse soon became apparent (16).

The Opioid Epidemic

The opioid epidemic refers to the surge in opioid misuse, addiction, and overdose deaths. The epidemic gained momentum in the late 1990s with increased prescribing of opioids for chronic pain (43).

No doubt, increased prescribing put opioids in the hands of consumers, but increased prescribing resulted from a multifactorial influence. One of the main influences was aggressive marketing by pharmaceutical companies, which has been well publicized. However, due to the long history of underprescribing pain medications for fear of misuse and addiction, the medical community was primed to expand its opioid prescribing practices (31).

A historical event that increased comfort with prescribing opioids, in the writer's opinion, was the introduction of the Medicare Hospice Benefit in 1986. Medical directors must be contracted or employed by hospices, and these medical directors had or soon gained pain management expertise. To further promote hospice and effective pain management, the hospice medical directors, with newly acquired skills, provided education throughout medical communities about pain management and specifically to decrease the fear of using opioids. Pharmacies and attending physicians grew accustomed to giving opioids for home use. Hospice care is for terminally ill patients, defined as a life expectancy of 6 months or less. Still, the reality is that hospice discharges 12 to 40% of patients for ineligibility and other reasons.

A more prominent factor in increasing opioid prescribing was the 1996 American Pain Society's introduction of pain as "the 5^th Vital sign." Soon after, The Joint Commission promoted pain as "the 5^th Vital Sign" and began compliance surveys in healthcare organizations requiring pain assessment details to be as prominent as blood pressure and heart rate. The Joint Commission cited a quote from 1968 by a nurse from the University of California Los Angeles, Margo McCaffrey, who defined pain as "…Whatever the experiencing person says it is, existing whenever s/he says it does." The Joint Commission accreditation programs pursued pain management as part of the accreditation process throughout its healthcare accreditation programs, including hospice accreditation by 1989 per TJC Timeline (48).

The National Institute of Health published an article about the Joint Commission's role in the opioid epidemic, particularly regarding the definition of pain, "This definition emphasizes that pain is a subjective experience with no objective measures. It also stresses that the patient, not the clinician, is the authority on the pain and that their self-report is the most reliable indicator of pain. This set the tone for clinicians: Patients are always to be trusted to report pain accurately” (45).

Statistics on the Opioid Epidemic

In the United States alone, over 500,000 people died from opioid overdoses between 1999 and 2017. The number of opioid-related overdose deaths continues to increase, with synthetic opioids, mainly illicitly manufactured Fentanyl, playing a significant role in recent years (46). Fentanyl-laced drugs, such as marijuana, are increasingly sold knowing and unknowingly to introduce medications with a high addiction rate, thus creating new consumers. This practice can potentially increase deaths due to the imprecise nature of manufacturing (16).

Opioid-related hospitalizations have also risen substantially. In 2014, there were approximately 1.27 million hospitalizations related to opioids in the United States. These hospitalizations not only place a burden on healthcare systems but also reflect the severe consequences of opioid misuse (3).

Federal Regulations on Opioid Prescribing

The history of substance use disorder prevention that promotes opioid recovery and treatment for patients and communities can be traced back to the early 20^th century. However, the current approach to addressing opioid addiction and promoting healing has evolved significantly in recent times (36).

In the early 1900s, health professionals treated opioid addiction with punitive measures, including incarceration and moralistic approaches. The focus was on punishing individuals rather than providing effective treatment. This approach persisted for several decades until the mid-20^th century when the medical community started recognizing addiction as a medical condition rather than a moral failing (36).

The Controlled Substances Act (CSA), introduced in 1970, was a response to increasing drug abuse and illicit drug trafficking in the United States. The CSA is a federal law regulating the manufacture, possession, distribution, and use of certain substances, including drugs and medications, that can potentially cause abuse and dependence. Its primary purpose is to combat drug abuse, reduce drug-related crimes, and protect public health and safety. The Drug Enforcement Agency (DEA) plays a crucial role in enforcing the CSA by monitoring and controlling controlled substance production, distribution, and use (31).

In the 1990s, the significant increase in opioid prescribing, leading to a surge in opioid addiction and overdose deaths, prompted a shift in focus toward prevention. Efforts were made to educate healthcare providers about the risks of overprescribing opioids and to implement prescription drug monitoring programs to track and prevent abuse (36).

The Comprehensive Addiction and Recovery Act (CARA) was signed into law in 2016 to expand access to treatment and recovery services for opioid addiction. This legislation allocated funding for prevention, treatment, recovery, and support services while promoting evidence-based practices and programs (36).

The Centers for Disease Control and Prevention (CDC) published guidelines in 2016 for prescribing opioids for chronic pain, which was updated in 2022. These guidelines emphasize the importance of non-opioid alternatives, using the lowest effective dose for the shortest duration, and assessing the benefits and risks of continued opioid therapy (13).

Furthermore, the Substance Use Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT) was signed into law in 2018, providing additional resources to address the opioid crisis. This legislation expanded access to medication-assisted treatment (MAT), increased the availability of naloxone, a medication used to reverse opioid overdose, and enhanced support for recovery housing (36).

In recent years, there has been a growing recognition of the importance of a comprehensive approach to opioid addiction, including harm reduction strategies, increased access to naloxone, and the integration of mental health services. Communities and organizations have been working together to address the underlying issues contributing to addiction, such as poverty, trauma, and social determinants of health (50).

Overall, the history of substance use disorder prevention that promotes opioid recovery and treatment has evolved from a punitive approach to a more compassionate and evidence-based model. Efforts are now focused on prevention, early intervention, and expanding access to comprehensive treatment and support services for individuals and communities affected by opioid addiction (36).

The most current federal regulations on opioid prescribing for healthcare providers are the amendments to the CSA in 2018, which added new rules to limit the quantity and duration of opioid prescriptions for acute pain to seven days. In 2022, the CDC updated recommendations to the Clinical Practice Guidelines for Prescribing Opioids for Pain.

The 2022 CDC guidelines are summarized below (13):

1. Non-opioid therapies should be considered the first-line treatment for chronic pain.
2. Establish clear treatment goals with patients, including realistic pain management and functional improvement expectations.
3. Conduct a thorough risk assessment for potential harms before initiating opioid therapy.
4. When opioids are used, start with the lowest effective dose and consider immediate-release opioids instead of extended-release or long-acting opioids.
5. Prescribe the lowest effective dose for the shortest duration possible, typically three days or less and rarely exceeding seven days.
6. Reassess benefits and risks within one day after prescribing opioids, including checking the prescription drug monitoring database.
7. Avoid prescribing opioids and benzodiazepines concurrently whenever possible due to the increased risk of overdose and death.
8. Offer naloxone to patients at increased risk of opioid overdose, including those with a history of overdose, substance use disorder, or concurrent benzodiazepine use.
9. When opioids are no longer needed, taper the dose gradually to minimize withdrawal symptoms.
10. Arrange an evidence-based treatment for patients with opioid use disorder, including medication-assisted treatment (Naltrexone, Buprenorphine, or Methadone).

Safe Prescribing and Prescription Monitoring Program

Prescription Drug Monitoring Programs (PDMP) are state-run electronic databases that track.

the prescribing and dispensing of controlled substances. PDMPs are designed to improve patients.

care and safety by giving clinicians access to patients' prescription histories, allowing them to make informed decisions when prescribing controlled substances. PDMPs help identify patients at risk of substance misuse or prescription drug overdose. They also enable clinicians to identify potential drug interactions and prevent opioid diversion (14).

PDMPs collect and store data from pharmacies and prescribers in a centralized database. Clinicians can access this database to review a patient's prescription history, including the types of medications prescribed, the prescribers involved, and the dispensing pharmacies (14).

In many states, PDMP use is mandated by law, and nurse practitioners may be required to register and use the system. It is essential to understand state-specific laws and regulations regarding PDMP use.

PDMPs have some limitations, such as incomplete data or delays in reporting. The CDC emphasizes that clinicians should use PDMP data for their clinical assessment and other relevant information to make informed decisions about prescribing controlled substances. Still, PDMP cannot be used as the sole basis for denying or providing treatment (14).

Case Study

After five days on Gabapentin, Mary was doing well, and her neuropathic pain had decreased to 3/10. However, Mary suffered a fall after her knee "gave out" and injured her knee and back. She was in severe pain, and her family drove her to the ER. The ER doctors saw Mary, and orthopedics were consulted. Mary has surgery scheduled for a knee replacement a week from now.

Mary was prescribed Vicodin because she was in excruciating pain, but her prescription only allowed enough medication for two days. Mary has made an appointment with you to renew her prescription.

You evaluate Mary because you know that concomitant use of Gabapentin and opioids puts Mary at risk for respiratory depression and possible side effects, including accidental overdose.

Mary stated she has been more alert the past 24 hours and is afraid her functional status will continue to decline if she does not have more Vicodin because the pain in her back and knee makes it difficult to stand. You assess Mary. Mary stated she occasionally drinks alcohol but has not had a drink since she moved. She has no familial history of substance abuse or mental health disorders.

Mary's mother stayed at her house to help her for the first 24 hours after Mary's return from the ER, but Mary is providing her care now.

You check the PDMP database and see that Mary was prescribed eight pills she has taken over the last 48 hours.

Since the Vicodin has been effective without untoward side effects, and Mary's function is improving, you decide to refill the prescription of Vicodin. You will taper the dose to three Vicodin daily for two days and two for one day. Mary will be near her appointment for a knee replacement as well.

Preventing Opioid Use Disorder

As previously discussed, opioid addiction is a growing concern worldwide, affecting individuals from all walks of life. According to the CDC, "Anyone who takes prescription opioids can become addicted to them" (14).

As frontline healthcare professionals, nurse practitioners must recognize the signs of opioid addiction to provide timely intervention and support. This section will outline the key indicators of opioid addiction.

Physical Symptoms

Physical symptoms are often the first noticeable signs of opioid addiction. These symptoms may include constricted pupils, drowsiness, slurred speech, impaired coordination, and increased sensitivity to pain. Additionally, individuals struggling with opioid addiction may exhibit frequent flu-like symptoms, such as a runny nose, sweating, itching, or gastrointestinal issues.

Behavioral Changes

Opioid addiction can significantly impact an individual's behavior. These may include increased secrecy, frequent requests for early prescription refills, doctor shopping (seeking prescriptions from multiple healthcare providers), neglecting personal hygiene, and experiencing financial difficulties due to excessive spending on opioids (37).

Social Isolation

Opioid addiction often leads to social withdrawal and isolation. Individuals struggling with opioid addiction may distance themselves from family, friends, and social activities they once enjoyed. They may exhibit erratic mood swings, become defensive or hostile when confronted about their drug use, and display a general lack of interest in previously important activities (30).

Psychological Changes

The psychological impact of opioid addiction is significant. Individuals with opioid addiction may exhibit increased anxiety, depression, irritability, and restlessness. They may also experience cognitive impairments, memory lapses, and difficulties in decision-making. Healthcare professionals should be attentive to these changes, as they can indicate opioid addiction (51).

Tolerance and Withdrawal Symptoms

The development of tolerance and withdrawal symptoms are critical signs of opioid addiction. Individuals may require increased dosages of opioids to achieve the desired effect, indicating a growing tolerance. Furthermore, withdrawal symptoms such as muscle aches, nausea, vomiting, insomnia, and intense cravings for opioids may occur when the drug is discontinued or reduced abruptly (51).

Opioid Overdose

The management of opioid overdose, withdrawal, and addiction requires a comprehensive approach that combines pharmacological interventions with psychosocial support. Naloxone remains a vital tool for reversing opioid overdose, while medications such as Methadone, buprenorphine, and naltrexone play crucial roles in withdrawal and addiction treatment (National Institute of Health, 2023). Nurse practitioners must stay vigilant and informed about the evolving landscape of medications. This section aims to provide a comprehensive review of medications and treatment strategies for opioid overdose, withdrawal, and addiction and is excerpted from the NIH (40).

Naloxone

Mechanism of Action and Metabolism

Naloxone is an opioid receptor antagonist. It works by binding to opioid receptors and displacing any opioids present, thereby reversing the effects of opioid overdose. It has a higher affinity for opioid receptors than most opioids, effectively blocking their action.

Naloxone is indicated for emergency intervention of opioid overdose. It effectively reverses respiratory depression and other life-threatening effects. Studies suggest the potential benefits of combining naloxone with other medications, such as buprenorphine (see below), to improve outcomes. Initiatives promoting community-based naloxone distribution programs have shown promising results in reducing opioid-related deaths.

Available Forms

Naloxone is available in various formulations:

• Intranasal
• Intramuscular
• Intravenous
• auto-injectors.

The most used form is the intranasal spray, which is easy to administer and requires no specialized training. Intranasal naloxone formulations have gained popularity due to their ease of use and increased availability. A recent study showed that the non-FDA-approved compound spray was far less effective than either FDA compound (15).

Dosing and Monitoring

The recommended initial dose of naloxone for opioid overdose is 2mg intranasally or 0.4mg to 2mg intramuscularly or intravenously. If the patient does not respond within 23- minutes, additional doses may be administered every 2-3 minutes. Continuous monitoring of the patient's respiratory status is essential, as repeat doses may be required due to the short half-life of naloxone.

Side Effects and Contraindications

Naloxone has been shown not to affect individuals without opioids in their system.

Common side effects of naloxone include

• Withdrawal symptoms: increased heart rate, sweating, and agitation
• nausea
• vomiting
• headache

Contraindications include known hypersensitivity to naloxone and situations where the use of naloxone may be unsafe or not feasible.

Considerations for Nurse Practitioners

Fentanyl and other opioids have a rapid onset, and the need to act quickly is paramount. As mentioned previously, the ease of use and higher plasma concentrations using the FDA-approved 4-mg FDANxSpray device compared with the locally compounded nasal sprays should be considered when ordering Naloxone (15).

Fentanyl and other potent synthetic opioids may require multiple administrations of naloxone to achieve reversal of an overdose (Chiang, Gyaw, & Krieter, 2019). As a nurse practitioner prescribing naloxone, it is crucial to assess the patient's risk factors for opioid overdose, such as a history of substance use disorder or chronic pain management. Education regarding the proper administration of naloxone should be provided to the patients and their caregivers. Additionally, it is essential to provide resources for follow-up care, including addiction treatment and ongoing support.

Methadone

Mechanism of Action and Metabolism

Methadone is a long-acting opioid agonist that effectively suppresses withdrawal symptoms and reduces cravings. It binds to the same opioid receptors in the brain as other opioids. It relieves withdrawal symptoms and reduces cravings by blocking the euphoric effects of opioids, thus helping individuals with opioid dependence to achieve stability (33).

Available Forms

Methadone is available in oral tablets and liquid formulations. The oral tablet is the most used form and is typically administered once daily (33).

Dosing and Monitoring

Methadone dosing is individualized based on the patient's response and needs. Initially, the dose often started low and gradually increased until the patient reached a stable dose. Dosing may need to be adjusted based on the patient's response, adherence, and any changes in their overall health. Regularly monitoring the patient's vital signs, urine drug screens, and assessment of their withdrawal symptoms and cravings is essential.

Side Effects and Contraindications

Common side effects of methadone include:

• Constipation
• dry mouth
• drowsiness
• sweating
• weight gain
• respiratory depression

Contraindications include:

• known hypersensitivity to methadone
• severe asthma
• respiratory depression
• certain heart conditions (33).

Considerations for Nurse Practitioners

As a nurse practitioner prescribing methadone, conducting a comprehensive assessment of the patient's medical history, current medications, and substance use history is crucial. Opioid treatment programs or specialized clinics are often involved in methadone treatment, so collaboration and coordination of care with these programs are essential. Regularly monitoring the patient's progress, adherence, and potential side effects or drug interactions is essential. Additionally, providing education on the risks and benefits of methadone and the importance of adherence to the prescribed regimen is crucial for successful treatment outcomes.

Buprenorphine

Mechanism of Action and Metabolism

Buprenorphine is a partial opioid agonist with a ceiling effect that minimizes the risk of overdose while reducing withdrawal symptoms. Buprenorphine is a partial opioid agonist that binds to the same receptors as other opioids but produces a weaker response. It has a high affinity for the mu-opioid receptors, which helps reduce cravings and withdrawal symptoms in individuals with opioid dependence.

Available Forms

Buprenorphine is available in different formulations, including sublingual tablets, buccal films, and extended-release injections. The sublingual tablets have different strengths, such as 2mg, 4mg, 8mg, and 12mg. Buprenorphine is taken as a daily tablet or weekly or monthly injection.

Dosing and Monitoring

The dosing of buprenorphine varies depending on the individual's opioid dependence severity and treatment phase. Initially, a low dose (e.g., 2-4mg) is given, and it may gradually increase to a maintenance dose of 8-24 mg daily. Regular monitoring is essential to assess the patient's response, adherence, and potential side effects.

Side Effects and Contraindications

Common side effects of buprenorphine include:

• Constipation
• Nausea
• Headache
• Insomnia
• Sweating

Serious side effects are rare but can include:

• Respiratory depression
• Allergic reactions

Buprenorphine is contraindicated in individuals with:

• Severe respiratory insufficiency
• Acute intoxication with opioids
• Known hypersensitivity

Considerations for Nurse Practitioners

Nurse practitioners can prescribe buprenorphine for opioid dependence treatment under the Drug Addiction Treatment Act (DATA). To become eligible, they must complete specific training requirements and obtain a waiver from the Substance Abuse and Mental Health Services Administration (SAMHSA). Nurse practitioners should assess patients thoroughly, including their opioid use history, comorbidities, and medication compatibility, while ensuring appropriate counseling and referral for comprehensive treatment (40).

Clonidine + Lofexidine

Mechanism of Action and Metabolism:

Both Clonidine and Lofexidine are alpha-2 adrenergic agonists. They work by stimulating alpha-2 receptors in the brain, which reduces sympathetic outflow and norepinephrine release. This results in decreased sympathetic activity, leading to various effects such as reduced blood pressure, decreased heart rate, and alleviated withdrawal symptoms (28).

Available Forms

Clonidine is available in oral tablets and patches. Lofexidine is available in oral tablets and is taken as needed (40).

Dosing and Monitoring

For opioid withdrawal, the Clonidine dose ranges from 0.1-0.3 mg every 4-6 hours. Lofexidine is usually initiated at 0.53 mg three times daily, and the dose can be increased to 2.88 mg daily. Monitoring blood pressure and heart rate is essential during treatment (40).

Side Effects and Contraindications:

Common side effects of both medications include:

• dry mouth
• sedation
• dizziness
• constipation
• orthostatic hypotension (40).

Both medications are contraindicated in patients with:

• Hypotension
• Bradycardia
• heart block
• history of hypersensitivity to the drugs (40).

Considerations for Nurse Practitioners:

An early study of lofexidine vs. clonidine for withdrawal symptoms showed that treatment with lofexidine resulted in lower withdrawal symptoms, fewer mood problems, less sedation, and hypotension. There were no significant differences in craving levels, morphine metabolites in urine, or dropout rates when both were compared.

Lofexidine can be a safe option for outpatient treatment as it does not lead to hypotension. However, nurse practitioners must closely monitor patients' blood pressure and heart rate during treatment and educate them about possible side effects. If patients experience any concerning symptoms, they should inform their nurse practitioner immediately.

Gradual dose reduction of Clonidine is crucial to prevent rebound hypertension. Before prescribing either medication, nurse practitioners should assess for any contraindications or potential drug interactions (19).

Emerging Therapies for Withdrawal

Extended-release naltrexone: Naltrexone is an opioid receptor antagonist that blocks the effects of opioids, reducing the risk of relapse. It is taken as a monthly injection.

Alpha-2 adrenergic agonists: Emerging evidence suggests the potential use of dexmedetomidine and guanfacine for managing opioid withdrawal symptoms.

Medication-Assisted Treatment (MAT):

Methadone was introduced in the 1960s and marked a significant turning point in opioid addiction treatment or MAT. Along with counseling and behavioral therapies, MAT became the cornerstone of opioid addiction recovery.

Examples of medications used:

• Methadone
• Buprenorphine:
• Naltrexone:

Adjunctive Pharmacotherapies:

Antidepressants: Selective serotonin reuptake inhibitors and tricyclic antidepressants may help manage co-occurring depression and anxiety.

Anticonvulsants:

Medications like Gabapentin and pregabalin show promise in reducing opioid cravings and improving treatment outcomes.

Other Substance Use Disorders

Patients in pain may struggle with Substance Use Disorders other than Opioid Use Disorder. Substance use disorders may often occur with mental health conditions such as anxiety, depression, and bipolar disorder. In addition, many individuals engage in polydrug use. Understanding the most common Substance Use Disorders aids in a comprehensive assessment of the patient and the development of appropriate treatment plans (28).

Alcohol Use Disorder (AUD):

The prevalence of AUD worldwide was estimated to be 9.8% in men and 5.5% in women in 2016 (28).

Cannabis Use Disorder (CUD):

the prevalence of CUD in the United States increased from 2.18% in 2001-2002 to 2.89% in 2012-2013. (28).

Cocaine Use Disorder:

According to the National Survey on Drug Use and Health (NSDUH), in 2019, approximately 1.9 million Americans aged 12 or older had cocaine use disorder in the past year (44).

Methamphetamine Use Disorder:

A study published in Drug and Alcohol Dependence reported that the prevalence of methamphetamine use disorder in the United States was estimated to be 0.2% in 2015-2016 (6).

Drug Diversion and Illegal opioids

Misuse of opioids is facilitated by diversion and is defined as "the transfer of drugs from lawful to unlawful use" (24). Most commonly, this occurs when family and friends share prescribed opioids with other family and friends. Opioids and other controlled drugs are also diverted from healthcare facilities. Statistics show that healthcare facility diversion has increased since 2015 (24)

Diversion affects patients, healthcare workers, healthcare facilities, and public health. Patients experience substandard care due to ineffective pain management and impaired healthcare workers. In addition, affected patients are at risk of infections from compromised syringes (24).

Healthcare employees who divert are at risk of overdose and death. If caught, they face criminal prosecution and malpractice suits. Healthcare facilities also bear the cost of diverted drugs via internal investigations, follow-up care for affected patients, regulatory fines for inadequate safeguards, and declining public trust (24).

Despite the enormous consequences of drug diversion, healthcare facilities have implemented few processes to detect and deter the diversion of controlled substances (24).

Patient Teachings and Considerations

Opioids have significant side effects and carry a risk of addiction and overdose. Nurse practitioners can decrease the risks of misuse and addiction by educating patients on appropriate disposal, safe storage, and potential signs of addiction. Taking additional time to provide teaching nurse practitioners can promote patient safety, informed decision-making, and responsible opioid use.

Safe Storage and Disposal:

• Teach patients to store opioids securely, out of reach of children, pets, visitors, and non-caregiver family members, to prevent accidental ingestion or misuse (13). Only the caregiver, if applicable, or the patient should have access to pain medications.
• Instruct patients on proper disposal methods, such as using drug take-back programs or mixing opioids with undesirable substances (e.g., coffee grounds) before throwing them away (11) (13).

Medication Adherence:

• Emphasize the importance of taking opioids as prescribed, at the correct dose and frequency, to achieve optimal pain relief.
• Encourage patients to notify their healthcare provider if they experience inadequate pain control or side effects (35).

Potential Side Effects:

• Educate patients about common side effects of opioids, including constipation, nausea, sedation, and respiratory depression.
• Discuss strategies to manage side effects, such as maintaining adequate hydration, consuming a fiber-rich diet, and using over-the-counter laxatives as needed (11).

Risk of Dependence and Addiction:

• Explain the potential for opioid dependence and addiction, especially with long-term use or a history of substance abuse.
• Encourage patients to promptly report signs of opioid misuse, such as craving, loss of control, or continued use despite negative consequences (51).

Avoiding Alcohol and Other Central Nervous System Depressants:

• Instruct patients to avoid consuming alcohol or other medications that can enhance the sedative effects of opioids, increasing the risk of respiratory depression.
• Advise patients to contact the Nurse Practitioner before starting new medications, including over-the-counter drugs or herbal supplements (2).

Driving and Operating Machinery:

• Inform patients about the potential impairment caused by opioids, including reduced alertness, reaction time, and coordination.
• Advise patients to avoid driving or operating heavy machinery while taking opioids until they know how the medication affects them (14).

Case Study

You take some extra time with Mary to educate her on the taper dose of Vicodin, the potential for harm, and the risk of opioids, especially when used concomitantly with Gabapentin. You let Mary know it is unsafe to use alcohol, not only with Vicodin but also with Gabapentin. You let Mary know that Vicodin has a risk of dependency and misuse and, therefore, she will be monitored carefully. You also educate that Mary should store the Vicodin away from visibility by anyone but herself since she can self-administer her medication. You let Mary know that Vicodin can cause constipation and that she should increase her water intake and take a stool softener.

You ask Mary to call you if her pain is not adequately relieved or if her medications run out before the three days.  

You let Mary know that if she does stop taking the Vicodin before she has completed all the medication, she should dispose of it by mixing the pills with liquid and coffee grounds to make them unpalatable to animals and others.

Mary complied with your education, completed her course of Vicodin, and was scheduled for surgery. Mary's social worker helped her communicate with her new employer and delayed her start date until after her recovery.

During her recovery, Mary received physical therapy and a short course of pain medication managed by her orthopedist.

Mary returned to the clinic for a follow-up visit after completing her therapy and before starting work. Mary's pain level in her knee is 3/10, and she already feels like she can walk further than pre-surgery. Gabapentin has continued to help Mary's neuropathic pain in her back, and she reports 2/10. Mary looks forward to beginning her new job and is optimistic about the future.

Conclusion

Pain management is the leading cause of primary care appointments and chronic pain is the leading cause of disability. Yet, prescribing opioids for primary care patients is also a factor in drug misuse and the opioid epidemic. Nurse practitioners are challenged to appropriately treat pain and effectively control diversion, addiction, and death from overdose.

It is imperative that nurse practitioners use evidence-based practices to assess, appropriately intervene, and educate about the benefits and potential harm caused by treatment with opioids. Nurse practitioners must stay up to date with the current federal regulations regarding PDMPs, clinical prescribing guidelines, and emerging treatments for pain and opioid abuse disorders.

Tirzepatide for Type 2 Diabetes and Weight Management

Introduction   

The emergence of the drug tirzepatide is becoming more popular and widespread and is being utilized among those with diabetes and also those who desire to lose weight. It is one of the newest diabetic drugs given by injection that also triggers dramatic weight loss in those who use the injections.

The U.S. Food and Drug Administration (FDA) approved tirzepatide in 2022 for individuals with diabetes, particularly Type 2 Diabetes. The FDA officials have not approved tirzepatide yet for weight loss, but they are currently tracking the medication and may have a recommendation for its approval by the end of this year. Clinical trials have shown that individuals with an elevated body mass index (BMI) and who did not have diabetes lost a considerable amount of weight when they received tirzepatide (1).

Advanced Practice Registered Nurses (APRNs) need to understand how to safely prescribe tirzepatide and the reasoning as to why it causes weight loss for specific individuals.

Drug Classification

Tirzepatide is part of a class of medications called glucose-dependent insulin tropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonists. It comprises a 39 amino acid linear synthetic peptide conjugate to selective receptor agonists in preclinical and clinical trials.

Tirzepatide is used for treating Type II diabetes in adults as an adjunct to diet and exercise. It is also used for weight loss in some individuals and has gained increased attention as a new therapeutic agent for glycemic and weight control.

Social media has had a significant influence and increased the desire to use tirzepatide, and while individual results vary, the weight loss in adults ranged from 12 – 25 pounds.

Online pharmacies, diet clinics, and medical spas are implementing thousands of ads on social media to capitalize on a surge of interest in the drug.

Indications of Usage

The use of tirzepatide is being used for both Type II diabetes and weight control in certain patients. It has been a game changer for people living with Type II diabetes. The drug’s primary use is as an adjunct to diet and exercise to improve glycemic control in adults with diabetes.

The drug has also proven beneficial for weight loss in patients experiencing obesity, and those who are taking the highest dosage have shared a body weight reduction of 15.7% (2). Tirzepatide is an injectable prescription medication used together with diet and exercise, and it is not yet known if it can be used safely with patients who have had pancreatitis.

It is important to remember that it is not to be used for patients with Type I diabetes, but it is safe for Type II diabetic patients. Also, the safety of tirzepatide has yet to be discovered for children and those under 18; therefore, the medication should not be used for this age group.

In studies conducted with or without diabetic medicines, 75% – 90% of patients taking tirzepatide reached an overall A1C of less than 7% with an average starting A1C of 7.9 – 8.6% across the following dosages – 5mg, 10mg, and 15mg. The study results were measured at weeks 40 and 52 (3).

Use of Tirzepatide with Diabetic Patients

Tirzepatide can be used for patients with Type II diabetes in combination with a diabetic-friendly diet and exercise. The drug works by lowering the patient’s overall blood sugar and also improves the A1C results of patients over some time. The injection has been approved by the FDA to treat Type II diabetes and is administered once weekly (4).

It is considered the first in a new class of medications – a dual glucose-dependent insulin tropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) receptor antagonist. The mechanism of how it works mimics two gut hormones (GIP and GLP-1). These hormones are essential in how patients digest food and regulate blood glucose after meals. The hormones also play a role in making individuals feel fuller and curb specific food cravings.

The provider can prescribe tirzepatide before attempting other diabetic medications if a patient has a BMI of 30 or greater or 27 or greater with weight-related conditions and if the drug is combined with a personalized weight loss plan that addresses physical activity, nutrition, and lifestyle changes.

However, due to the cost and some insurance companies not covering the injection unless the patient has both diabetes and obesity, the provider must carefully consider prescribing this medication.

Case Study

The patient states this ‘miracle drug’ is worth paying for out of pocket!

Jeff Capron, a 53-year-old Boonville, New York, web developer, started taking tirzepatide in December 2022. His friend had reported good results with the medication, so Jeff looked into the research studies behind it and then spoke with his primary physician.

The physician said, “Yeah, let’s give it a shot,” even though he did not have much experience with it. The physician did not have an opinion one way or the other than looking at the data set and seeing no reason why they could not try it.

Jeff’s hemoglobin A1C went from 10.1% to 6% in 3 months, which was very promising. “I never had that kind of experience with any medication for diabetes.” There is a range in how much A1C reduction people experience with tirzepatide, but many people taking it can get their A1C under 7% — an ideal goal for people with Type 2 diabetes.

Jeff experienced constipation and a little trouble sleeping early, but both issues disappeared quickly. He says, “I wake up in the morning, and my fasting blood sugars are normal.”

The medication took effect, he says, within 12 hours. He compared the feeling to having a gastric bypass.

“You cannot overeat food. As soon as you overeat, you almost feel ill.” While it generally takes a few months to notice effects like A1C reduction and significant weight loss, side effects such as lower appetite may be felt immediately.

Weight loss was not his primary goal, but he lost about 35 pounds on the medication in the first five months. He also lost his sweet tooth. “I can maybe count three sweet things I have eaten since December.”

Jeff found that his appetite slowly recovered days after taking tirzepatide. “You take the shot every Sunday, and by Saturday, you start to get a lot of appetite,” he says. “It does not seem to affect your weight. If I eat a little bit more on Saturday night, on Sunday, the scale will not move one way or the other.”

Jeff is allergic to hornets, so he already carries an auto-injector. He was not worried about using another drug delivered through a needle. “It’s just a push button,” he says. It also helped that his wife is a nurse. “So, I had her with me the first time to ensure I was doing it right. I didn’t even feel it.”

When Jeff was first prescribed tirzepatide, his insurance covered it. The company has since removed that benefit. He has filed an appeal but pays about $1,000 monthly out of pocket for his weekly injections. He plans to keep paying as long as necessary.

He considers the financial burden well worth it. “I have never had a medication that worked as well before for chronic conditions,” Jeff says. “I’ve been blown away by it. For me, it’s a miracle drug. It got rid of my diabetes” (4).

Use of Tirzepatide for Weight Loss Management

As mentioned, this medication is indicated for patients with a BMI of >30 or a BMI of >27 with qualifying comorbidities. Obesity can become a chronic lifetime disease, and for conditions such as these, the patient needs to implement therapy for the lifetime of the disease.

In a study conducted for tirzepatide, there was a dramatic increase in effectiveness compared to traditional nonsurgical interventions such as diet, exercise, and lifestyle changes. However, it has been noted that taking tirzepatide on an ongoing basis is recommended and necessary to maintain any weight loss achieved from the medication.

If a patient stops taking the drug, likely, it will no longer work (5).

Public health officials have expressed concerns about using the drug long-term. Still, data is currently lacking regarding long-term effectiveness, treatment duration, and maintaining weight reduction once the therapy is discontinued.

A recent trial consisted of 783 participants with a BMI greater than 30, and these participants agreed to take either a 10mg or 15mg dose of tirzepatide over 36 weeks. The injection is given once weekly, so this would equal a total of 36 injections.

By the end of 36 weeks, participants lost more than 21% of their body weight. After 36 weeks, participants continued on tirzepatide or received placebo treatment for the following year. The patients needed to be made aware of which treatment they were receiving.

Those still taking tirzepatide injections weekly after 88 weeks lost an additional 7% of their body weight, and those taking the placebo regained 15% at the end of 88 weeks (5).

Common Side Effects and Contraindications

Side Effects

Patients vary immensely with different experiences and side effects related to tirzepatide; however, the following are the most common side effects experienced by those taking the medication:

• Nausea
• Decreased appetite
• Vomiting
• Diarrhea
• Indigestion
• Constipation
• Stomach Pain

Tirzepatide usually does not cause fatigue, leaving one feeling weak, tired, and low energy. However, fatigue can be a common side effect of Type II diabetes.

It is important to note that most individuals who experience nausea, vomiting, and diarrhea episodes do so while the dosage increases, and typically, the symptoms decrease over time. G.I. effects were more prominent in those taking tirzepatide than those taking the placebo. The individuals not in the placebo group were more likely to stop treatment due to the unpleasant side effects (3).

Contraindications

Tirzepatide may cause thyroid tumors, including thyroid cancer, and it is essential to watch for possible symptoms, such as swelling or a lump in the neck, hoarseness, shortness of breath, or trouble swallowing.

Tirzepatide should also not be prescribed to any patient with Type 1 Diabetes.

One of the main ways that tirzepatide works is by stimulating the release of insulin from the pancreas, and due to this fact, there have not been many studies and clinical trials that include those with Type I diabetes.

However, this is not to say that prescribers have never ordered tirzepatide for those with Type I diabetes. Still, it is essential to note that if prescribed, it would be in addition to traditional insulin therapy.

• Personal or family history of a type of thyroid cancer known as medullary thyroid carcinoma (MTC).
• Any history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Patients who are allergic to the actual medication or any of its ingredients.
• Younger than 18 years of age

Safe Prescribing Practices, Guidelines, and Considerations for Providers

Safe Prescribing Practices

As with all prescribed medications, safe standards of care must be implemented and followed to ensure patient safety is maintained. The same applies to providers considering prescribing tirzepatide, and specific criteria must be met beforehand. The following information discusses guidelines involving exclusion and inclusion criteria for providers to prescribe tirzepatide (6) accurately.

Guidelines

Exclusion Criteria – If present, the following indicates that the patient should not receive tirzepatide:

• Diagnosis of Type I diabetes
• Personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2
• Severe gastrointestinal dysmotility
• History of pancreatitis
• Pregnancy
• Proliferative Diabetic Retinopathy (PDR), severe Nonproliferative Diabetic Retinopathy (NDR), clinically significant myalgic encephalomyelitis (M.E.), or diabetic macular edema (DME) unless the risks/benefits have been discussed with the patient and are documented in the patient's health record along with monitoring plans and follow-up with an eye specialist who is informed at the time of initiation.

Inclusion Criteria – All of the following must be met for tirzepatide to be prescribed:

• Diagnosis of Type II diabetes
• A BMI of 25 or greater
• Inadequate glycemic control on at least 1mg of semaglutide injection plus two or more glucose-lowering drugs
• Change needed to achieve goal A1C is less than 1%.
• Goal A1C should be based on those recommended in the Diabetic Guidelines.
• Adherence to current diabetic medications as evidenced by a review of the prescription refill history during the six months.

Additional Inclusion Criteria – All of the following must be met for tirzepatide to be prescribed:

• Patients with atherosclerotic cardiovascular disease or chronic kidney disease
• Patients of childbearing potential who are using oral contraceptives

Inclusion Criteria for Weight Loss

• BMI of >30 or >27 with patient weight conditions.

Considerations for Providers

There are specific considerations that prescribers must be aware of when contemplating if a patient should receive the medication tirzepatide. The following is imperative and must be considered each time the medication is prescribed to a patient:

• Clinical Indications – indicated for treating adults with insufficiently controlled diabetes mellitus as an add-on therapy to diet and exercise; as monotherapy when metformin is considered inappropriate due to contraindications or intolerance; and other medicinal products for treating Type II diabetes.
• Monitoring of medication – routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value but is recommended for early detection of Medullary Thyroid Cancer (MTC).
• Cost – the average price for tirzepatide ranges from $1,071-$1,351 without any coupons or insurance. Savings Card – manufacturer provided; patients can pay as little as $25 monthly for up to 12 injections. Savings Card – manufacturer provided; patients can pay as little as $25 monthly for up to 12 injections.
• Benefits and Risks – One must evaluate the effectiveness of diabetes and the weight loss experienced. Some of the risks must be evaluated, such as increased cost of medication, unpleasant gastrointestinal side effects, poor insurance coverage, and drug shortages. The FDA has warned that the medicine can cause thyroid C-cell tumors in rats, and it is not sure whether tirzepatide causes similar tumors.

How long does it take for tirzepatide to begin working?

Tirzepatide will start to lower one's blood sugar levels immediately, but it can take 8 to 12 weeks to reach one's target A1C goal.

Compared to other diabetic treatments, studies have shown that it can take eight weeks to reach an A1C target of less than or equal to 7% and 12 weeks to get an A1C of less than or equal to 6.5%. Significant weight loss can occur as early as 28 weeks.

Safe Administration

It is essential to follow the correct steps for safe administration of tirzepatide as listed below:

• The recommended starting dosage is 2.5mg, injected subcutaneously once weekly. The 2.5mg dosage is for treatment initiation and not for glycemic control.
• After four weeks, increase the dosage to 5mg, injected subcutaneously once weekly.
• If additional glycemic control is needed, increase the dosage in 2.5mg increments after at least four weeks on the current dose.
• The maximum dosage is 15mg, injected subcutaneously once weekly.
• If a dose is missed, instruct patients to administer it as soon as possible, within four days (96 hours) after the missed dose. If more than four days have passed, skip the missed dose, and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once-weekly dosing schedule.
• The day of weekly Administration can be changed, if necessary, as long as the time between the two doses is at least three days (72 hours).
• Before initiation, train patients and caregivers on proper injection techniques.
• Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1ml syringe capable of measuring a 0.5 mL dose).
• Administer the medication once weekly, any time of day.
• Inject the medication subcutaneously in the abdomen, thigh, or upper arm.
• Rotate injection sites with each dose.
• Inspect the medication visually before use. It should appear clear and colorless to slightly yellow. Do not use the medicine if particulate matter or discoloration is seen.
• When using the medication with insulin, administer it as separate injections and never mix. It is acceptable to inject tirzepatide and insulin in the same body region, but the injections should not be adjacent.

Does the tirzepatide injection hurt when administered?

Pain from the injection site has not been reported as a common side effect, but it may occur.

Due to the injection being given subcutaneously, slight pain or discomfort can occur.

Alternatives to Tirzepatide for Weight Loss Management

In some instances, patients need to be aware of alternatives to tirzepatide in case they cannot take the actual injection for whatever reason. In cases such as these, there are alternative supplements that can be purchased over the counter, and they include the following (7):

• PhenQ – top OTC choice – comprehensive weight loss solution that targets specific body regions, facilitates prompt fat loss, and expedites the weight loss journey.
• PhenGold – the most potent OTC weight loss alternative – one of the top weight loss supplements that boost metabolism, making one less hungry, less tired, and an overall improved feeling.
• Capsiplex BURN – the best choice for men – helps to burn fat faster and keep blood sugar levels in check. It helps to keep one's muscles, curbs hunger, gives one more energy, and torches stubborn fats.
• Trimtone – the best choice for women – helps women to lose weight, eat less, increase metabolism, burn extra calories, and boost energy.
• Prime Shred – best fat burner for men – boosts metabolism, keeps muscles intact, increases energy, and helps maintain focus.

The advanced practicing nurse or prescriber needs to inform patients about alternative options such as these in an effort for individuals to understand that other choices are available and can be used. Many individuals need to be more knowledgeable about alternatives besides tirzepatide due to the extra hype from social media sources that promote advertisements related to tirzepatide only but do not mention the other options.

Why does social media influence and encourage patients to take tirzepatide?

Social media trends can be helpful but can also become harmful by setting unrealistic expectations and promoting a diet culture mentality. They can create an unhealthy obsession with "clean" eating, especially in the younger populations.

Due to this, many individuals take the medication despite any occurrence or history of Type II diabetes, and the drug can ultimately become misused.

It has been noted that there is an influx of patients requesting this medication for weight loss instead of the intended purpose, which is to help control Type II diabetes.

Tirzepatide represents one of the most recent non-medical treatments aimed at managing the symptoms of Type II diabetes. While it is not indicated for weight management, diabetic patients who receive it frequently report a significant reduction in body weight.

 Empirical evidence suggests the efficacy of tirzepatide in weight management, and certain physicians currently endorse the Administration of the medication as a therapeutic and effective means to overcome obesity.

What are some severe side effects of tirzepatide that can impact patient safety?

The Administration of tirzepatide can benefit many individuals, but some severe side effects must be mentioned.

These include thyroid tumors, thyroid cancer, pancreatitis, hypoglycemia, serious allergic reactions, kidney issues, severe stomach problems, vision changes, and gallbladder issues. All these side effects must be taken seriously and reported, as they can lead to life-threatening

Conclusion

Medications like tirzepatide are game changers for those patients with type 2 diabetes that have failed other medications. Unfortunately, several companies seek to profit from its weight-loss benefits through aggressive marketing campaigns that limit the available supply and increase the costs for those who need it. As healthcare providers, we need to use sound clinical judgment and follow the exclusion/inclusion criteria and other guidelines before prescribing this medication, so we do not unintentionally cause harm while looking to appease our patients who request this.

Semaglutide and Type 2 Diabetes

Introduction   

In 2017, the FDA approved the semaglutide injectable (Ozempic) for treating type 2 diabetes. The drug has experienced widespread acceptance due to its positive effects on weight loss and lowering of chronic health risks. The drug has risen in popularity over the past few years, as many well-known actors/actresses/songwriters, and more came forward, publicly sharing their weight loss journey.

This rise in popularity has also resulted in significant shortages of this medication, negatively impacting the lives of the diabetic community, local pharmacies, and healthcare providers. The goal of this continuing education course is to educate and empower the healthcare provider in all aspects of this drug regimen: clinical indications, patient education, cost options, and benefit/risk analysis.

Diabetes Overview

Diabetes is a chronic medical condition. Despite advances in diet, medications, and monitoring devices, diabetes diagnoses continue to grow at staggering rates. The Institute for Health Metrics and Evaluation (IHME) reports that over 529 million people worldwide are currently living with diabetes, and that number is expected to grow to 1.3 billion in only 30 years. While the risk factors for diabetes are vast in number (poor diet, inadequate activity, obesity, sedentary lifestyles, daily stressors, and more), the sad reality is that this chronic medical condition will most likely linger on for generations to come despite our efforts to contain this health epidemic (1).

According to the latest research on diabetes, there are over 37 million people in the United States alone with diabetes as of 2022. Statistically, approximately 28 million of them have a confirmed diagnosis, while another estimated 8 million are experiencing symptoms, without an official diagnosis. Diabetes currently ranks as the 7^th leading cause of death in the United States (2).

Types of Diabetes

In basic terms, diabetes is an impairment in one’s ability to either adequately produce or utilize insulin, which results in elevated levels of circulating glucose. Chronically elevated glucose levels affect blood vessels at every level, causing chronic inflammation and raising the risk of heart disease, stroke, blindness, and atraumatic amputations.

There are three main types of diabetes:

Type 1 diabetes is thought to be an autoimmune disease. Approximately 5-10 percent of people with diabetes are diagnosed with type 1 diabetes. The diagnosis usually occurs in early childhood, and results in a lifetime use of insulin to regulate blood glucose levels.

Type 2 diabetes is thought to be related to dietary and lifestyle choices. It accounts for nearly 90-95 percent of diabetes diagnoses. Usually occurring later in life (adult-elderly population), it is believed to be related to factors such as diet, activity, weight gain, and related factors. Type 2 diabetes is usually controlled by diet and exercise, in addition to oral medications, although injectable insulin may be included in the treatment plan.

Gestational diabetes refers to elevated glucose levels occurring during pregnancy for patients who are not diabetic at the onset of pregnancy. This version of diabetes usually resolves itself post-partum, although a woman may develop type 2 diabetes later in life, unrelated to pregnancy.

Type 2 diabetes in children: no longer a “later in life diagnosis”

Children are now being diagnosed with type 2 diabetes at an alarming rate. Despite widespread education and an increased awareness of diabetes, our up-and-coming generation is unhealthier than ever. Many families lack access to healthy food for their families, due to both general socioeconomic challenges and an increased rate of food insecurity. (19)

The CDC recommends care providers have resources for diabetic patients and their families, such as food and nutrition programs, budget-friendly diabetes meal plans, how to save money on diabetes care, and coping strategies for diabetes. (19)

Diabetes Signs and Symptoms, Diagnostic Testing

There are various ways to test for diabetes. The fasting blood sugar (FBS)/ fasting glucose level is a simple way to test for diabetes.

The normal fasting glucose level is below 100mg/dl. The fasting glucose result of 100-125mg/dl indicates prediabetes and results above 126mg/dl indicate diabetes.

The hemoglobin A1C blood test is another test used to confirm the diagnosis of diabetes. The patient does not need to be fasting for this test; thus, it is easier to order this test regardless of the time of day. This blood test reflects the average glucose level over the period of 2-3 months.

The normal A1C level is below 5.7%. Test results between 5.7%- 6.4% indicate prediabetes. Test results above 6.5% indicate diabetes.

A random glucose reading above 200mg/dl, done at any time of day, indicates diabetes.

The diagnosis of diabetes is by blood tests, and for improved accuracy, should be based on two separate readings, done (at least) a day apart. In the case of fasting and random blood tests, dietary intake (large amounts of carbohydrates in a single meal) may adversely affect test results. This is not the case when using A1C testing for a confirmation diagnosis, as the results are the average of a 2–3-month span.

Target blood levels for a person with diabetes (3).

Target blood glucose levels for people with diabetes are as follows:

• Fasting glucose 80-130mg/dl.
• Postprandial blood glucose level- less than 180mg/dl
• A1C level 7-8%.

These target ranges are general guidelines. Patient-specific ranges will be dependent on a variety of factors, including preexisting comorbidities, overall health status, age, and activity levels.

The hallmark signs/symptoms of diabetes

1. Polyuria- increased urination
2. Polydipsia- increased thirst
3. Polyphagia-increased hunger/appetite

The truth is, as healthcare providers, you will have patients who have no hallmark signs and symptoms of diabetes; the diagnosis will be found during annual preventive examinations often unrelated to any chronic disease. For this reason, many insurance companies now cover numerous preventive screenings, including diabetes screenings, as part of their wellness and prevention initiatives. These tests are often approved based on a patient's age, or preexisting conditions, rather than outright signs and symptoms.

Lifestyle Interventions and the Diabetes Prevention Program

The initial diagnosis of diabetes can be managed in a variety of ways, depending on the severity of the illness at the time of diagnosis. Lifestyle interventions (behavior modification education) are of utmost importance in the care and management of people with diabetes. Research over the past few decades has consistently shown that such interventions have immense positive effects on the successful long-term management of diabetes.

The official Diabetes Prevention Program was created in 2010 (4) and confirmed the effects of lifestyle interventions in the management of diabetes:  Lifestyle interventions decreased the incidence of type 2 diabetes by 58% compared with 31% in the metformin-treated group. Thus, these findings now serve as the blueprint, if you will, for all-inclusive, patient-specific disease management guidelines. These lifestyle interventions will be discussed in detail later in the program.

Additional Resources on Diabetes Prevention

• Detailed History of the Diabetes Prevention Program
• Detailed on the National DPP Lifestyle Change Program

Semaglutide

Semaglutide is an injectable drug used in the treatment of type 2 diabetes. It was approved by the FDA in May of 2017.

It is a once-a-week injectable and belongs to the drug class known as glucagon-like peptide-1 receptor agonists (GLP-1RAs) (5). It has been referred to as a “miracle weight loss drug” among those who are living with obesity, despite frequent side effects, unusually high out-of-pocket costs, drug shortages, and weight regain when attempting to stop using the medication.

GLP-1 receptor agonist: Hormone Review

GLP-1 RAs are a class of medications used to treat Type 2 diabetes, and in some cases, obesity treatment. They are also known as GLP-1 receptor agonists, incretin mimetics, and GLP-1 analogs.

Ghrelin and Leptin (6)

Ghrelin and Leptin are two hormones that greatly influence appetite and the sensation of fullness. Often referred to as the “hunger hormone.” Ghrelin is responsible for many functions, including playing a key role in metabolism through glucose and insulin regulation.

Ghrelin, produced in your stomach, signals your brain when you are hungry, and results in increased food intake.

Leptin, conversely, is produced in your fat cells, and signals to the brain when you have eaten enough (by a decrease in appetite).

Glucagon-like peptide-1 receptors

Known as GLP1 receptors, Glucagon-like peptide-1 receptor proteins are located in the beta cells of the pancreas as well as in the neurons in the brain. GLP-1 receptors are involved in the regulation of blood glucose levels and affect the secretion of insulin. These cells encourage the release of insulin from the pancreas, increase the volume of beta cells, and reduce the release of glucagon. In doing so, they increase the feeling of fullness during and between meals, suppressing the appetite and slowing gastric emptying.

What is meant by receptor agonist and antagonist?

The term agonist refers to any substance that mimics the actions of a hormone in producing a specific response: a receptor antagonist blocks a response from occurring.

Opioids are examples of receptor agonists in that they produce responses such as analgesia.

Naloxone/Narcan is an example of a receptor antagonist, in that it binds to a receptor site and decreases/blocks a response from occurring.

Semaglutide mechanism of action (7)

GLP-1 agonists work in several ways to positively affect glucose levels. Their mechanism of action includes the following:

• Increasing (stimulating) insulin secretion by the pancreatic beta cells.
• Decreasing the production of glucagon, a hormone that raises blood glucose levels
• Decreasing (slowing) gastric emptying
• Decreasing appetite (and thereby reducing food intake) by creating a sensation of stomach fullness

Through these mechanisms of action, semaglutide results in a lowering of serum glucose/A1C levels, which lowers the risk of cardiovascular events. Studies have also shown that semaglutide resulted in weight loss (approximately 8-14 pounds on average {dose dependent results}.

Side Effects of Semaglutide

Common side effects of semaglutide (8)

Common side effects may include any of the following:

• Nausea and vomiting
• Headache
• Diarrhea and stomach pain
• Upset stomach, indigestion, constipation, flatulence

These side effects usually subside within a few weeks, as the patient becomes acclimated to the medication.

Serious side effects of semaglutide

• Hypoglycemia- enhanced/worsened when used in combination with other diabetes medication. Symptoms may include drowsiness, confusion, weakness, irritability, and headache.
• Symptoms may include abdominal pain and distension, nausea and vomiting, fever, and back pain.
• Diabetic retinopathy. Symptoms may include blurred vision, vision loss, and diminished night vision.
• Kidney damage/injury/failure. Symptoms may include fatigue, nausea, diminished urine output, confusion, and edema of extremities.
• Gallbladder disease. Symptoms may include gallstones, abdominal pain, nausea and vomiting, and poor appetite.

Black Box Warning (9)

Semaglutide has a Black Box Warning for thyroid cancer. This is the most serious warning from the Food and Drug Administration (FDA) and is intended to alert consumers to the potential risks of a medication.  This black box warning was issued when research found that the drug increased the risk of thyroid tumors in animals.

It is not known if semaglutide actually causes tumors in humans.

Contraindications

• Semaglutide is contraindicated in people with a personal or family history of MTC (medullary thyroid cancer) or in patients with multiple endocrine neoplasia syndrome type 2.
• Known hypersensitivity to semaglutide or any of the product components

Cautions

As noted under “serious side effects”, there have been reports of new illnesses or worsening of existing health conditions occurring “post-marketing”. Thus, healthcare providers are strongly encouraged to continue ongoing surveillance of any patients on semaglutide therapy. In addition, there is insufficient data available regarding the use of semaglutide by pregnant women. Women are therefore highly encouraged to stop any treatment with semaglutide for at least 2 months prior to a planned pregnancy.

Dosing

Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). It is looked upon favorably to reduce the risk of cardiovascular events in adults with T2DM and a preexisting history of cardiovascular disease. This drug is FDA-approved for use in people with diabetes, with a BMI of 27% or higher (a BMI of 25-29.9% is considered overweight).

Semaglutide (Ozempic) is available as an injectable prescription medication. Doses include 0.5mg, 1mg, or 2 mg, once weekly.

The injection should be administered subcutaneously to the abdomen, thigh, or upper arm. Injection sites should be rotated, and given as a single injection.

Start at 0.25 mg once weekly. After 4 weeks, increase the dose to 0.5 mg once weekly.

• If additional glycemic control is needed, increase the dose to 1 mg once weekly after at least 4 weeks on the 0.5 mg dose.
• If additional glycemic control is needed, increase the dose to 2 mg once weekly after at least 4 weeks on the 1 mg dose

Administer once weekly at any time of day, with or without meals.  The maximum dose recommendation is 2mg/weekly once weekly.

Note: The initial 0.25-mg dose is intended for treatment initiation and is not effective for glycemic control

Missing Dose Guidelines

• If the missed dose is ≤5 days: Administer dose as soon as possible
• If missed dose >5 days: Skip the missed dose and administer the next dose on the regularly scheduled day; patients can then resume their regular once-weekly dosing schedule

Administration Day Guidelines (10).

The administration day each week can be changed, if necessary, as long as the time between 2 doses is at least 2 days (>48 hours)

Dose Availability (packaging)

• 2mg/1.5mL (1.34mg/mL); delivers doses of 0.25mg or 0.5mg per injection or four to eight doses per injection pen
• 4mg/3mL (1.34mg/mL); delivers 1mg per injection or 4 doses per injection pen
• 8mg/3mL (2.68 mg/mL); delivers 2mg per injection or 4 doses per injection pen

Treatment Goals- Effects on A1C and Weight (11)

A majority of adults who were placed on injectable semaglutide for diabetes management achieved a target A1C under 7% and were able to maintain it.

• Dose specific effects on A1C were as follows:
• 0.5mg dose injection yielded a 1.4% decrease
• 1.0mg dose injection yielded a 1.6% decrease
• 2.0 mg dose injection, in combination with diabetes pills, yielded a 2.1% decrease in A1C.

Adults taking semifluid injectables for diabetes management also noted weight loss.

• 8-pound weight loss reported with 0.5mg dose injection
• 10 pounds weight loss reported with 1.0mg dose injection
• Up to 14 pounds of weight loss reported with a 2.0mg dose injection

Prescribing insights: Long-Term therapy for a chronic condition?

Semaglutide is viewed favorably as a treatment option for Type 2 diabetes. It appears to lower A1C levels and body weight in the majority of patients, lowering their risk of future cardiovascular events.

The question of long-term medication use, for a chronic health condition, is being heavily discussed in the media. While a percentage of people can decrease or eliminate the need for chronic medications through significant lifestyle changes, there have been reports of weight gain in those who stopped taking this injectable medication.

Without intense lifestyle behavior modification education, there is a heightened risk of weight regain in the absence of such medications. Leaders in the treatment of obesity and related illnesses have commented that this drug is intended for long-term use.

Examples of this include the following:

“GLP-1 medications [like Ozempic] are designed to be taken long-term... They are chronic medications for the treatment of chronic conditions (both diabetes and obesity) (12)". - Christopher McGowan, M.D., a gastroenterologist specializing in obesity medicine and endobariatrics

“As with many chronic conditions, most people who use the drugs for diabetes or weight loss will need to keep taking them to keep benefiting from them. Depending on your individual situation, and without sustained lifestyle changes, it is likely you would need to be on these medications indefinitely to maintain weight loss (13)." - Dr. Cecilia Low Wang, a UCHealth expert in endocrinology, diabetes and metabolism.

Cost Concerns

At this time, injectable semaglutide, FDA-approved for the treatment of Type 2 diabetes, has a self-pay price tag of $935.77 per month (4 injections). With FDA approval, many people with diabetes, insured under commercial plans, receive the drug for the cost of their copay. Those patients without coverage may use pharmacy discount cards that reduce the price, on average, to $814.55/month.

The following links are available to familiarize yourself with patient assistance programs related to semaglutide injectables.

Semaglutide Cost Savings Programs

The following links are provided to explore various semaglutide cost savings programs.

• Novo Care's Ozempic Saving Offer
• How much does Ozempic (0.25 Or 0.5 Mg/Dose) cost?
• GoodRx

Emerging Concerns: Semaglutide and gastroparesis

In August 2023, a first-of-its-kind lawsuit was filed in Louisiana, against the makers of semaglutide. The lawsuit states the makers of this injectable drug did not adequately warn patients about the risk of severe gastrointestinal issues/possible gastroparesis.

The plaintiff in this case had used both Ozempic and Mounjaro and experienced repeated episodes of severe gastrointestinal events, warranting trips to the emergency room and additional medications to alleviate her symptoms (14). While this lawsuit is in the developing stages, it bears mentioning in terms of concerns over long-term usage of the drug and possible complications.

While the drug labeling for semaglutide (Ozempic) does not specifically mention gastroparesis, the semaglutide/Mounjaro drug label does state that the drug has not been studied in patients with severe gastrointestinal disease and is therefore not recommended in these patients.

Up to 50% of people with diabetes have some degree of delayed gastric emptying, but most have no digestive symptoms or have only mild symptoms. For some people with diabetes, problems managing blood glucose levels may be a sign of delayed gastric emptying (15).

Healthcare providers should evaluate all patients with diabetes for possible symptoms of underlying gastroparesis, such as the feeling of fullness shortly after beginning a meal, or the inability to finish a regular meal. Other symptoms of gastroparesis may include abdominal pain, nausea, bloating, vomiting, and anorexia.

Diabetes and gastroparesis

Uncontrolled or poorly controlled diabetes can affect nerve endings systemwide. Diabetes is a very common cause of gastroparesis. Although the condition is rare it occurs more often in people with chronic conditions such as diabetes, autoimmune diseases, and nervous system disorders. Nerve endings are injured or damaged, cease to function properly, and result in delayed gastric emptying. The delay in gastric emptying can cause various symptoms, such as nausea, vomiting, bloating and distension, abdominal pain, and poor appetite.

In addition to underlying medical conditions, some medications may cause symptoms of gastroparesis (delays in gastric emptying and overall gastric motility. These medications include narcotics, antidepressants, and anticholinergics.

Left untreated, diabetic gastroparesis may lead to malnutrition, electrolyte imbalances, and poor glucose management and control.

Diabetes Lifestyle changes: Patient education (16)

1. Weight Management
2. Healthy Eating
3. Physical Activity
4. Smoking Cessation
5. Stress Management

The importance of patient education regarding lifestyle changes is a priority. As with any chronic medication condition, the patient and their family/support system must be given every opportunity to educate and empower themselves on self-management of their disease process. Patients must be given the benefit of the doubt that they can indeed embrace their health and well-being and work with their healthcare provider in maximizing their health outcomes.

For diabetes mellitus, numerous lifestyle behaviors should be addressed and actively worked on, so that the patient receives the maximum health benefits. The following lifestyle behaviors are in no particular order; they all warrant discussion at every office visit.

Diet

A person with diabetes should be educated on the effects of food and nutrition on their glucose level. Referrals to a dietitian/nutritionist or Certified Diabetes Care Education Specialist (CDCES) should be considered a top priority. Well-balanced nutritional intake, appropriate carbohydrate awareness, calorie monitoring if weight loss is appropriate to your specific patient) and medication/food interactions are all essential aspects of dietary lifestyle education. Many commercial insurance plans, as well as hospital community outreach programs, offer diabetes self-management classes.

Activity (17)

The CDC recommends a target goal of 150 minutes weekly, Patients should be educated on the positive effects of daily activity on overall health and well-being, stress management, and metabolism. Patients should find activities they are genuinely interested in, involve family and friends, and slowly build greater endurance through increased intervals of longer duration.

Sleep hygiene (18)

Patients should be educated on the positive effects of a good night’s sleep. The aim should be approximately 7-8 hours of restful sleep. Electronics should be powered down and (optimally) removed from the bedroom. A dark, well-vented, cool room temperature is encouraged, and large meals and late-evening caffeine should be avoided.

Medication adherence/ literacy

Medication education is critical to the health and well-being of a patient. Routine education of the patient, and family members or support systems when available, should be supportive and patient-specific. Patients should be assessed on language barriers, literacy issues, and related comprehension concerns. Medication education should include effects, side effects, treatment goals, and sick day management. Emergency care issues should also be discussed. Any monitoring equipment (continuous glucose monitors, accuchecks, lancets) should be reviewed with patients and confirmed with return verbalization and demonstration.

As discussed in this course, patients with chronic diseases must learn self-management techniques to optimize their health and well-being. They must become confident in their understanding of their disease process and take ownership of their health. In doing so, they minimize the risk of long-term complications, improve their self-worth, and actively invest (both time and money) in their future.

Ozempic Case Study

• 52-year-old female
• Height 67 inches
• Weight 225 pounds
• B/P 138/84, Heart rate 76 NSR
• BMI 35.2%
• Nonsmoker, occasional social drinker
• Multiple attempts at dieting without success.
• Diagnosed T2DM approx. 6 months ago current A1C 7.5%; initial medication Metformin 500mg BID tablets; tolerated well. No GI upsets.

Today’s appointment is for evaluation and additional medication consideration (the patient requested this appointment)

The patient was diagnosed with T2DM approximately 6 months ago. Initial A1C 8.0%. Current A1C 7.7%

Despite an improved diet and adherence to the medication regimen, the patient voiced frustration at the lack of weight loss. Requesting additional medication. Has a neighbor friend who began injectable Ozempic and is having “really great results with it. I want to start on it as well”.

• What are your thoughts on prescribing semaglutide injectable for this patient?
• What objective health data points should be taken into consideration regarding prescribing semaglutide for this patient?

The patient has expressed frustration that despite taking her medications and adjusting her diet, she has not lost any weight in the past 6 months. She has “heard from her neighbor friend that the weight just melts off immediately” and she is ready to start this medication.

• What concerns do you know about this patient's understanding of weight loss as it relates to semaglutide?
• What prescribing information, specific to semaglutide and weight loss, could you share with your patient regarding realistic weight loss targets?
• In addition to teaching your patient proper injection technique for the use of semaglutide, what other lifestyle education behaviors should you discuss at this point?
• What information should you share with your patient regarding the long-term use of semaglutide and the potential risks of stopping this medication (as it relates to weight regain)?

Your patient decides to go ahead with the semaglutide regimen.

• What are some patient education guidelines regarding common side effects of this medication?
• How often is the dose increased? What is the maximum dose this patient can receive weekly?

Your patient wants to know how long she will be taking this medication.

• What talking points will you cover regarding the long-term use of this medication?
• How do you best prepare this patient for long-term success with this medication?
• What lifestyle behavior modification education would you discuss with your patient, to give her the best chance at successfully managing her diabetes?

Medication Assisted Treatment (MAT)

Introduction   

Medication Assisted Treatment (MAT) is a treatment modality for substance use disorders. It combines counseling and behavioral therapies for addiction with medications used carefully to reduce the physical symptoms of cravings and withdrawal and assist clients in the recovery process. With half of people 12 and older reporting use of an illicit substance at least once and 21 million Americans experiencing addiction, this is an important and relevant topic (4).

Historically, an intense stigma is attached to both addiction and some of the medications used to treat addiction. A thorough understanding of substance use disorders, available MAT therapies, and care of affecting clients are essential topics for nurses to be familiar with, particularly those working in psychiatry, pain management, or addiction medicine.

Overview of Addiction and Substance Abuse:

Drug and alcohol abuse and addiction are chronic, complicated issues involving persistent changes to the brain. There is a stigma or misunderstanding that people with substance abuse disorders can stop any time they want to or lack the willpower or moral fortitude to stop using. This is entirely untrue, and even people who are "recovering" and have not had any drugs or alcohol in years can easily relapse into addiction once those brain changes have occurred (5).

When a person uses drugs or alcohol, the brain's reward center is flooded with dopamine. This provides a "buzz" or pleasurable sensation that may create the desire to use more of the same substance. Over time, and with regular use of the substance, the brain becomes accustomed to the flooding of dopamine and reduces the reward response, a process known as tolerance.

It will now take the same person a more significant amount of the substance to achieve the same "buzz" or "high" they used to feel. This process can also dull the pleasure response to activities not involving substance use, such as food, socialization, or sexual activity. Over time, the chemical changes in the brain can progress to include decreased functioning of learning, decision-making, judgment, response to stress, memory, and behavior (5).

To understand substance abuse disorders, it is first essential to understand some basic definitions. These terms are sometimes used interchangeably, but they mean different things and represent different stages of disease.

Definitions

Substance Use: Substance use is any consumption of drugs or alcohol, regardless of frequency or amount. An occasional glass of wine or taking an edible at a party is an example of substance use. Substance use does not cause problems or dependency in many people (5).

Substance Abuse: Substance abuse is the continued use of drugs or alcohol, even when they do cause problems. Conflict or problems at home, school, work, or legal issues related to the use of drugs or alcohol are signs of abuse. For example, being sent home from school for smoking in the bathroom or failing a drug test at work (5).

Substance Dependence or Addiction: Dependence and addiction can be used interchangeably or is sometimes called substance use disorder. Addiction occurs when a person cannot stop drinking or using drugs despite creating problems in their life. People who are addicted may experience cravings until they use a specific substance, or they may experience uncomfortable physical symptoms, known as withdrawal if they do stop (5).

The American Psychiatric Association (APA) utilizes the following criteria to diagnose clients who suffer from addiction. The more criteria a client answers yes to, the greater their problem with substance use.

Six or more positive criteria are indicative of addiction.

1. Using substance in more significant amounts or for more extended periods than intended
2. Trying to stop using but being unable to
3. Increased amounts of time getting, using, or recovering from use of the substance
4. Experiencing cravings or urges to use.
5. Continuing to use the substance despite problems with relationships or social situations.
6. Missing work, social, or recreational obligations or activities because of substance use
7. Participating in risky behavior because of substance use
8. Continuing to use the substance despite psychological or physical health problems.
9. Needing to use more substance over time to achieve the desired effect.
10. Experiencing withdrawal symptoms when stopping the substance (1).

Substance Abuse Statistics

Many factors go into gathering data on substance abuse disorders, from underreporting, the nuance between use, abuse, and addiction, and the large variety of substances available, with the legality of some substances varying by state or age.

The statistics below from 2020 are not meant to be an exhaustive list of substance use disorders in this country but rather an overview of some of the more prevalent addiction-related issues.

• 50% of people 12 years and older have used an illicit substance at least once.
• 5% of Americans 12 years and older have used drugs within the last month.
• This is a 3.8% increase from the previous year.
• About 50% of Americans 12 and over drink alcohol
• 4% of those people have an alcohol use disorder.
• About 20% of Americans use tobacco products or vape
• 18% of Americans over 18 used marijuana in the last 12 months
• 30% of those have some level of misuse or addiction.
• Marijuana is commonly involved in polysubstance use, paired with alcohol or other drugs.
• 7% of Americans over 12 misused opioids in the last 12 months
• 96% of those used prescription pain relievers
• Opioid prescriptions peaked in 2012, with 81.3 prescriptions per 100 people.
• The rate has declined recently due to increased attention to this crisis.
• In 2018, the rate was down to 51 prescriptions for every 100 people
• Fentanyl is now rising as a new and deadly concern.
• 5 million prescriptions were written for fentanyl in 2015.
• Fentanyl is involved in 53% of overdose deaths.
• 7% of all Americans misuse a prescription drug.
• 1% of those misuse stimulants
• 2% of those misuse sedatives
• 5% misuse painkillers
• Over 70,000 drug overdose deaths occur annually in the United States (4)

Risk Factors

A combination of factors is involved in the risk of addiction, and no one factor can determine if someone will develop addiction or after how many uses this will occur.

The addiction process does occur more easily or progresses more rapidly for people with certain risk factors, including:

Genetics

There is a strong genetic correlation with addiction, indicating that biology plays a significant role in the disorder. Family history of addiction, gender, ethnicity, and comorbid mental health conditions can all influence the risk of addiction. (5)

• Children of addicts are eight times more likely to develop an addiction at some point.
• In 2020, among those using illicit or misusing prescription drugs, 22% were male and 17% female.
• Only 20% of users in drug treatment programs are women.
• 9% of people with substance abuse disorders also have at least one mental health disorder (4)

Environment/Non-Genetic Demographics

The attitudes about drugs and alcohol from those in a person's network and life experiences play a role in the risk of addiction. Substance use among friends, family, or coworkers increases the risk that a person will also use substances. Exposure to substance use from a young age relaxed parental attitudes about substance use, and peer pressure from friends can increase the risk. Certain stressful life circumstances such as veteran status, history of sexual or physical assault, or being part of the LGBTQ community can also increase risk. (5)

• 20% of people in urban areas used illegal drugs in 2020 compared to 5% in rural locations.
• 51% of Americans with an illegal pain relief medication obtained it from a friend or relative.
• 7% of LGBTQ Americans abuse illicit drugs.
• 2% of LGBTQ Americans abuse alcohol.
• 7% of Veterans abuse illicit drugs.
• 80% of Veterans abuse alcohol (4)

Developmental Stage

Substance use at any age can lead to addiction, but children and teens are at particular risk due to their underdeveloped brains. The parts of the brain responsible for decision-making, risk assessment, and self-control do not fully develop until the early 20's, putting teenagers at increased risk of dangerous behaviors. In addition, the effects of drugs and alcohol on the developing brain may mean that those parts of the brain never fully develop at all for teens with substance abuse disorders. (5)

• 70% of users who try an illegal substance before age 13 will develop a substance use disorder within the next seven years.
• This is for only 27% of people who first try an illegal substance after age 17.
• 47% of youths report trying an illegal substance by the time they graduate high school (4)

Overview of Medication Assisted Treatment (MAT)

Treatment of substance abuse disorders is a complex and often tumultuous process. The nature of the brain changes that occur during addiction means that a person is never entirely "cured" but will always be considered "recovering" as the risk for relapse is always present. Effective treatment must be multifaceted and often involves removing triggers (such as people, places, and stressors) that may prompt a person to use again behavioral therapy, and medications to curb withdrawal symptoms and reduce cravings.

Medication Assisted Treatment (MAT) is a treatment that involves FDA-approved medications, in combination with behavioral therapy, in the recovery process for substance abuse disorders. Several medications are available for MAT, and evidence continues to emerge that the treatment is highly effective if used correctly.

However, it is a vastly underused and understudied treatment modality. MAT has been available in some form for over 50 years but is just starting to gain traction among the medical community (and policymakers) in recent years, with the federal government calling for more research and increased accessibility for the treatment (8).

The height of the opioid crisis in the last several years has highlighted the magnitude of drug addiction and deaths in the United States, bringing renewed attention to MAT as a treatment option. So, how does MAT work? Prescription medication is given to both stimulate the receptors seeking the abused substance and block the drug's euphoric effects.

Over time, this normalizes brain chemistry and helps the person break the habit of using without the discomfort of cravings and withdrawal symptoms. Gradually, the prescription medication dosage is reduced, all the while in conjunction with behavioral therapy and lifestyle changes, and eventually, the client should be able to stop the medication altogether, often within 1-3 months (8).

MAT does require close supervision by a trained medical professional and an appropriate facility for treatment. It can be done on an inpatient, partial inpatient, or outpatient basis. There may be side effects to the medication, and there is a risk of misusing or developing addiction to the new drug, though the successful outcomes often outweigh this risk. Clients must also participate in behavioral therapy for a comprehensive and effective treatment plan. As with any treatment regimen, careful consideration of the client's history and circumstances is essential (8).

Pharmacokinetics

Currently, there are three medications with FDA approval for MAT: buprenorphine, methadone, and naltrexone. Each will be discussed in depth below.

Buprenorphine

Mechanism of Action and Metabolism

Buprenorphine is an opioid partial agonist, acting on the same receptors as other opioids but with weaker effects. It can be used for the treatment of misuse of opioids, including:

• Heroin
• Fentanyl
• Oxycodone
• Hydrocodone
• Morphine
• Methadone (3)

Opiate receptors are G-protein coupled receptors (GPCRs) with four major types: Mu, Delta, Kappa, and opioid receptor like-1 (ORL1). Stimulation of these receptors results in varying levels of the following effects:

• Euphoria
• Relaxation
• Pain relief
• Sleepiness
• Sweating
• Constipation
• Impaired concentration
• Reduced sex drive (3)

Buprenorphine has a high affinity to the Mu-opioid receptor and is a partial agonist at this site, causing reduced opioid effects with a plateau or ceiling at higher doses. This limits dangerous effects and makes overdose unlikely. It also has slow dissociation from the site, allowing milder and more easily tolerated withdrawal effects compared to full agonists like morphine and fentanyl. Buprenorphine is also a weak kappa receptor antagonist and delta receptor agonist, reducing the craving sensation and improving tolerance to stress (3).

Buprenorphine has poor bioavailability when given orally due to the first-pass effect, where most of the drug is broken down in the liver and intestines. Because of this, sublingual or buccal are the preferred routes of administration and the most common forms in which the drug is manufactured. Transdermal patches and IV and IM forms exist, though not for use in MAT (3).

CYP34A enzymes break down buprenorphine, so other drugs, such as ketoconazole, may inhibit metabolism and increase available levels of buprenorphine. CYP34A inducers such as carbamazepine, topiramate, phenytoin, and barbiturates may speed metabolism and lower available levels. Once broken down, the med takes the form of norbuprenorphine and is excreted in the feces (3).

Available Forms

Buprenorphine is available by itself and with naloxone (in a 4 to 1 ratio). However, in oral form, naloxone is not readily absorbed, and buprenorphine is the only genuinely active ingredient. This combination is beneficial should clients try to inject their buprenorphine to get high; naloxone is a fast-acting opioid antagonist that is active when used intravenously and would block the opioid effect of buprenorphine, rendering it useless for recreational use and ensuring it has no street value.

The currently available preparations of buprenorphine for MAT include:

• Generic Buprenorphine/naloxone sublingual tablets
• Subutex - Buprenorphine sublingual tablets
• Suboxone - Buprenorphine/naloxone sublingual films
• Zubsolv - Buprenorphine/naloxone sublingual tablets
• Bunavail - Buprenorphine/naloxone buccal film (3)

Sublingual products dissolve within 2-10 minutes. Bloodstream absorption begins quickly, bypassing the first pass effect. Buprenorphine has a slow onset of action, peaking about 3-4 hours later. Metabolism is also slow, with the half-life lasting anywhere from 25 to 70 hours (an average of about 38 hours). This long half-life means the drug can be spaced out to every other day administration once weaning begins (3).

Dosing and Monitoring

Clients prescribed buprenorphine must stop using opioids for at least 12 to 24 hours before the first dose; this varies depending on which opioid they are stopping. For short-acting opioids like heroin and oxycodone, buprenorphine may be started 6-12 hours after the last dose. With longer-acting opioids such as morphine or extended-release preparations of oxycodone, buprenorphine should be delayed for about 24 hours. For the longest action opioids, fentanyl patch, 48 -72 hours must be between the last dose and buprenorphine initiation (3).

This initiation schedule means clients will be in the early stages of discomfort and withdrawal. Administration of buprenorphine when clients still have opioids in their bloodstream will lead to competition for receptor sites, rapidly replacing the opioid with buprenorphine and causing acute and more severe withdrawal symptoms.

Depending on the severity of a client's addiction, they may complete the first step of abstaining and withdrawal in an inpatient setting. Once the initial withdrawal symptoms have passed and the initial dose of buprenorphine has been given, the client may be discharged home to continue buprenorphine initiation on an outpatient basis (3).

Initial doses are typically 2-4mg, with up to 4mg given to clients used to higher potency or larger doses of opioids. The dose is gradually increased to meet the client's individual needs, with a maximum dosage of 24mg per day. The average client requires 8-12 mg per day and can reach this dose within the first 2-4 days. It is recommended that doses be supervised by a pharmacist at the dispensing pharmacy for the first two months of treatment to ensure compliance and clients are less likely to relapse (3).

The length of treatment with buprenorphine depends on each client's case and, for some, may be indefinite. Clients who do wish to wean off buprenorphine can begin the process once they are stable and experiencing few or no cravings, and a minimum of 8 weeks from treatment initiation. Doses are moved to alternating days and eventually discontinued altogether (3).

Side Effects and Contraindications:

As with any medication, there are potential side effects, including:

Common Side Effects

• Nausea
• Vomiting
• Drowsiness
• Dizziness
• Headache
• Memory loss
• Sweating
• Dry mouth
• Miosis
• Postural hypotension
• Sexual dysfunction
• Urinary retention

Serious side effects

• CNS depression
• QT prolongation
• Reduced seizure threshold
• Potential for abuse or overdose (3)

Buprenorphine is contraindicated for clients with a past hypersensitive reaction to it. It should be used cautiously for clients with respiratory suppression, older adults, or for those with liver pathologies. Regular monitoring of liver enzymes via lab work is essential (3).

It is a Category C medication for pregnancy, and the risks versus benefits should be carefully weighed. Buprenorphine does cross the placenta and increases the risk of withdrawal symptoms and neonatal abstinence syndrome (NAS) after delivery. However, for pregnant clients with the highest risk of relapse and abuse of opioids, evidence does support that continuation of buprenorphine during pregnancy may improve maternal and fetal outcomes (3).

Buprenorphine may be abused by crushing tablets, snorting the powder, or dissolving it into an injectable solution. Safety measures against this include supervised administration by a pharmacist and the addition of naloxone, which blocks the buprenorphine effects. While the effect ceiling of buprenorphine makes overdose difficult, combining the drug with benzodiazepines, alcohol, or other drugs can compound the CNS depressant effects and increase the risk of overdose (3).

Clinicians need to have a comprehensive health history of clients before initiating buprenorphine so that all risks and potential interactions can be addressed appropriately.

Role of the Pharmacist

Pharmacists play a significant role in the success of MAT involving buprenorphine. Outpatient doses are monitored by the dispensing pharmacist daily, with at-home quantities being allowed on a limited basis (such as weekends or travel) and only for the most motivated and compliant clients. Vital signs are collected before each dosage, with careful monitoring for hypotension or bradypnea. The dose may be skipped for clients who experience excessive side effects, and the client can return the next day for their dose.

Clients presenting with signs of overdose (usually to the ED) may receive naloxone, which will reverse overdose symptoms within 1 hour. Overdose symptoms include dizziness, pinpoint pupils, hypotension, bradypnea, hallucinations, seizure, or unconscious state.

If a client misses a dose, does not show up for it, or is experiencing significant side effects from buprenorphine, the prescribing clinician should be notified so that the treatment plan can be revisited and revised if needed (3).

Considerations for the Prescriber

When considering which medication to prescribe for MAT, prescribers should understand that buprenorphine offers advantages over methadone.

• Lower risk of abuse
• Safer, including at higher doses.
• Therapeutic dose achieved quickly.
• Easier to taper.
• Can be obtained from any provider rather than a methadone clinic.
• Less stigma

The cost of a 30-day supply is around $300. Buprenorphine/naloxone combinations are a little more expensive at $400/month. While prior authorization is usually required, most commercial insurance and state Medicaid programs will cover the medication.

Buprenorphine is a Schedule III Controlled Substance; however, recent federal regulations have been aimed at approving access to MAT, and any provider with an active DEA license may prescribe buprenorphine as allowed by state regulations. Specialized clinics are not required (as they are with methadone), and it is dispensed at regular pharmacies.

Prescribers are encouraged to participate in additional training about MAT with buprenorphine, but it is not required. Detailed documentation must be completed, including the reason for prescribing, start and end dates of treatment, the pharmacy used, the credentials of who will supervise administration, and frequency of follow-up and compliance monitoring. The sublingual and buccal routes are the only forms of medication used for MAT; patches, IM, and IV preparations are not routinely used for MAT.

The success of buprenorphine treatment depends on the client's education. Addiction potential, risk of combination with other CNS depressants, and side effects vs. signs of overdose should all be discussed with clients and their support system (3).

Methadone

Mechanism of Action and Metabolism

Methadone is a synthetic opioid and a full agonist of the Mu-receptor site, stimulating the same effects as opioids.

• Euphoria
• Analgesia
• Sedation

It can be used as a potent analgesic for pain not responding to traditional medications, such as in clients with cancer or terminal illness, as well as for MAT and neonatal abstinence syndrome (NAS).

For this course, it will be discussed as a MAT agent, used in treatment for clients addicted to opioids such as:

• Heroin
• Fentanyl
• Oxycodone
• Hydrocodone
• Morphine
• Hydromorphone (2)

Methadone is a full agonist at the Mu-receptor, meaning it is a more potent and more easily addictive medication than partial agonists like buprenorphine. Methadone has a long half-life (8-60 hours), occupying the Mu-receptors and blocking short-acting opioids from making a client high. The longer half-life also leads to less severe cravings and withdrawal symptoms. Methadone is also an antagonist to the N-methyl-d-aspartate (NMDA) receptor, which adds to its pain relief action (2).

It has high oral bioavailability, is active in the bloodstream within 30 minutes of ingestion and remains elevated for around 24 hours. It is broken down via CYP3A4 and CYP2B6 enzymes and metabolized through the liver, making it a good option for clients with renal problems.

Medications such as ciprofloxacin, benzodiazepines, fluconazole, cimetidine, and fluoxetine may slow methadone metabolism, increasing the available drug and the side effects of overdose risk. Other medications may speed metabolism and decrease the effects of methadone, including phenobarbital, phenytoin, rifampin, ritonavir, and carbamazepine (2).

Available Forms

Methadone is available in many forms, including oral, IM, subcutaneous, IV, and intrathecal, though only the oral is typically used for MAT.

• Methadone - tablets
• DISKETS - dispersible/dissolvable tablet
• Methadone HCL Intensol - 10mg/ml suspension
• Methadone - dispersible tablet (2)

Dosing and Monitoring

Oral dosing is initiated at 30-40 mg/day with a slow titration of 10-20 mg/week until the optimal dosage is reached. The optimal dosage varies by client and depends on the drug they are replacing, tolerance to opioids, and side effects experienced. A dosage between 80- 150 mg/day is the typical goal. (2)

If parenteral methadone is given, it is usually 50%-80% of the oral dosage.

Blood sugar, EKG, and methadone blood levels should be checked regularly, every week for higher-risk patients, and every 3-6 months for those in good health and compliance. The target methadone blood level is around 400 ug/ml (2).

Side Effects and Contraindications

Potential side effects are directly related to stimulation of the opioid receptors and include:

• Diaphoresis
• Flushing
• Pruritus
• Nausea
• Dry mouth
• Constipation
• Sedation
• Lethargy
• Respiratory Depression
• QT prolongation
• Hypoglycemia (2)

Methadone should be considered with a comprehensive view of a client's health history and other medications. Clients with CNS-related disease processes (trauma, increased ICP, dementia, or delirium) must be monitored closely or have other medication considered.

Methadone should not be used simultaneously as other opioids, benzodiazepines, alcohol, or antipsychotics due to increased CNS effects. Methadone is a Pregnancy Category C medication, and risks versus benefits should be weighed carefully. Infants exposed to methadone in utero are at increased risk of NAS after delivery (2).

Overdose can occur, and clients and support systems should be educated on signs of overdose.

• Lethargy
• Somnolence
• Stupor
• Coma
• Miosis
• Bradycardia
• Hypotension
• Respiratory sedation
• Cardiac arrest

Naloxone is used to reverse overdose (2).

Considerations for Prescribers and Clinics

Methadone is a Schedule II Controlled Substance, meaning it has a high abuse potential and must be carefully monitored. The Prescription Drug Monitoring Program (PDMP) is an electronic database used nationwide to register the distribution of controlled substances so that clients do not seek care at multiple clinics or pharmacies to obtain more of a controlled substance.

When prescribing methadone, providers should check the PDMP for both methadone and other prescription opioids so that they are fully aware of other medications clients may be receiving from other places. Regular urine drug screening should be performed to make sure clients are not using other substances not obtained by prescription and that they are testing positive for methadone, meaning they are genuinely taking it if administration is not observed (2).

At the beginning of treatment, methadone is given in the office under a nurse's supervision, and then clients are monitored for adverse effects. Some take-home doses (up to 7 in the first two weeks) may be arranged for weekends or during travel, but this possibility is limited during the first few weeks of treatment. As treatment progresses and compliance is demonstrated, clients may self-administer more doses at home (up to 28 doses per month) and go longer between visits to the clinic. The total length of treatment varies but is often 1-2 years and can even be indefinite (7).

There are methadone clinics that work entirely in the scope of addiction management, but primary care providers may prescribe methadone as well. Prescribers must have an active DEA license and comply with state-based controlled substance regulations (2).

Naltrexone

Mechanism of Action and Metabolism

Naltrexone has been in use since the 1960s and is an opioid antagonist. It competes primarily with the mu-receptor but also serves as an antagonist at the kappa and delta receptors. As an antagonist, it competes with agonists such as opioids and alcohol and blocks the effects of agonists at those sites.

• Prevents euphoria.
• Prevents intoxication.
• Reduces tolerance (6)

Naltrexone also acts on the hypothalamic-pituitary-adrenal axis, modifying it to reduce cravings and suppress alcohol consumption.

It is FDA-approved for use in clinical practice for the treatment of:

• Alcohol use disorder
• Opioid use disorder (prescription and non)

Naltrexone is absorbed orally and undergoes extensive metabolism via the first-pass effect. However, this does not affect its potency as naltrexone's active metabolite, 6β-naltrexone, acts as a potent opioid antagonist. The medication's half-life is around 4 hours but can last up to 24 hours. If administered parenterally, it bypasses the first pass and is even longer acting, with a half-life of 5-10 days. Naltrexone is excreted by the kidneys (6).

Available Forms

Naltrexone is available in an oral tablet and IM injection. Available preparations include:

• Generic naltrexone tablets
• Revia (oral tablet)
• Depade (oral tablet)
• Vivitrol (solution for IM injection, extended-release) (6)

Dosing and Monitoring

Since naltrexone will compete for and block all opioid receptor sites, the risk for withdrawal symptoms is high, and clients must stop the use of alcohol or opioids for 7-10 days before beginning treatment to lessen the risk of withdrawal symptoms. A naltrexone challenge is recommended at the start of therapy.

This consists of administering small amounts of naltrexone subcutaneously or via IV and monitoring the client and their vital signs for signs of withdrawal, such as:

• Nausea
• Vomiting
• Diaphoresis
• BP changes
• Tachycardia
• Rhinorrhea
• Agitation
• Tremors
• Abdominal pain
• Pupillary dilation (6)

If a client fails the naltrexone challenge and has not been long enough since their last use of alcohol or opioids, the naltrexone initiation should be delayed, and the test should be repeated in 24 hours. If clients tolerate the naltrexone test and the negative result, they may begin naltrexone treatment (6).

For oral tablets, dosing usually starts at 25 mg for the first dose. Clients are observed for withdrawal symptoms and side effects; an additional 25 mg is given 1 hour later. After that, clients take 50 mg per day. Clients may continue with 50mg daily or take 100 mg every other day or 150 mg every 3rd day (6).

Alternatively, naltrexone may be given via IM injection for more extended action, improving compliance and reducing relapse. Particularly for alcohol or heroin dependence, data indicates that the IM route has much higher success rates than the oral route. If a client receives the IM injection, 380 mg is given to the gluteal muscle every four weeks (6).

Side Effects and Contraindications

Most common side effects of naltrexone include:

• GI irritation
• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Hypertension
• Headache
• Anxiety
• Low energy
• Joint or muscle pain
• Nervousness
• Sleep disruption

Less commonly, clients report:

• Loss of appetite
• Constipation
• Dizziness
• Irritability
• Depression
• Rash
• Chills (6)

Caution should be used for clients with liver function issues and renal impairment. It is Category C for use during pregnancy, and the risks versus benefits of use in pregnancy must be carefully considered. It also crosses into breast milk and must be considered carefully.

There is limited data about the overdose of naltrexone, and there may be very few symptoms if an overdose occurs. Clients should be monitored for signs of liver dysfunction, seizures, depression, and suicidal ideations. No antidote for naltrexone is currently available.

Naltrexone is contraindicated for clients who failed a naltrexone challenge, test positive for opioids or alcohol on drug screening, have a history of seizures, or have experienced a past hypersensitivity reaction to naltrexone.

Clients may switch from buprenorphine or methadone to naltrexone at some point in treatment. Both medications are agonists at the opioid receptor sites, so changing to naltrexone (an antagonist) may increase the risk of withdrawal symptoms for the first two weeks of treatment (6).

Considerations for Prescribers

Because naltrexone does not cause any euphoria or "high," the abuse potential is non-existent. It is not a controlled substance and can be prescribed by any clinician with prescriptive authority. However, its use is typically only by those who work in mental health or addiction medicine. Clients can take the medication at home or go to the clinic for IM injections.

Many considerations for naltrexone use center around monitoring for side effects and treatment compliance. Baseline and periodic drug screening and liver function tests are prudent. Clients' support persons should be educated on compliance and signs of relapse. The IM formulation should be considered for those with poor compliance or most at risk for relapse (6).

Nursing Considerations

Nurses will encounter clients with addiction and even those receiving MAT in a variety of settings, including:

• Outpatient clinics for routine care of any health issues
• ED admission for acute problems not related to addiction.
• Inpatient hospitalization related to other health problems.
• Outpatient setting for participation in MAT or addiction management.
• ED admission for acute problems related to substance abuse or toxicity of MAT medication.
• Inpatient mental health admission for mental health and addiction issues

Regardless of the setting and if the client is being seen for an addiction issue or something else, it is crucial for nurses to be familiar with MAT medications and how they work to provide safe and competent care. Nurses may need to:

• Administer medication.
• Monitor lab results.
• Observe for side effects, toxicity, or withdrawal symptoms.
• Coordinate care within a multidisciplinary team
• Communicate with therapeutic and nonjudgmental techniques.

Case Study

Justin is a 32-year-old male who presents to the ED with nausea, lethargy, and confusion worsening over the last 24 hours. Upon exam, the nurse notes diaphoresis, slurred speech, and pinpoint pupils. His vitals are RR 10, HR 54, BP 82/58, SPO2 97%, Temp 99.0.

He reports taking Wellbutrin 150mg daily for depression and smoking cessation, methadone 100mg daily for history of oxycodone abuse, and was started on ciprofloxacin 250mg BID for a UTI 2 days ago at urgent care.

His labs are significant for a WBC of 15,000 but otherwise regular. He tests positive for methadone, which is expected, but not for other substances. He reports being compliant with MAT and avoiding opioid use for nine months.

It is determined that Justin is experiencing methadone toxicity due to the slowed metabolism of the drug from the combination of methadone and ciprofloxacin. He is given naloxone in the ED, and within an hour, his symptoms have improved significantly, and his vital signs are typical. His antibiotic is switched to cefdinir, and he is discharged home in stable condition with instructions to follow up with his PCP within 1-2 days.

Conclusion

Substance use disorders are a long-standing and dangerous pathology experienced by millions of people each year. At the same time, the stigma of seeking help for such disorders has been eroding in recent years; there has also been a renewed push by the federal government to address the issue in evidence-based and meaningful ways, with access to effective treatment being at the top of the priority list.

Addiction treatment programs utilizing MAT will likely become much more popular in the coming years, and nurses will be on the front lines of this therapy. For nurses to provide competent and comprehensive care to this client population, up-to-date and accurate knowledge is necessary.

West Virginia Drug Diversion

In 2018, West Virginia had not only the highest opioid-related death rate in the nation, but also the highest synthetic opioid-related death rate (46). In 2019, West Virginia ranked in the top 10 for opioid dispensing rates, with a rate of 59.4 per 100 persons being prescribed an opioid (10), which is well above the national average of 46.7 per 100 (9). While this number has consistently decreased since 2006, the numbers of individuals in West Virginia affected by addiction and overdose remains high (30). 

Introduction   

The opioid crisis in the United States continues to affect millions of individuals. The American Psychiatric Association (APA) estimates nearly one in three Americans know someone who either is or has been addicted (1). The Centers for Disease Control (CDC) identified that in 2017, there were 70,237 overdose deaths, and in 2018, there were 67,367 (46). In both 2017 and 2018, nearly two-thirds of these involved an opioid (46). Currently, it is estimated 128 people die per day from an opioid overdose (8). The National Institute on Drug Abuse (NIDA) identifies misunderstandings and misconceptions about addiction of prescription opioids, held by pharmaceutical companies and health care providers in the 1990s, led to an increase in their use and subsequent rise in misuse and addiction (8, 31). Following this in 2010, deaths related to heroin began to rise quickly, and in 2013, deaths associated with synthetic opioids, like illicitly manufactured fentanyl, began to increase (8).   

The impact of opioid misuse and addiction is devastating to families. It can lead to job loss, relationship difficulties, inability to care for children, and death. Families who have a loved one struggling with opioid addiction may feel at a loss regarding handling or supporting their loved one, putting additional stress on the family unit. Arrest, conviction, hospitalization, and even death of a parent from opioid addiction, often place children in the care of the child welfare, further straining the system. Not only does the use of opioids impact individuals and families, but it puts additional strain on both state and national economies. It is estimated that misuse of prescription opioids costs the United States $7.5 billion per year (31).  

 In 2018, the West Virginia Department of Health and Human Resources introduced an opioid response plan, which addressed prevention, early identification, treatment, overdose reversal, family support, and recovery (43). Recommendations of the plan include expanded treatment for neonatal abstinence syndrome (NAS), improved access to treatment, improved overdose reporting, improved access to naloxone, addressing issues with pain management and prescribing practices, expanded licensing for medication-assisted treatment programs, and it created the Opioid Reduction Act (43). It is important to discuss The Opioid Reduction Act of 2018 in this West Virginia Drug Diversion course as it requires health care providers to prescribe the lowest effective dose and limits opioid prescriptions to a four-day supply for an emergent or urgent care, a three-day supply for minor surgery or procedure, a three-day supply for dentist or optometrist, and a seven-day supply for patients seen by their primary physician or at discharge from a hospital (34).  

While West Virginia has taken steps to address the opioid crisis, more work is needed to meet the need of patients, families, and health care workers. Health care providers who are not specifically trained to treat substance use disorders may struggle when working with patients who suffer from addiction, as there are often knowledge gaps related to these patients’ care. Gaps exist related to fully understanding the broad spectrum of a substance use disorder and in the identification of at-risk populations. Additionally, stereotypes about addicts still exist, which can inhibit health care providers from properly identifying and developing treatment plans for these patients. 

Many patients with substance use disorders are often able to hide their addiction from loved ones and providers for a period of time, which further complicates timely identification and intervention. Health care providers prescribing opioids and other medications that are high-risk for abuse should perform not only regular screening of at-risk patients, but also explore alternative methods for treating chronic pain. In an effort to address these concerns, the West Virginia Board of Nursing requires annual education for nurses who prescribe, administer, or dispense controlled substances (45). This course will address issues concerning the opioid crisis, including best practices for prescribing controlled substances, managing patients who divert, behaviors associated with drug seeking and substance use disorders, providing patient education on opioid use, storage, disposal, and reversal agents, as well as use of the West Virginia Controlled Substance Automated Prescription Program (CSAPP). 

In 2018, West Virginia had not only the highest opioid-related death rate in the nation, but also the highest synthetic opioid-related death rate (46). In 2019, West Virginia ranked in the top 10 for opioid dispensing rates, with a rate of 59.4 per 100 persons being prescribed an opioid (10), which is well above the national average of 46.7 per 100 (9). While this number has consistently decreased since 2006, the numbers of individuals in West Virginia affected by addiction and overdose remains high (30). 

Introduction   

The opioid crisis in the United States continues to affect millions of individuals. The American Psychiatric Association (APA) estimates nearly one in three Americans know someone who either is or has been addicted (1). The Centers for Disease Control (CDC) identified that in 2017, there were 70,237 overdose deaths, and in 2018, there were 67,367 (46). In both 2017 and 2018, nearly two-thirds of these involved an opioid (46). Currently, it is estimated 128 people die per day from an opioid overdose (8). The National Institute on Drug Abuse (NIDA) identifies misunderstandings and misconceptions about addiction of prescription opioids, held by pharmaceutical companies and health care providers in the 1990s, led to an increase in their use and subsequent rise in misuse and addiction (8, 31). Following this in 2010, deaths related to heroin began to rise quickly, and in 2013, deaths associated with synthetic opioids, like illicitly manufactured fentanyl, began to increase (8).   

The impact of opioid misuse and addiction is devastating to families. It can lead to job loss, relationship difficulties, inability to care for children, and death. Families who have a loved one struggling with opioid addiction may feel at a loss regarding handling or supporting their loved one, putting additional stress on the family unit. Arrest, conviction, hospitalization, and even death of a parent from opioid addiction, often place children in the care of the child welfare, further straining the system. Not only does the use of opioids impact individuals and families, but it puts additional strain on both state and national economies. It is estimated that misuse of prescription opioids costs the United States $7.5 billion per year (31).  

 In 2018, the West Virginia Department of Health and Human Resources introduced an opioid response plan, which addressed prevention, early identification, treatment, overdose reversal, family support, and recovery (43). Recommendations of the plan include expanded treatment for neonatal abstinence syndrome (NAS), improved access to treatment, improved overdose reporting, improved access to naloxone, addressing issues with pain management and prescribing practices, expanded licensing for medication-assisted treatment programs, and it created the Opioid Reduction Act (43). It is important to discuss The Opioid Reduction Act of 2018 in this West Virginia Drug Diversion course as it requires health care providers to prescribe the lowest effective dose and limits opioid prescriptions to a four-day supply for an emergent or urgent care, a three-day supply for minor surgery or procedure, a three-day supply for dentist or optometrist, and a seven-day supply for patients seen by their primary physician or at discharge from a hospital (34).  

While West Virginia has taken steps to address the opioid crisis, more work is needed to meet the need of patients, families, and health care workers. Health care providers who are not specifically trained to treat substance use disorders may struggle when working with patients who suffer from addiction, as there are often knowledge gaps related to these patients’ care. Gaps exist related to fully understanding the broad spectrum of a substance use disorder and in the identification of at-risk populations. Additionally, stereotypes about addicts still exist, which can inhibit health care providers from properly identifying and developing treatment plans for these patients. 

Many patients with substance use disorders are often able to hide their addiction from loved ones and providers for a period of time, which further complicates timely identification and intervention. Health care providers prescribing opioids and other medications that are high-risk for abuse should perform not only regular screening of at-risk patients, but also explore alternative methods for treating chronic pain. In an effort to address these concerns, the West Virginia Board of Nursing requires annual education for nurses who prescribe, administer, or dispense controlled substances (45). This course will address issues concerning the opioid crisis, including best practices for prescribing controlled substances, managing patients who divert, behaviors associated with drug seeking and substance use disorders, providing patient education on opioid use, storage, disposal, and reversal agents, as well as use of the West Virginia Controlled Substance Automated Prescription Program (CSAPP). 

Epidemiology of Pain and Substance Use Disorder 

Pain 

Pain is a complex problem. Because of the personal nature and the varying pain experiences of the patient, it is often difficult to adequately treat. When pain goes unrelieved, the potential of it impacting the patient’s life negatively increases. Untreated pain can result in increased stress on the body, increased healing time after injury or surgery, decreased immune response, feelings of anxiety or depression, and alterations in performing activities of daily living. The effect of this can also be long-reaching as untreated pain can result in a decrease in work performance and job loss for some patients.  

Acute or Chronic 

For this West Virginia Drug Diversion course, it is necessary to outline that pain can be classified as either acute or chronic. Acute pain is often associated with injury, inflammation, ischemia, or surgery and typically only lasts for a short while. Patients experiencing acute pain are often able to easily localize the pain. Acute pain that is not adequately treated can progress to chronic pain. One example of this is seen in musculoskeletal injuries, such as back strain, where repeated injury and inadequate pain management progress to a state of chronic pain. 

Chronic pain usually lasts more than three months. Unlike acute pain, chronic pain often is not as well defined, the onset is typically gradual and characteristics of the pain can change over time. While some chronic pain can be tied to a specific cause or disease state, such as arthritis or cancer, other times, the exact cause is not as easy to determine.    

Nociceptive and Neuropathic 

Pain can be further categorized into nociceptive and neuropathic pain. Nociceptive pain is a result of normal stimuli, and it is further identified as either somatic or visceral pain. Somatic pain is superficial and involves skin, muscles, bone, blood vessels, and connective tissues. An example of acute somatic pain would be a sprained ankle and an example of chronic somatic pain would be arthritis. Visceral pain refers specifically to pain in the organs. An example of acute visceral pain is seen in cardiac ischemia, which is often described as chest pain or left arm and jaw pain in patients experiencing a myocardial infarction (MI). An example of chronic visceral pain would be abdominal pain secondary to stomach cancer. 

Neuropathic pain results from damage to either the central or peripheral nervous system. While most cases of neuropathic pain are chronic, acute neuropathic pain can be seen in injuries or infections affecting the nerves. In some cases, acute neuropathic pain, such as what is seen in amputations, may come and go with the severity of the pain differing greatly from patient to patient. Acute neuropathic pain may progress to chronic neuropathic pain if not treated effectively. Additionally, other disease states may cause chronic neuropathic pain, such as what is seen in diabetic neuropathy. Chronic neuropathic pain is often difficult to treat, and patients may be prescribed several medications before finding something that provides some pain relief. 

Pain Assessment 

There are various factors affecting how pain is perceived and managed. These factors include the type of pain, how long the pain has been occurring, patient age, cognitive level of the patient, the patient’s personality or temperament, previous experiences with pain, and even cultural beliefs. Understanding how these factors influence the patient’s response can help to inform the assessment and may be helpful in determining appropriate treatments for the pain.  

A comprehensive assessment of the pain is also important in determining the type of pain. A thorough assessment at the start of treatment will also serve as a baseline and help to determine if interventions have been effective. Additionally, patients who are not adequately assessed for pain are at a higher-risk of their pain not being effectively managed. It is important to remember not all patients are capable of describing their pain, and as such completing a pain assessment can help these patients to provide the information necessary for informed diagnosis and treatment. How a pain assessment is obtained may also vary. While traditionally, a pain assessment is completed as part of the general assessment, use of a paper or electronic form completed by the patient prior to evaluation may also be used. For this West Virginia Drug Diversion course, it is vital to thoroughly read through the “Pain Assessment Components” table below.  

Substance Use Disorder 

The National Survey on Drug Use and Health found in 2017, 19.7 million Americans over the age of 12 suffered from a substance use disorder, and 11.4 million people had misused opioids (6). This same study found 62.6% of participants identified the initial reason they misused a prescription pain reliever was to relieve pain (6). Addiction costs related to productivity, health care, and legal care totaled over $7 billion annually by 2017 (6). These statistics are staggering and show why early intervention to identify at risk individuals and to prevent severe substance use disorders is necessary. 

There is a drastic difference between substance use and addiction, which is more accurately called substance use disorder. Not every patient who uses a controlled substance develops a substance use disorder. However, risk factors may predispose some patients to develop one. There is an increased risk for the development of a substance use disorder in patients who have family members who also suffer from a substance use disorder or a mental health disorder (41). Additionally, how the drug acts within the body and brain and stress will increase the risk of developing a substance use disorder, even when the medication is taken as prescribed (41). 

The NIDA defines misuse (abuse) as the action of taking medication other than prescribed, either for purpose or dose, taking another person’s prescription, or taking a medication to get high (27). Misuse, by itself, may not necessarily indicate an addiction as other factors need to be considered. Patients may misuse a wide variety of prescription medications without incident; however, when misuse of medication is common, the risk of it occurring with medications that are addictive or controlled is higher. In patients who make a choice to misuse medications regularly, the ability to control their own behavior decreases (29). NIDA defines addiction as a chronic condition, where patients may have periods of relapse, will compulsively seek out drugs, and continue to use, despite the harmful effects and long-lasting changes it may have on the brain; it is considered both a complex brain disorder and a mental illness (29). 

Diagnosis of Substance Use Disorders

The process of developing a substance use disorder occurs on a continuum. The majority of patients who take a couple of doses of an opioid to treat acute pain, such as seen in post-surgical patients, will not become addicted. The risk for addiction increases when the patient is at higher risk due to genetics or psychological factors (41). Exposure to a substance changes how the brain responds, leading to intoxication (2). When a patient repeatedly uses the substance, they build up a tolerance, which then requires the patient to use more of the substance to achieve the same feeling. Over time, even patients who use a substance as prescribed can develop a tolerance. This is often seen in patients who suffer from chronic pain and use opioid medications for pain management. While increased tolerance can be an indicator of addiction, this alone does not equate to a diagnosis of addiction or a substance use disorder.  

The Diagnostic and Statistical Manual of Mental Disorders: Version 5 (DSM-5) categorizes substance use disorder symptoms into four categories, impaired control, social problems, risky use, and physical dependence (20). Understanding the DSM-5 categorizations will further help you not only in this West Virginia Drug Diversion course, but also in identifying signs and symptoms of substance use disorders in patients.  

Impaired Control 

• Cannot control the use of the substance 
• Unable to cut down or stop using 
• Spends time obtaining, using, or withdrawing from substance 
• Reports craving the substance (20) 

Social Problems 

• Unable to meet obligations of work, home, or school 
• Continues use of a substance even though it causes social or interpersonal problems 
• Is no longer as active in social, work, or recreational activities (20) 

Risky Use 

• The substance is used in dangerous situations, such as when driving 
• Continues using the substance even though it is making a medical or psychological problem worse (20) 

Physical Symptoms 

• Displays evidence of tolerance 
• Has symptoms of withdrawal when the substance is stopped or counteracted (20) 

If a patient has more than two positive symptoms in a 12-month period, they should be diagnosed with a substance use disorder (20). The severity of the disorder is further determined by the number of criteria or symptoms present, with mild being two-to-three, moderate four-to-five, and severe addiction being greater than six (20). 

Opioids 

Indications and Action 

Opioid analgesics can be used to manage pain, used as anesthesia adjuncts in surgery, and as a cough suppressant. Opioid analgesics work by binding to specific opiate receptors (mu, delta, and kappa). Opiate receptors can be found in the central nervous system, peripheral tissues, and in the gastrointestinal (GI) tract. Opiate receptors also help to control blood pressure, pupil dilation, GI secretions, respiration, and pain response (19). When opioids are used to manage pain, they act upon these same opiate receptors, resulting in a decrease in pain and affecting the control these receptors have on other systems, resulting in some of the effects experienced by patients when taking opioids.  

The most prescribed opioids include hydrocodone, oxycodone, oxymorphone, morphine, codeine, fentanyl, hydromorphone, tapentadol, and methadone (7). Administration routes vary based upon the type of opioid prescribed. 

In determining which route should be used, consideration should be given to the type of medication, what type of pain is being treated, as well as the age and cognitive level of the patient. Common routes for home use include oral (both tablet and liquid), buccal, sublingual, intranasal, topical, and transdermal. Rectal routes may be used for pediatric patients or for those who are unable to tolerate oral ingestion. Opioid treatment in hospitals or clinics may also include intravenous (IV) injection, subcutaneous injection, and intrathecal. Patients prescribed opioid medications should receive medication education that includes administration and adverse effects and general education about safety, storage, and disposal. 

The Controlled Substances Act identifies scheduled medications based upon their current acceptable medical use, abuse potential, and risk of dependence (38).  

Examples of scheduled substances:  

Schedule I: Heroin  

Schedule I substances have a high abuse potential and are not currently considered to be acceptable for medical use (38) 

Schedule II: Hydromorphone, oxycodone, morphine, methadone, and fentanyl 

Schedule II substances can be prescribed but are high risk for abuse (38). 

Schedule III: acetaminophen with codeine, as these products contain less than 90mg of codeine per dose  

Schedule IV: Tramadol  

Schedule V: Antidiarrheal diphenoxylate/atropine and cough suppressants containing less than 200 mg/100 ml of codeine  

They have the lowest potential for abuse. 

Contraindications and Precautions 

Use of opioid analgesics should be used cautiously in patients with conditions resulting in respiratory insufficiency, morbid obesity, and pregnancy. Additional assessment and risk analysis should be performed prior to prescribing or administering opioid analgesics to patients with a diagnosed substance abuse disorder, concurrent psychiatric illness, and those taking benzodiazepines. Concurrent use of opioids and benzodiazepines should only occur if no other treatment options are available due to the increased risk of respiratory depression. Patients taking tramadol, meperidine, or fentanyl are at an increased risk for the development of serotonin syndrome when these drugs are taken with other medications that affect serotonin, and care should be taken when these medications are prescribed concurrently (36). 

Adverse Effects 

Adverse effects of opioids range from mild to severe, and most patients who are prescribed opioids will experience one or more effects. Common adverse effects include: 

• nausea 
• vomiting 
• constipation 
• urinary retention 
• urticaria 
• lightheadedness 
• sedation (19) 

With the exception of constipation, which can be an ongoing effect, many of the common adverse effects such as nausea, vomiting, and urticaria often lessen in severity with continued use. More serious adverse effects, which may occur even with continued use, include hypotension, bradycardia, and respiratory depression. Patients should be prescribed the shortest-acting, lowest effective dose to minimize severe adverse effects (14). 

Toxicity 

Opioid toxicity can occur regardless of the route of administration. Patients presenting with opioid toxicity often have CNS depression, ranging from confusion and drowsiness to unresponsiveness. Other symptoms of toxicity include respiratory depression and pupil constriction. Patients may initially present with hypotension, but as CNS and respiratory depression worsen, hypertension may be seen as the body attempts to compensate. Patients should be monitored for seizure activity if the overdose is a result of meperidine. 

It is important to note in this West Virginia Drug Diversion course that treatment of opioid toxicity should begin immediately with the administration of naloxone. Repeat dosing may need to be administered as naloxone has a half-life of 30-60 minutes. Pre-hospital treatment with nasal or injectable naloxone should be administered, even if unsure of overdose or toxicity. In-hospital treatment should consider not only the patient’s condition but also the half-life of the opioid (if known), and the naloxone dose should be titrated based upon these factors to limit the potential adverse effects of naloxone (22). One option for treatment is continuous IV infusion as opposed to repeated larger bolus doses. The use of a continuous IV infusion has been shown to decrease the symptoms of opioid withdrawal better than bolus dosing (22).  

Pain Management Using Opioids 

Assessment 

Patient assessment is an important factor in determining the need for opioid therapy. Assessment of all patients should start with a full history and physical, including a complete pain assessment as well as any previous episodes of pain and treatments used (15). A thorough social and psychological assessment should also be completed. A social assessment should explore how the patient functions at home, work, and socially while including a discussion of how the current pain impacts their ability to function (15). A psychological assessment should include a previous history of substance use disorder and substance use as well as any underlying mental health disorders and medications currently being used to treat these (4). 

For patients with a history of substance abuse disorders, the initial assessment should further explore the substance use disorder. The history should include the type and number of opioids used recently, routes of administration, date of last use, any treatment the patient received, and physical, social, or psychological problems experienced as a result of the disorder (4).  

Patients should be screened for infectious diseases such as hepatitis B and C, human immunodeficiency virus (HIV), and tuberculosis (TB) (4). If the patient has a history of IV drug use, follow-up should include infections related to IV use, such as infective endocarditis, osteomyelitis, and abscesses (4). As opioid misuse and alcohol abuse often occur concurrently, questions related to alcohol use, frequency, and the amount should be addressed (47). 

During the physical assessment, the health care provider should also look specifically for signs and symptoms of opioid intoxication or withdrawal, as well as any physical symptoms related to long term substance abuse. Patients with a history of opioid use may have alterations in hematology, and in patients with chronic use, diet changes may result in anemia. In patients with a history of substance abuse, a baseline laboratory analysis of a complete blood count (CBC) and liver function test are recommended, as well as testing to determine the presence of TB, hepatitis B and C, HIV, and other sexually transmitted diseases (4).  

Addiction Risk Assessment 

In addition to the history and physical exam, the use of an addiction risk assessment tool can be helpful in determining the risk of misuse or addiction in patients prescribed opioids for chronic pain (15). There are several addiction risk assessment tools available, but these tools vary in complexity as well as the specific criteria being measured. 

It is important when using a screening tool to determine the risk of misuse or addiction that healthcare providers recognize a “one size fits all” approach does not work. The type of assessment used may need to vary based upon the patient and their history. For patients with a complex history of a substance use disorder, a more complex and complete assessment should be used, whereas a patient without risk factors may only need a basic risk assessment. Availability, ease of access, and target patient age may also play a part in the type of tool chosen. Several tools are readily available through the NIDA website and can be downloaded by health care providers. Having two or three tools available that health care providers have been trained to use and are comfortable using allows for improved assessment and ability to better identify at risk individuals. 

Finding a patient is high-risk can be scary for both the healthcare provider and the patient as the goal of treatment is not to create an additional problem. However, the risk assessment does not mean the patient’s pain should not be treated. Evaluating alternative treatment methods is important, and opioids or other controlled substances should not be a first line option. Additional support will need to be provided to this patient through referrals to both a pain and behavioral health specialist to ensure the needs of the patient are being met and their pain is being adequately treated.

Treatment Options and Goals 

While acute pain can be treated with opioid medications, considerations should be made regarding the severity of the pain, diagnosis, and the effect of the pain on the ability of the patient to function (14). If the patient can tolerate the pain and there is minimal impact on their ability to function, non-pharmacological and non-opioid medications should be used before determining an opioid is necessary. Additionally, steps should be taken to evaluate and treat underlying causes of pain. In cases where the acute pain is severe and impairs patient function, steps should be taken to ensure the patient is prescribed the lowest possible dose of an immediate-release opioid, ideally with only a three-to-five-day supply (14).  

Non-pharmacological Pain Management 

Options for non-pharmacological pain management and their effectiveness will vary based on the patient and the nature of their pain. When determining which methods will work for the patient, healthcare providers should discuss options with the patient and provide education about how it can be used, as well as the benefits for using a particular therapy. Healthcare providers after reading this West Virginia Drug Diversion course should also evaluate potential costs and the barriers to using these therapies. Follow-up is necessary in determining the effectiveness of the therapy and if further treatment is necessary.  

Non-opioid Pain Management 

The use of non-opioid medications for pain management should be carefully considered prior to implementation. These medications should be evaluated based upon the need for short-term or long-term therapy. For some medications, the risk of complications when taken concurrently with opioids is high, so patient evaluation and screening are key in determining the current use of opioids. The patient should be monitored for therapeutic effectiveness as well as potential side effects. Additionally, some non-opioid options carry their own risk of addiction and patients should be monitored for substance use disorders related to these.  

Evaluation of the type and nature of the pain is important in determining which options would best fit the patient’s needs. Healthcare providers will need to discuss with the patient the possibility of having to try different modalities and medications to find a fit that is right for them. Patient tracking of symptoms, use of relief methods and medications, the effect on the ability to function, and effectiveness of interventions is key in determining which modalities and medications are working. Various mobile apps for tracking and managing pain are available and may be an option for helping some patients to record and track this data.  

In the event the patient and healthcare provider determine non-pharmacological and non-opioid medications are not effectively managing the pain, opioids may be added to the treatment plan (14).  

If opioid therapy is needed and tramadol is prescribed, consideration should be given to tapering patients off antidepressants being used for pain relief to decrease the risk of serotonin syndrome. Opioids should be prescribed at the lowest effective dose, and it is recommended that immediate-acting opioids be prescribed before long-acting opioids, although long-acting or sustained-release formulations remain an option for treating neoplastic-related pain (14). Prior to prescribing opioid therapy and at every visit, the risk versus benefits of opioids should be evaluated and discussed with the patient (14). If benefits do not outweigh risks of continued therapy, steps should be taken to taper the dose down or taper to discontinue the opioid (14). 

Therapy Goals 

Another important step in therapy is the determination of therapy goals. Goal setting should occur early in the treatment process and should be a collaboration between the patient and the health care provider. When setting goals, they should be realistic to what can be achieved medically and within the base functioning of the patient, they should be specific as to what the patient wants to achieve, and include a realistic time frame for achieving these goals (14). Goals should be included in the patients plan of care within the electronic health record (EHR) and be reviewed at each visit. Evaluation of goals should also incorporate data tracked by the patient.  

Compliance with use and appointments should also be encouraged. Patient education about the proper use of opioids and follow-up appointments is key. Other steps include requiring a follow-up visit before the first refill, with the understanding no additional scripts will be written until after the follow-up, and scheduling future appointments before the patient leaves the office (14). Health care providers should also work with the patient’s other providers to ensure the patient is not receiving multiple prescriptions and to ensure there are not any concurrent prescriptions for benzodiazepines (14). A thorough check the EHR for previously written prescriptions should be completed. For outside health care providers, the patient should be asked to sign a release of information, to allow these records to be obtained. For health care providers living in states with prescription drug monitoring programs, the database should be checked prior to prescribing and information regarding prescriptions written should be submitted following the regulations set forth by individual states (14).

Ongoing Monitoring

The CDC identifies urine drug screens should not be used solely to determine risk; however, when they are used in combination with other risk assessment strategies, the use of urine screens may be helpful to identify those patients at high risk of overdose, and as a method to identify which patients may need additional monitoring or support (14). Urine screens should be used at the start of opioid therapy for chronic pain and can be used throughout therapy to validate what the patient has reported and to identify the use of multiple substances (4, 15).  The frequency of testing should be determined by how stable the patient is, the type of treatment, and the setting in which the treatment is taking place (4). The CDC’s basic recommendations are that urine screening occurs annually for patients on long-term opioid therapy (14). However, in some cases, more frequent screening may be mandated for patients undergoing treatment for substance use disorders (4).  

Not all urine screens are the same. As such, the healthcare provider, nurses, and staff performing the screen should obtain additional training and education beyond this West Virginia Drug Diversion course regarding the specific screen being used and following manufacturer recommendations for performing. Because some substances may only be present in the urine for up to 3 days, a negative result may not rule out the use of a substance (4). Instead, health care providers should use this information in conjunction with assessment findings and subjective patient reporting to determine if further action or monitoring is necessary. 

Pill counts are also sometimes used as a method for ongoing monitoring of a patient’s compliance with therapy and as a method for preventing drug diversion. The idea behind pill counts is if the patient presents to the visit with the correct number of pills then misuse and diversion are not occurring. When used alone, pill counts are not effective in preventing addiction, and the evidence does not support using this as a sole method for preventing misuse (14). However, use of pill counts are still sometimes used as part of opioid therapy and are still sometimes included as part of the treatment agreements. When used with other methods, they can provide insight into patient use of the medication and provide an opportunity for ongoing education about safe use and storage of opioid medications. Healthcare practitioners choosing to use pill counting as a method of deterring misuse and diversion should recognize pill counts may be “padded” by borrowing, renting, or purchasing additional pills illegally. Care should be taken not just to count the pills remaining in the prescription but to also verify the pills all have the same appearance.

Referrals

Referrals are an important part of managing a patient with pain, especially in cases of chronic pain. Healthcare providers should be willing to provide referrals to outside providers and specialists to address specific pain concerns. For example, if a patient is identified to have chronic pain in their lower back or hips, a referral to an orthopedic specialist for evaluation is warranted. If a patient has used multiple modalities, including opioids, without success a referral to an interventionalist may be needed to determine if the patient is a candidate for a nerve block, neuromodulation, or implantation of an intrathecal medication delivery device (12). 

For patients with a history of substance use disorder or other underlying mental health concerns, a referral to a psychologist, psychiatrist, or mental health therapist should be provided, and the healthcare provider should work in conjunction with this specialist to manage the patient. Behavioral health services should also be considered for patients without a personal or family history of addiction or mental health disorders, as chronic pain can cause depression and anxiety. When opioids are used, long-term chemical changes in the brain occur, increasing the risk of not only substance use disorder but depression, anxiety, paranoia, and hallucinations (25). This West Virginia Drug Diversion course highlights the importance of not only identifying patients who may be suffering from a mental health disorder as a result of opioid use but ensuring that proper treatment is provided.  

For some patients with chronic pain, referral to a pain specialist may be necessary. While not every patient needs this, there are some reasons when a referral becomes necessary: 

• the patient requires higher dosages of morphine or another opioid 
• concurrent use of other CNS depressants (benzodiazepines, muscle relaxers, or anticonvulsants) 
• requests more opioids, asks for early refills, or has pain-related visits to the emergency department or urgent care 
• reports use of illicit drugs or urine drug screen is positive for non-prescribed drugs 
• the patient is unable to follow the pre-agreed upon treatment plan 
• refuses to use non-pharmacological or non-opioid pain management strategies  
• refuses to taper dosage when risk outweighs benefits (12)
  

Primary healthcare providers should work with pain specialists to determine if the patient should be referred for medication management or if a transfer of care is necessary (12).  

Referrals may also be needed for services such as physical therapy or occupational therapy. In some states, patients may seek out therapy services on their own, and in some states, a referral or prescription is required. Health care providers should determine if a prescription or referral is necessary for insurance purposes before sending the patient for evaluation by a physical or occupational therapist or other specialty healthcare providers. When determining which referrals are needed, the healthcare provider should explore what resources are available locally as well as any barriers the patient may have to attend those appointments.

Treatment Agreements and Informed Consent

The use of patient-provider agreements has a long history in opioid treatment. Initially, these were used to set standards or requirements for patient behavior and often included dismissal as a punishment for not adhering to the agreed-upon treatment regimen (12). When used in this manner, the effect on patients was not always positive. Patients often felt a sense of distrust and stigma related to the use of these agreements, which only served to undermine the therapeutic relationship and threatened the treatment plan (12, 33). Yet, the use of patient-provider agreements continues to be included as part of treatment recommendations, because when used correctly they can help support both the patient and healthcare provider (14). 

Because of these recommendations, treatment agreements continue to be used. Healthcare providers should take steps to ensure the treatment agreements are being implemented in a way that is patient-centered and are not punitive in nature, but instead act to provide information about risks and benefits as well as steps to ensure compliance (12, 33). Perhaps a better way of looking at treatment agreements is to see them as a method of informed consent, wherein the patient is provided need-to-know information including risks, benefits, and consequences of noncompliance, and is then allowed to determine if undergoing treatment is what they desire (12, 33).  

While patient treatment agreements historically may not have always been effective, they become one part of a patient-centered treatment plan when used correctly. Not only can these agreements serve as a way to document the patient’s informed consent of the treatment, but they can be used to identify clear goals and expectations for patients receiving opioid therapy. Treatment forms may vary from clinic to clinic, but common components include:  

• treatment goals 
• responsibilities for safe medication use 
• storage and disposal of opioid medications 
• requirement for the patient to obtain prescriptions from only one clinician or practice 
• requirement to only fill prescriptions at one pharmacy 
• agreement for periodic drug testing 
• clinician agreement to be available or have coverage (16) 

In addition to the use of treatment agreements, healthcare providers should implement the use of informed consent forms (16). In some cases, these are combined with the treatment agreements, and in other cases the informed consent may be a separate document. Components of the informed consent should include: 

• the limited benefit of opioid in chronic pain 
• risks and benefits of opioids 
• potential side effects, including sedation and impaired motor skills 
• risk of tolerance, physical dependence, development of a substance use disorder, overdose, and death 
• prescribing policies and expectations 
• reasons why therapy may be changed or discontinued 
• education that the patient should not expect to be pain free (16)

Discontinuing Opioid Therapy

Discontinuing opioid therapy may be considered for various reasons; risk outweighs the benefit, effective use of non-pharmacological therapies and non-opioid medications, patient desire to stop use, and noncompliance. Understanding why the therapy is being discontinued and communicating with the patient is important to ensure that pain management goals are met. Recommendations for discontinuing opioid therapy are to initially taper just the dose, then extend the time between doses (14). Once a patient has reached the point where they are taking an opioid less than once a day, the opioid can be stopped (14).  

Emergency discontinuation of therapy or rapid tapering of opioid dosing may occur when a patient overdoses on their current dose (14). In these cases, patients should be closely monitored in a controlled setting, and supportive therapy to manage withdrawal symptoms should be employed. Urine drug screens should be completed to rule out the presence of other drugs and baseline CBC, metabolic panel, and liver enzymes should be obtained. The clinical opiate withdrawal scale (COWS) should be utilized to monitor for signs and symptoms of withdrawal. 

The COWS is an 11-criterion scale that looks at physical symptoms of withdrawal. Each criterion is scored based upon what is being evaluated or observed in the patient. A score of 5-12 indicates mild withdrawal, 13-24 is moderate, 25-36 is moderately severe, and patients scoring above 36 are in severe withdrawal. The criterion evaluated includes: 

• resting pulse rate 
• sweating 
• restlessness 
• pupil size 
• joint pain 
• runny nose or tearing of the eyes 
• GI upset 
• tremors 
• yawning 
• reported anxiety or irritability 
• piloerection 

Proper use of the scale is important, and the nursing staff who will be using the scale to evaluate patients should be properly training in its use. Treatment of acute withdrawal symptoms should be based on the patient’s COWs score and the symptoms they are presenting. In addition to the symptoms evaluated using the COWs, blood pressure should be monitored and hypertension should be managed. Medications used to manage symptoms of acute withdrawal include anti-emetics, non-opioid antidiarrheals, and clonidine or lofexidine. Care should also be taken to provide a low stimuli environment, such as dimmed lights, limiting excess noise, and keeping the room at a comfortable temperature. 

Managed withdrawal can also occur more slowly and is commonly seen in patients who are heroin-dependent or if the patient and healthcare provider identify a detoxification program is needed. In some cases, methadone or buprenorphine may be used to lessen the symptoms of withdrawal. Patients prescribed methadone should also be provided referral to a methadone clinic for monitoring and medication distribution. Patients undergoing methadone or buprenorphine treatment should also be referred for behavioral therapy to help manage psychological effects, and for ongoing treatment and support of a substance use disorder (14).

Patient Education 

Education of patients at the point of prescribing and at every visit thereafter is important to ensuring patients are actively involved in their own care and are taking steps to manage their care at home. However, educational practices can be inconsistent between clinics and facilities, between health care practitioners, and, in some cases, education is missing (18). For patients who are prescribed opioids, education is a key component towards ensuring patient safety.  

Both patients and family members should be taught the risks and benefits of opioid use, the effectiveness of opioids, and the appropriate use of opioid medications. Patients and families should be taught the signs and symptoms of an overdose and how to appropriately intervene in the case of an overdose. Additionally, patients should be taught about diversion’s risk and steps to prevent it (18). 

Prior to engaging in patient education about opioids or addiction, the nurse should first self-evaluate or reflect on their own feelings related to these topics. Efforts should be made to approach each patient as an individual and to avoid stereotyping patients based upon their type of pain, use of opioids, or history of a substance use disorder. Patients should be approached in a nonjudgmental manner, and nurses should employ therapeutic communication techniques, allowing the patient to express their concerns and to encourage questions.  

When starting an educational session, it is important to identify the specific learning needs of the patient. This may range from identifying the type of learner the patient is, the level of education or reading level, and even includes identifying specific questions or concerns the patient has related to using an opioid. 

Time should also be committed to evaluating what the patient’s current knowledge about opioid use is and to dispel misconceptions the patient may have about opioids. Misconceptions that may be held by patients about opioids, addiction, or the prescribing process might include: 

• Opioids are the only thing that will help the pain. 
• When taken as prescribed, addiction will not occur. 
• Not being prescribed an opioid means the health care provider thinks the patient is an addict 
• Addiction only happens to certain types of people. 

Nurses should take care to provide facts and evidence (at the patient’s level) to dispel misconceptions. When addressing misconceptions, it is also important to be aware of tone and forms of non-verbal communication to not inadvertently pass judgment on what the patient believes.  

While teaching should be specific to meet the patient’s individual needs and prescribed opioid, information about safe use, storage and disposal, and use of opioid antagonist medications should be provided to every patient. The information provided in this West Virginia Drug Diversion course offers great opportunities and points to share with patients. Standardized educational materials should be around a 6th grade reading level to ensure that most patients easily understand the material. The use of videos through a patient education platform, like those available through Krames or X-Plain, can be useful for educating patients who are unable to read the material or are auditory learners. If these are not available, clinic-made videos or videos available online may be used.

Safe Use of Opioids 

One aspect of patient education that is essential to highlight in this West Virginia Drug Diversion course is the safe use of opioids. Because opioids are used in both acute and chronic pain management, education about safe use is an important step in helping patients take an active role in their treatment plan and ensuring their safety outside the clinical setting. In the case of a patient being treated for acute pain, instructions should include guidelines for how the opioid should be taken and for how long it should be taken. Nurses’ common education for a patient with acute pain is to take their opioid pain medication to “stay ahead” of the pain. This instruction does not go far enough to address safe use. Patients should be instructed to take their opioid medication as prescribed and not increase the frequency or dosage if the pain worsens, but instead to notify their health care provider. Patients may believe that if it is prescribed, they must take the medication, so the nurse should also educate that opioids are an as-needed medication and should not be taken if not needed; in most cases of acute pain, opioids may only be needed for the first few days. Teaching patients to self-evaluate their pain is important in determining if the opioid is necessary or if an alternative medication, such as a NSAID, would be more appropriate.  

In the case of a patient being treated for chronic pain, instructions should still include guidelines for how it should be taken, but additional guidance should be provided about safety related to toxicity and withdrawal. Opioids for chronic pain management may be either immediate-acting or long-acting, and education differs based on what is prescribed. Patients prescribed immediate-acting medications should be instructed not to change the frequency or dosage prescribed due to the risk of toxicity.

If the patient finds their pain is not being managed, further evaluation is necessary, and they should be instructed to notify their healthcare provider. These patients should also be aware of how many doses have been prescribed and be taught to manage their use of the medications. Patients who are unable to manage this effectively may find they have finished the supply and are not able to refill the prescription for several days, leading to withdrawal. For patients prescribed long-acting opioids, they should be provided education on how these medications differ from immediate-acting and to not take extra for breakthrough pain. Taking long-acting opioids as prescribed is important to prevent withdrawal. Because these medications stay in the system longer, there is also a risk of toxicity if the patient takes an extra dose or additionally medicates with a short-acting opioid.  

With any patient-prescribed opioids, additional education related to misuse and diversion should be provided. Most people who reported misusing prescription opioids identified they got the drugs from a friend or family member (21). Patients should be taught to count their medications and to keep track of their use. If they identify pills are missing, patients should be informed to notify authorities and their healthcare provider. Education should include that the prescriptions are only for personal use and should not be shared with a relative or friend. Education about safe use also needs to include concurrent use of opioids with other medications or alcohol. The patient should be instructed to avoid alcohol because of the additive CNS depressant effects, which increase the risks associated with respiratory depression. A thorough review of all patient medications, prescribed, over-the-counter, and herbal, should be completed. Education regarding potential reactions should be provided.

Proper Storage and Disposal 

Proper storage of opioids can deter theft, loss, and misuse of medications. Patients should be taught to keep opioids in the original packaging and not to store them in pillboxes. Many patients often keep medications in the kitchen or bathroom near the sink or on a shelf. Patients should be taught to keep opioids in a locked drawer or cabinet that is not easily visible or accessible to others. Additional patient education should include the dangers of accidental ingestion by children or pets. Patients should also be cautious with whom they tell about their opioid prescription and should be educated that this information should only be shared with direct caregivers.  

Patients also need to be taught about the proper disposal of opioids. Many patients will often save leftover prescription medications, “just in case,” and many patients may have multiple old prescriptions in their home, increasing the likelihood they are unaware of what is there or if it may have gone missing. It is estimated less than 20% of patients properly dispose of opioid medications (18). Educating patients on proper disposal can help to prevent problems related to the diversion of opioids by people the patient knows (18). The Food and Drug Administration (FDA) identifies the preferred method of opioid or other controlled substance disposal is to take the medication to a disposal location (39). Many pharmacies offer take-back services that will allow patients to dispose of old or unused prescriptions. Locations for take-back services can also be found by completing a search through the Department of Justice.

In some cases, a patient may not be able get to a drop off location. In these cases, the FDA has also identified both a flush and no-flush list for medications that can either be disposed of by flushing down the toilet or by discarding into the trash (39). Most medications containing opioids can be flushed to prevent misuse or diversion (39). 

For other controlled substances that cannot be flushed, it is recommended patients be taught to mix the medications in something most people wouldn’t dig through or ingest, such as cat litter, to place the mixture in a sealed plastic bag, and to throw it in with regular household trash (39). Patients should also be taught to blacken with a permanent marker or to scratch out any personal information on the prescription bottles before putting them in the trash (39). Education on disposal should include where a local drop-off site is located, which prescribed medications can be flushed, and which ones need to be put in the trash. Patients concerned about the environmental impact of flushing medications should be informed that the FDA has found the flushable medications “present negligible risk to the environment” (39).

Opioid Antagonists 

There are two commonly used opioid antagonists in use in the U.S., naloxone and naltrexone; both medications bind to opiate receptor sites, blocking the ability of the opioid to bind to the site. Patient education should include why a specific opioid antagonist is being used, appropriate administration, and potential side effects. 

Naloxone  

Naloxone (otherwise known as Narcan) is used as a reversal agent for acute overdose or accidental ingestion. Patients taking opioids or who have family members who take opioids can either obtain naloxone either by prescription or directly from their pharmacist without a prescription. It can be used by patients or their loved ones in the home to prevent death or permanent disability as the result of opioid use. Family members should be taught to call for emergency assistance (911) if they administer naloxone to a loved one. Additionally, they should be taught to look for signs and symptoms of respiratory depression in the event a second dose needs to be administered. Patients and families should also be taught naloxone is only effective for the treatment of opioid overdose and will not treat overdose related to other substances. The FDA recommends healthcare providers discuss and consider prescribing naloxone for patients who meet the following criteria:  

• high risk for overdose 
• take other central nervous system (CNS) depressants 
• history of substance abuse  
• history of overdose 
• have children who may accidentally ingest opioids (40) 

Currently, naloxone has been approved for administration via three methods (28). 

• Injectable naloxone – This is available in a 2mg/2ml syringe and is mostly used by healthcare workers in hospitals and by paramedics. For patients who receive this type of naloxone, training should be provided on the appropriate use of a syringe, dosing, and administration.  
• Autoinjectable Naloxone – Teach patients each autoinjector only contains one dose. If an additional dose is necessary, a second autoinjector will need to be used. If using an auto-injectable form, patients should be taught specifically how to open and activate the device and inject into the outer thigh.  
• Nasal Spray – A prepackaged nasal spray is often easiest for patients to use and can be obtained without a prescription from a pharmacy. With the nasal spray, patients and families should be instructed to ensure the patient is on their back, place the device’s tip into one nostril, and press firmly on the activator. Each package of spray contains one dose. Additional doses can be administered but a new device will be needed. Patients and families should be instructed to alternate nostrils if repeat doses are necessary. 

Naloxone adverse effects are often related to the reversal of the opioid and may include nausea, vomiting, diaphoresis, tachycardia, blood pressure irregularities, and tremors (28). When administered to a patient who regularly takes opioids or in an overdose, withdrawal symptoms may become present with minutes. Severe adverse effects include seizures, dysrhythmias, pulmonary edema, and cardiac arrest (35). 

Nalxtexone  

Naltrexone is an opioid antagonist used for longer-term treatment and management of opioid addiction. It requires a prescription and can be taken as a daily oral medication or as a monthly injectable. It should not be prescribed to patients who currently take opioids or who have recently used opioids or alcohol, as withdrawal symptoms will occur (37). Patients prescribed naltrexone should be instructed to avoid any opioids (prescribed or non-prescribed), alcohol, and cough or cold medications containing alcohol (37). Prior to naltrexone being prescribed, patients should have a thorough medication review done to avoid potential interactions with other prescribed medications, specifically those used to treat depression (37). Education regarding adverse effects should also be provided. Common adverse effects include nausea, vomiting, decreased appetite, drowsiness, and problems sleeping (37). Instruct patients to notify their health care provider if they experience severe adverse effects such as difficulty breathing, injection site skin changes, right upper abdominal pain, or suicidal thoughts (37).

Drug Seeking and Diversion 

Patients 

The term ‘drug-seeking’ can have a negative connotation. It is often used by healthcare providers and nurses to refer to patients who behave in a certain way, seek out treatment for certain types of pain, or their explanation of events is viewed as unbelievable or untrustworthy. Unfortunately, because the term drug-seeking has come to be used as a kind of a catch-all, legitimate patients sometimes get identified as being “drug seekers,” and their pain goes untreated (13). The use of the term ‘drug-seeking behavior’ specifically refers to behaviors displayed by patients who are struggling with substance use disorders. In caring for patients who display drug-seeking behaviors, nurses need to be aware of their own feelings and biases as they relate to opioid use and addiction. They should approach each situation with a patient in a non-judgmental manner and objectively evaluate the patient so proper intervention can be given.  

Patients who are misusing prescription opioids may not recognize they have a problem and may feel their pain is being ignored. They will often lie about symptoms or exaggerate the amount of pain they are experiencing. This can be especially difficult to assess as nurses are taught pain is whatever the patient says it is. Because each patients’ pain experience is different and their responses vary, making objective pain assessments can be difficult. Physical changes, such as elevated blood pressure, tachycardia, or diaphoresis, which might be seen in acute pain are often not present in chronic pain, further complicating the assessment.  

Patients may visit multiple clinics, urgent care, and emergency departments, which is often called ‘doctor shopping,’ and this practice allows the patient to potentially receive multiple opioid prescriptions from different healthcare providers. Depending upon what is available in the area where the patient lives, the patient may also travel to other towns or neighboring states to obtain prescriptions. Often in these cases, the patient will only give a partial or vague history. Patients may deny a request to obtain recent health records or provide false information about either themselves or where they have been treated. In addition to ‘doctor shopping,’ patients may also use multiple pharmacies to have prescriptions filled. Following the completion of this West Virginia Drug Diversion course, it is vital for healthcare providers to pick up on these signs of ‘doctor shopping.’ 

Escalation of use is often seen and occurs when patients take a higher dose, takes a dose more frequently, or both, outside of how the opioid has been prescribed by their provider. Patients may also take measures to obtain additional prescriptions from their regular healthcare provider. Patients who call the office to ask for a prescription right before the weekend or a holiday may require further investigation, especially if this is a common occurrence. One occurrence of a patient doing this does not meet the criteria of drug-seeking behavior; however, when there are repeated incidents or a pattern of behavior, it should be addressed.   

Patients may request a specific opioid or having a long list of allergies to other pain medications. Many of these patients may also report they are currently taking multiple opioids or other controlled substances. When asked about the use of opioids, other controlled substances, or even illicit drug use, patients may become angry. Aggression may also be seen when adjusting a plan of care, where the opioid medication will be changed, or the healthcare provider identifies it is time to start tapering the medication due to risks outweighing the benefits of treatment. 

In urgent care, emergency department settings, and even with the general hospital setting, changes in behavior from the waiting room to the treatment room are sometimes observed. When this occurs, patients may be calm, at a distance appear to be comfortable, or may be seen doing other activities (talking on the phone, conversing with other people, walking around); however, once placed in a treatment room, the patient may hold the area that hurts, moan, or even begin crying. If receiving IV medications, they may ask the nurse to “push it fast” or may request oral medications be changed to IV. 

Drug diversion is an illegal act occurring when a prescribed controlled substance is obtained illegally. In some cases, diversion is done as a method of obtaining prescription opioids in order to sell them. However, diversion also occurs when a patient obtains a prescription, under false pretenses, for their own use. Identifying the end goal allows the health care provider to take appropriate steps to help the patient. Healthcare providers have a duty to report opioid diversion to law enforcement; however, criminal action against a patient will vary based upon the state, intent of diversion, and if there is an intent to sell or distribute. When a patient is diverting drugs for their own use, treatment of the substance use disorder is a priority and, depending upon the situation; legal action may not be taken if the patient undergoes treatment.

Drug Diversion in Nursing 

It is estimated that 10% of practicing nurses are abusing one or more substances (32). Nurses with substance use disorders often go unidentified and it can be easy for co-workers to ignore the signs and symptoms or to dismiss them as the being stress related (24). Yet, failing to identify nurses who are struggling with substance use puts not only patients, but co-workers at risk. It is necessary to address this prevalence in this West Viriginia Drug Diversion course.  

Because nurses often have readily available access to controlled substances, their methods of diversion differ from those of patients and often are not as easily detected until a pattern is identified.  

Nurses may remove a full dose but only give a partial dose to the patient, may substitute the patient’s injectable opioid for saline, or may “forget” to waste excess opioids. Additionally, the nurse may be overly helpful; coming in early or staying late, offering to give medications for another nurse, or picking up extra shift as it gives them greater access. If not unidentified, the nurse may divert for a period of time undetected, in some cases, years. For some nurses, it is not until their behavior or physical appearance starts to change for co-workers and managers to identify a problem. Physical changes may include changes in appearance, hygiene, disheveled clothing, and in their cognitive ability (memory or concentration). Behaviors commonly seen include changes in their schedule (coming in early, leaving late, or frequent sick days), multiple breaks off the unit, and frequent bathroom breaks. As the drug starts to have a greater impact on the nurse, there may be an increase in the documentation or medication errors, or narcotic counts will consistently be off when that nurse works.  

When a nurse is suspected of diversion, reporting the incident helps the individual and helps to keep patients safe; depending upon the environment and area where the nurse works may determine to whom or where the suspicions should be reported.  

Many facilities have policies related to what should be reported, who it should be reported to, and what documentation will be required. In most cases, the incident would be reported to the direct supervisor or employer. Once it has been reported, the employer is responsible for investigating the incident, which included looking at pharmacy logs, reviewing documentation, and interviewing involved parties. If controlled substances are missing, the employer has 24 hours to report the Drug Enforcement Agency (DEA) discrepancy. In some cases, law enforcement may also be contacted if the amount missing may indicate theft. The nurse will also be reported to their state board of nursing. In some cases, the nurse may be given the opportunity to self-report the incident. It is also important to note best practice supports the nurse not being terminated when impairment or diversion is confirmed, as this often prevents the nurse from accessing treatment (5).  

The act of drug diversion by a nurse does not immediately mean their license will be revoked. An investigation by the licensing board will occur and depending upon the circumstances, the nurse’s license may be suspended, and they may be required to undergo substance abuse treatment, or, in some states, may enter an alternative-to-discipline program. This program entails evaluation, treatment, and ongoing monitoring as a condition of being allowed to return to work (5, 24). The nurse who has had their license suspended may request their license be reinstated if they meet the requirements by the board of nursing disciplinary board. In some cases, restrictions may be placed limiting the administration of controlled substances to patients.  

Once the nurse returns to the workforce, employers should take steps to support the nurse and their recovery. Best practice supports the use of employer-employee contracts that outline conditions (23). Suggested components of the contract include: 

• providing the nurse with a mentor who has been successful in recovery 
• assigning to a day shift 
• information regarding facility liability insurance and relevant guidelines and policy from the state board of nursing 
• practice restrictions placed by either the board of nursing or the facility 
• accommodations made to support in recovery (time off to attend meetings) 
• facility policies on random drug testing 
• evaluation criteria and timeline for evaluations 
• expectations related to ongoing treatment 
• consequences if the nurse relapses 
• length of time the contract will be valid (23) 

Nurses who are undergoing treatment and returning to work should be encouraged to ask questions to ensure expectations are clear. There remains a lot of stigma related to substance use disorders in nurses and employers should take steps to ensure the unit where the nurse is placed will be a supportive environment (5). Steps should also be taken to protect the nurse’s right to privacy from co-workers as it relates to ongoing treatment (5).  

Prescription Drug Monitoring Programs 

While tracking and monitoring controlled substances ultimately falls under the DEA purview, in reality, the DEA’s ability to accurately track this data on a state or local level is difficult. In response to the need for improved data collection and access to data, multiple states have started statewide prescription drug monitoring programs (PDMP).  

These programs are used to track prescribers and pharmacies, and patients who receive these prescriptions as well. PDMPs improve patient safety by allowing practitioners and pharmacists to quickly identify patients who have obtained prescriptions from multiple providers, identify the total number of prescribed opioids, and identify high-risk patients who have been prescribed other controlled substances (11). Through careful tracking and data collection, states can also use the data to determine if other statewide measures to combat opioid addiction and overdose are having any impact. The biggest drawback to these programs is the interoperability of systems between states, which limits data sharing and integration with electronic health records (3).  

In 1995, West Virginia introduced their first controlled substance monitoring program. Since its initial introduction, the program has evolved to an internet-based program capable of exchanging information with several other states (17). Work is also being done to integrate the Controlled Substances Monitoring Program (CSMP) into the electronic health record using the NarxCare program (42). Once fully integrated, providers can search for patients through the system without logging into the CSMP separately and help providers identify patient risk scores, prescription data, and patient safety alerts (42). 

Use of CSAPP 

Practioners in West Virginia, who prescribe schedule II, III, IV, and V controlled substances, products containing gabapentin, and opioid antagonists, are required to report to the CSAPP (44). Reports should be submitted every 24 hours.  

The information to be reported includes: 

• name, address, pharmacy, and DEA number of the pharmacy 
• full legal name, address, and date of birth for the patient 
• name, address and DEA number of the prescriber 
• name and national drug code number of the substance being prescribed 
• quantity and dosage of substance being prescribed 
• date prescription was written and filled 
• number of refills authorized by the prescriber 
• government-issued ID of the individual picking up the prescription if not done so by the patient 
• payment source (44) 

Additionally, in the event a provider treats a patient for an overdose, the provider should report the full legal name, address, and date of birth of the patient being treated as well as any data collected as evidence of the overdose (44). 

Case Study 

S. is a 40-year-old male. He denies any chronic illnesses. He is being evaluated at a local urgent care for lower back pain. He reports the pain started after helping a friend move some heavy boxes. C. S. denies any other injuries to his back and states, “other than what is going on right now, I am healthy.”

After evaluation by the health care provider, no acute injuries were identified, and he was diagnosed with back strain. He received instructions to ice his back, was provided exercises to strengthen his back muscles, was prescribed hydrocodone/APAP 5/500mg for the pain, and instructed to follow up with his primary health care provider.  

Based upon what has been learned, what should have been done differently at this urgent care visit regarding prescriptions provided to C. S.?

It has now been one year since C. S.’s initial diagnosis of back strain. Since then, he has had repeated visits for back pain and has progressed to needing daily opioid medication to manage the pain. He reports the pain got to the point where he struggled to complete tasks at his job, and frequently had to call in sick. Recently, he lost his job as a construction worker, a job he had for 17 years. C. S. is being evaluated at his primary health care provider’s office due to his reports of chronic back pain.  

What priority assessments should be obtained regarding C. S.’s pain and current opioid use?  

What diagnostic tests should be performed and why are these tests important?

After meeting with his health care provider, C. S. has agreed to the use of non-pharmacological and non-opioid therapy for his chronic back pain. He reports he is willing to try anything that will make him feel better and get back to work.  

What non-pharmacological modalities or non-opioid medications might he benefit from receiving?  

As part of the treatment plan for C. S. what referrals might need to be made?  

What considerations need to be taken into account when prescribing treatments and making referrals?

During the visit with the health care provider, C. S.’s frequent visits to the urgent care and emergency department are addressed. C. S. admits to often taking more of the hydrocodone than he should have because the pain was so bad.  

Based upon what is known about C. S., what type of ongoing monitoring should be used? 

Why is this monitoring the best choice for C. S.?

S. has agreed to the proposed treatment plan but he also expresses he is worried his family and friends will only see him a drug addict. He expresses concern that because of his opioid use he won’t be able to go back to work. 

What should the nurse include in the teaching plan for C. S?  

Summary 

Pain is a complex process that differs for each patient and is not always easily treated. A thorough assessment is necessary to determine the type of pain present. This assessment also serves to aid in diagnosis and as a baseline for determining the effectiveness of prescribed interventions. For patients with pain, who are using opioids, there is a risk of developing tolerance and dependence upon the drug, resulting in the development of a substance use disorder—previously known as an addiction, substance use disorders are now recognized by the APA and are further categorized in the DMS-5. This important step has helped to further awareness of the problem among health care providers and provides clear guidelines for the diagnosis of the disorder.  

The CDC has identified best practice guidelines to prescribing opioid therapy: 

• Implement non-pharmacological and non-opioid medications before using opioids for pain 
• Identify realistic goals addressing both pain and level of function 
• Educate patients on both the risks and benefits of opioid therapy 
• Prescribe immediate-release and the lowest effective dose for patients who need opioid therapy 
• When prescribing opioids for acute pain, only prescribe what the patient will need for three days 
• Regularly evaluate risk versus benefit and taper dosage or discontinue if benefits do not outweigh the risks 
• Evaluate risk factors for misuse and addiction 
• Use PDMP data to inform decision-making and identify patients at high risk for overdose. 
• Implement urine drug screening at initiation of therapy and annually 
• Avoid prescribing both opioids and benzodiazepines 
• Offer treatment for patients with substance use disorder (14) 

When non-pharmacological and non-opioid options have been attempted without success, opioid therapy remains an option for pain management. Patient education related to opioid use should focus on the medication being prescribed and address both administration and adverse effects. Additional education related to the safe use of opioids, storage and disposal, and the use of opioid antagonists should also be provided.  

The incidence of substance use disorder is the U.S. remains high, even in light of steps taken by federal and states governments to address the problem. The cost of addressing opioid misuse takes a heavy toll on the healthcare system and both state and federal budgets, but these pale in comparison to the impact on patients and families who are suffering under the heavy burden of substance use disorders. Everyday patients and their families are affected by opioids and feel the impacts of joblessness, broken families, and death from overdose as result of the opioid epidemic. Measures taken by the state of West Virginia have raised awareness of the problem and have helped address concerns related to prescribing and access, but the work is not done; this West Virginia Drug Diversion course is just one step in the right direction. Continuing education about prescribing, administering, and dispensing controlled substances is essential to help curb over-prescribing and to help identify patients at risk of substance use disorders, so early intervention can be provided. Likewise, patient education is needed to ensure patients are taught the skills to safely use opioids to manage their pain and to be prepared to take an active role in their treatment plans.  

Constipation Management and Treatment

Introduction   

In the realm of healthcare, where every aspect of patient well-being is meticulously tended to, constipation is a condition that often remains in the shadows. Often dismissed as a minor inconvenience, constipation is a prevalent concern that can have significant repercussions on the health and comfort of hospitalized and long-term care patients (8).  

Imagine a scenario where a middle-aged patient, recently admitted to a hospital for a non-related condition, is experiencing discomfort due to constipation. Despite the patient's hesitation to bring up this seemingly "embarrassing" topic, a skilled nurse takes the initiative to initiate an open conversation.  

By actively listening and empathetically addressing the patient's concerns, the nurse alleviates the discomfort and also plays a crucial role in preventing potential complications. This scenario exemplifies the pivotal role that nurses play in the comprehensive management of constipation. 

Envision a long-term care facility where an elderly resident's mobility is limited, leading to a sedentary lifestyle. As a result, this individual becomes more susceptible to constipation, which could potentially lead to more severe issues if left unattended. Here, the nurse's expertise in identifying risk factors and tailoring interventions comes into play.  

By suggesting gentle exercises, dietary adjustments, and adequate hydration, the nurse transforms the resident's daily routine, ensuring a healthier digestive tract and enhanced overall well-being. 

Through the above scenarios, it becomes evident that constipation is not merely a minor inconvenience but a legitimate concern that warrants attention. As the first line of defense in patient care, nurses are uniquely positioned to identify, address, and holistically prevent constipation.  

Nurses possess the knowledge and skills to create a profound impact on patient lives by acknowledging and addressing this issue. This course aims to equip nurses with an in-depth understanding of constipation, enabling them to be proactive vigilant advocates for patient comfort, bowel health, and overall well-being. 

Epidemiology  

To truly comprehend the significance of constipation in healthcare settings, it's essential to grasp its prevalence and impact. Statistics reveal that constipation holds a prominent spot in healthcare challenges, with up to 30% of patients in hospitals and long-term care facilities experiencing this discomfort (4). This means that in a unit with 100 patients, nearly a third of them might be grappling with constipation-related issues.  

Even though constipation transcends demographics, elderly patients, who are a substantial part of long-term care settings, are more susceptible to constipation due to factors like decreased mobility, altered dietary habits, and medication use. Understanding this demographic predisposition is crucial for nurses as it guides their vigilance in recognizing and managing constipation among this vulnerable group. By unraveling its prevalence and its penchant for affecting diverse patient groups, nurses can step into their roles armed with knowledge, ready to make a tangible difference in patient lives. 

Etiology/Pathophysiology  

Embarking on the journey to comprehend constipation's root causes and underlying mechanisms offers a fascinating glimpse into the intricate workings of the digestive system. The digestive system is a well-orchestrated symphony where even a slight disruption can lead to a discordant note, constipation being one such note.  

Constipation arises from an intricate interplay of factors. Lifestyle choices, such as physical inactivity, dietary habits, and even medication use, can disturb the symphony of digestion. These disruptions impact the stool's consistency, its journey through the intestines, and the efficiency of water absorption.  

Some examples of how lifestyle choices can cause constipation include the following: 

• The digestive tract, like a finely tuned instrument, requires regular movement to maintain its rhythm and balance. Without physical activity to nudge food along, its journey through the digestive process slows down, potentially leading to constipation. 
• Mismanagement of water absorption in the colon can also contribute to constipation. Excess absorption of water in the colon can turn the stool hard and dry, making it a formidable challenge to pass.  
• When fiber is lacking in the diet, stool encounters resistance and sluggishness, akin to a symphony losing its guiding rhythm. This lack of fiber can lead to constipation, underscoring the importance of dietary choices in maintaining a harmonious digestive process (10). 

Understanding the above dynamics empowers nurses to decode the origins of constipation and tailor interventions that restore the harmonious rhythm of the digestive orchestra. Just as a conductor guides a symphony to its crescendo, nurses can orchestrate the path to relief and comfort for patients grappling with constipation. 

Signs and Symptoms  

Constipation's signs and symptoms are the stars that guide nurses toward effective management. Infrequent bowel movements, excessive straining, abdominal discomfort, and bloating are like constellations, revealing the narrative of digestive imbalance. 

Recognizing the constellation of signs and symptoms becomes the compass guiding nurses toward effective care. Just as a seasoned sailor navigates by the stars, nurses navigate constipation's landscape by deciphering the cues that patients present. 

Research by Anderson and Brown (1) reveals that patients grappling with constipation often experience infrequent bowel movements as a telltale sign. Nurses, armed with this insight, recognize that infrequent bowel movements warrant vigilant assessment and timely interventions. 

Excessive straining, much like tugging at sails in adverse winds, emerges as another hallmark of constipation (6). Patients' tales of discomfort during bowel movements point to an underlying imbalance. Nurses adeptly interpret this discomfort as a call for action, initiating strategies that ease the passage of stool and restore harmony to the digestive symphony. 

Discomfort serves as an indicator of the digestive system's struggle to find its equilibrium. Nurses, like skilled navigators, probe further, discerning the nuances of the discomfort to tailor interventions that address its root cause (11). 

Bloating is another symptom. Research by Smith and Williams (9) illuminates the link between constipation and bloating. This connection heightens nurses' vigilance, prompting them to delve into patients' experiences and offer relief from the discomfort. 

Pharmacological/Non-Pharmacological Treatment 

Constipation management encompasses a harmonious blend of pharmacological and non-pharmacological strategies. Just as a symphony thrives on a balanced ensemble, nurses can orchestrate a symphony of relief and comfort by selecting the right interventions for each patient's unique needs. Through this holistic approach, nurses play a pivotal role in restoring the digestive symphony to its harmonious rhythm. 

Pharmacological 

As nurses step into the realm of constipation management, they encounter a diverse array of strategies that can harmonize the digestive symphony. Picture a pharmacist's shelf adorned with an assortment of medications, each with a specific role in alleviating constipation. 

Fiber supplements work by increasing stool bulk and promoting regular bowel movements. They're gentle and mimic the natural process, ensuring a harmonious flow. 

Osmotic laxatives introduce more water into the stool, creating a balanced blend of moisture, preventing dry and challenging stools, and facilitating movement.  

Stimulant laxatives stimulate bowel contractions, hastening the stool's journey through the digestive tract. They're like the energetic beats that invigorate a symphony, leading to a rhythmic and effective passage. 

Lastly, stool softeners ensure that the stool is neither too hard nor too soft, striking the perfect balance. They act by moistening the stool, making it easier to pass without straining. By introducing this harmony, stool softeners contribute to patient comfort. 

Non-pharmacological 

Beyond the realm of medications lies an equally vital avenue: non-pharmacological interventions. Nurses can craft a holistic care plan, carefully considering dietary adjustments and lifestyle modifications as the foundation. Examples of non-pharmacological interventions include the following: 

A diet rich in fiber guides the stool's journey with ease. Nurses can educate patients on incorporating fruits, vegetables, and whole grains, ensuring a harmonious flow through the intestines. 

Engaging in regular physical activity not only stimulates bowel movements but also enhances overall well-being. Nurses can encourage patients to integrate movement into their routines, contributing to a dynamic and efficient digestive process. 

Relaxation techniques play a vital role in constipation management. Nurses can provide guidance on techniques like deep breathing or gentle abdominal massages that soothe the digestive tract, facilitate a smoother passage, and transform discomfort into relaxation. 

Complications 

Constipation complications can disrupt the symphony of health. Nurses, armed with knowledge and interventions, become conductors of comfort, guiding patients toward a harmonious journey free from discomfort and dissonance. Through their skilled care, nurses harmonize the symphony of patient well-being, preventing complications and promoting relief. Examples of complications include the following. 

Hemorrhoids 

These are swollen blood vessels around the rectal area that cause pain, itching, and even bleeding during bowel movements. Nurses can educate patients about preventive measures, such as adequate fiber intake, staying hydrated, and avoiding straining during bowel movements. 

Anal Fissure 

This is a small tear in the anal lining that can cause pain and bleeding, disrupting daily life. Nurses can gently guide patients toward hygiene practices and proper self-care, restoring comfort and preventing further disruption. 

Fecal Impaction 

Here, the stool accumulates, creating an obstruction that can be likened to an unexpected pause in flow. This impaction causes severe discomfort and can even lead to bowel obstruction. Nurses should be attentive to patients at risk of fecal impaction, promptly intervening with measures such as stool softeners, gentle digital disimpaction, and regular bowel assessments.  

Rectal Prolapse 

This protrusion of the rectal lining is a disruptive problem that not only causes physical discomfort but also emotional distress. Nurses can empower patients by educating them about the importance of managing constipation and preventing rectal prolapse.  

Nausea and Vomiting 

The buildup of waste and toxins can trigger these unsettling symptoms. Nurses should be vigilant, recognizing these cues as a sign of digestive imbalance. Collaborating with healthcare teams, nurses can address the underlying constipation, restoring harmony and alleviating discomfort. 

Bowel Obstruction 

This is a medical emergency. Patients experience severe abdominal pain, bloating, and the inability to pass stool or gas. Nurses should be well-equipped to recognize these symptoms and act swiftly, seeking immediate medical intervention.  

Prevention  

Prevention is composed of dietary choices, hydration, exercise, and lifestyle awareness. Nurses, as conductors of preventive care, guide patients toward a harmonious journey of well-being. By embracing preventive measures, patients become active participants in the symphony of their health, ensuring that the digestive rhythm remains soothing and uninterrupted. Sample preventive measures include the following: 

Dietary Adjustments 

Nurses can educate patients about the importance of incorporating fiber into their diets. Picture a patient's plate adorned with vibrant fruits, vegetables, and whole grains — these fiber-rich choices act as the brushstrokes that create a smooth flow through the digestive system.  

Hydration 

Like the gentle spray that keeps a garden vibrant, staying adequately hydrated ensures the digestive landscape remains fluid and inviting. Nurses can encourage patients to drink sufficient water, allowing the stool's journey to be as effortless as the water's flow.  

Exercise 

Nurses can guide patients in incorporating regular physical activities like brisk walks, or gentle stretching into their daily routines, creating a rhythm that enhances bowel motility and overall well-being. Movements, much like instrument tuning before a performance, prepare the digestive system for optimal function.  

Lifestyle Awareness 

Nurses can educate patients about the importance of timely bowel movements and creating a comfortable environment for digestion. Patients can cultivate their well-being by avoiding prolonged periods of sitting and adopting healthy toileting habits.  

Patient Education 

Nurses can provide insights into the importance of fiber-rich foods, hydration, and movement. By empowering patients with knowledge, nurses equip them with the tools needed to prevent constipation and maintain digestive well-being.   

Nursing Implications 

Nurses are instrumental in managing constipation and improving patient outcomes. Nurses should be skilled in assessing patients for constipation risk factors, communicating effectively about symptoms, and tailoring interventions to individual patient needs. Collaborating with other healthcare professionals to develop comprehensive care plans is essential. Examples of useful nursing skills include: 

Holistic Assessment 

Nurses are vigilant observers, attuned to the nuances of patient well-being. Like skilled detectives, nurses delve into patients' histories, medications, and lifestyles, identifying constipation risk factors. Holistic assessments allow nurses to understand the unique backdrop against which constipation may unfold. Armed with this knowledge, nurses can tailor interventions that resonate with each patient's needs (12). 

Effective Communication 

Envision a nurse as a skilled communicator, bridging the gap between patient concerns and medical insights. Like a translator, nurses help patients express their symptoms and experiences, ensuring nothing gets lost in translation. Effective communication not only nurtures trust but also facilitates accurate assessment, enabling nurses to identify constipation-related cues and initiate timely interventions (14). 

Collaboration with Multidisciplinary Teams 

Consider a care setting where the patient's well-being is a collective effort, much like an orchestra composed of diverse instruments. Nurses collaborate with physicians, dietitians, physical therapists, and other healthcare professionals to ensure a harmonious approach to constipation management. This interdisciplinary collaboration ensures that each note of patient care resonates in unison, creating a symphony of comprehensive well-being (7). 

Patient-Centered Care Plans 

Imagine nurses as architects of care plans, designing blueprints that reflect patients' unique needs and preferences. Just as architects tailor a building to its occupants, nurses craft patient-centered care plans that incorporate dietary preferences, lifestyle routines, and individualized interventions. This tailored approach ensures that patients feel heard and empowered in their constipation management journey (13). 

Education and Empowerment 

Envision nurses as educators, empowering patients with knowledge that transforms them into active participants in their care. Much like a guide, nurses navigate patients through the maze of constipation management strategies, ensuring clarity and understanding. By imparting information about dietary choices, hydration, exercise, and self-care, nurses equip patients with the tools needed to harmonize their digestive well-being (2). 

Continuous Monitoring and Evaluation 

Imagine nurses as diligent conductors, continuously assessing the rhythm of constipation management. Just as a conductor listens to every note, nurses monitor patients' responses to interventions, ensuring their effectiveness. Regular evaluation allows nurses to fine-tune strategies, ensuring that the symphony of constipation management remains harmonious and effective (5). 

Compassionate Support 

Envision nurses as compassionate companions on the patient's constipation management journey. Like trusted friends, nurses offer emotional support, addressing patients' concerns and fears with empathy. This compassionate approach fosters a sense of security and trust, enabling patients to navigate the challenges of constipation with resilience and a sense of camaraderie (3). 

Conclusion

Constipation is a significant concern that impacts the comfort and well-being of hospitalized and long-term care patients. Nurses' proactive role in identifying, managing, and preventing constipation is essential for promoting patient health. By employing a combination of pharmacological and non-pharmacological interventions, nurses can significantly enhance patient comfort and quality of life.  

Envision nurses as educators who share the symphony of knowledge with patients, empowering them to become proactive partners in their well-being. With insights about dietary choices, hydration, exercise, and relaxation techniques, patients become active participants in the harmony of their digestive health. 

Think of nurses as vigilant observers, continuously assessing the rhythm of constipation management, listening to every note, monitoring patient responses, and adjusting interventions to ensure a harmonious and effective approach.  

Finally, visualize nurses as compassionate companions on the constipation management journey. They offer unwavering support, much like friends sharing the weight of challenges. This compassionate presence fosters trust, comfort, and a sense of unity, creating a symphony of emotional well-being alongside physical relief. 

As this course concludes, let us remember that constipation management is not just about alleviating discomfort but about orchestrating a symphony of care that encompasses every aspect of the patient’s experience.  

By blending knowledge, empathy, and skill, nurses elevate constipation management from a routine task to a transformative experience. With this newfound understanding, nurses are prepared to guide patients toward a harmonious symphony of relief, comfort, and overall well-being. 

Spinal Cord Injury: Bowel and Bladder Management

Introduction   

Imagine one day you are able to walk and take care of your own needs. Now, imagine one week later you wake up no longer able to walk, feel anything below your waist, or hold your bowels.  

This is a reality for many people who sustain spinal cord injuries. Managing changes in bowel and bladder function is one of many challenges that people with spinal cord injuries and their families or caregivers face.  

This course will provide learners with the knowledge needed to assist patients who have spinal cord injuries with bowel and bladder management to improve the quality of life in this group.

Spinal Cord Injuries: The Basics

Spinal Cord Function 

Before defining a spinal cord injury, it is important to understand the function of the spinal cord itself. The spinal cord is a structure of the nervous system that is nestled within the vertebrae of the back and helps to distribute information from the brain (messages) to the rest of the body [1].  

These messages result in sensation and other neurological functions. While it may be common to primarily associate the nervous system with numbness, tingling, or pain, nerves serve an important purpose in the body’s function as a whole.

Spinal Cord Injury Definition 

When the spinal cord is injured, messages from the brain may be limited or entirely blocked from reaching the rest of the body. Spinal cord injuries refer to any damage to the spinal cord caused by trauma or disease [2]. Spinal cord injuries can result in problems with sensation and body movements.  

For example, the brain sends messages through the spinal cord to muscles and tissues to help with voluntary and involuntary movements. This includes physical activity like running and exercising, or something as simple as bowel and bladder elimination.  

Spinal Cord Injury Causes 

Spinal cord injuries occur when the spinal cord or its vertebrae, ligaments, or disks are damaged [3]. While trauma is the most common cause of spinal cord injuries in the U.S., medical conditions are the primary causes in low-income countries [4] [2]. 

Trauma 

• Vehicle accidents: Accounts for 40% of all cases [2] 
• Falls: Accounts for 32% of all cases [2] 
• Violence: Includes gun violence and assaults; accounts for 13% of all cases [2] [5] 
• Sport-related accidents: Accounts for 8% of all cases [2] 

Medical Conditions 

• Multiple Sclerosis (MS): Damage to the myelin (or insulating cover) of the nerve fibers [1] 
• Amyotrophic Lateral Sclerosis (ALS): Lou Gehrig’s disease, damage to the nerve cells that control voluntary muscle movements [1] 
• Post-Polio: Damage to the central nervous system caused by a virus [1] 
• Spina Bifida: Congenital defect of the neural tube (structure in utero that eventually forms the central nervous system) [1] 
• Transverse Myelitis (TM): Inflammation of the spinal cord caused by viruses and bacteria [1] 
• Syringomyelia: Cysts within the spinal cord often caused by a congenital brain abnormality [1] 
• Brown-Sequard Syndrome (BSS): Lesions in the spinal cord that causes weakness or paralysis on one side of the body and loss of sensation on the other [1] 
• Cauda Equina Syndrome: Compression of the nerves in the lower spinal region [1] 

Spinal Cord Injury Statistics 

According to the World Health Organization, between 250,000 and 500,000 people worldwide are living with spinal cord injuries [4]. In the U.S., this number is estimated to be between 255,000 and 383,000 with 18,000 new cases each year for those with trauma-related spinal cord injuries [6]. 

Age/Gender 

Globally, young adult males (age 20 to 29) and males over the age of 70 are most at risk. In the U.S., males are also at highest risk, and of this group, 43 is the average age [2].  

While it is less common for females to acquire a spinal cord injury (2:1 ratio in comparison to males), when they do occur, adolescent females (15-19) and older females (age 60 and over) are most at risk globally [4].  

Race/Ethnicity 

In the U.S. since 2015, around 56% of spinal cord injuries related to trauma occurred among non-Hispanic whites, 25% among non-Hispanic Black people, and about 14% among Hispanics [6].  

Mortality 

People with spinal cord injuries are 2 to 5 times more likely to die prematurely than those without these injuries (WHO, 2013). People with spinal cord injuries are also more likely to die within the first year of the injury than in subsequent years. In the U.S., pneumonia, and septicemia – a blood infection – are the top causes of death in patients with spinal cord injuries [6]. 

Financial Impact 

Spinal cord injuries cost the U.S. healthcare system billions each year [6]. Depending on the type, spinal cord injuries can cost from around $430,000 to $1,300,000 in the first year and between $52,000 and $228,000 each subsequent year [6].  

These numbers do not account for the extra costs associated with loss of wages and productivity which can reach approximately $89,000 each year [6]. 

Spinal Cord Injuries: Types and Complications

Four Levels of the Spinal Cord 

• Cervical (vertebrae C1 – C8): Neck; controls the back of the head down to the arms, hands, and diaphragm 
• Thoracic (vertebrae T1 – T12): Upper mid-back; controls the chest muscles, many organs, some back muscles, and parts of the abdomen 
• Lumbar (vertebrae L1 – L5): Lower back; controls parts of the lower abdomen, lower back, parts of the leg, buttocks, and some of the external genital organs 
• Sacral (vertebrae S1 – S5): Lower back; controls the thighs down to the feet, anus, and most of the external genital organs 

Types of Spinal Cord Injuries 

Spinal cord injuries may be classified by level and degree of impairment. There are four types of spinal cord injuries [5]. 

Injury Level 

• Tetraplegia or Quadriplegia: Injury at the cervical level; loss of feeling or movement to the head, neck, and down. People with this type of spinal cord injury have the most impairment. 
• Paraplegia: Injury at the thoracic level or below; limited or complete loss of feeling or movement to the lower part of the body.  

Impairment 

• Incomplete spinal cord injury: Some sensation and mobility below the level of injury as the spinal cord can still transmit some messages from the brain. 
• Complete spinal cord injury: Total loss of all sensation and mobility below the level of injury. Spinal cord injuries of this type have the greatest functional loss. 

Spinal Cord Injury Complications 

Complications from spinal cord injuries can be physical, mental, or social, and can impact overall quality of life. There are six common complications of spinal cord injuries [2]. 

Depression 

Studies show that 32.9% of adults with disabilities experience frequent mental distress [7]. Mental distress may be related to functional limitations, chronic disease, and the increased need for healthcare services.  Up to 37% of people with spinal cord injuries develop depression [2]. 

Pressure injuries 

People with spinal cord injuries may have problems with circulation and skin sensation– both risk factors for pressure injuries. Some may be bedridden or wheelchair-bound which also places them at risk for pressure injuries. Up to 80% of people with spinal cord injuries will have a pressure injury during their lifetime and 30% will have more than one [2].  

Spasticity 

Around 65% - 78% of people with spinal cord injuries have spasticity [2]. Spasticity is uncontrolled muscle tightening or contraction. The damage from spinal cord injuries causes misfires in the nervous system leading to twitching, jerking, or stiffening of muscles. 

Autonomic dysreflexia 

In some people with spinal cord injuries, a full bladder or bowel distention can cause a potentially dangerous condition called autonomic dysreflexia. The full bladder or bowel triggers a sudden exaggerated reflex that causes an increase in blood pressure. This condition is also associated with a severe headache, low heart rate, cold skin, and sweating in the lower body [8]. 

Respiratory problems 

If the diaphragm function is affected, as with cervical spinal cord injuries, there may be breathing difficulties. People with lumbar spinal cord injuries can even have respiratory problems as the abdominal muscles are used to breathe. 

Sexual problems 

Due to changes in muscle function and depending on the degree of damage, people with spinal cord injuries may have problems with arousal and climax due to altered sensations and changes in sexual reflexes.  

Changes in bowel and bladder function 

Many people with spinal cord injuries lose bowel control. Bowel problems can include constipation, impaction, and incontinence. They may also have problems with urination, for example, urinary retention. 

Bowel and Bladder Dysfunction in Spinal Cord Injuries 

This section will cover the normal function of the bowel and bladder, and the types of bowel and bladder dysfunction that occurs in patients with spinal cord injuries.

Normal Bowel and Bladder Function 

In normal bowel and bladder function, when the rectum or bladder fills with stool/urine and presses on area nerves (stimulation), the message is sent to the spinal cord which sends it to the brain. The brain gives the person the “urge” feeling, allowing an option to control the elimination or not.  

Whatever decision the person makes, the brain sends the message back to the spinal cord, which in turn sends a message to the elimination muscles (anal and bladder sphincters) to either relax or stay closed until the person is ready. In people with spinal cord injuries, the messages are limited or blocked, leading to problems with bowel and bladder control [9] [10].  

Bowel Dysfunction with Spinal Cord Injuries 

Reflex hypertonic neurogenic bowel occurs when a rectum full of stool presses against area nerves sending a message to the spinal cord, but it stops there. The message never makes it to the brain, so the person never gets the urge.  

As a result, a reflex is set off, prompting the spinal cord to send a message to the anal muscle (sphincter) instead, causing it to relax and release the stool. This condition leads to bowel incontinence and usually occurs in spinal injuries at the cervical and thoracic levels [9] [10]. 

Flaccid hypotonic bowel occurs when area nerves are also stimulated by a full rectum, but the message does not even reach the spinal cord, so there is no reflex. The anal sphincter is always in a relaxed state.  

As a result, the bowels simply empty when they are full, and this can occur at any time without the person having the ability to control it. This condition results in bowel incontinence and can lead to constipation as the patient does not have the urge and may not have the ability to push. This condition usually occurs in spinal injuries at the lumbar level [9] [10]. 

Bladder Dysfunction with Spinal Cord Injuries 

Reflex neurogenic bladder occurs when the bladder automatically starts to contract after filling with a certain amount of urine. The person has no urge to go as the messages are either limited or blocked from reaching the brain, therefore leading to loss of bladder control. Similar to reflex hypertonic neurogenic bowel, the full bladder triggers are nerves that set off a reflex, prompting the spinal cord to send messages to the bladder releasing urine outside of the person’s control [9] [10]. 

Acontractile bladder occurs when the bladder loses muscle tone after a spinal cord injury, lessening its ability to contract, leading to bladder distention, and dribbling of urine. People with this condition need to use urinary catheters to help empty the bladder [9]. 

The Nurse’s Role in Bowel and Bladder Management 

This section will cover how nurses can assess, intervene, and teach when caring for patients with spinal cord injuries who have bowel and bladder dysfunction.

Nurse Assessments 

When caring for patients with spinal cord injuries, nurses should obtain a detailed bowel and bladder history including diet, fluid intake, medications, and elimination patterns/habits [11]. Many of these patients may already manage their own bowel and bladder care at home.  

If so, the nurse should obtain the patient’s current regimen and communicate the information to the physician. The physician may choose to continue the regimen or adjust as needed based on the patient’s current illness/condition.  

Questions the nurse can ask the patient: 

• What does your typical diet consist of? 
• How much fluid do you drink on a daily basis? 
• How often do you have a bowel movement or urinate? 
• Do you schedule your bowel movements with assistance from medications? 
• Are there certain body positions or things you do to help you pass stool more easily?
• How often do you use an intermittent urinary catheter for bladder relief? 
• How much time do you spend on your bowel and bladder regimens? 
• Do you care for all of your elimination needs or does someone help you? 
• How does your bowel and bladder dysfunction affect your quality of life? 

Some assessments may be observed. For example, nurses may notice that the patient has a surgically placed permanent suprapubic urinary catheter or colostomy (when the bowel is cut somewhere above the level of the rectum and diverted to the outside of the abdomen). 

Nurse Interventions 

Since many patients with spinal cord injuries have problems with bowel and bladder function, elimination must be scheduled. Nurses can help by implementing bowel and bladder programs and providing education and support to patients, families, or caregivers.  

Regimens 

Follow the patient’s home bowel and bladder regimen (as ordered). This may include maintaining intermittent catheterization every few hours or administering suppositories daily.  

For patients who do not have a regimen already or wish to modify their current one, encourage them to pay attention to how often they urinate and pass stools, elimination problems, foods that alleviate or worsen the problem, and medications or other things that help. This can be done through a diary. 

Dietary Considerations 

Educate patients on the importance of a fiber-rich diet to avoid constipation. Patients should also be made aware that high-fat foods, spicy foods, and caffeine can alter gut dynamics and lead to bowel incontinence episodes [12]. 

Fluid Intake 

Some patients may avoid drinking enough water to avoid bladder complications (e.g., frequent incontinent episodes) [12]. However, nurses should educate patients on the importance of adequate fluid intake to prevent constipation. Patients should be made aware that bladder and bowel elimination regimens go hand in hand. 

Bladder Elimination 

For bladder dysfunction, help patients perform intermittent urinary catheterization as needed or place a temporary urinary catheter (as ordered). 

Bowel Elimination 

For bowel dysfunction, administer ordered suppositories and laxatives to help the bowels move (use suppositories in conjunction with the level of sensation the patient has near the anus/rectum) [9]. Changes in body position may help as well.  

While many of these interventions may not work in some patients with spinal cord injuries, bowel irrigation (water enemas) may be helpful [11]. Surgical placement of a colostomy may be indicated if all other measures have failed [11]. 

Emotional Support 

Ensure privacy and sensitivity during all elimination care as patients may experience embarrassment or frustration. 

Education for Families or Caregivers 

Provide education to families or caregivers on the importance of helping patients stay consistent with their elimination regimen, follow diet and fluid intake recommendations, and comply with medication orders.  

Referrals 

Inform the physician if interventions are not effective or if the patient, family, or caregiver has a special need (e.g., counselor or dietician). Refer patients and families or caregivers to support groups as needed.

Support Groups and Resources 

Christopher and Dana Reeve Foundation 

Christopher Reeve – an actor who was left paralyzed after an equestrian accident – and his wife Dana’s legacy lives on through their foundation, an organization that advocates for people living with paralysis [13].  

Miami Project to Cure Paralysis 

In response to his son, who acquired a spinal cord injury during college football, NFL Hall of Famer Nick Buoniconti and world-renowned neurosurgeon Barth A. Green, M.D. started a research program aimed at finding a cure for paralysis and discovering new treatments for many other neurological injuries and disorders [14]. 

National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) 

The National Institute on Disability, Independent Living, and Rehabilitation Research, a part of the U.S. Department of Health and Human Services’ Administration for Community Living, helps people with disabilities integrate into society, employment, and independent living [15].  

Paralyzed Veterans of America (PVA)  

A group of World War II veterans who returned home with spinal cord injuries, started this organization to support those with spinal cord injuries and dysfunction. Today, the organization focuses on quality health care, research and education, benefits, and civil rights to affected veterans [16].  

United Spinal Association 

The United Spinal Association supports people with spinal cord injuries and those in wheelchairs. The organization advocates for disability rights like access to healthcare, mobility equipment, public transportation, and community support. Support groups can be found on their website [17).  

Conclusion

Spinal cord injuries can have devastating effects on patients and their families. Management of basic bodily functions like bowel and bladder elimination should be made as easy as possible for these patients.

When nurses learn how to effectively help patients with spinal cord injuries better manage their own bowel and bladder regimens, quality of life and health outcomes may be improved for this group.

Pressure Injury Prevention, Staging and Treatment

Introduction   

When hearing the term HAPI, what comes to mind? The fact is, HAPI may not necessarily generate happy thoughts. Hospital-acquired pressure injuries (HAPIs) are a significant problem in the U.S. today. In fact, pressure injuries in general – whether acquired in a hospital or not – are a global problem.

Many articles have noted that staging and differentiating pressure injuries can be overwhelming for nurses [9]. The purpose of this course is to equip learners with the knowledge needed to reduce pressure injuries, resulting complications, financial risk, and associated death. The information in this course will serve as a valuable resource to nurses from all specialties and backgrounds.

What is a pressure injury?

The National Pressure Injury Advisory Panel (NPIAH) defines pressure injuries as “localized damage to the skin and underlying soft tissue usually over a bony prominence or related to a medical or other device” [17]. Pressure injuries can present as intact or opened skin and can be shallow or deep. Pressure injuries can be quite painful for patients and may require extensive treatment.

Prior to 2016, pressure injuries were termed “pressure ulcers.” However, since ulcer implies “open skin,” the NPIAH changed it to “pressure injury” as the skin is not always open with some of these injuries [22][25].

What causes a pressure injury to develop?

Pressure 

Intense and/or prolonged pressure on the patient’s skin and/or tissue can cause compromised blood flow and decreased sensation [7]. This can occur when patients lay or sit on a bony prominence for an extended period of time [16].  

Bony prominences are areas where you can easily feel a bone underneath the skin or tissue when palpating. These can include the heels, hips, elbows, and tailbone. Approximately two-thirds of all pressure injuries occur on the hip and buttocks area [7]. 

Friction and Shear 

Friction and shear often happen when patients slide down in bed, for example, when the head of the bed is raised. Although “friction and shear” are often used together, there is actually a difference between the two.  

While friction occurs when skin is dragged across a coarse surface (leading to surface-level injuries), shearing occurs when internal bodily structures and skin tissue move in opposite directions (leading to deep-level injuries) [10]. Shearing is often associated with a type of pressure injury called deep tissue injury (occurring in the deeper tissue layers rather than on the skin’s surface) [10].

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What are risk factors for developing a pressure injury? 

There are numerous risk factors for pressure injuries – some of which may not be directly related to the skin. These risk factors can be categorized as either intrinsic factors (occurring from within the body) or extrinsic (occurring from outside of the body) [2][13]. 

Intrinsic Risk Factors 

- Poor skin perfusion (e.g., peripheral vascular disease or smoking) 

- Sensation deficits (e.g., diabetic neuropathy or spinal cord injuries) 

- Moist skin (e.g., urinary incontinence or excessive sweating) 

- Inadequate nutrition (particularly poor protein intake) 

- Poor skin elasticity (e.g., normal age-related skin changes) 

- End of life/palliative (leads to organ failure including the skin) 

- Limited mobility (i.e., bedridden, or wheelchair-bound) 

Extrinsic Risk Factors 

- Physical and chemical restraints (leads to limited mobility) 

- Undergoing a procedure (laying down for extended periods of time) 

- Length of hospital stay (for HAPIs) 

- Medical devices (can lead to medical device-related pressure injuries)

Statistical Evidence 

This section will cover pressure injury statistics both globally and nationally. This section will also cover the impact pressure injuries have on healthcare.

What is happening on a global scale? 

In a global study, researchers found that the prevalence (all cases) and incidence (new cases) of pressure injuries in 2019 were 0.85 million and 3.17 million, respectively – numbers that have decreased over time [23][25]. Numbers were disproportionately high in high-income North America, Central Latin America, and Tropic Latin America [25]. Numbers were lowest in Central Asia and Southeast Asia. The report revealed that although numbers are high overall, they are much lower than what they were predicted to be, which may be attributed to better prevention and treatment initiatives.

What is happening nationally? 

In the U.S., 2.5 million people develop pressure injuries each year [1]. This number does not account for the many people trying to manage pressure injuries on their own at home (i.e., when family acts as the caregiver).  

HAPIs in particular are a growing problem. The most recent data on hospital-acquired conditions in the U.S. shows that from 2014 to 2017, HAPIs increased by 6% (647,000 cases in 2014 to 683,000 in 2017) [6]. Each year 60,000 patients in the U.S. die as a direct result of pressure injuries [1]. 

How do pressure injuries impact healthcare? 

Pressure injuries can be quite costly to the healthcare system. These injuries can lead to persistent pain, prolonged infections, long-term disability, increased healthcare costs, and increased mortality [1].  

In the U.S., pressure injuries cost between $9.1 - $11.6 billion per year [1]. These injuries are complex and can be difficult to treat [7]. Often requiring an interdisciplinary approach to care, the costs of one pressure injury admission can be substantial. Individual care for patients with pressure injuries ranges from $20,900 to $151,700 per injury [1]. Not to mention, more than 17,000 lawsuits are related to pressure injuries every year [1].  

Due to the significant impact that these injuries have on healthcare, prevention and accurate diagnosis is imperative.

Staging and Diagnosis 

The section will cover the staging, varying types, and diagnosis of pressure injuries.  

What is the difference between wound assessment and staging? 

Pressure injury staging is more than a basic wound assessment. Wound assessment includes visualizing the wound, measuring the size of the wound, paying attention to odors coming from the wound, and lightly palpating the area on and/or around the wound for abnormalities. Pressure injury staging, however, involves determining the specific cause of injury, depth of skin or tissue damage, and progression of the disease.  

What are the six stages of pressure injuries? 

According to NPIAP guidelines, there are six types of pressure injuries – four of which are stageable [14]. 

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Stage 1 

In Stage 1 pressure injuries, there is intact skin with a localized area of non-blanchable erythema (pink or red in color), which may appear differently in darkly pigmented skin. Before visual changes are noted, there may be the presence of blanchable erythema or changes in sensation, temperature, or firmness. Stage 1 pressure injuries do not have a purple or maroon discoloration (this can indicate a deep tissue pressure injury). 

Stage 2