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Asthma Treatment and Monitoring

Introduction   

When hearing the phrase asthma, what comes to mind? If you’re an advanced practice registered nurse (APRN) with prescriptive authority, you’ve definitely heard of asthma before. Even as a nurse or maybe before nursing school, conversations about prescription drug use and respiratory health existed every so often.

Presently, patients seek guidance and information on various health topics from APRNs, including medication management and respiratory health. The information in this course will serve as a valuable resource for APRNs with prescriptive authority of all specialties, education levels, and backgrounds, to learn more about medications that can treat and manage asthma.

Defining Asthma 

What Is Asthma? 

Asthma is a non-communicable chronic health condition that affects the airways of the lungs and affects millions of people nationwide. Asthma is often diagnosed in childhood and can resolve in adulthood or continue for the rest of a patient’s life. Several studies postulate the cause of asthma, but there is no definitive cause.  

Genetics, age, environmental exposures, smoking, and a history of allergies are thought to play a role in asthma severity and development. Clinical presentation of asthma often includes trouble breathing, chronic airway inflammation, and airway hyperresponsiveness. Assessment for asthma often includes patient history, clinical presentation, spirometry testing, and pulmonary function tests (PFTs). 

What Are the Stages of Asthma? 

Since asthma is a chronic condition, several established guidelines can be used to determine the severity of asthma and explore possible medication options. Depending on the stage of asthma and patient response to existing therapy, treatment and management vary.  

The four stages of asthma include intermittent, mild, moderate, and severe. Based on the 2020 National Asthma Education and Prevention Program (NAEPP) guidelines, here is the standard criteria for what constitutes each stage of asthma (2). 

Intermittent asthma is characterized with the following clinical presentation and assessment (2): 

• Patient history of respiratory symptoms, such as cough, trouble breathing, wheezing, or chest tightness <2 times a week 
• Asthmatic flare-ups are short-lived with varying intensity  
• Symptoms at night are <2 a month 
• No asthmatic symptoms between flare-ups 
• Lung function test FEV 1 at >80% above normal values 
• Peak flow has <20% variability am-to-am or am-to-pm, day-to-day 

Mild persistent asthma is characterized with the following clinical presentation and assessment (2): 

• Patient history of respiratory symptoms, such as cough, trouble breathing, wheezing, or chest tightness 3-6 times a week 
• Asthmatic flare-ups may affect activity level and can vary in intensity 
• Symptoms at night are 3-4 times a month 
• Lung function test FEV1 is >80% above normal values 
• Peak flow has less than 20-30% variability 

Moderate persistent asthma is characterized with the following clinical presentation and assessment (2): 

• Patient history of respiratory symptoms, such as cough, trouble breathing, wheezing, or chest tightness daily 
• Asthmatic flare-ups may affect activity level and can vary in intensity 
• Symptoms at night are >5 times a month 
• Lung function test FEV1 is 60%-80% of normal values 
• Peak flow has more than 30% variability 

Severe persistent asthma is characterized with the following clinical presentation and assessment (2): 

• Patient history of respiratory symptoms, such as cough, trouble breathing, wheezing, or chest tightness continuously  
• Asthmatic flare-ups affect activity level and often vary in intensity 
• Asthmatic symptoms at night are constant 
• Lung function test FEV1 is <60% of normal values 
• Peak flow has more than 30% variability 

Based on patient history, clinical presentation, and these criteria, treatment can be administered to decrease the symptoms of the patient. If a patient presents with symptoms that are outside of your scope of work or understanding, you can always refer patients to a pulmonologist or asthma specialist.  

Often times, more severe cases of asthma and asthma emergencies require increased frequency and dosing of asthma-related medications. Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history, pulmonary function, and health history prior to prescribing asthma medications (1). 

What Are Asthmatic Emergencies? 

Asthmatic emergencies are if a patient has asthma symptoms that are beyond what they typically experience and are unable to function without immediate medical intervention. Asthma emergencies can occur as a result of a patient being unable to access their asthmatic medications, being exposed to a possible allergen, or being under increased stress on the body.  

Asthmatic emergencies often require collaborative medical intervention, increased dosages of medications discussed below, and patient education to prevent future asthmatic emergencies (1).  

What If Asthma Is Left Untreated? 

Depending on the clinical presentation and severity of asthma, asthma can cause several long-term complications if left untreated. If asthma is not properly managed, several complications, such as chronic obstructive pulmonary disease (COPD), decreased lung function, permanent changes to the lungs’ airways, and death can occur (1, 2).  

Defining Asthma Medications 

What Are Commonly Used Medications to Manage Asthma? 

Commonly used medications to manage asthma include inhaled corticosteroids, oral corticosteroids, short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), long-acting muscarinic antagonists (LABAs), adenosine receptor antagonists, leukotriene modifiers, mast cell stabilizers, and monoclonal antibodies. The dosage, frequency, amount of asthma management medications, and medication administration route can all vary depending on clinical presentation, patient health history, and more.  

How and Where are Asthma Medications Used? 

Asthma medications can be used routinely or as needed for management of asthma symptoms depending on the patient. Asthma medications can be used at home, in public, and in health care facilities. Depending on the specific asthma medication and dosage, these medications can be taken by mouth, by an external device, such as an inhaler, via subcutaneous injection, or via intravenous solution (1).  

What Are the Clinical Criteria for Prescribing Asthma Medication? 

Clinical criteria for prescribing asthma medication can depend on the clinical presentation of a patient. Assessment of lung health and patient history are essential to determining the dosage and medications needed for adequate asthmatic symptom control.  

Clinical guidelines from reputable organizations, such as the National Asthma Education and Prevention Program (NAEPP), the National Institutes of Health (NIH), the Global Initiative for Asthma (GINA), and the American Academy of Family Physicians (AAFP) can provide insight into the latest recommendations for asthma management (1, 2). In addition, local laws or health departments might have recommendations for asthma medication guidelines.  

What Is the Average Cost for Asthma Medications? 

Cost for asthma medications can significantly vary depending on the type of medication, insurance, dosage, frequency, medication administration route, and other factors. Cost is among a leading reason why many patients cannot maintain their medication regime (3). If cost is a concern for your patient, consider reaching out to your local pharmacies or patient care teams to find cost effective solutions for your patients.  

Inhaled Corticosteroids Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Inhaled Corticosteroids  

Commercially available inhaled corticosteroids include: ciclesonide (Alvesco HFA), fluticasone propionate (Flovent Diskus, Flovent HFA, Armon Digihaler), budesonide (Pulmicort Flexhaler), beclomethasone dipropionate (QVAR RediHaler), fluticasone furoate (Arnuity Ellipta), and mometasone furoate (Asmanex HFA, Asmanex Twisthaler).  

Clinical criteria for prescribing an inhaled corticosteroid includes adherence to the latest clinical guidelines, patient medical history, patient clinical presentation, and drug availability (4).  

Inhaled Corticosteroids Method of Action 

Inhaled corticosteroids have an intricate mechanism of action involving several responses to the immune system. Inhaled corticosteroids decrease the existing initial inflammatory response by decreasing the creation and slowing the release of inflammatory mediators. Common inflammatory mediators include histamine, cytokines, eicosanoids, and leukotrienes. Inhaled corticosteroids can also induce vasoconstrictive mechanisms, which, as a result, can lead to less blood flow, resulting in less discomfort and edema (4).  

In addition to anti-inflammatory properties, inhaled corticosteroids can create a localized immunosuppressive state that limits the airways’ hypersensitivity reaction, which is thought to reduce bronchospasms and other asthma-associated symptoms. It is important to note that inhaled corticosteroids often do not produce therapeutic effects immediately, as many patients may not see a change in their asthma symptoms for at least a week after beginning inhaled corticosteroid therapy (4).  

Inhaled Corticosteroids Side Effects 

Every medication has the possibility of side effects, and inhaled corticosteroids are no exception. Common side effects of inhaled corticosteroids include oral candidiasis (thrush), throat irritation, headache, and cough.  

Patient education about rinsing their mouth and oral hygiene after use is essential to avoid the possibility of thrush and other oral infections and irritations. More severe side effects can include prolonged immunosuppression, reduction in bone density, and adrenal dysfunction (4).  

Inhaled Corticosteroids Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with inhaled corticosteroids, so additional medication, increased dosage, a change in frequency, or a new medication class might need to be considered (4).  

Oral Corticosteroids Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Oral Corticosteroids  

Commercially available oral corticosteroids include methylprednisolone, prednisolone, and prednisone. Clinical criteria for prescribing an oral corticosteroid includes adherence to the latest clinical guidelines, patient medical history, patient clinical presentation, and drug availability (4).  

Oral Corticosteroids Method of Action 

Methylprednisolone and prednisolone have a method of action as intermediate, long-lasting, synthetic glucocorticoids, have COX-2 inhibitory properties, and inhibit the creation of inflammatory cytokines (5). 

Prednisone is a prodrug to prednisolone and has anti-inflammatory and immunomodulating glucocorticoid properties. Prednisone has a method of decreasing inflammation by reversing increased capillary permeability and suppressing the movement of certain leukocytes (6).  

Oral Corticosteroids Side Effects 

Every medication has the possibility of side effects, and oral corticosteroids are no exception. Methylprednisolone and prednisolone have possible side effects of skin changes, weight gain, increased intraocular pressure, neuropsychiatric events, neutrophilia, immunocompromised state, fluid retention, and GI upset.  

Consider monitoring symptoms and overall health of patients on systemic corticosteroids to assess for long-term side effects (5). Prednisone has possible side effects of changes in blood glucose, changes in sleep habits, changes in appetite, increased bone loss, an immunocompromised state, changes in adrenal function, and changes in blood pressure (6).  

Oral Corticosteroids Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with oral corticosteroids, so additional medication, increased dosage, a change in frequency, or a new medication class might need to be considered (6).  

Short-Acting Beta Agonists (SABAs)  

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – SABAs 

Common commercially available SABAs include albuterol sulfate (ProAir HFA, Proventil HFA, Ventolin HFA), albuterol sulfate inhalation powder (ProAir RespiClick, ProAir Digihaler), levalbuterol tartrate (Xopenex HFA), and levalbuterol hydrochloride (Xopenex) (4). 

SABAs Method of Action 

Short-acting beta-agonists (SABAs) have a rapid onset as broncho-dilating medications. SABAs, especially albuterol in emergent situations, are used often to quickly relax bronchial smooth muscle from the trachea to the bronchioles through action on the β2-receptors.  

While SABAs are effective bronchodilators in the short term for asthma symptoms, SABAs do not affect the underlying mechanism of inflammation. As a result, SABAs are often used for short-acting intervals, such as few hours, and have limited capabilities to prevent asthma exacerbations alone (4). SABAs can be administered via meter-dosed inhalers, intravenous, dry powder inhalers, orally, subcutaneously, or via nebulizer.  

SABAs Side Effects 

Every medication has the possibility of side effects, and SABAs are no exception. Because of the beta receptor agonisms, possible SABA side effects include increased heart rate, chest pain, chest palpitations, body tremors, and nervousness (4). Because of the short half-life of SABAs, chronic side effects are not typically observed.  

SABAs Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with SABAs, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4).  

Long-Acting Beta Agonists (LABAs) 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – LABAs 

Common commercially available LABAs are salmeterol and formoterol (7).  

LABAs Method of Action 

Long-acting beta-agonists (LABAs) have a rapid onset like SABAs, but also have a longer half-life. LABAs are used often as asthma maintenance medications to relax bronchial smooth muscle from the trachea to the bronchioles through action on the β2-receptors. While SABAs are effective bronchodilators in the short term for asthma symptoms, LABAs are effective bronchodilators in the long term for asthma symptoms.  

Like SABAs, LABAs do not affect the underlying mechanism of inflammation. LABAs can be administered via meter-dosed inhalers, intravenous, dry powder inhalers, orally, subcutaneously, or via nebulizer. LABAs are often effective for 12-hour durations (7). 

LABAs Side Effects 

Every medication has the possibility of side effects, and LABAs are no exception. Like SABAs, because of the beta receptor agonisms, possible LABA side effects include increased heart rate, chest pain, chest palpitations, body tremors, and nervousness (7). Other more prolonged side effects can include changes in blood glucose levels and changes in potassium levels with prolonged LABA use (7).  

LABAs Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with LABAs, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4).  

In addition, there are combination inhaled corticosteroid/LABA medications that can be considered, such as fluticasone propionate and salmeterol (Advair Diskus, Advair HFA, AirDuo Digihaler, AirDuo RespiClick, Wixela Inhub), fluticasone furoate and vilanterol (Breo Ellipta), mometasone furoate and formoterol fumarate dihydrate (Dulera), and budesonide and formoterol fumarate dihydrate (Symbicort) (4). 

Long-Acting Muscarinic Antagonists (LAMAs) 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – LAMAs 

Common commercially available LAMAs include two inhalation powders via inhalers known as tiotropium bromide (Spiriva Respimat) and fluticasone furoate, umeclidinium, and vilanterol (Trelegy Ellipta) (4).  

LAMAs Method of Action 

Both drugs mentioned above are long-acting muscarinic antagonists (LAMAs). LAMAs work to alleviate asthmatic symptoms by antagonizing the type 3 muscarinic receptors in bronchial smooth muscles, resulting in relaxation of muscles in the airway (4). Because LAMAs are long-acting, they are not recommended for cases of acute asthma exacerbations or asthmatic emergencies (4). 

LAMAs Side Effects 

Possible LAMA side effects include urinary retention, dry mouth, constipation, and glaucoma (4).  

LAMAs Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with LAMAs, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4). 

Adenosine Receptor Antagonists Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Adenosine Receptor Antagonists 

The commercially available adenosine receptor antagonist for asthma management is theophylline as a pill or intravenous (8). 

Adenosine Receptor Antagonists Method of Action 

The method of action for theophylline is acting as a nonselective adenosine receptor antagonist, acting as a competitive, nonselective phosphodiesterase inhibitor, and reducing airway responsiveness to histamine, allergens, and methacholine (8).  

Adenosine Receptor Antagonists Side Effects  

Common side effects of theophylline include GI upset, headache, dizziness, irritability, and arrythmias (8).  

Adenosine Receptor Antagonists Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with theophylline, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4). 

Leukotriene Modifiers Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Leukotriene Modifiers 

Commercially available leukotriene modifiers include montelukast (Singular) and zafirlukast (Accolate) as oral pills taken once a day. Zileuton (Zyflo CR) is a 5-lipoxygenase inhibitor that also modifies leukotriene activity (4).  

Leukotriene Modifiers Method of Action 

Montelukast and zafirlukast work to control asthma-related symptoms by targeting leukotrienes, which are eicosanoid inflammatory markers. Montelukast works in particular by blocking leukotriene D4 receptors in the lungs, thus allowing decreased inflammation in the lungs and increased relaxation of lung smooth muscle (9).  

Zafirlukast works by being a competitive antagonist at the cysteinyl leukotriene-1 receptor (CYSLTR1) (10). Zileuton is a 5-lipoxygenase inhibitor, in which 5-lipoxygenase is needed for leukotriene creation. Blocking 5-lipoxygenase decreases the formation of leukotrienes at several receptors. As a result of decreased leukotriene production, there is decreased inflammation, decreased mucus secretion, decreased bronchoconstriction (11). 

Leukotriene Modifiers Side Effects 

Possible side effects of montelukast include headaches, GI upset, and upset. Neuropsychiatric events, such as nightmares, changes in sleep, depression, and suicidal ideation are more severe side effects associated with montelukast.  

Possible side effects of zafirlukast include headache, GI upset, and hepatic dysfunction (9).  

Possible side effects of zileuton include hepatic dysfunction, changes in sleep, changes in mood, headaches, and GI upset. When the leukotriene modifiers, neuropsychiatric side effects are to be monitored for in particular, especially for suicidal ideation (9,10,11).  

Leukotriene Modifiers Alternatives 

Some patients might not report their symptoms alleviating with leukotriene modifiers, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4). 

Mast Cell Stabilizer Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Mast Cell Stabilizer 

A commercially available mast cell stabilizer is cromolyn available via metered-dose inhaler and nebulizer solution (12).  

Mast Cell Stabilizer Method of Action 

Cromolyn has a method of action in which it inhibits the release of inflammatory mediators from cells, such as the release of histamine and leukotrienes (12).  

Mast Cell Stabilizer Side Effects 

Every medication has the possibility of side effects, and cromolyn is no exception. Common side effects of cromolyn include dry throat, throat irritation, drowsiness, dizziness, cough, headache, and GI upset (12).  

Mast Cell Stabilizer Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with mast cell stabilizers, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4). 

Monoclonal Antibody Pharmacokinetics 

Health care provider professional discretion and patient condition should guide therapy. Consider reviewing a patient’s medication history and health history prior to prescribing asthma medications.  

Drug Class – Monoclonal Antibody 

Commercially available monoclonal antibodies include Omalizumab (Xolair), mepolizumab (Nucala), reslizumab (Cinqair), benralizumab (Fasenra), dupilumab (Dupixent), and tezepelumab-ekko (Tezspire). Omalizumab, mepolizumab, benralizumab, dupilumab, and texepelumab-ekko are available via subcutaneous injection. Reslizumab is available via intravenous solution (4). 

Monoclonal Antibody Method of Action 

Omalizumab is an anti-IgE monoclonal antibody that works by inhibiting the binding of IgE to mast cells and basophils. As a result of decreased bound IgE, activation and release of mediators, such as histamine, in the allergic response are decreased (13).  

Mepolizumab, reslizumab, and benralizumab are interleukin (IL)-5 antagonists. These IL-5 antagonists inhibit IL-5 signaling, allowing for a decrease in the creation and survival of eosinophils. However, the full method of action for IL-5 antagonists is still unknown, as more evidence-based research is needed (4, 15).  

Dupilumab is an IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. This inhibition of the IL-4Rα subunit allows for the decrease of IL-4 and IL-13 cytokine-induced inflammatory responses (14). 

Tezepelumab-ekko is an IgG antibody that binds to the thymic stromal lymphopoietin (TSLP) and prevents TSLP from interacting with the TSLP receptor. Blocking TSLP decreases biomarkers and cytokines associated with inflammation. Knowing this, the full method of action for Tezepelumab-ekko is still unknown, as more evidence-based research is needed4,15.  

Monoclonal Antibody Side Effects 

Possible side effects of omalizumab include injection site reactions, fracture, anaphylaxis, headache, and sore throat (13). Possible side effects of mepolizumab, reslizumab, and benralizumab include injection site reactions, headache, and hypersensitivity reactions (4). Possible side effects of dupilumab include joint aches, injection site reactions, and headache (14). Possible side effects of tezepelumab-ekko include injection site reactions and headache (14). 

Monoclonal Antibody Alternatives 

While there are clinical criteria for asthma medications, everyone can respond to medications differently. Some patients might not report their symptoms alleviating with monoclonal antibodies, so additional medication, increased dosage, a change in frequency, or an additional medication class might need to be considered (4). 

Nursing Considerations 

Nurses remain the most trusted profession for a reason, and APRNs are often pillars of patient care in several health care settings. Patients turn to nurses for guidance, education, and support. While there is no specific guideline for the nurses’ role in asthma education and management, here are some suggestions to provide quality care for patients currently taking medications to manage asthma or concerned about possibly having asthma. 

• Take a detailed health history. Often times, respiratory symptoms, such as a cough or trouble breathing, are often dismissed in health care settings, or seen as “common symptoms with everyone.” If a patient is complaining of symptoms that could be related to asthma, inquire more about that complaint.  

Ask about how long the symptoms have lasted, what treatments have been tried, if these symptoms interfere with their quality of life, and if anything alleviates any of these symptoms. If you feel like a patient’s complaint is not being taken seriously by other health care professionals, advocate for that patient to the best of your abilities.  

• Review medication history at every encounter. Often times, in busy clinical settings, reviewing health records can be overwhelming. Millions of people take asthma medications at varying dosages, frequencies, and times of day. Many people with asthma take more than one medication to manage their symptoms.  

Ask patients how they are feeling on the medication, if their symptoms are improving, and if there are any changes to medication history.  

• Be willing to answer questions about asthma, respiratory health, and medication options. Society stigmatizes open discussions of prescription medication and can minimize symptoms of asthma, such as a chronic cough.  

There are many people who do not know about medication options or the long-term effects of undiagnosed or poorly managed asthma. Be willing to be honest with yourself about your comfort level discussing topics and providing education on asthma medications and asthma clinical assessment options.  

• Inquire about a patient’s life outside of medications, such as their occupation, living situation, and smoking habits. Household exposures, such as carpets or pets, can trigger asthma. Occupations with high exposure to smoke can also trigger asthmatic symptoms. Smoking, living with someone who smokes, or residing in an area with high levels of pollution can also influence asthma symptoms.  

Discuss possible solutions to help with symptoms, such as improving ventilation, increasing air quality, and mask wearing when possible.  

• Communicate the care plan to other staff involved for continuity of care. For several patients, especially for patients with severe asthma, care often involves a team of nurses, specialists, pharmacies, and more. Ensure that patients’ records are up to date for ease in record sharing and continuity of care. 

• Stay up to date on continuing education related to asthma medications, as evidence-based information is always evolving and changing. You can then present your new learnings and findings to other health care professionals and educate your patients with the latest information. You can learn more about the latest research on asthma and asthma-related medications by following updates from evidence-based organizations.  

How can nurses identify if someone has asthma?  

Unfortunately, it is not always possible to look at someone with the naked eye and determine if they have asthma. While some people might have visible asthmatic symptoms, such as wheezing or trouble breathing, asthmatic clinical presentation can significantly vary from person to person.  

APRNs can identify and diagnose if someone has asthma by taking a complete health history, listening to patient’s concerns, and offering pulmonary function testing. 

What should patients know about asthma medications?  

Patients should know that anyone has the possibility of experiencing side effects medications for asthma management, just like any other medication. Patients should be aware that if they notice any changes in their mood, experience any sharp headaches, or feel like something is a concern, they should seek medical care.  

Nurses should also teach patients to advocate for their own health in order to avoid untreated or undetected asthma and possible chronic complications from asthma or asthma-related medications.  

Here are important tips for patient education in the inpatient or outpatient setting: 

• Tell the health care provider of any existing medical conditions or concerns (need to identify risk factors). 
• Tell the health care provider of any existing lifestyle concerns, such as tobacco use, other drug use, sleeping habits, occupation, diet, menstrual cycle changes (need to identify lifestyle factors that can influence asthmatic medication use, asthma severity, and asthma management). 
• Tell the health care provider if you have any changes in your breathing, such as pain with deep breathing or persistent coughing (potential asthma exacerbation symptoms or possibility of asthma medications not being as effective for treatment). 
• Tell the nurse of health care provider if you experience any pain that increasingly becomes more severe or interferes with your quality of life. 
• Keep track of your health, medication use, and health concerns via an app, diary, or journal (self-monitoring for any changes). 
• Tell the health care provider right away if you are having thoughts of hurting yourself or others (possible increased risk of suicidality is a possible side effect for montelukast use). 
• Take all prescribed medications as indicated and ask questions about medications and possible other treatment options, such as non-pharmacological options or surgeries. 
• Tell the health care provider if you notice any changes while taking medications or on other treatments to manage asthma (potential worsening or improving health situation). 

Research Findings 

What Research on Asthma Medication Exists Presently? 

There is extensive publicly available literature on asthma and asthma-related medications via the National Institutes of Health and other evidence-based journals (1,2,4).  

What are some ways for people who take asthma medications to become a part of research? 

If a patient is interested in participating in clinical trial research, they can seek more information on clinical trials from local universities and health care organizations. 

Conclusion

Asthma is a chronic condition that affects many people from their childhood to their aging years. As more medications for asthma come onto the market and more evidence-based approaches to asthma and lung care emerge, APRNs will be at the forefront of primary care and asthma care across the lifespan.  

Case Study #1 

Susie is a mom to a 15-year-old named Jill. She arrives at the pediatric asthma and allergy specialist practice for a new patient visit. Susie reports that she notices Jill is having trouble sleeping at night and coughing more during the day for the past month. Jill plays soccer with her school, but her mom is concerned about coughing and trouble sleeping interfering with her sports.  

Susie knows that her dad has asthma, and Jill spends a lot of time with her aunt who smokes cigarettes. Jill has a history of generalized anxiety disorder and reports no smoking, no drinking, and no recreational drugs. Jill also wants to learn more about her lung health, as she wants to play soccer professionally one day.  

• What are some specific questions you’d want to ask about Jill’s coughing and respiratory health? 
• What are health history questions you would want to highlight? 
• What are some tests or lab work would you suggest performing?  

Case Study #2 (Continued) 

Susie also shares that she is dating a new partner who vapes in the home, and they recently got a pet puppy in the home. She states that Jill had trouble sleeping at night and coughing a lot when she was younger, but Susie thought Jill grew out of it. Susie wants to learn more about if Jill has asthma like her grandfather, if there are any ways to manage this cough, and if there are any tests that can determine Jill’s lung health in the office today. 

• What sort of tests can be done in-office to assess pulmonary function? 
• What sort of environmental exposures can trigger respiratory conditions?  

Susie agrees to have Jill do allergy testing and to do an in-office pulmonary function test for teenagers. Jill also wants to learn more about spirometry that you mentioned earlier and how to monitor her health outside of the office since she’s busy with school and soccer and doesn’t want to come to the office every time there’s a problem.  

Susie is open to medication options for Jill but doesn’t want anything that will interfere too much with Jill’s social time with her friends. Susie and Jill also want to know if this is a health condition that Jill will have forever or if Jill will grow out of this.  

• Knowing Susie’s concerns and Jill’s age, what are some talking points about reducing possible asthma triggers? 
• How would you explain asthma as a chronic health condition to an adolescent patient?  
• Given Jill and Susie’s concerns about medications, what would be some possible medication options to consider after reviewing Jill’s pulmonary function test results and patient history? 

SSRI Use in Major Depressive Disorder

Introduction   

When hearing the phrase selective serotonin reuptake inhibitors, what comes to mind? If you’re an advanced practice registered nurse (APRN) with prescriptive authority, you’ve heard of SSRIs before. Even as a nurse or maybe before nursing school, conversations about prescription drug use and mental health existed every so often.

Presently, patients seek guidance and information on various health topics from APRNs, including medication management, women’s health, and mental health. The information in this course will serve as a valuable resource for APRNs with prescriptive authority of all specialties, education levels, and backgrounds to learn more about SSRIs and major depressive disorder (MDD).  

Defining SSRIs 

What Are SSRIs? 

Selective serotonin reuptake inhibitors, known as SSRIs, are a type of pharmacological drug class. SSRIs have existed for the past several decades as a class of prescription medications that can manage major depressive disorder (MDD) and other mental health conditions (1).

While this course focuses explicitly on SSRI use in MDD management, SSRIs are also Food and Drug Administration (FDA) approved to manage obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD). In addition, several off-label uses for SSRI include management for binge eating disorder and menopausal vasomotor symptoms.  

How and Where Are SSRIs Used? 

SSRIs are commonly prescribed to manage MDD and other mood disorders in the U.S. and around the world in pediatric, adult, and geriatric populations (1, 2). SSRIs can be taken by mouth as a pill, capsule, or liquid oral solution. Presently, SSRIs cannot be offered via intravenous, rectal, buccal, or injection routes.  

What Is the Clinical Criteria for Prescribing SSRIs? 

Clinical criteria for prescribing SSRIs can vary depending on the intention for the SSRI. In the case of MDD, several factors can play a role in the clinical criteria for prescribing SSRIs. A patient’s adherence to swallowing a pill daily, dosage given the patient’s weight, medical history, and MDD concerns, and prior experience with other medications can influence prescribing SSRIs. When considering prescribing SSRIs for MDD management, consider assessing the patient for MDD first, taking a detailed health history, and discussing the risk versus benefits of starting SSRIs for this patient (1, 3).  

What Is the Average Cost for SSRIs? 

Cost for SSRIs can significantly vary depending on the type of SSRI, insurance, dosage, frequency, and other factors. Cost is among leading reasons why many patients cannot maintain their medication regime (4). If cost is a concern for your patient, consider reaching out to your local pharmacies or patient care teams to find cost-effective solutions for your patients.  

What Is Major Depressive Disorder (MDD)? 

Major depressive disorder (MDD) is a mental health condition in which a person has consistent appetite changes, sleep changes, psychomotor changes, decreased interest in activities, negative thoughts, suicidal thoughts, and depressed mood that interfere with a person’s quality of life (5). According to the Diagnostic and Statistical Manual of Mental Health Disorders, a patient must have at least five persistent mood related symptoms, including depression or anhedonia (loss of interest in activities once enjoyed), that interferes with a person’s quality of life to be formally diagnosed with MDD. Note that MDD does not include a history of manic episodes, and pediatric populations can present with more variable MDD symptoms (5). As an APRN, you can assess for MDD by doing a detailed patient health history or having a patient complete the Patient Health Questionnaire-9 (PHQ-9) – a depression assessment tool (5). 

SSRI Pharmacokinetics  

Drug Class SSRIs 

Selective serotonin reuptake inhibitors, known as SSRIs, are a type of pharmacological drug class part of the antidepressant drug class. They can be prescribed at various dosages depending on the patient history, severity of major depressive disorder (MDD), other medication use, and other factors based on patient-centered decision making. Currently, SSRIs that are FDA approved for MDD management include paroxetine, sertraline, citalopram, escitalopram, vilazodone, and fluoxetine. SSRIs can be prescribed for the oral route and are available via capsule, tablet, or liquid suspension/solution. SSRIs can be taken at any time of day. They can be taken with or without food, though vilazodone in particular is recommended with food. SSRIs are often prescribed to be taken once a day, sometimes twice a day, depending on the severity of MDD. Health care provider professional discretion and patient condition should guide therapy (1).  

SSRIs are metabolized by and known to affect the cytochrome P450 system. CYP2D6 inhibitors include escitalopram, citalopram, sertraline, paroxetine, and fluoxetine. Fluoxetine and fluvoxamine are inhibitors of CYP2C19. Fluvoxamine is an inhibitor of CYP1A2. Consider reviewing a patient’s medication history and health history prior to prescribing SSRIs (1).   

SSRIs Method of Action 

SSRI method of action has been subject to several studies, especially in the last few years. Serotonin is a neurotransmitter that plays a role in mood and other bodily functions. It can be measured in plasma, blood, urine, and CSF (6). It is important to note that serotonin is rapidly metabolized to 5-hydroxyindoleacetic acid (5-HIAA) (6). SSRIs work by inhibiting the reuptake of serotonin at certain chemical receptors, thereby increasing serotonin activity and concentration (1). SSRIs inhibit the serotonin transporter (SERT) at the presynaptic axon terminal.  

By obstructing the SERT, a higher amount of serotonin (5-hydroxytryptamine or 5HT) remains in synaptic clefts. This higher amount of serotonin can then stimulate postsynaptic receptors for a more extended period (1). While SSRIs can increase serotonin activity, there is some evidence that suggests the possibility of long-term SSRI use reducing serotonin concentration (6). In addition, the clinical response to SSRIs in patients with MDD can take anywhere from a few to several weeks to emerge (7). While some research suggests that there are initial improvements in mood, evidence remains inconclusive as to the exact time SSRIs can take to provide a therapeutic response for patients (7). Also, while research suggests that SSRIs can increase serotonin levels, there is still mixed evidence on the exact method of action for SSRIs (7).  

As a result, it is important to counsel patients that SSRIs can take a few weeks to provide a therapeutic response and to monitor mood and symptoms while taking SSRIs.  

SSRI Side Effects 

Every medication has the possibility of side effects, and SSRIs are no exception. Fortunately, SSRIs are known to have less side effects than other drug classes of antidepressants, such as monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs). The most commonly known side effects of SSRIs include weight gain, sleep changes, headache, gastrointestinal issues, drowsiness, orthostatic hypotension, and sexual function changes (1).  

Sleep changes can include an increased desire to sleep, increase in the amount of time sleeping, or insomnia. Gastrointestinal issues can include an upset stomach, nausea, or dry mouth. Mood changes, such as anxiety, are possible side effects as well. Sexual function changes can include erectile dysfunction, libido changes, impaired orgasmic response, and vaginal dryness (1, 8).  

There are more serious possible side effects of SSRIs as well. For instance, SSRIs have the possible side effect of QT prolongation, which if left untreated or undiagnosed, can lead to fatal cardiac arrythmias (1, 8). In particular, the SSRI citalopram has been shown to have more of a risk for QT prolongation compared to other SSRIs. Also, like any other medication that can possibly increase levels of serotonin in the body, there is a possibility of serotonin syndrome as a complication of SSRI use. Possible serotonin syndrome clinical manifestations include increased blood pressure, increased sweating, increased reflex ability, and increased dry eyes (8). Due to the wide varied range of side effects, patient counseling, monitoring, and education is essential when prescribing SSRIs. 

SSRI Black Box Warning  

In 2004, the FDA issued a black box warning for SSRIs and other antidepressant medications due to the possible increased risk of suicidality in pediatric and young adult populations (up to age 25). When considering SSRI use in patients under 25 and knowing MDD is a risk factor for suicidality, having a conversation with the patient about risks versus benefits must be considered. However, in the past several years since the FDA’s warning, there is no clear evidence showing a correlation between SSRIs and the increased risk of suicidality (1, 8). Health care provider professional discretion and patient condition should guide therapy. 

SSRI Alternatives 

MDD can be a complex, chronic condition to manage with varying clinical presentation and influence on a patient’s quality of life. There are several alternatives to SSRI use, such as: (1, 9) 

• Other prescription drugs 
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly known SNRIs include milnacipran, venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran. 
  • Atypical antidepressants. Commonly known atypical antidepressants include bupropion and mirtazapine. 
  • Tricyclic antidepressants (TCAs). Commonly known TCAs include amitriptyline, desipramine, imipramine, clomipramine, doxepin, and nortriptyline. 
  • Monoamine oxidase inhibitors (MAOIs). Commonly known MAOIs include phenelzine, tranylcypromine, isocarboxazid, and selegiline. 
• Psychotherapy, such as cognitive behavioral therapy (CBT) or interpersonal therapy 
• Electroconvulsive therapy (ECT) 
• Vagus Nerve Stimulation (VNS) 
• Transcranial Magnetic Stimulation (TMS) 

Nursing Considerations 

Nurse’s Role 

What Is the Nurses’ Role in SSRI Patient Education and Management? 

Nurses remain the most trusted profession for a reason, and APRNs are often pillars of patient care in several health care settings. Patients turn to nurses for guidance, education, and support. While there is no specific guideline for the nurses’ role in SSRI education and management, here are some suggestions to provide quality care for patients interested in or currently taking SSRIs to manage current or suspected major depressive disorder (MDD). 

1. Take a detailed health history. Often times, mental health symptoms, such as depressive thoughts or anxiety, are often dismissed in health care settings, even in mental health settings. If a patient is complaining of symptoms that could be related to major depressive disorder, inquire more about that complaint. Ask about how long the symptoms have lasted, what treatments have been tried, if these symptoms interfere with their quality of life, and if anything alleviates any of these symptoms. If you feel like a patient’s complaint is not being taken seriously by other health care professionals, advocate for that patient to the best of your abilities.  
2. Review medication history at every encounter. Often times, in busy clinical settings, reviewing health records can be overwhelming. While a vast number of people take SSRIs, many are no longer benefiting from the medication. Ask patients how they are feeling on the medication, if their symptoms are improving, and if there are any changes to medication history.  
3. Ask about family history. If someone is complaining of symptoms that could be related to MDD, ask if anyone in their immediate family, such as their parent or sibling, experienced similar conditions.   
4. Be willing to answer questions about mental health and SSRIs. Society can often stigmatize open discussions of prescription medication and mental health. SSRIs are no exception. There are many people who do not know about the benefits and risks of SSRIs, the long-term effects of unmanaged MDD, or possible treatment options. Be willing to be honest with yourself about your comfort level discussing topics and providing education on SSRIs and MDD.  
5. Communicate the care plan to other staff involved for continuity of care. For several patients, MDD management often involves a team of mental health professionals, nurses, primary care specialists, pharmacies, and more. Ensure that patients’ records are up to date for ease in record sharing and continuity of care. 
6. Stay up to date on continuing education related to SSRIs and mental health conditions, as evidence-based information is always evolving and changing. You can then present your new findings to other health care professionals and educate your patients with the latest information. You can learn more about the latest research on SSRIs and mental health by following updates from evidence-based organizations.  

Identifying Major Depressive Disorder 

How can nurses identify if someone has major depressive disorder?  

Unfortunately, it is not possible to look at someone with the naked eye and determine if they have MDD. APRNs can identify and diagnose if someone has MDD by taking a complete health history, listening to patient’s concerns, having patients complete the PHQ-9 questionnaire and communicating any concerns to other health care professionals (9). 

Patient Education 

What should patients know about SSRIs?  

Patients should know that anyone has the possibility of experiencing side effects of SSRIs, just like any other medication. Patients should be aware that if they notice any changes in their mood, experience any sharp headaches, or feel like something is a concern, they should seek medical care. Due to social stigma associated with mental health and SSRI use, people may be hesitant to seek medical care for fear of being dismissed by health care professionals (1, 6). In addition, side effects (that interfere with the quality of life) are often normalized (1, 6). However, as more research and social movements discuss mental health and SSRI use more openly, there is more space and awareness for SSRI use and mental health.  

Nurses should also teach patients to advocate for their own health in order to avoid progression of MDD and possible unwanted side effects of SSRIs. Here are important tips for patient education in the inpatient or outpatient setting.  

• Tell the health care provider of any existing medical conditions or concerns (need to identify risk factors) 
• Tell the health care provider of any existing lifestyle concerns, such as alcohol use, other drug use, sleeping habits, diet, menstrual cycle changes (need to identify lifestyle factors that can influence SSRI use and MDD) 
• Tell the health care provider if you notice any changes in your mood, behavior, sleep, sexual health (including vaginal dryness or erectile dysfunction), or weight (possible changes that could hint at more chronic side effects of SSRIs) 
• Tell the health care provider if you have any changes in urinary or bowel habits, such as increased or decreased urination or defecation (potential risk for SSRI malabsorption or possible unwanted side effects) 
• Tell the nurse of health care provider if you experience any pain that increasingly becomes more severe or interferes with your quality of life 
• Keep track of your mental health, medication use, and health concerns via an app, diary, or journal (self-monitoring for any changes) 
• Tell the health care provider right away if you are having thoughts of hurting yourself or others (possible increased risk of suicidality is a possible side effect for SSRI use) 
• Take all prescribed medications as indicated and ask questions about medications and possible other treatment options, such as non-pharmacological options or surgeries 
• Tell the health care provider if you notice any changes while taking medications or on other treatments to manage your MDD (potential worsening or improving mental health situation) 

Research Findings 

What Research on SSRIs exists presently? 

There is extensive publicly available literature on SSRIs via the National Institutes of Health and other evidence-based journals.  

What are some ways for people who take SSRIs to become a part of research? 

If a patient is interested in participating in clinical trial research, they can seek more information on clinical trials from local universities and health care organizations. 

Case Study 

Case Study Part 1 

Susan is a 22-year-old Black woman working as a teacher. She arrives for her annual exam at the local health department next to her place of work. She reports nothing new in her health, but she says she’s been feeling more tired over the past few months. Susan reports having some trouble sleeping and trouble eating but doesn’t feel too stressed overall. She heard one of her friends talking about SSRIs and wants to try them, but she’s never taken prescription medications long-term before. She also thinks she might have some depression because she looked at some forums online and resonated with a lot of people’s comments.  

Case Study Part 2 

Susan agrees to complete bloodwork later this week and thinks she might have a family history of depression. She said that no one in her family talks about mental health, but she heard about depression from her friends recently and family a long time ago. She’s back in the office a few weeks later, and her labs are within normal limits. Susan states she’s still feeling fatigued and feeling a bit more hopeless these days. She denies thinking about hurting herself or others. 

Case Study Part 3 

Susan completed the PHQ-9 questionnaire and had a high score. After discussing her responses with her, you diagnose her with MDD. Susan admits that she is open to trying SSRIs. She is also open to seeing a therapist, as she states that she’s never been to therapy. She would like resources on any therapy services, medication options, and non-pharmacological options to help her manage her condition.  

Conclusion

Major depressive disorder is a complex chronic health condition that affects many people nationwide. SSRIs are often a first-line pharmacological option for MDD management. However, clinical presentation and symptom management with SSRIs can vary widely. While some patients would prefer a low-dose SSRI, others will need a higher dose and possible extra medication management. Education and awareness of SSRIs can influence the lives of many people.  

Safe Prescribing of Opioids 

Introduction   

For centuries, humans have been using, developing, and synthesizing opioid compounds for pain relief. Opioids are essential for treating patients who are experiencing severe and sometimes even moderate pain. Chronic pain can negatively affect our lives. In 2011, the cost of chronic pain ranged from $560 to $635 billion in direct medical expenses, lost productivity, and disability. An estimated one in five U.S. adults had chronic pain (11).

Introduction of opioid drug class, indications for use, most prescribed opioids, and their effects.

Opioids usually bind to mu-opioid receptor sites, where they have agonist effects, providing pain relief, sedation, and sometimes feelings of euphoria. Opiates refer only to natural opioids derived from the poppy plant. The term "opioids" includes all-natural, semi-synthetic, and synthetic opioids.

Opioids are classified into several categories based on their origin and chemical structure:

1. Natural Opioids (Opiates): These come from the opium poppy plant. Examples include morphine and codeine.
2. Semi-Synthetic Opioids: These are natural opioids that are chemically modified. Examples include drugs like oxycodone, hydrocodone, oxymorphone, and hydromorphone.
3. Synthetic Opioids: These opioids are entirely synthesized in a laboratory and do not have a natural source. Examples include fentanyl, tramadol, and methadone (4).

Providers must always caution patients about the benefits and risks. The main advantage of opioid medication is that it will reduce pain and improve physical function. A provider may use a 3-item Pain, Enjoyment of Life, and General Activity (PEG) Assessment Scale:

1. What number best describes your pain on average in the past week?
2. What number best describes how, during the past week, pain has interfered with your enjoyment of life?
3. What number best describes how, during the past week, pain has interfered with your general activity?

The desired goal is a 30% improvement overall with opioid treatment. (Centers for Disease and Control)

Providers must also go over potential side effects and warnings. Side effects include sedation, dizziness, confusion, nausea, vomiting, constipation, itching, pupillary constriction, and respiratory depression. Providers should discuss the importance of taking medication as prescribed. Taking opioids in larger than prescribed dosage, or in addition to alcohol, other illicit substances, or prescription drugs, can lead to severe respiratory depression and death. Individuals should not drive when taking opioids due to the sedating effects and decreased reaction times.

There are now thousands of different Food and Drug Administration (FDA) approved opioids available for providers to prescribe. They can be administered via other routes and come in various potencies. The strength of morphine is the "gold standard" used when comparing opioids. A morphine milligram equivalent (MME) is the degree of µ-receptor agonist activity. The following is a sample of some of the most prescribed opioids and their MME:

To utilize this information, multiply the dose for each opioid by the conversion factor to determine the quantity in MMEs. For example, tablets containing hydrocodone 5 mg and acetaminophen 325 mg taken four times a day would include a total of 20 mg of hydrocodone daily, equivalent to 20 MME (11).

A history of opioids leading to the current epidemic

While the current opioid epidemic has caused devastating effects in recent years, destruction from opioids has been going on for centuries. In the early 1800s, physicians and scientists became aware of the addictive qualities of opium. This finding encouraged research to develop safer ways to deliver opioids for pain relief and cough suppression, which led to the development of morphine. By the mid-1800s, with commercial production and the invention of the hypodermic needle, morphine became easier to administer.  

During the Civil War (1861 to 1865), injured soldiers were sometimes treated with morphine, and some developed lifelong addictions after the war. Without other options for pain relief, physicians kept giving patients morphine as treatment. Early indicators that morphine should be used cautiously were largely ignored. Between 1870 and 1880, the use of morphine tripled. Even with the problems associated with opioids, they continued to serve a vital part in the pain treatment of patients, and their use and development continued (6).  

Opioid prescribing increased fourfold during 1999–2010. Along with the increase in opioid prescriptions during this time, how they were prescribed also changed; opioids were increasingly prescribed at higher dosages and for longer durations. The number of people who reported using OxyContin for non-medical purposes increased from 400,000 in 1999 to 1.9 million in 2002 and to 2.8 million in 2003. This was accompanied by an approximately fourfold increase in overdose deaths involving prescription opioids (8).  

In 2020, approximately 1.4 million people were diagnosed with opioid use disorder (OUD), of those associated with opioid painkillers, as opposed to 438,000 who have heroin-related OUD (1, 4). Over 100,000 people died of a drug overdose, with 85% involved in an opioid (1, 4).  

Widespread efforts were made to combat this growing issue. The prescribing rate peaked and leveled off from 2010-2012 and has been declining since 2012. In 2021, an estimated 2.5 million adults had been diagnosed with OUD. However, the amount of MME of opioids prescribed per person is still around three times higher than in 1999 (5). 

 Controlled Substances

On July 1, 1973, the Drug Enforcement Administration (DEA) was established in the United States. The Diversion Control Division oversees pharmaceuticals. Within this Division are five levels of controlled substances, which classify illicit and medicinal drugs (7).  

Schedule I Controlled Substances

No medical use, lack of accepted safety for use under medical supervision, and high abuse potential.

Examples of Schedule I substances are heroin, lysergic acid diethylamide (LSD), and marijuana (cannabis).

Schedule II/IIN Controlled Substances (2/2N)

High potential for abuse, which can lead to severe dependence.

Examples include hydromorphone, methadone, meperidine, oxycodone, and fentanyl. Other narcotics in this class include morphine, opium, codeine, and hydrocodone.

Some examples of Schedule IIN stimulants include amphetamine, methamphetamine, and methylphenidate.

Other substances include amobarbital, glutethimide, and pentobarbital.

Schedule III/IIIN Controlled Substances (3/3N)

Less potential for abuse than substances in Schedules I or II, and abuse may lead to moderate or low physical dependence or high psychological dependence.

Include drugs containing not more than 90 milligrams of codeine per dosage unit like Acetaminophen with Codeine and buprenorphine.

Schedule IN non-narcotics includes benzphetamine, phendimetrazine, ketamine, and anabolic steroids such as Depo®-Testosterone.

Schedule IV Controlled Substances

Have a low potential for abuse relative to substances in Schedule III.

Examples include alprazolam, carisoprodol, clonazepam, clorazepate, diazepam, lorazepam, midazolam, temazepam, and triazolam, Tramadol.

Schedule V Controlled Substances

Low potential for abuse relative to Schedule IV and primarily consist of medications that have small quantities of narcotics.

Examples include cough preparations containing not more than 200 milligrams of codeine per 100 milliliters or per 100 grams and ezogabine (10).

Explore behaviors that indicate opioid seeking, misuse, or addiction in patients.

Opioid use disorder (OUD) causes significant impairment or distress. Diagnosis is based on the following criteria: unsuccessful efforts to reduce or control use or use that leads to social problems and a failure to fulfill obligations at work, school, or home. The term Opioid Use Disorder is the preferred term; "opioid abuse or dependence" or "opioid addiction" have negative connotations and should be avoided. (3).

OUD occurs after a person has developed tolerance and dependence, resulting in a physical challenge to stop opioid use and increasing the risk of withdrawal. Tolerance happens over time when a person experiences a reduced response to medication, requiring a larger amount to experience the same effect. Opioid dependence occurs when the body adjusts to regular opioid use. Unpleasant physical symptoms of withdrawal occur when medication is stopped. Symptoms of withdrawal include anxiety, insomnia, abdominal pain, vomiting, diarrhea, etc. (5).

Patients who have OUD may or may not have practiced drug misuse. Drug misuse, the preferred term for "substance abuse," is the use of illegal drugs and the use of prescribed drugs other than as directed by a doctor, such as using more amounts, more often, or longer than recommended or using someone else's prescription (3).

Some indications that a patient may be starting to have unintended consequences with their opioid prescription may include the following symptoms: craving, wanting to take opioids in higher quantities or more frequently, difficulty controlling use, or work, social, or family issues. If providers suspect OUD, they should discuss their concerns with their patients nonjudgmentally and allow the patient to disclose related concerns or issues. Providers should assess the presence of OUD using the DSM-5 criteria.

Providers can use validated screening tools such as:

• Urine and oral fluid toxicology testing
• Drug Abuse Screening Test (DAST)
• Tobacco, Alcohol, and/or other Substance use Tools (TAPS)
• A three-question version of the Alcohol Use Disorders Identification Test (AUDIT-C)

The following patients are at higher risk for OUD or overdose:

• History of depression or other mental health conditions
• History of a substance use disorder
• History of overdose
• Taking 50 or greater MME/day or taking other central nervous system depressants with opioids

The 12 components of the CDC’s recent guidelines for opioid prescribing.

In 2022, the CDC updated the 2016 guidelines to help prescribers navigate prescribing opioids amid an epidemic. These guidelines are directed toward prescribing medications to adults to be taken in the outpatient setting, for example, primary care clinics, surgery centers, urgent cares, and dental offices. These do not apply to providers caring for individuals with sickle-cell disease, cancer, those receiving inpatient care, or end-of-life or palliative care. They are also intended to serve as a guideline, and each treatment plan should be specific to the unique patient and circumstances.

Some of the Goals of the guidelines are to:

• Improve communication between providers and patients about treatment options and discuss the benefits and risks before initiating opioid therapy.
• Improve the effectiveness and safety of treatment to improve quality of life.
• Reduce risks associated with opioid treatment, including opioid use disorder (OUD), overdose, and death.

Recommendation #1: Determining when it is appropriate to initiate opioids for pain.

An essential part of the prescribing process is determining the anticipated pain severity and duration based on the patient’s diagnosis. Pain severity can be classified into three categories when measured using the standard 1-10 numeric scale. Pain scores 1-4 are considered mild, 5-6 are moderate, and 7-10 severe. Opioids are typically used for moderate to severe pain.

The patient’s diagnosis will allow the provider to determine if pain initially falls into one of the following three categories of anticipated duration: acute, subacute, and chronic. Acute pain is expected to last for one month or less. Acute pain often is caused by injury, trauma, or medical treatments such as surgery. Unresolved acute pain may develop into subacute pain if not resolved in 1 month. If pain exceeds three months, it is classified as chronic. Pain persisting longer than three months is chronic. It can result from underlying medical conditions, injury, medical treatment, inflammation, or unknown cause.

The CDC guidelines state that non-pharmacologic and non-invasive methods are the preferred first-line method of analgesia, such as heat/cold therapy, physical therapy, massage, rest, or exercises, etc. Despite evidence supporting their use, these therapies are only sometimes covered by insurance, and access and cost can be barriers, particularly for uninsured persons who have limited resources, no reliable transportation, or live in rural areas where treatments are not available.

When this is insufficient, non-opioid medications, such as Gabapentin, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAID), should be considered next. Selective antidepressants and anticonvulsant medications may also be effective. Some examples of when these drugs may be appropriate include neuropathic pain, lower back pain, musculoskeletal injuries (including minor pain related to fractures, sprains, strains, tendonitis, and bursitis), dental pain, postoperative pain, and kidney stone pain.

Providers, however, must also consider the risks and benefits of long-term NSAID use because it may also negatively affect a patient’s gastrointestinal and cardiovascular system. Depending on the diagnosis, a patient may also require an invasive or surgical intervention to treat the underlying cause to alleviate pain.

If the patient has pain that does not sufficiently improve with these initial therapy regimens, at that point, opioids will be the next option to be considered.

It does not mean that patients should be required to sequentially “fail” nonpharmacologic and non-opioid pharmacologic therapy or use any specific treatment before proceeding to opioid therapy. Example: A patient for whom NSAIDs are contraindicated has recently sustained a rotator cuff injury and is experiencing moderate pain to the point at which it is disturbing their sleep, and it will be several weeks before they can have surgery.

Recommendation #2: Discuss with the patient realistic treatment goals for pain and overall function.

Ideally, goals include improving quality of life and function, including social, emotional, and physical dimensions. The provider should help guide these patients to realistic expectations based on their diagnosis. This may mean that the patient may anticipate reduced pain levels but not complete elimination of pain. The provider should discuss the expected or typical timeframe where they may need medications.

If medications are anticipated for acute or subacute pain, a discussion about the expected timeframe for pain should be highlighted in the debate. The patient may then better understand if their recovery is progressing. For chronic conditions, the conversation will focus on or may emphasize the overall risks of beginning long-term medication therapy. They may also advise patients, particularly those with irreversible impairment injuries, that they may experience reduced pain but will not regain function. A withdrawal plan will be discussed if opioid therapy is unsuccessful or the risk vs. benefit ratio is no longer balanced.

The second section of recommendations covers the selection of opioids and dosages.

Recommendation #3: Prescribe immediate-release (I.R.) opioids instead of extended-release and long-acting (ER/LA) opioids when starting opioid therapy.

Immediate-release opioids have faster-acting medication with a shorter duration of pain-relieving action. ER/LA opioids should only be used in patients who have received specific dosages of immediate-release opioids daily for at least one week. Providers should reserve ER/LA opioids for severe, continuous pain, for example, individuals with cancer. ER/LA opioids should not be for PRN use. The reason for this recommendation is to reduce the risk of overdose. A patient who does not feel adequate relief or relief fast enough from the ER/LA dose may be more inclined to take additional amounts sooner than recommended, leading to a potential overdose.

Recommendation #4: Prescribe the lowest effective dose.

Dosing strategies include prescribing low doses and increasing doses in small increments. Prescribe the lowest dose for opioid patients. Carefully consider risk vs. benefits when increasing amounts for individuals with subacute and chronic pain who have developed tolerance. Providers should continue to optimize non-opioid therapies while continuing opioid therapy. It may include recommendations for taking non-opioid medications in addition to opioids and non-pharmacologic methods.

Providers should use caution and increase the dosage by the smallest practical amount, especially before increasing the total opioid dosage to 50 or greater morphine milligram equivalent (MME) daily. Increases beyond 50 MME/day are less likely to provide additional pain relief benefits. The greater the dosage increases, the tendency for risk also increases. Some states require providers to implement clinical protocols at specific dosage levels.

Recommendation #5: Tapering opioids includes weighing the benefits and risks when changing the opioid dosage.

Providers should consider tapering to a reduced dosage or tapering and discontinuing therapy and discuss these approaches before initiating changes when:

• The patient requests dosage reduction or discontinuation,
• Pain improves and might indicate the resolution of an underlying cause,
• Therapy has not reduced pain or improved function,
• Treated with opioids for a long time (e.g., years), and the benefit-risk balance is not clear.
• Receiving higher opioid dosages without evidence of improvement.
• Side effects that diminish the quality of life or cause impairment.
• Opioid misuse
• The patient experiences an overdose or severe event.
• Receiving medications or having a condition that may increase the risk of an adverse event.

Opioid therapy should not be discontinued abruptly unless there is a threat of a severe event, and providers should not rapidly reduce opioid dosages from higher dosages.

Patient agreement and interest in tapering will be key components of successful tapers. Integrating behavioral and non-opioid treatment and interventions for comorbid mental health conditions before/during a taper can help manage pain, strengthen the therapeutic relationship between the provider and patient, and improve the likelihood of positive tapering outcomes. When dosages are reduced or discontinued, a taper slow enough to reduce symptoms and withdrawal should be used. Patients should receive education on possible withdrawal symptoms and when to contact the provider.

For those taking opioids for a shorter duration, a 10% decrease of the original dose per week or slower until close to 30% of the initial amount is reached, followed by a weekly reduction of roughly 10% of the remaining dose) is less likely to trigger withdrawal. Tapers of 10% per month or less are better tolerated than rapidly tapering off when patients have been taking opioids for a longer duration (e.g., for a year or longer). Significant opioid withdrawal symptoms can indicate the need to slow the taper rate further. Short-term medications might also help manage withdrawal symptoms. Providers should follow up frequently (at least monthly) with patients engaging in opioid tapering.

Close monitoring is required for patients who cannot taper and who continue on high doses or otherwise high-risk opioid regimens and should collaborate with patients to mitigate overdose risk. Some patients with unanticipated challenges to tapering may need to be evaluated for OUD.

The third section focuses on the duration of opioid therapy and routine patient follow-up.

Recommendation #6: Prescribing no greater quantity than needed for the expected duration of severe pain requiring opioids.

A few days or less is often enough when opioids are used for common causes of nonsurgical acute pain. Many states have passed legislation that limits initial opioid prescriptions for acute pain to less than seven days. Many insurers and pharmacies have enacted similar policies. Providers should avoid prescribing additional opioids to patients if pain continues longer than expected.

Providers should prescribe and advise opioid use only as needed rather than on a scheduled basis (e.g., one tablet every 4 hours). Limiting the duration of therapy can decrease the need to taper. However, tapering may need to be considered if patients take these medications around the clock for more than a few days.

Longer durations of therapy may be needed when the injury is expected to result in prolonged severe pain (e.g., greater than seven days for severe traumatic injuries). Patients should be evaluated at least every two weeks if they are receiving opioids for acute pain. Suppose opioids are continued for a month or longer. In that case, providers should address potentially reversible causes of chronic pain so that the length of therapy does not continue to extend.

Recommendation #7: Evaluate the benefits and harms of opioid therapy regularly.

The benefits and risks for Evaluating benefits and risks within 1-4 weeks of starting long-term opioid therapy for subacute and chronic pain should be evaluated within 1-4 weeks of initiating therapy and after dosage increases.

The evaluation should include patient perspectives on progress and challenges in moving toward treatment goals, including sustained improvement in pain and function. The Three-item Pain, Enjoyment of Life, and General Activity (PEG) assessment scale could be utilized to help determine patient progress.

Providers should also ask patients about common adverse effects, such as constipation and drowsiness, and assess for outcomes that might be early warning signs for more serious problems such as overdose or OUD.

Patient re-evaluation should occur after therapy begins (about two weeks) when ER/LA opioids are prescribed if the total daily opioid dosage is greater than or equal to 50 MME/day or if there is a concurrent benzodiazepine prescription. These individuals are at a higher risk for overdose. Follow-up for individuals starting or increasing the dosage of methadone is recommended every 2-3 days for the first week. Providers should reassess all patients receiving long-term opioid therapy at least every three months.

The last section of recommendations covers patients at risk for OUD and overdose.

Recommendation #8: Use strategies to mitigate risk by evaluating risk for opioid-related harms, discussing risk with patients, and incorporating risk reduction strategies into the treatment plan.

The patient’s habits (including alcohol and illicit drug use) and behavioral and mental health must be considered. Patients with a history of substance use disorders, depression, and/or mental health disorders have a higher risk of overdose and OUD. Even though the dangers of opioid therapy are higher with these patients, they may still require opioid treatment for pain management.

Psychological distress can interfere with the improvement of pain and/or function in patients experiencing chronic pain; using tools like the Generalized Anxiety Disorder (GAD)-7 and the Patient Health Questionnaire (PHQ-9 or PHQ-4) to assess for anxiety, post-traumatic stress disorder (PTSD), and depression might help providers improve overall pain treatment outcomes. They should also ensure that treatment for depression and other mental health conditions is effective, consulting with behavioral health specialists when needed.

Additionally, providers should:

• Educate on the risks of overdose when opioids are combined with other drugs or alcohol.
• Use caution when prescribing opioids for people with sleep-disordered breathing due to their increased risk for respiratory depression. The provider may ascertain if a patient is compliant with prescribed CPAP.
• Use caution and increased monitoring for patients with renal or hepatic insufficiency.
• Use caution and increased monitoring for patients aged 65 years or older.
• Offering naloxone when prescribing opioids, particularly to patients at increased risk for overdose.

If patients experience a nonfatal opioid overdose, providers should evaluate for OUD. Providers should reduce opioid dosage, discontinue opioids when indicated, continue monitoring, and support for patients prescribed or not prescribed opioids.

Recommendation #9: Reviewing prescription drug monitoring program (PDMP) data.

Providers should review PDMP data specifically for prescription opioids, benzodiazepines, and other controlled medications patients have received from additional prescribers to determine all the opioids the patient could potentially receive. Patients with multiple prescriptions and from various providers are at an increased risk for overdose or OUD. PDMP data should be reviewed before initial drugs for subacute or chronic pain and at least every three months during long-term opioid therapy.

Recommendation # 10: Considering the benefits and risks of [urine] toxicology testing.

Toxicology testing should be used to inform and improve patient care. Providers, practices, and health systems should minimize bias in testing and not test based on assumptions about different patients.

Recommendation # 11: Use caution when prescribing opioid pain medication and other medications concurrently.

Benzodiazepines and opioids can cause CNS depression and potentiate opioid-induced decreases in respiratory drive. Because other CNS depressants can potentiate respiratory depression associated with opioids, benefits vs. risks should be considered.

Recommendation # 12: Offering or arranging treatment for OUD if needed.

Includes referring a patient to a specific treatment center where behavior therapy and medications may be prescribed.

Prescription Drug Monitoring Programs (PDMP) and Electronic Prescribing.

Prescription Drug Monitoring Programs (PDMP) is a database that keeps track of controlled substance prescriptions. It helps to improve opioid prescribing, inform clinical practice, and protect at-risk patients. A pharmacist must enter controlled substances into the state PDMP when dispensing them. When the pharmacist enters this data, it may occur at various intervals, from one month, daily, or even "real-time." However, a PDMP is only helpful if providers check the system before prescribing (10).  

Some states have implemented legislation that requires providers to check a state PDMP before prescribing certain controlled substances and in certain circumstances. Most current mandates require that all prescribers query PDMPs when prescribing any opioid. Some states require prescribers to query PDMPs every time a controlled substance is prescribed, while others require a query only for the initial prescription. Subsequent checks of PDMPs also vary from every time a drug is issued to specific intervals (e.g., every 90 days, twice a year, annually) should prescribing continue.  

Some mandates have categorical requirements; e.g., a query must be made if the prescription is over a three-day or seven-day supply or if a certain prescribed level of MME is exceeded. Other states' mandates are based on subjective criteria, e.g., a prescriber's judgment of possible inappropriate use or the prescriber's discretion regarding whether to query the PDMP. Finally, some states mandate that only prescribers in opioid treatment programs, workers' compensation programs, or pain clinics must query PDMPs (10, 11).  

In addition to PDMPs, there has been an increase in requirements for providers to utilize Electronic Prescribing for Controlled Substances (ECPS). Electronic prescribing programs for both providers and pharmacies must meet DEA requirements. The DEA's March 31, 2010, conditions were updated on July 27, 2023 (12).  

On January 1, 2023, the Centers for Medicare and Medicaid Services (CMS) implemented additional requirements for controlled substances for recipients of Medicare Part D. There are over 51 million U.S. people enrolled in Medicare Part D (Center for Medicare Advocacy, 2023). In addition to state laws, these rules require that prescribers e-prescribe at least 70 percent of controlled substances for patients that have Medicare Part D. A waiver may be approved if the prescriber cannot conduct electronic prescribing due to circumstances beyond the provider's control (12).  

Starting June 27, 2023, the 'Consolidated Appropriations Act of 2023' requires new or renewing Drug Enforcement Administration (DEA) registrants, to have at least one of the following: 

• A total of eight hours of training from specific organizations on opioid or other substance use disorders 
• Board certification in addiction medicine or addiction psychiatry from the American Board of Medical Specialties, American Board of Addiction Medicine, or the American Osteopathic Association 
• Graduation within five years and status in good standing from medical, advanced practice nursing, or physician assistant school in the U.S. that included an opioid or other substance use disorder curriculum of at least eight hours (11, 12).  

Providers must follow either state law or DEA/CMS regulations, whichever is more stringent. The following map indicates various rules in each state, which will continue to change when new legislation is enacted (11, 12).  

Important teaching points about opioid storage and disposal.

Safe Storage 

Patients should understand that prescription opioids need to be stored securely (i.e., keeping them in a locked area). This is especially true if children, teens, and other visitors in the house may be aware of their presence. Teens and young adults are the biggest misusers of prescription pain medication. In 2018, over 695,000 youths ages 12–17 and 1.9 million young adults ages 18–25 reported misusing prescription pain medication in the past year. Young people may misuse prescription opioids for many reasons, including curiosity, peer pressure, and wanting to fit in. Another reason teens and young adults may decide to take prescription opioids is because they can be easier to get than other drugs. Studies show that 53% percent of people over 12 who obtained prescription pain medication for non-medical use received them from a friend or relative (13).  

Safe Disposal 

Patients should be advised on how to get rid of unused or expired medications. The best option is to immediately take them to a drug take-back site, location, or program. These sites or programs can be found online, or the pharmacist may have information. If it is not feasible for the patient to get rid of the drug using a take-back program, the patient should be advised to check if it is on the FDA flush list. If it is, the medication should be flushed down the toilet. Again, the list of drugs is available on the FDA website. If it is not on that list, it should be discarded in the trash at home.  

Patients should follow these disposal instructions: Mix medicines (liquid or pills; do not crush tablets or capsules) with an unappealing substance such as dirt, cat litter, or used coffee grounds. Next, place the mixture in a container such as a sealed plastic bag; then throw away the container in your trash at home. Last, the patient should remove or permanently cover all personal information on the prescription label of empty medicine bottles or packaging, then trash or recycle the open container (14).  

OUD treatment, including medications.

Treatment for OUD is multi-faceted and typically includes both mental health components and FDA-approved OUD treatment medications. Mental health components may consist of counseling or a structured treatment program. Cognitive behavioral therapy (CBT) may also be beneficial. A potential barrier to OUD treatment, on the provider's and patient's behalf, is the perception that patients must engage in counseling to start or continue receiving OUD treatment medication. While the mental health components are essential, there may be barriers for patients to begin mental health treatment programs, which include expense, travel, and available openings within the programs. Medication therapy may be a helpful start for these patients (9). 

FDA-approved medications indicated for the treatment of OUD include methadone, buprenorphine, and naltrexone. Suboxone is a combination drug composed of buprenorphine and naltrexone.  

Medication has several advantages as part of the OUD treatment plan.  

• Help the individual to remain safe and comfortable during detox. 
• Reduce or eliminate cravings for opioids 
• Minimize relapse since the individual is not experiencing uncomfortable withdrawal symptoms 
• Allow the individual to focus on therapy without being distracted by withdrawal symptoms and cravings 
• Increase safety in cases of overdose 

Methadone 

Methadone is a full agonist opioid and is a Schedule II controlled medication. Methadone can be prescribed purely for the treatment of pain, as well as for OUD. Methadone treatment for OUD can only be provided through a Substance Abuse and Mental Health Services (SAMHSA)-certified opioid treatment program. Patients taking methadone to treat OUD must receive the medication under the supervision of a clinician. After consistent compliance, patients may take methadone at home between program visits. The length of methadone treatment should be a minimum of 12 months. Methadone doses are often adjusted and readjusted. Methadone is slowly excreted, and there is overdose potential if not taken as prescribed (9).  

Buprenorphine 

Buprenorphine is a partial agonist opioid. Buprenorphine can be prescribed by any provider with a current, standard DEA registration as a Schedule III Controlled Substance. Like opioids, it produces effects such as euphoria or respiratory depression. With buprenorphine, however, these effects are weaker than those of full opioids such as heroin and methadone. It also has unique pharmacological properties that help lower the potential for misuse and diminish the effects of physical dependency opioids, such as withdrawal symptoms and cravings (9). Subutex was a brand-name version of buprenorphine, discontinued in 2011 after new formulations that were less likely to be misused were developed.  

Naltrexone 

Naltrexone is an opioid antagonist, not addictive, and does not cause withdrawal symptoms. It blocks the euphoric and sedative effects of opioids by binding and blocking opioid receptors and reduces and suppresses opioid cravings. There is no potential for misuse and diversion. Naltrexone can be prescribed in any setting and can be taken as a pill or once monthly extended-release intramuscular injection (9).  

It was estimated 2021 that of the 2.5 million people with OUD, only 36% received any treatment, and only 22% received medications. A part of the July 27, 2023, Consolidated Appropriations Act amended the Controlled Substances Act to eliminate the requirement that providers obtain a specific waiver (a DATA waiver) to prescribe buprenorphine (including Suboxone) to treat opioid use disorder, known as the X-waiver. Additionally, there are no longer any caps on the number of patients a practitioner can treat. This, however, does not change the requirements for methadone treatment (15).  

Case Study #1

Patient Name: John Henderson,

Gender: Male

Age: 60

Height: 6' 1"

Weight: 190 lbs.

He is employed as a grocery store manager. Reports not using tobacco; drinks alcohol occasionally and has no illicit drug use. He has hypertension and high cholesterol and takes Losartan 50mg daily and Atorvastatin 20 mg daily.

This patient presents to a primary care office with pain and stiffness in the shoulder joint, which has progressively worsened for six months following rotator cuff surgery. He states his pain is unchanged, and he has a limited range of motion. It has been interfering with his ability to do his job. He said he went to physical therapy for a few weeks after his surgery but admitted he did not often complete the home exercise program regimen. An MRI was obtained and showed he had adhesive capsulitis. What are treatment options to consider for "frozen shoulder"?

Given the patient's diagnosis, non-opioid therapy options include nonsteroidal anti-inflammatory drugs, intraarticular glucocorticoid injections, steroid injections into the shoulder joint, range of motion exercises, physical therapy, and consulting with an orthopedic specialist who may recommend a joint manipulation under anesthesia. Each of these should be considered before opioid therapy.

Nursing Considerations 

Nurses remain the most trusted profession for a reason, and advanced practice registered nurses (APRNs) are often pillars of patient care in several health care settings. Patients turn to nurses for guidance, education, and support. While there are no specific guidelines for the nurse’s role in opioid education and management, here are some suggestions to provide quality care for patients currently taking opioid medications. 

Obtain a Detailed Health History 

Often times, pain and mental health can be dismissed and overlooked in health care settings. If a patient is complaining of symptoms that could be related to pain, inquire more about that complaint. Ask about how long the symptoms have lasted, what treatments have been tried, if these symptoms interfere with their quality of life, and if anything alleviates any of these symptoms. If you feel like a patient's complaint is not being taken seriously by other health care professionals, advocate for that patient to the best of your abilities. A detailed pain assessment and history can provide context for opioid pain management and a patient's plan of care. When taking a health history, ask about any prior surgeries, major life stressors in the past year, or any prior opioid usage.  

Review the Medication History 

Often times, in busy clinical settings, reviewing health records can be overwhelming. Many people take pain medications, including opioids, for various reasons. Ask patients how they are feeling on the medication, if their symptoms are improving, if there are any changes to medication history, and if they use any other substances other than prescribed medications, such as alcohol, tobacco, or other drugs. Remember, prescription medications are not the only medications people take. Confirm medication route, dosage, frequency, and all the details to make sure you and the patient are on the same page and to avoid medication errors and complications. Medication history should be reviewed at every encounter. 

Avoid Making Judgements 

Society often stigmatizes open discussions of prescription medication and pain. Patients may avoid asking for pain medication for fear of being perceived as a "drug seeker." Other times, patients may have OUD and continuously ask for an increased number of opioid medications. Be willing to be honest with yourself about your comfort level discussing topics and providing education on opioid medications, drug interactions, and pain management. Be willing to address any questions/concerns the patients may have without making judgements. 

Communicate the Plan of Care 

Communicate the plan of care to other staff involved for continuity of care. For several patients, especially for patients with chronic pain or who use opioids long-term, care often involves a team of mental health professionals, physical therapists, nurses, specialists, pharmacies, and more. Ensure that patients' records are up to date for ease in record sharing and continuity of care and to reduce the incidence of opioid medication errors. 

Engage in Self Learning 

Stay up to date on continuing education related to opioid medications, pain management, and prescribing regulations. Evidence-based information and scope of practice is always evolving and changing. You can then present your new learning and findings to other health care professionals and educate your patients with the latest information. You can learn more about the latest research on pain management medications, non-pharmacological pain management options, and opioids by following updates from evidence-based organizations, such as the CDC or your local health department.  

Perform Pain Assessments  

As we know, it is not possible to look at someone with the naked eye and determine if they are in pain. Sometimes, it may be obvious when a patient is in pain (e.g., visible lacerations) and need pain management options, such as opioids. Other times, pain management is addressed as a result of taking a complete health history, listening to patient's concerns, completing a pain assessment, and offering testing to determine the cause of pain. 

Assess for Opioid Use Disorder 

While it is not possible to look at someone and determine if they have OUD, APRNs should pay attention to certain behaviors, for example, when a patient continually asks for more opioid medications or mentions that they are experiencing many symptoms common to those of OUD. OUD may be diagnosed as a result of completing a health history, listening to patient's concerns, and offering testing to determine the cause of pain. Remember, anyone can have OUD, and no two OUD patients appear the same.  

Provide Patient Teaching 

Patients should know that anyone has the possibility of experiencing side effects of opioid medications, just like with any medication. Patients should be aware that if they notice any changes in their breathing, changes in their heart rate, or feel like something is a concern, they should seek medical care. Because of social stigma associated with opioids and pain management, people may be hesitant to seek medical care because of fear, shame, and embarrassment. However, as more research and social movements discuss opioid use, there is more space and awareness for opioid education and opioid overdose prevention.  

Nurses should also teach patients to advocate for their own health in order to avoid possible opioid complications and poor pain management.  

Here are important tips for patient education in the inpatient or outpatient setting.  

• Tell the health care provider of any existing medical conditions or concerns (need to identify risk factors) 
• Tell the health care provider of any existing lifestyle concerns, such as alcohol use, other drug use, sleeping habits, diet, menstrual cycle changes (need to identify lifestyle factors that can influence opioid use and pain management) 
• Tell the health care provider of any prior experiences with opioid medication (if applicable) and any medication reactions or side effects (need to identify risk factors, address pain management appropriately, identify any allergies, and avoid possible opioid overdose symptoms) 
• Tell the health care provider if you have any changes in your breathing, bodily functions, or heart rate (potential opioid overdose symptoms) 
• Tell the nurse or health care provider if you experience any pain that increasingly becomes more severe or interferes with your quality of life 
• Keep track of your pain, overall health, medication use, and health concerns via an app, diary, or journal (self-monitoring for any changes) 
• Tell the health care provider right away if you are having thoughts of hurting yourself or others (possible increased risk of suicidality and public safety concerns) 
• Take all prescribed medications as indicated and ask questions about medications and possible other treatment options, such as non-pharmacological options or surgeries 
• Tell the health care provider if you notice any changes while taking medications or other treatments to manage your pain (potential worsening or improving health situation) 

Research

There is extensive publicly available literature on opioids medications. These can be found via the National Institutes of Health website and other evidence-based journals. As research is dependent upon the available of study participants, there are several ways people who take opioids can become part of research. If a patient is interested in participating in clinical trial research, APRNs can encourage them to seek more information on clinical trials from local universities and health care organizations. 

Case Study #2

• Patient: Pilar 
• Age: 40 
• Height: 5' 1" 
• Weight: 135 lbs. 

Pilar presents to the urgent care clinic today complaining of a severe migraine, which started yesterday. Her history includes a hip injury following a car accident three years ago in which she developed chronic post-traumatic arthritis in the hip. After a total hip arthroplasty, she was diagnosed with heterotopic ossification (bone grows in tissue where it shouldn’t). For the past year, she has been taking 20 mg of oxycodone twice daily to manage chronic hip pain after unsuccessful non-opioid therapies. She has three children with no known pregnancy or postpartum complications. She previously worked part-time as an administrative assistant but has been off work since the car accident. She has post-traumatic stress disorder (PTSD) related to the accident. She has been prescribed Xanax 0.5mg up to three times daily for anxiety. She does not smoke, drink alcohol, or take illicit substances. 

• What are some specific questions you'd want to ask about the hip arthritis? 
• What are some health history questions you'd want to highlight? 
• What lab work or testing would you suggest to perform?  

For her migraine, Pilar stated she needed to take more of her oxycodone to deal with the pain and because she could not sleep last night. She is concerned because she is running out of pills. She said her primary care doctor's office was closed, so she came to the urgent care.  

• What are some non-pharmacological interventions you can do for Pilar's pain? 
• What are some questions you'd want to ask about her migraine? 
• What are side effects of opioids would you discuss with her? 

Here are some things to consider for Case Study #2.  

• Discuss concerns with the patient. This includes taking the opioid more often than prescribed, potential problems with respiratory depression, and overdose.  
• Recommend trying eletriptan or dihydroergotamine nasal spray first rather than additional opioids. 
• Review the PDMP to see the prescription history for this patient. Attempt to contact the primary care provider to develop a plan of care. 
• Consider conducting toxicology testing 
• Consider offering naloxone  
• Use the DSM-5 criteria to assess the presence (and severity) of OUD or arrange an assessment with a substance use disorder specialist. Offer treatment for OUD if it is confirmed. 

Case Study #3 

Sabrina is a 16-year-old Black high school student working as a waitress at a local restaurant. She arrives to the local pediatric emergency room after her shift with her mom because she thinks she is experiencing a sickle cell crisis. Sabrina reports that she has these crises every few months, and this is probably the third time she's been in this much pain. She reports being at this same ER last year for something similar. Her mother is completing paperwork and would like Sabrina to get some pain medication as well.  

• What are some specific questions you'd want to ask about her health? 
• What are some health history questions you'd want to highlight? 
• What lab work or testing would you suggest to perform?  
• What pain assessments would you perform on Sabrina? 

Sabrina agrees to provide bloodwork, complete imaging, and be admitted. She said that no health care provider talked to her about how painful sickle cell crises can be, and she doesn't routinely take pain medication because she "doesn't want to be addicted." Sabrina and her mom heard about pain management options for these extremely painful episodes from social media and the internet and would like Sabrina to get her pain controlled. Sabrina said that she had some opioids last time she was in the ER, but she doesn't remember the name. Her mom doesn't remember the name either, but she remembers it was in an IV medication.  

• How would you discuss Sabrina's pain management concerns? 
• Given Sabrina's age, medical history, and prior history of opioid use, what medication options would be appropriate for a sickle cell crisis in an adolescent?  

Sabrina has been in the pediatric ER for over a day receiving IV hydromorphone. She reports some relief, but Sabrina and her mom are concerned. Sabrina wants to live her life like a normal teenager without being in the hospital every few months for pain. Her mom asks if there is a way to have pain medication at home. Both Sabrina and her mom would like to know if there is anything that can be done to help with the pain outside of medications as well. Sabrina doesn't want to use pain medications daily but wants to have them at home just in case she can't get to the hospital.  

• Knowing Sabrina's concerns, what are some possible non-pharmacological pain management options? 
• Knowing Sabrina's health history, what would be some patient education talking points about at-home opioid medications and possible side effects?   
• What are some possible consequences of leaving pain improperly managed?  

Conclusion

Even providers who do not prescribe opioids should be familiar with the effects of opioids and OUD due to its high prevalence in the United States. Understanding the types of pain, how pain occurs, and how it impacts a person's quality of life is especially important. There is still an associated stigma among patients who use Opioids to treat chronic pain conditions. It is essential to recognize that there are times when opioid use is appropriate, as long as the provider practices the recommended guidelines and sound clinical judgment.

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.

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? 

Migraine Management 

Introduction   

This course will guide you on a journey to unravel the complexities of migraines and empower you with the knowledge and skills needed for effective pharmaceutical interventions.  

According to recent studies by (34), migraines involve changes in brain activity, neurotransmitter levels, and vascular function, resulting in throbbing headaches accompanied by sensitivity to light and sound. Diverse classes of migraine medications are available, such as Triptans and calcitonin gene-related peptide (CGRP) inhibitors and understanding their mechanisms of action enables healthcare professionals to make informed decisions in prescribing and administering treatments (18).  

Furthermore, recent research by (26) emphasizes the importance of recognizing warnings related to migraine medications. In this course, we will learn the details of medications for effective management of migraines and delve into ways of ensuring patient safety when dealing with them.  

Definition 

Migraines are recurrent, pulsating headaches often accompanied by other symptoms such as nausea, sensitivity to light, and sensitivity to sound. According to recent studies by (17), migraines are recognized as a complex neurological disorder involving abnormal brain activity and a cascade of events leading to pain and associated symptoms.  

The impact of migraines extends beyond physical pain, influencing various aspects of life, and recent literature by (14) highlights the profound effect on the quality of life, with disruptions in daily activities, work, and social interactions. For example, a professional experiencing frequent migraines might struggle to meet work deadlines and engage in social events. Recent advancements in diagnostic criteria by (15) emphasize the importance of a precise definition to ensure appropriate treatment strategies. Therefore, understanding the definition is crucial for accurate diagnosis and effective communication between healthcare providers and patients. 

Migraine Medications 

Understanding the various classes of migraine medications is like having a diverse toolkit to address the complexities of this neurological disorder. By exploring the different classes of medications, healthcare professionals can tailor their approach and make informed decisions based on individual patient profiles and specific migraine characteristics (20).  

It is crucial to recognize that migraine medications are not one-size-fits-all. Each patient is unique, and their response to medications may vary. Recent literature by (12) emphasizes the importance of an individualized approach when considering the best medication for each patient. Here’s a list of migraine medications in addition to important details to consider:  

Triptans  

Triptans are a class of medications specifically designed for the acute treatment of migraines. According to (39), they are not meant for preventive use but are highly effective in providing relief during an ongoing migraine attack. They work by narrowing blood vessels and inhibiting the release of certain chemicals in the brain associated with migraine symptoms (39). Let’s see more details below as described by (7), (39), (29). 

Drug Class 

Belonging to the serotonin (5-HT) receptor agonists class, Triptans modulate the effects of serotonin receptors in the brain. The various types of Triptans include Sumatriptan, Rizatriptan, Eletriptan, and others. Each Triptan has unique characteristics, such as the onset of action and duration, allowing healthcare professionals to tailor prescriptions based on individual patient needs. 

Benefits 

Triptans offer several benefits in the management of migraines. One of the primary advantages is their ability to provide rapid and effective relief from migraine symptoms, including headache pain, nausea, and sensitivity to light and sound. The prompt onset of action is particularly valuable for individuals aiming to resume their daily activities quickly. Triptans are available in various formulations, including oral tablets, nasal sprays, and injectables, allowing for flexibility in administration. 

Side Effects 

While generally well-tolerated, Triptans may cause side effects. Common side effects include mild sensations of warmth or tingling, dizziness, and tightness or pressure in the chest. It is crucial for healthcare professionals to consider the patient's medical history and potential contraindications, such as cardiovascular issues, before prescribing Triptans. In rare cases, more severe side effects like chest pain and changes in heart rate may occur, necessitating immediate medical attention. 

Clinical Effects 

The clinical effects of Triptans are profound, offering relief to individuals experiencing acute migraine attacks. The primary outcomes include: 

• Pain Relief: Triptans are highly effective in reducing the intensity of migraine-associated pain. By targeting the vascular and neuronal components of migraines, these drugs provide rapid relief, allowing patients to resume their normal activities. 
• Relief of Associated Symptoms: Beyond pain relief, Triptans address accompanying symptoms such as nausea, photophobia, and phonophobia. This comprehensive effect enhances the overall patient experience during a migraine episode. 
• Prevention of Migraine Progression: Triptans, when administered early in the migraine attack, can prevent the progression of the headache phase to more severe stages. This early intervention is crucial for optimizing outcomes and minimizing the impact of migraines on daily life. 
• Improvement in Functional Impairment: Migraines often result in functional impairment, limiting individuals' ability to perform daily tasks. Triptans restore functional capacity, allowing patients to regain control over their activities. 

Nonsteroidal Anti-Inflammatory Drugs (NSAIDSs)  

Nonsteroidal anti-inflammatory drugs, commonly known as NSAIDs, constitute a class of medications used in the treatment of migraines. According to (6), these drugs are characterized by their anti-inflammatory, analgesic, and antipyretic properties. NSAIDs are versatile, as they are not exclusively used for migraines but are also used for various other pain and inflammatory conditions (6). Let’s see more details below as described by (25), (40), (6) and (28). 

Drug Class 

NSAIDs encompass a broad class of medications, including well-known examples such as ibuprofen, naproxen, and aspirin. They function by inhibiting enzymes called cyclooxygenases (COX), thereby reducing the production of inflammatory prostaglandins. This mechanism provides relief from pain and mitigates inflammation associated with migraines. 

Benefits 

The primary benefit of NSAIDs in migraine management lies in their ability to alleviate pain and reduce inflammation. They are particularly effective for individuals experiencing mild to moderate migraines. NSAIDs offer a rapid onset of action, making them suitable for individuals seeking prompt relief. Additionally, these medications are available over-the-counter in many formulations, providing accessibility for patients. 

Side Effects 

While NSAIDs are generally well-tolerated, they may cause side effects, especially with prolonged or excessive use. Common side effects include gastrointestinal issues such as stomach upset or ulcers. Healthcare professionals need to consider a patient's medical history, including conditions like gastric ulcers, before prescribing NSAIDs. In rare cases, more severe side effects like cardiovascular events may occur, emphasizing the importance of cautious use. 

Clinical Effects 

The clinical effects of NSAIDs in migraine management encompass various aspects. Here’s a list of some of them. 

• Pain Relief: NSAIDs are effective in providing pain relief during acute migraine attacks. By reducing prostaglandin levels, they alleviate headache symptoms and contribute to the overall comfort of individuals experiencing migraines. 
• Inhibition of Inflammatory Responses: The anti-inflammatory properties of NSAIDs are particularly beneficial when migraines are associated with inflammatory processes. NSAIDs help mitigate inflammation, reducing the severity and duration of migraine attacks. 
• Improvement in Associated Symptoms: Beyond pain relief, NSAIDs address associated symptoms such as nausea and photophobia, enhancing the overall patient experience during a migraine episode. 
• Prevention of Migraine Progression: When administered early in the migraine attack, NSAIDs can prevent the progression of headaches to more severe stages. This early intervention is critical for optimizing outcomes and minimizing the impact of migraines on daily life. 

Calcitonin Gene-Related Peptide (CGRP) Inhibitors 

Calcitonin gene-related peptide (CGRP) inhibitors represent a modern class of medications revolutionizing the landscape of migraine management. According to (11), these drugs specifically target CGRP, a neuropeptide involved in dilating blood vessels and transmitting pain signals. By inhibiting CGRP, these inhibitors aim to modulate migraine pathways and reduce the frequency and severity of attacks (11). Let’s see more details below as described by (23) and (11). 

Drug Class 

CGRP inhibitors belong to a unique drug class designed explicitly for migraine prevention. Examples of CGRP inhibitors include Erenumab, Fremanezumab, and Galcanezumab. These medications are administered via subcutaneous injections, typically monthly or quarterly. The focus on preventive therapy distinguishes CGRP inhibitors from acute treatment options like Triptans. 

Benefits 

The primary benefit of CGRP inhibitors lies in their efficacy in preventing migraines. Clinical trials have demonstrated a significant reduction in the frequency of monthly migraine attacks among individuals using CGRP inhibitors. This preventive approach is especially valuable for those with frequent and debilitating migraines, offering a chance to enhance their quality of life. 

Moreover, CGRP inhibitors are well-tolerated with fewer side effects than other preventive medications. They provide a targeted and specific intervention, addressing the underlying mechanisms of migraines without causing widespread effects on other bodily functions. 

Side Effects 

While generally well-tolerated, CGRP inhibitors may have some side effects. Local injection site reactions, such as redness or swelling, are common but typically mild. It is crucial for healthcare professionals to monitor and address any adverse effects promptly. Additionally, ongoing research is essential to further understand the long-term safety profile of these medications. 

Clinical Effects 

The clinical effects of CGRP inhibitors are transformative in the realm of migraine management, offering a novel approach to prevention. Primary clinical effects include the following: 

• Reduction in Migraine Frequency: One of the hallmark effects of CGRP inhibitors is a significant reduction in the frequency of migraine attacks. By consistently blocking CGRP receptors, these medications disrupt the migraine cascade, leading to a sustained preventive effect. 
• Improvement in Migraine Severity: CGRP inhibitors not only reduce the frequency but also contribute to a decrease in the severity of migraine attacks. This comprehensive effect enhances the overall quality of life for individuals suffering from chronic migraines. 
• Enhanced Functional Capacity: Migraines often result in functional impairment, limiting individuals' ability to perform daily tasks. CGRP inhibitors restore functional capacity, allowing patients to regain control over their activities and participate more fully in their daily lives. 
• Well-Tolerated Profile: CGRP inhibitors are generally well-tolerated, with a favorable side effect profile. This characteristic enhances patient adherence to preventive treatment, a critical factor in long-term migraine management. 

Beta-Blockers 

Beta-blockers are a class of medications that have found a significant place in migraine management. Initially developed for cardiovascular conditions, beta-blockers have demonstrated efficacy in preventing migraines by reducing the frequency and severity of attacks (32). According to (32), these medications work by blocking the effects of adrenaline, leading to reduced heart rate and blood pressure. Let’s see more details below as described by (32) and (27). 

Drug Class 

Beta-blockers encompass various medications, with examples such as propranolol, metoprolol, and timolol commonly prescribed for migraine prevention. These drugs fall into the broader category of antihypertensive medications but are repurposed for their preventive benefits in migraine care. Unlike acute treatments, which provide relief during an ongoing attack, beta-blockers are taken regularly to reduce the overall occurrence of migraines. 

Benefits 

The primary benefit of beta-blockers in migraine management is their preventive action. Clinical studies have shown that beta-blockers can significantly reduce the frequency of migraines, making them particularly suitable for individuals with chronic or frequent attacks. This preventive approach aims to enhance the overall quality of life for those who experience migraines regularly. 

Beta-blockers are especially beneficial for individuals with comorbid conditions such as hypertension or heart disease. By addressing both cardiovascular concerns and migraines, these medications offer a comprehensive therapeutic approach. 

Side Effects 

While generally well-tolerated, beta-blockers may cause side effects that individuals need to be aware of. Common side effects include fatigue, dizziness, and changes in sleep patterns. Healthcare professionals need to monitor patients regularly and adjust the dosage or consider alternative medications if side effects become problematic. Beta-blockers are typically avoided in individuals with certain heart conditions, emphasizing the importance of an individualized approach. 

Clinical Effects 

The clinical effects of beta-blockers in migraine management encompass various dimensions. See some examples below: 

• Reduction in Migraine Frequency: Beta-blockers are known for their ability to reduce the frequency of migraine attacks significantly. This preventive effect is especially valuable for individuals experiencing chronic migraines, enhancing their overall quality of life. 
• Alleviation of Migraine Severity: Beyond frequency reduction, beta-blockers contribute to a decrease in the severity of migraine attacks. This comprehensive effect enhances the overall comfort of individuals during migraine episodes. 
• Improvement in Associated Symptoms: Beta-blockers have been shown to address associated symptoms such as nausea and sensitivity to light. By modulating the autonomic nervous system, these medications offer a holistic approach to migraine management. 
• Cardiovascular Benefits: Beta-blockers provide additional benefits for individuals with comorbidities due to their primary use in cardiovascular conditions. This dual action allows for comprehensive management of both migraine and cardiovascular health. 

Anticonvulsants 

Anticonvulsants, originally developed to control seizures in epilepsy, have emerged as a valuable class of medications in the preventive management of migraines (9). According to (9), these drugs, also known as antiepileptic drugs (AEDs), work by stabilizing electrical activity in the brain and reducing the frequency and severity of migraine attacks. Let’s see more details below as described by (32) and (9). 

Drug Class 

Anticonvulsants comprise a diverse class of medications, including Topiramate, Valproic acid, and Gabapentin. While their primary use may be in epilepsy, the preventive benefits of certain anticonvulsants extend to migraines. These medications are taken regularly to provide ongoing protection against migraines. 

Benefits 

The primary benefit of anticonvulsants in migraine management is their preventive action. Clinical trials have demonstrated the efficacy of certain anticonvulsants, such as topiramate, in significantly reducing the frequency of migraines. This preventative approach is particularly suitable for individuals with chronic or frequent attacks, aiming to improve overall quality of life. 

Anticonvulsants are especially valuable for individuals who may not find relief or experience intolerable side effects with other preventive medications. The versatility of this drug class allows healthcare professionals to tailor treatment plans based on individual patient characteristics and responses. 

Side Effects 

While generally well-tolerated, anticonvulsants may cause side effects that individuals need to be aware of. Common side effects include drowsiness, dizziness, and gastrointestinal disturbances. It is crucial for healthcare professionals to monitor patients regularly and adjust the dosage or consider alternative medications if side effects become problematic. Additionally, certain anticonvulsants may have specific considerations, such as the need to regularly monitor liver function in individuals taking Valproic acid. 

Clinical Effects 

The clinical effects of anticonvulsants in migraine management encompass the following dimensions: 

• Reduction in Migraine Frequency: Anticonvulsants are known for their ability to significantly reduce the frequency of migraine attacks. This preventive effect is particularly valuable for individuals experiencing chronic migraines, substantially improving their overall quality of life. 
• Alleviation of Migraine Severity: Beyond frequency reduction, anticonvulsants contribute to a decrease in the severity of migraine attacks. This comprehensive effect enhances the overall comfort of individuals during migraine episodes. 
• Improvement in Associated Symptoms: By modulating neurotransmission and neuronal excitability, Anticonvulsants address associated symptoms such as nausea and sensitivity to light. This holistic approach contributes to a more comprehensive management of migraines. 
• Beneficial in Comorbid Conditions: Anticonvulsants, due to their broader neurological effects, can be helpful for individuals with comorbid conditions such as epilepsy or mood disorders. This dual benefit allows for comprehensive management and improves overall well-being. 

Clinical Criteria for Prescribing 

In migraine management, prescribing medications involves a comprehensive understanding of clinical criteria to tailor interventions effectively. This section explores the clinical factors guiding the prescription of migraine medications and the decision-making process for healthcare providers. Here are some of the factors. 

Frequency and Severity of Migraine Attacks 

An essential consideration in prescribing migraine medications is the frequency and severity of migraine attacks experienced by the patient. For instance, a patient suffering from frequent and severe attacks may benefit from preventive medications to reduce the overall frequency and intensity of migraines (31).  

Individual Response to Pain and Associated Symptoms 

The subjective experience of pain and associated symptoms during migraines varies among individuals. A patient who experiences intense nausea and vomiting may require medications with rapid onset and alternative formulations, such as nasal sprays or injectables, to address these specific symptoms effectively (8).  

Impact on Daily Functioning and Quality of Life 

Prescribing migraine medications involves considering the impact of migraines on a patient's daily functioning and overall quality of life (24). For example, a working professional with migraines that significantly impede productivity may require acute medications with fast-acting formulations for quick relief during work hours.  

Comorbid Conditions and Patient Preferences 

Comorbid conditions and patient preferences are pivotal factors in prescribing migraine medications. A patient with comorbid cardiovascular issues may require careful consideration of medication options to mitigate potential risks (2).  

Pharmacokinetics 

Understanding the pharmacokinetics of migraine management medications enables healthcare professionals to tailor treatment plans based on individual patient characteristics, ensuring maximum therapeutic benefit. Let’s get into more details for each of the medications listed above: 

Triptans 

Absorption 

Triptans exhibit distinct pharmacokinetic properties that influence their efficacy and onset of action. Following oral administration, Triptans are absorbed through the gastrointestinal tract and the rate of absorption varies among different Triptans, contributing to differences in their clinical profiles. (39) 

Distribution 

Upon absorption, Triptans undergo distribution to reach target sites in the body, primarily the central nervous system. Their lipophilic nature allows them to penetrate the blood-brain barrier, enabling interaction with serotonin receptors implicated in migraine pathophysiology. The distribution of Triptans influences their ability to exert effects centrally and peripherally. (39) 

Metabolism 

Metabolism is a crucial aspect of triptan pharmacokinetics, occurring predominantly in the liver. The enzyme responsible for triptan metabolism is monoamine oxidase-A (MAO-A). (39) 

Excretion 

The final phase in the pharmacokinetic journey of Triptans is excretion, primarily through renal and biliary routes. Renal excretion eliminates the unchanged drug and its metabolites, while biliary excretion expels metabolites via the bile into the gastrointestinal tract. The interplay between metabolism and excretion contributes to the overall pharmacokinetic profile of Triptans. Variations in renal function may influence the elimination of the half-life of certain Triptans, impacting the duration of their therapeutic effect. (39) 

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 

Absorption 

Following oral administration, NSAIDs are absorbed in the gastrointestinal tract, with the rate and extent varying among different agents. For instance, ibuprofen exhibits rapid absorption, making it suitable for prompt relief during acute migraine attacks. On the other hand, naproxen has a longer duration of action due to slower absorption, making it well-suited for sustained pain relief. (28) 

Distribution 

Upon absorption, NSAIDs embark on a journey of distribution throughout the body. Their lipophilic nature allows for penetration into various tissues, including inflamed areas. The distribution influences the drug's ability to reach target sites, such as the central nervous system, where NSAIDs exert their analgesic and anti-inflammatory effects. This property is particularly relevant in the context of migraines, where the inflammatory component contributes to pain. (28) 

Metabolism 

Metabolism plays a role in shaping the pharmacokinetic profile of NSAIDs, occurring primarily in the liver. Enzymes such as cytochrome P450 contribute to the biotransformation of NSAIDs into metabolites. The metabolism of NSAIDs can vary among individuals, impacting factors such as drug efficacy and potential side effects. For example, the metabolism of certain NSAIDs, like diclofenac, can be influenced by genetic polymorphisms, contributing to interindividual variability in drug response. (21) 

Excretion 

The final phase of the NSAID journey involves excretion, predominantly through the kidneys. Unchanged NSAIDs and their metabolites are eliminated via urine. Considerations of renal function are crucial in the context of NSAID use, as impaired kidney function can lead to prolonged drug half-life and increased risk of adverse effects. Regular monitoring of renal function is essential, especially in individuals with conditions that may affect kidney health. (21) 

Calcitonin Gene-Related Peptide (CGRP) 

Absorption 

Administered via subcutaneous injections, CGRP inhibitors such as Erenumab and Fremanezumab enter the bloodstream directly, allowing for precise control over drug levels. This mode of administration ensures a reliable and consistent absorption rate, contributing to the predictability of therapeutic outcomes. (11) 

Distribution 

Following absorption, CGRP inhibitors are distributed throughout the body, focusing on target sites implicated in migraine pathophysiology, like the central nervous system. (11) 

Metabolism 

Unlike many traditional medications, CGRP inhibitors follow a different path in terms of metabolism. Due to their biotechnological origin as monoclonal antibodies, these drugs do not undergo significant hepatic metabolism. Instead, proteolytic enzymes break them down into smaller peptides and amino acids, which occur systemically. This unique metabolic pathway aligns with the specificity of CGRP inhibitors, minimizing interactions with hepatic enzymes and potential drug-drug interactions. (37) 

Excretion 

The final phase of the CGRP inhibitor journey involves excretion, primarily through the kidneys via renal clearance. This aspect is particularly relevant when considering individual patient factors such as renal function, as impaired kidney function can affect the clearance of CGRP inhibitors and influence their duration of action. (37) 

Beta-Blockers 

Absorption 

Administered orally, beta-blockers like propranolol and metoprolol are absorbed through the gastrointestinal tract. Depending on the condition of the gastrointestinal tract, the rate and extent of absorption can vary, impacting the time it takes for these medications to reach therapeutic levels in the bloodstream. (27) 

Distribution 

Once absorbed, beta-blockers embark on distribution throughout the body. Their lipophilic nature enables penetration through cell membranes, allowing them to reach target tissues, including the heart and blood vessels. In the context of migraine management, the distribution properties of beta-blockers are crucial for their ability to modulate the autonomic nervous system centrally and peripherally, leading to the desired preventive effects against migraines. (27) 

Metabolism 

The metabolism of beta-blockers occurs primarily in the liver, where enzymes play a role in their biotransformation. Genetic polymorphisms in these enzymes can contribute to interindividual variability in drug metabolism. (27) 

Excretion 

The final phase of the beta-blocker journey involves excretion, predominantly through the kidneys, where unchanged beta-blockers and their metabolites are eliminated via urine. The renal excretion of these drugs is relevant when considering individual patient factors, such as renal function, as impaired kidney function can affect the clearance of beta-blockers and influence their duration of action. (27) 

Anticonvulsants 

Absorption  

Typically administered orally, anticonvulsants like topiramate and valproic acid are absorbed through the gastrointestinal tract. The rate and extent of absorption play a crucial role in determining the onset of action and overall effectiveness. (9) 

Distribution  

Following absorption, anticonvulsants undergo distribution throughout the body. Their lipophilic nature allows them to penetrate the blood-brain barrier, reaching target sites in the central nervous system relevant to migraine pathophysiology. The distribution properties of anticonvulsants contribute to their ability to modulate neuronal excitability centrally and exert preventive effects against migraines. (9) 

Metabolism 

Metabolism is a crucial aspect of anticonvulsant pharmacokinetics. This occurs predominantly in the liver and enzymes play an important role in the biotransformation of anticonvulsants into metabolites. The metabolism of anticonvulsants can vary among individuals, impacting factors such as drug efficacy and potential side effects. For example, valproic acid undergoes extensive hepatic metabolism, and variations in enzyme activity can lead to interindividual variability in drug response. (30) 

Excretion  

The final phase in the anticonvulsant journey involves excretion, primarily through the kidneys. Unchanged anticonvulsants and their metabolites are eliminated via urine. This renal excretion is relevant when considering individual patient factors such as renal function, as impaired kidney function can affect the clearance of anticonvulsants and influence their duration of action. (30) 

Warnings Related to Migraine Medications 

Understanding potential warnings related to migraine medications is essential for healthcare professionals to ensure safe and effective treatment. Here are some factors to consider.  

Medication Safety 

Migraine medications, whether preventive or acute, come with specific warnings that need careful attention. For instance, some medications may have contraindications for individuals with certain medical conditions or those taking specific medications concurrently. According to (34), healthcare providers must be vigilant in assessing patient medical histories to identify potential contraindications. 

Addressing Cardiovascular Risks 

Certain migraine medications, such as Triptans, may pose cardiovascular risks, especially in individuals with pre-existing cardiovascular conditions (35). Therefore, it is crucial for healthcare providers to assess patients' cardiovascular health and consider alternative medications or dose adjustments for those at higher risk. For example, a patient with a history of myocardial infarction may be advised to avoid Triptans, and a different class of medication, like NSAIDs, may be recommended. 

Pregnancy and Lactation Considerations 

Warnings related to pregnancy and lactation are paramount. Some migraine medications may have potential risks during pregnancy, and healthcare providers must carefully weigh the benefits and risks when prescribing for pregnant or lactating individuals. For instance, valproic acid is associated with an increased risk of congenital disabilities, and alternative medications with a safer profile may be preferred for pregnant individuals seeking migraine relief (1). 

Managing Medication Overuse Headaches (MOH) 

A significant warning associated with migraine medications is the risk of medication overuse headaches (34). To prevent this problem, healthcare providers need to educate patients about the importance of adhering to prescribed dosages and avoiding excessive use of acute medications. Offering alternative strategies, such as lifestyle modifications and preventive medications, can be crucial in managing and preventing MOH. 

Alternatives to Migraine Medications 

According to (5), integrating alternative methods provides additional tools for healthcare professionals and empowers individuals seeking a more comprehensive and personalized approach to migraine care. Here are some alternative approaches: 

Holistic Lifestyle Modifications 

Holistic management of migraines involves lifestyle modifications that can significantly impact the frequency and severity of attacks. For instance, incorporating regular physical activity, maintaining a consistent sleep schedule, and managing stress through practices like mindfulness and yoga have shown promise in reducing migraine occurrence (5). Educating patients about these lifestyle changes empowers them to actively participate in their migraine management. 

Biofeedback and Relaxation Techniques 

Biofeedback and relaxation techniques offer non-pharmacological interventions that enhance self-awareness and control over physiological responses (22). These approaches teach individuals to recognize and manage stress triggers, ultimately reducing the frequency of migraines. For example, biofeedback training that monitors muscle tension and provides real-time feedback can effectively prevent migraines (22). 

Acupuncture and Acupressure 

According to (22), traditional Chinese medicine practices like acupuncture and acupressure have gained recognition for their potential in migraine management. Acupuncture involves the insertion of thin needles into specific points on the body, while acupressure applies pressure to these points. Research suggests that these methods reduce the frequency and intensity of migraines, providing an alternative avenue for individuals seeking non-pharmacological options (22). 

Nutritional Approaches 

Dietary modifications and nutritional approaches also play a role in holistic migraine management. For example, identifying and avoiding potential trigger foods, such as those containing tyramine or artificial additives, can be beneficial (10). Additionally, ensuring adequate hydration and incorporating anti-inflammatory foods into the diet may contribute to overall well-being and migraine prevention (10).  

Nursing Considerations 

Nurses play a pivotal role in the holistic care of individuals with migraines, contributing to both the preventive and acute aspects of management through various considerations. Here are some important considerations. 

Assessment and Patient Education 

A thorough assessment includes evaluating the frequency, duration, and severity of migraines and identifying triggers and associated symptoms (3). Additionally, nurses play a key role in patient education, ensuring individuals clearly understand their migraine condition, the prescribed medications, and potential side effects. For instance, educating a patient about the importance of early intervention with acute medications during a migraine attack empowers them to take timely action. 

Monitoring and Adverse Event Management 

Nurses actively monitor individuals undergoing migraine treatment, monitoring the response to medications and any potential adverse events. Regular monitoring includes assessing the effectiveness of preventive measures, tracking the frequency of migraine attacks, and identifying patterns that may require adjustments in the treatment plan (34). If adverse events or side effects occur, nurses are instrumental in managing them promptly, collaborating with healthcare providers to ensure the safety and well-being of individuals. 

Supportive Care and Holistic Approach 

Nursing considerations extend beyond medication management to supportive care and a holistic approach. Nurses provide emotional support, helping individuals cope with the impact of migraines on their daily lives. Moreover, they collaborate with other healthcare professionals to integrate holistic approaches such as lifestyle modifications, stress management, and alternative therapies into the overall care plan. According to (34), this collaborative and patient-centered approach enhances the effectiveness of migraine management. 

Documentation and Communication 

Accurate and thorough documentation of relevant patient information, medication administration details, and responses to treatment is a fundamental nursing responsibility in migraine management (34). In addition to that, clear and concise communication between nursing staff, healthcare providers, and other healthcare team members ensures continuity of care (34).  

Upcoming Research 

Staying ahead of the curve is essential for healthcare professionals to provide cutting-edge care and optimize outcomes for individuals with migraines. Upcoming research include the following: 

Advancements in Targeted Therapies 

Recent research has unveiled promising advancements in targeted therapies for migraine management. For example, research about monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway is proving to be effective in preventing migraines (12).  

Digital Health and Telemedicine in Migraine Care 

Integrating digital health technologies and telemedicine is a burgeoning trend in migraine management research. Smartphone applications for tracking migraine patterns, wearable devices for monitoring physiological parameters, and virtual consultations enable a more comprehensive and patient-centric approach (12). This shift toward digital solutions enhances data collection and facilitates remote monitoring and timely interventions, particularly in scenarios where in-person visits may be challenging (12). 

Genetic and Personalized Medicine Approaches 

Advancements in genetic research are paving the way for personalized medicine in migraine care. Understanding the genetic underpinnings of migraines can guide the development of targeted interventions tailored to an individual's unique genetic profile. This personalized approach could revolutionize treatment strategies, allowing for more precise and effective interventions based on the genetic factors contributing to a person's migraines (13). 

Exploration of Lifestyle and Environmental Influences 

Upcoming research increasingly focuses on the intricate interplay between lifestyle, environmental factors, and migraines; and studies examining the impact of factors such as diet, sleep patterns, and environmental triggers contribute valuable insights (13). For instance, research may reveal specific dietary components that act as triggers or protective factors for migraines, allowing healthcare professionals to offer targeted lifestyle recommendations. 

Conclusion

In conclusion, this course focused on empowering learners not only with knowledge about migraine management, but with the practical insights and skills crucial for excellence in migraine care. The journey doesn’t end here; it extends into the realm of compassionate practice, where the combination of scientific understanding and safety measures transforms care providers into formidable advocates for those navigating the complexities of migraines. 

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