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Pennsylvania Child Abuse Recognition and Reporting

Introduction   

For healthcare professionals who work with children in any capacity, there almost always comes a time when the very troubling issue of child abuse is encountered. Though disturbing, abusive situations for children are the reality for nearly 380,494 children nationally each year (7). Child abuse may encompass physical or sexual abuse, neglect, exposure to violence or drug use, or any other physically or psychologically harmful situation. The effects of child abuse can last long into adulthood, and children who are abused grow up to have higher rates of depression, anxiety, addiction, eating disorders, post-traumatic stress disorder (PTSD), and many other psychological and medical problems (10). 

Child Welfare in the State of Pennsylvania 

The Pennsylvania Child Protective Services Law (CSPL) (23 Pa.C.S. Chapter 63, Child Protective Services) (Pennsylvania General Assembly, 2021) was enacted in 1975 to protect children and provide a framework for law enforcement and persons identified as mandated reporters to take the appropriate action to ensure the safety and stability of the family. 

In order for abusive situations to be reported accurately and handled most effectively, it is first important to understand how the Child Welfare System works, specifically for this course, in the state of Pennsylvania. The state supervises and provides funding for each of the 67 counties which administer child welfare services. One of the roles of each county is to handle reports from both Child Protective Services (CPS) and General Protective Services (GPS). 

In the Commonwealth of Pennsylvania, child welfare is state-supervised and county-administered. When a case is reported, trained professionals categorize the report either as a CPS case, GPS case, or not needing further processing. Cases identified as CPS require abuse investigations because the alleged act or failure to act has been identified as one of the ten categories of abuse in the CPSL. 

Child Protective Services Cases 

Child Protective Services (CPS): The services and activities provided by the department and each county agency for child abuse cases.  

CPS handles reports that there is a reasonable suspicion a child is the victim of non-accidental physical injury, sexual abuse or exploitation, or injury resulting from neglect or omission of care by a parent or caregiver. These reports require an investigation (6).  

Examples of CPS cases:   

• Causing bodily injury to a child through any recent act or failure to act. 
• Fabricating, feigning, or intentionally exaggerating or inducing medical symptoms or disease results in potentially harmful medical evaluation or treatment to the child through any recent act. 
• Causing or substantially contributing to serious mental injury to a child through any act or failure to act or a serious of such acts or failures to act. 
• Causing sexual abuse or exploitation of a child through any act or failure to act. 
• Creating a reasonable likelihood of bodily injury to a child through a recent act or failure to act. 
• Creating a likelihood of sexual abuse or exploitation of a child through any recent act or failure to act. 
• Causing serious neglect of a child. 
• Engaging in the following recent per se acts. 
• Causing the death of the child through any act or failure to act. 
• Engaging a child in a severe form of trafficking in persons or sex trafficking, as those term are defined under section 103 of the Trafficking Victims Protection Act of 2000. 

General Protective Services Cases 

General Protective Services (GPS): Those services and activities provided by each county agency for cases requiring protective services. As defined by the department in regulations.  

GPS responds to reports that do not quite reach the level of abuse or neglect but require intervention to prevent serious harm from occurring. These incidents include issues like improper shelter or hygiene, school truancy, inappropriate discipline, and being left without a parent or guardian for longer than is age-appropriate or abandoned altogether. These allegations are less severe and do not require a full investigation, mostly offering an opportunity for parents or caregivers to receive education on how to improve conditions to best support a child’s health and development (3). In these cases, the act or failure to act is detrimental to a child but does not fall under the 10 categories of child abuse as per the CPSL. These services can assist parents in being able to recognize and correct the conditions that are harmful to their children.   

Cases identified as GPS require an assessment for services and support. In these cases, the act or failure to act is detrimental to a child but does not fall under the ten categories of child abuse as per the CPSL. These services can assist parents in being able to recognize and correct conditions that are harmful to their children.  

Examples of GPS (Services to prevent the potential for harm to a child who meets one of the following conditions):  

• Is without proper parental care or control, subsistence, education as required by law, or other care or control necessary for his physical, mental, or emotional health or morals.  
• Has been placed for care or adoption in violation of the law.  
• Has been abandoned by his parents, guardian, or other custodian.  
• Is without a parent, guardian, or legal custodian.  
• Is habitually and without justification truant from school while subject to compulsory school attendance.  
• Has committed a specific act of habitual disobedience of the reasonable and lawful commands of his parent, guardian, or other custodian and who is ungovernable and found to be in need of care, treatment, or supervision.  
• Is under ten years of age and has committed a delinquent act.  
• Has been formally adjudicated dependent under section 6341 of the Juvenile Act (relating to adjudication), and is under the jurisdiction of the court, subject to its conditions or placements and who commits an act which is defined as ungovernable in subparagraph (VI).  
• Has been referred to under section 6323 of the Juvenile Act (relating to informal adjustment), and who commits an act which is defined as ungovernable in subparagraph (VI). 

It should be noted that the person filing the report may list their claim as suspected child abuse, but it is ultimately up to the person conducting the investigation to determine if abuse or maltreatment has occurred and if the suspicion qualifies for filing through CPS or GPS. The child abuse investigator for the county is responsible for conducting the investigation and officially classifying the reports; mandated reporters should not attempt to investigate the situation or gather further information than what first prompted their report (6).  Discuss in framework of duties of the mandated reporter and reasonable suspicion of abuse. 

Case Study  

Case Study No. 1- please read the scenario and reflect on the type of abuse that is occurring. 

A mother of two small children aged six and nine is planning to go on a three-day weekend trip with her new boyfriend. She is unable to find adequate childcare for the children and does not want to take them along on the trip, so she decides she will leave her children alone for three days. She figures there is enough food and water to keep them satisfied for three days. She gives them strict instructions not to answer the door or the phone to anyone and to not make loud noises. The neighbors notice some strange noises coming from the house and go by to check in. They discover the children are alone at home. They tell the neighbors they are hungry and fear being in the house by themselves, when asked where their mother is, the children say she went on a trip the day before. The neighbors take the children to their home and call law enforcement. 

Are children aged six and nine competent enough to care for themselves for an extended period without adult supervision? 

Current Patterns of Abuse 

Though anyone under the age of 18 can be a victim of child abuse, not all children are at equal risk of maltreatment. Pennsylvania statutes §6303 defines a child is an individual under 18 years of age. Young children are at the greatest risk, largely because they have limited verbal abilities to ask for help or tell someone what is going on. Children under 12 months of age are at the highest risk, with 45.6% being the victim of some form of abuse or neglect.  

Abuse can take many forms as well, with neglect being the most common form of child abuse nationally at 76% of affected children. Physical abuse accounts of 16% of cases, sexual abuse is 10.1%, and psychological/emotional is 6.4% (1). Many children also experience more than one type of abuse.  

Tragically, abuse and neglect are sometimes lethal, with nearly 1,820 children dying from maltreatment in 2021. A staggering 66.2% of those children were under the age of 3 (1).  

Child abuse occurs in homes of all races, socioeconomic statuses, educational levels, and religions. Being a victim of abuse has the potential for lifelong consequences for children, increasing their risk of teen pregnancy, drug and alcohol abuse, criminal activity, and even incarceration as an adult. About 30% of the time, abused children enter a cycle of abuse and grow up to abuse their own children as well (1).  

Understanding who is most at risk can help healthcare professionals identify potential victims of abuse within the populations they serve. Early and accurate detection of maltreatment can not only remove a child from a dangerous situation, but it can also set them on a better trajectory for their future and even quite literally save their life.  

Child Welfare in the State of Pennsylvania 

In addition to understanding when and how to report abuse, healthcare professionals must be able to recognize when abuse might be occurring. The common signs vary by type of abuse and no two situations are likely to be the same, but there are common indicators that should be used to alert healthcare providers to potentially ominous situations.  

Definition of Child Abuse 

Definition of Child Abuse according to the Pennsylvania Child Abuse Services Law    

Pennsylvania Child Protective Services Law (CPSL) (23 Pa.C.S. Chapter 63, Child Protective Services) states the term “child abuse” shall mean intentionally, knowingly, or recklessly doing any of the following:  

• Child:  An individual under 18 years of age 
• Act or failure to act; Recent act; Recent act or failure to act; or a series of acts or failures to act 
  • Act:  Something that is done to harm or cause potential harm to a child 
  • Failure to act:  Something that is NOT done to prevent harm or potential harm to a child 
  • Recent act:  Any act committed within two (2) years of the date of the report to DHS or county agency 
  • Recent act or failure to act:  Any act or failure to act committed within two (2) years of the date of the report to DHS or county agency 

• Intentionally, knowingly, or recklessly 
  • Intentionally:  Done with the direct purpose of causing the type of harm that resulted 
  • Knowingly:  Awareness that harm is practically certain to result 
  • Recklessly:  Conscious disregard of substantial and unjustifiable risk 

• Doing any of the following: 
  • Causing bodily injury to a child through any recent act or failure to act. 
  • Fabricating, feigning, or intentionally exaggerating or inducing a medical symptom or disease which results in a potentially harmful medical evaluation or treatment to the child through any recent act.  
  • Causing or substantially contributing to serious mental injury to a child through any act or failure to act or a series of such acts or failures to act.  
  • Causing sexual abuse or exploitation of a child through any act or failure to act. 
  • Creating a reasonable likelihood of bodily injury to a child through any recent act or failure to act.  
  • Creating a likelihood of sexual abuse or exploitation of a child through any recent act or failure to act.  
  • Causing serious physical neglect of a child. 
  • Engaging in any of the following recent acts: 
    • Kicking, biting, throwing, burning, stabbing or cutting a child in a manner that endangers the child.  
    • Unreasonably restraining or confining a child, based on consideration of the method, location or the duration of the restraint or confinement.  
    • Forcefully shaking a child under one year of age. 
    • Forcefully slapping or otherwise striking a child under one year of age. 
    • Interfering with the breathing of a child. 
    • Causing a child to be present at a location while a violation of 18 Pa.C.S. § 7508.2 (relating to operation of methamphetamine laboratory) is occurring, provided that the violation is being investigated by law enforcement.  

• Leaving a child unsupervised with an individual, other than the child’s parent, who the actor knows or reasonably should have known:  
  • Is required to register as a Tier II or Tier III sexual offender under 42 Pa.C.S. Ch. 97 Subch. H (relating to registration of sexual offenders), where the victim of the sexual offense was under 18 years of age when the crime was committed.  
  • Has been determined to be a sexually violent predator under 42 Pa.C.S. § 9799.24 (relating to assessments) or any of its predecessors.  
  • Has been determined to be a sexually violent delinquent child as defined in 42 Pa.C.S. § 9799.12 (relating to definitions).  

• Causing the death of the child through any act or failure to act. 
• Engaging a child in a severe form of trafficking in persons or sex trafficking, as those terms are defined under section 103 of the Trafficking Victims Protection Act of 2000 (114 Stat. 1466, 22 U.S.C §7102). 

Definitions of Types of Child Abuse 

Sexual Abuse or Exploitation 

“Sexual abuse or exploitation” is considered any of the following:  

The employment, use, persuasion, inducement, enticement, or coercion of a child to engage in or assist another individual to engage in sexually explicit conduct, which includes, but is not limited to, the following:  

• Looking at the sexual or other intimate parts of a child or another individual for the purpose of arousing or gratifying sexual desire in any individual.  
• Participating in sexually explicit conversation either in person, by telephone, by computer or by a computer-aided device for the purpose of sexual stimulation or gratification of any individual.  
• Actual or simulated sexual activity or nudity for the purpose of sexual stimulation or gratification of any individual.  
• Actual or simulated sexual activity for the purpose of producing visual depiction, including photographing, videotaping, computer depicting or filming.  

This paragraph does not include consensual activities between a child who is 14 years of age or older and another person who is 14 years of age or older and whose age is within four years of the child’s age.  

Any of the following offenses committed against a child: 

• Rape as defined in 18 Pa.C.S. § 3121 (relating to rape). 
• Statutory sexual assault as defined in 18 Pa.C.S. § 3122.1 (relating to statutory sexual assault).  
• Involuntary deviate sexual intercourse as defined in 18 Pa.C.S. § 3123 (relating to involuntary deviate sexual intercourse).  
• Sexual assault as defined in 18 Pa.C.S. § 3124.1 (relating to sexual assault). 
• Institutional sexual assault as defined in 18 Pa.C.S. § 3124.2 (relating to institutional sexual assault).  
• Aggravated indecent assault as defined in 18 Pa.C.S. § 3125 (relating to aggravated indecent assault).  
• Indecent assault as defined in 18 Pa.C.S. § 3126 (relating to indecent assault). 
• Indecent exposure as defined in 18 Pa.C.S. § 3127 (relating to indecent exposure). 
• Incest as defined in 18 Pa.C.S. § 4302 (relating to incest). 
• Prostitution as defined in 18 Pa.C.S. § 5902 (relating to prostitution and related offenses).  
• Sexual abuse as defined in 18 Pa.C.S. § 6312 (relating to sexual abuse of children). 
• Unlawful contact with a minor as defined in 18 Pa.C.S. § 6318 (relating to unlawful contact with minor).  
• Sexual exploitation as defined in 18 Pa.C.S. § 6320 (relating to sexual exploitation of children).  

Bodily Injury 

“Bodily injury” is defined as impairment of physical condition or substantial pain.  

• Impairment: If, due to the injury, the child’s ability to function is reduced temporarily or permanently in any way 
• Substantial pain:  If the child experiences what a reasonable person believes to be substantial pain 

Serious Mental Injury 

“Serious mental injury” A psychological condition, as diagnosed by a physician or licensed psychologist, including the refusal of appropriate treatment, that:  

• Renders a child chronically and severely anxious, agitated, depressed, socially withdrawn, psychotic or in reasonable fear that the child’s life or safety is threatened; or  
• Seriously interferes with a child’s ability to accomplish age-appropriate developmental and social tasks.  

Serious Physical Neglect 

“Serious physical neglect” Any of the following when committed by a perpetrator that endangers a child’s life or health, threatens a child’s well-being, causes bodily injury or impairs a child’s health, development or functioning:  

• A repeated, prolonged or egregious failure to supervise a child in a manner that is appropriate considering the child’s developmental age and abilities.  
• The failure to provide a child with adequate essentials of life, including food, shelter or medical care. 

Recognizing Indicators for Child Abuse 

Categories and Indicators of Child Abuse per the PA Department of Human Services (2023) 

Bodily Injury 

• Unexplained bruises or injuries 
• Inconsistency when explaining how an injury occurs or providing extraordinary/unbelievable descriptions. 
• Bruises that you would not typically see in their age group. 
• Multiple bruises that all appear to be in different stages of healing. 
• Bruises that resemble the shape of an object (eg. a hand mark from a slap). 

Serious Mental Injury 

• Fearful 
• Shy/difficulty maintaining relationships with other peers 
• Dependence on adults 
• Eating and/or Speech disorders 
• Bed-wetting 
• Self-harm 
• Low self-esteem and feelings of inadequacy 

Sexual Abuse  

Indicators: 

• Sexually promiscuous 
• Developmental age-inappropriate sexual play and/or drawings 
• Cruelty to others 
• Cruelty to animals  
• Fire setting 
• Anxious 
• Withdrawn 
• Sleep disturbances 
• Bedwetting 
• Pain or irritation in genital/anal area 
• Difficulty walking or sitting. 
• Difficulty urinating 
• Pregnancy 
• Positive testing for sexually transmitted disease(s) (e.g., HIV) 
• Excessive or injurious masturbation 

Serious Physical Neglect  

Indicators: 

• Not registered in school 
• Inadequate or inappropriate supervision 
• Poor impulse control 
• Frequently fatigued  
• Parentified behaviors 
• Lack of adequate medical and dental care 
• Often hungry 
• Lack of shelter  
• Weight is significantly lower than normal for their age and gender 
• Developmental delays 
• Persistent (untreated) conditions (e.g., head lice, diaper rash) 
• Exposure to hazards (e.g., illegal drugs, rodent/insect infestation, mold) 
• Clothing that is dirty, inappropriate for the weather, too small, or too large 

Components, Categories, and Exclusionary Criteria of Child Abuse 

A clear understanding of who is involved in an abuse or neglect situation and what actions (or inactions) specifically qualify as abuse is necessary for mandated reporters like healthcare professionals.  

When considering a child abuse scenario, a child is anyone under the age of 18.  

A perpetrator is someone “who has committed child abuse as defined in this section.” 

The term includes only the following: 

• A parent of the child. 
• A spouse or former spouse of the child’s parent. 
• A paramour or former paramour of the child’s parent. 
• A person 14 years of age or older and responsible for the child’s welfare or having direct contact with children as an employee of a childcare services, a school, or through a program, activity, or service. 
• An individual 14 years of age or older who resides in the same home as the child. 
• An individual 18 years of age or older who do not reside in the same home as the child but is related within the third degree of consanguinity or affinity by birth or adoption to the child.  
• An individual 18 years of age or older who engages a child in severe forms of trafficking in persons or sex trafficking, as those terms are defined under section 103 of the Trafficking Victims Protection Act of 2000. 

Only the following may be considered a perpetrator for failing to act, as provided in this section:  

• A parent of the child. 
• A spouse or former spouse of the child’s parent. 
• A paramour or former paramour of the child’s parent. 
• A person 18 years of age or older and responsible for the child’s welfare. 
• A person 18 years of age or older who resides in the same home as the child. 

Please Note: 

• Nothing under the PA CPSL requires a person who has reasonable cause to suspect a child is a victim of child abuse to identify the person responsible for the child abuse in order to make a report of suspected child abuse. 

The CPSL allows for school employees to be considered perpetrators under the definition provided for “person responsible for the child’s welfare” or person “having direct contact with children.”       

School employee: An individual who is employed by a school or who provides a program, activity, or service sponsored by a school. The term does not apply to administrative or other support personnel unless the administrative or other support personnel have direct contact with the children.  

Person responsible for the child’s welfare: A person who provides permanent or temporary care, supervision, mental health diagnosis or treatment, training or control of a child in lieu of parental care, supervision, and control. 

Direct contact: The care, supervision, guidance or control of children OR routine interaction with children.  

As mentioned previously, child abuse falls into four main categories: neglect, physical abuse, sexual abuse, and serious mental injury. Many different acts fall into each category, but in general, intentionally causing harm to a child in any of these ways or failing to care for a child in a way that prevents harm from occurring is considered abuse (2).  

Case Study 

Case study No. 2 – Please read the scenario below and take a moment to reflect and examine how this untimely tragedy could have been prevented. 

One of the most extreme cases of child abuse occurred in Indiana in 1965 to a child named Sylvia Likens. The child was 16 years old when she was placed in the care of a neighborhood woman named Gertrude due to her family experiencing financial instability at the time. During her time at Gertrude’s house, Sylvia suffered all sorts of abuse daily at her hand. She was beaten, humiliated, deprived of basic life necessities and even forced to undress in front of a group of neighborhood boys on one occasion. Gertrude eventually had Sylvia stop going to school. Throughout her experience, neighborhood children and some adults witnessed her abuse and never reported it to the authorities. School officials at the time failed to recognize the common indicators of abuse and sadly Sylvia eventually died, succumbing to injuries and serious physical neglect. Although extremely tragic, her case led to Indiana’s Mandated Reporter Law, with the aim of preventing such atrocities as what Sylvia had to experience from ever happening again. 

Were there opportunities for someone to report this abuse to the authorities? What types of abuse did Sylvia endure? 

Exclusions of Child Abuse  

An exclusion is determined when substantiating a report, not when making a report.  

Pennsylvania Child Protective Services Law states:  

Definitions (23 Pa.C.S. § 6303): 

• Restatement of culpability – Conduct that causes injury or harm to a child or creates a risk of injury or harm to a child shall not be considered child abuse if there is no evidence that the person acted intentionally, knowingly or recklessly when causing the injury or harm to the child or creating a risk of injury or harm to the child. 
• Child abuse exclusions — The term “child abuse” does not include any conduct for which an exclusion is provided in section 6304 of the PA CPSL (relating to exclusions from child abuse). 

Please Note: 

• Nothing in the PA CPSL requires a person who has reasonable cause to suspect a child is a victim of child abuse to consider the exclusions from child abuse before making a report of suspected child abuse. 
• Exclusions from child abuse are considered/determined by DHS or the investigating agency after receipt of a referral/report. 

Such exclusions under Pennsylvania Child Protective Services Law include:    

Environment Factors 

Environmental factors that may cause harm but are out of a caretaker’s control, like inadequate shelter, clothing, medical care, or financial instability that are beyond the control of the parent or person responsible for the child’s welfare with whom the child resides. This shall not apply to any childcare services as defined in this chapter, excluding an adoptive parent. 

Practice of Religious Beliefs (23 Pa.C.S. § 6304) 

“If, upon investigation, the county agency determines that a child has not been provided needed medical or surgical care because of sincerely held religious beliefs of the child’s parents or relative within the third degree of consanguinity and with whom the child resides – which beliefs are consistent with those of a bona fide religion” –  

• The county agency shall closely monitor the child and the child’s family and shall seek court-ordered medical intervention when the lack of medical or surgical care threatens the child’s life or long-term health.  
• All correspondence with the subject of the report and the records of the Department and the county agency shall not reference child abuse and shall acknowledge the religious basis for the child’s condition.  
• The family shall be referred for GPS, if appropriate. 
• This subsection shall not apply if the failure to provide needed medical or surgical care causes the death of the child.  
• This subsection shall not apply to any childcare service as defined in this chapter, excluding an adoptive parent.  

Use of force for supervision, control, and safety purposes 

Subject to rights of parents. 

The use of reasonable force on or against a child by the child’s own parent or person responsible for the child’s welfare shall not be considered child abuse if any of the following conditions apply:  

• The use of reasonable force constitutes incidental, minor, or reasonable physical contact with the child or other actions that are designed to maintain order and control.  
• The use of reasonable force is necessary: 
• to quell a disturbance or remove the child from the scene of a disturbance that threatens physical injury to persons or damage to property;  
• to prevent the child from self-inflicted physical harm; 
• for self-defense or the defense of another individual; or 
• to obtain possession of weapons or other dangerous objects or controlled substances or paraphernalia that are on the child or within the control of the child. 

Rights of Parents 

Rights of parents – Nothing in the PA CPSL shall be construed to restrict the generally recognized existing rights of parents to use reasonable force on or against their children for the purposes of supervision, control, and discipline of their children. Such reasonable force shall not constitute child abuse. 

Participation in events that involve physical contact with child –  (23 Pa.C.S. § 6304) 

“An individual participating in a practice or competition in an interscholastic sport, physical education, a recreational activity, or an extracurricular activity that involves physical contact with a child does not, in itself, constitute contact that is subject to the reporting requirements of the PA CPSL.” 

Child-on-child contact –(23 Pa.C.S. § 6304) 

“Harm or injury to a child that results from the act of another child shall not constitute child abuse unless the child who caused the harm or injury is a perpetrator as defined by the CPSL.” 

Notwithstanding the above, the following shall apply: 

• Acts constituting any of the following crimes against a child shall be subject to the reporting requirements of the PA CPSL:  
• Rape as defined in 18 Pa.C.S.§3121B.Involuntary deviate sexual intercourse as defined   in 18 Pa.C.S. §3123C. 
• Sexual assault as defined in 18 Pa.C.S.§3124.1D. 
• Aggravated indecent assault as defined in 18 Pa.C.S.§3125E. 
• Indecent assault as defined in 18 Pa.C.S.§3126F. 
• Indecent exposure as defined in 18 Pa.C.S.§3127. 
• No child shall be deemed to be a perpetrator of child abuse based solely on physical or mental injuries caused to another child in the course of a dispute, fight, or scuffle entered into by mutual consent. 
• A law enforcement official who receives a report of suspected child abuse is not required to make a report to DHS if the person allegedly responsible for the child abuse is a non-perpetrator child. 

Defensive Force 

Defensive force: Reasonable force for self-defense or the defense of another individual (relating to the use of force in self-protection) and (relating to the use of force for the protection of other persons), shall not be considered child abuse. 

Case Study 

Case Study No. 3 – please read the following scenario and answer the questions below: 

A three-year-old child is brought to the emergency department (ED) with fever, rash, sore throat, and worsening lethargy for six days. Upon arrival to the ED, she is limp and unresponsive, and the mother reports it has been nearly 24 hours since she was last awake. The family decided to take her to the hospital when she had a seizure at home an hour before. A history reveals that the family are Christian Scientists, and the child is unvaccinated and does not receive regular medical care as the family does not believe modern medicine is necessary or beneficial. The child is diagnosed with measles encephalitis and transferred to the pediatric intensive care unit (PICU), where she later dies. The PICU physician files a report with CPS.  

• Do the religious beliefs of the parents exclude them from potential child abuse allegations? Yes/No 

Correct Answer  

No – in this case there has been serious physical neglect caused by the delay from seeking medical attention which has caused the death of the child. 

• Is it the mandated reporter’s responsibility to determine if child abuse has occurred? Yes/No 

Correct Answer  

No – the mandated reporter only has a duty to report when they have reasonable belief that abuse may have occurred. The determination of whether child abuse has occurred will be made by CPS. 

Provision and Responsibilities for Reporting Suspected Child Abuse 

Persons Encouraged to Report 

Persons encouraged to report (23 Pa.C.S.§6312) 

While reporting suspected or known abuse should be a compulsion of anyone who encounters it, many people are considered persons encouraged to report and are encouraged to make reports when necessary, but not required by law. Persons encouraged to report may make an oral or written report of suspected child abuse or cause a report of suspected child abuse to be made to the Department, county agency, or law enforcement, if that person has reasonable cause to suspect that a child is a victim of abuse. Written reports must be submitted electronically. 

Hotline Number: 1-800-932-0313 

Child Welfare Portal 

Persons Required to Report: Healthcare Professionals 

Persons Required to Report (23 Pa.C.S.§6311) 

As a healthcare professional, you are considered a mandated reporter, meaning there are certain situations where you are required by law to make a report of suspected or confirmed abuse. 

• “Reasonable cause to suspect” may be a determination you make based on your training/experience and all known circumstances – to include “who”, “what”, “when”, and “how””, observations (e.g., indicators of abuse or “red flags”, behavior/demeanor of the child(ren), behavior/demeanor of the adult(s), etc.), as well as familiarity with the individuals (e.g., family situation and relevant history or similar prior incidents, etc.). It is also important to recognize how your feelings and personal biases may influence your conclusions and actions. 
• Some indicators may be more apparent than others depending on the type of abuse and/or depending on the child’s health, development, and well-being, as well as may be physically visible on the child’s body while other indicators may be present in the child’s behaviors. It is also worth acknowledging that some indicators may overlap and suggest a child is a victim of more than one type of child abuse. 

Basis For Reporting 

Persons required to report suspected child abuse (23 Pa.C.S. § 6311) section (b) 

(b) Basis to report  

• A mandated reporter enumerated in section 6311(a) of the PA CPSL shall make a report of suspected child abuse in accordance with section 6313 (relating to reporting procedure) if the mandated reporter has reasonable cause to suspect that a child is a victim of child abuse under any of the following circumstances: 
• The mandated reporter comes into contact with the child in the course of employment, occupation, and practice of a profession or through a regularly scheduled program, activity, or service. 
• The mandated reporter is directly responsible for the care, supervision, guidance, or training of the child, or is affiliated with an agency, institution, organization, school, regularly established church or religious organization, or other entity that is directly responsible for the care, supervision, guidance, or training of the child. 
• A person makes a specific disclosure to the mandated reporter that an identifiable child is the victim of child abuse. 
• An individual 14 years of age or older makes a specific disclosure to the mandated reporter that the individual has committed child abuse. 
• Nothing in section 6311 of the PA CPSL requires a child to come before the mandated reporter in order to make a report of suspected child abuse. 
• Nothing in section 6311 of the PA CPSL requires the mandated reporter to identify the person responsible for the child abuse in order to make a report of suspected child abuse. 

Persons Required to Report: Other Professions 

There are many other professions who are mandated reporters; in the state of Pennsylvania, this includes: 

• A person licensed or certified to practice in any health-related field under the jurisdiction of the Department of State.  
• A medical examiner, coroner, or funeral director. 
• An employee of a healthcare facility or provider licensed by the Department of Health, who is engaged in the admission, examination, care, or treatment of individuals.  
• A school employee. 
• An employee of a childcare service who has direct contact with children in the course of employment.  
• A clergyman, priest, rabbi, minister, Christian Science practitioner, religious healer or spiritual leader of any regularly established church or other religious organization.  
• An individual paid or unpaid, who, based on the individual’s role as an integral part of a regularly scheduled program, activity or service, is a person responsible for the child’s welfare or has direct contact with children. 
• An employee of a social services agency who has direct contact with children in the course of employment.  
• A peace officer or law enforcement official. 
• An emergency medical services (EMS) provider certified by the Department of Health. 
• An employee of a public library who has direct contact with children in the course of employment.  
• An individual supervised or managed by a person listed under paragraphs (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), and (13), who has direct contact with children in the course of employment.  
• An independent contractor. 
• An attorney affiliated with an agency, institution, organization, or other entity, including a school or regularly established religious organization that is responsible for the care, supervision, guidance or control of children.  
• A foster parent. 
• An adult family member who is a person responsible for the child’s welfare and provides services to a child in a family living home, community home for individuals with an intellectual disability or host home for children which are subject to supervision or licensure by the Department under Articles IX and X of the act of June 13, 1967, (P.L. 31, No. 21), known as the Public Welfare Code. 

Persons Required to Report: Staff Members of Institutions 

Persons required to report suspected child abuse ((23 Pa.C.S. § 6311) section (c) 

(c) Staff members of institutions, etc.  

• Whenever a person is required to report under section 6311(b) of the PA CPSL in the capacity as a member of the staff of a medical or other public or private institution, school, facility, or agency, that person shall report immediately in accordance with section 6313 (relating to reporting procedure) and shall immediately thereafter notify the person in charge of the institution, school, facility, or agency or the designated agent of the person in charge. 
• Upon notification, the person in charge or the designated agent, if any, shall facilitate the cooperation of the institution, school, facility, or agency with the investigation of the report. 
• Any intimidation, retaliation, or obstruction in the investigation of the report is subject to the provisions of 18 Pa.C.S. § 4958 (relating to intimidation, retaliation, or obstruction in child abuse cases). 
• The PA CPSL does not require more than one report from any such institution, school, facility, or agency. 

Privileged/Confidential Communications 

Privileged/Confidential Communications (23 Pa.C.S. § 6311.1) 

Mandated reporters may encounter situations where they have a reasonable suspicion of abuse through several different circumstances; including contact with the child through their job, direct involvement in the supervision or caretaking of the child, another person discloses the knowledge of abuse that is occurring to the child, or another person discloses that they themselves have abused the child. The child is not required to make a claim of abuse or even talk to the mandated reporter about it. Situations that reveal potential abuse must be reported even if the information is disclosed within a confidential relationship and reporting such incidents does not violate confidentiality laws (9).  

*Confidential communications apply to member of clergy as well as communications made to an attorney.  

Case Study 

Case Study No. 4 – read the following scenario and answer the questions below: 

A four-month-old child is brought to the pediatric clinic for a diaper rash. Upon measuring his length and weight, the nurse notes that the child has grown in length since his last visit two months ago but has only gained 3 oz, dropping from the 40th percentile to 5th percentile, and is now considered “Failure to Thrive.” Other than the diaper rash, the child is clean, though thin, and the mother shows appropriate affection for him in the office. When the nurse comments on his lack of growth, the mother admits she is having a hard time affording formula and has been diluting it to make it last longer. The nurse provides education about properly mixing formulas and information for the local Women Infants and Children (W.I.C.) program so that she can receive supplemental formula. Then, as a mandated reporter, the nurse contacts the Department of Human Services (DHS) for the county to report the situation.  

• Is there reasonable cause to suspect child abuse? Yes/No 

Correct Answer:  

Yes – failure to provide a child with the necessities of life can be considered neglect. Even though it is due to reported financial instability, the mandated reporter has a responsibility to report, and DHS will investigate further and make the determination if there is an exclusion or not. 

• Is this a scenario which has a basis to report in which the nurse must report as a mandated reporter? Yes/No 

Correct Answer:  

Yes – nurses are considered mandated reporters. The nurse has encountered the child through the practice of their profession.  

• Which of the following entities must the nurse notify of the suspected abuse? 
  • The child’s mother 
  • Supervisor of the pediatric clinic 
  • Law enforcement 
  • Department of Human Services 

Correct Answer: 

B and D – the nurse must notify DHS via the statewide toll-free telephone number and notify their supervisor or other designated person in the clinic in charge of following up with such cases. 

Human Trafficking 

Examples of severe forms of human trafficking include: 

Labor Trafficking 

Labor Trafficking is labor obtained by use of threat of serious harm, physical restraint, or abuse of legal process. An example of human trafficking is being forced to work for little or no pay in such a climate as a farm or a factory; domestic servitude in providing services within a household from 10-16 hours per day performing duties such as childcare, cooking, cleaning, yard work, and gardening.  

Another example would be the recruitment, harboring, transportation, provision, or obtaining a person for labor of services through force, fraud, or coercion for the subjection of involuntary servitude.  

• Peonage: paying off debt through work 
• Debt Bondage: debt slavery, bonded labor, or services for a debt or other obligation 
• Slavery: a condition compared to that of a slave in respect of exhausting labor or restricted freedom 

Sex Trafficking 

Sex trafficking is another form of severe human trafficking. It occurs when a commercial sexual act is induced by force, fraud, or coercion, or in which the person induced to perform such an act is not 18 years of age.  

Defined, Sex trafficking: the recruitment, harboring, transportation, provision, obtaining, patronizing, or soliciting of a person for the purpose of a commercial sex act. 

A commercial sex act is defined as any sex act on account of anything of value is given to or received by any person.  

At risk youth populations for human trafficking include, but not limited to, youth:  

• In the foster care system 
• Who identify as LGBTQ 
• Who are homeless or runaway 
• With disabilities 
• With mental health and/or substance abuse disorders 
• With a history of sexual abuse 
• With a history of being involved in the welfare system 
• Who identify as native or aboriginal 
• With family dysfunction 

Victim identification or warning signs to look out for in these populations include, but not limited to:  

• A youth that has been verified to be under 18 and is in any way involved in the commercial sex industry or has a record of prior arrest for prostitution or related charges. 
• Has an explicitly sexual online profile. 
• Excessive frequenting of internet chat rooms or classified sites. 
• Depicts elements of sexual exploitation in drawing, poetry, or other modes of creative expression. 
• Frequent or multiple sexually transmitted diseases or pregnancies. 
• Lying about or not being aware of their true age. 
• Having no knowledge of personal data, such as but not limited to: age, name, and/or date of birth. 
• Having no identification. 
• Wearing sexually provocative clothing.  
• Wearing new clothes of any style, getting hair and/or nails done with no financial means. 
• Secrecy about whereabouts. 
• Having late nights or unusual hours. 
• Having a tattoo that she/she is reluctant to explain.  
• Being in a controlling or dominating relationship. 
• Not having control of own finances. 
• Exhibit hyper-vigilance or paranoid behaviors. 
• Express interest in or in relationships with adults or much older men/women. 

Substance Exposed Infants and Plans of Safe Care 

Notification of Substance Exposed Infants by Healthcare Providers and Plans of Safe Care 

According to Act 54, a healthcare provider shall immediately give notice to the department if the provider is involved in the delivery or care of a child under one year of age and the healthcare provider has determined based on professional practice that the child was born affected by substance use or withdrawal symptoms resulting from prenatal drug exposure or a fetal alcohol disorder.  

A health care provider is defined as: A licensed hospital or health care facility or person who is licensed, certified, or otherwise regulated to provide health care services under the laws of Pennsylvania, including a physician, podiatrist, optometrist, psychologist, physical therapist, certified nurse practitioner, registered nurse, nurse midwife, physician’s assistant, chiropractor, dentist, pharmacist, or an individual accredited or certified to provide behavioral health services. 

Notification to the department can be made to ChildLine electronically through the Child Welfare Portal or at 1-800-932-0313. 

This notification is for the purpose of assessing a child and the child’s family for a plan of safe care and may not constitute a child abuse report.  

After notification of a child born affected by substance use or withdrawal symptoms resulting from prenatal drug exposure or a fetal alcohol spectrum disorder: 

• A multidisciplinary team meeting must be held prior to the child’s discharge from the healthcare facility. 
• The meeting will inform an assessment of the needs of the child and the child’s parents and immediate caregivers to determine the most appropriate lead agency for developing, implementing, and monitoring a plan of safe care. 
• The child’s parents and immediate caregivers must be engaged to identify the need for access to treatment for any substance use disorder or other physical or behavioral health condition that may impact the safety, early childhood development and well-being of the child. 
• Depending upon the needs of the child and parent(s)/caregiver(s), ongoing involvement of the county agency may not be required. 

Reporting Process    

All reports, whether mandated or not, should be made immediately by contacting the Pennsylvania Department of Human Services through the ChildLine hotline. 

(1-800-932-0313) 

Electronic Reporting 

Electronic reporting (23 Pa.C.S. § 6305) section (b) 

(b) Confirmation of reports – A confirmation by DHS of the receipt of a report of suspected child abuse submitted electronically shall relieve the person making the report of making an additional oral or written report of suspected child abuse, subject to section 6313 (relating to reporting procedure). 

Reporting Procedures 

Reporting procedure (23 Pa.C.S. § 6313) section (a) 

(a) Report by mandated reporter 

• A mandated reporter shall immediately make an oral report of suspected child abuse to DHS via the Statewide toll-free telephone number under section 6332 (relating to establishment of Statewide toll-free telephone number) (1-800-932-0313) or a written report using electronic technologies under section 6305 (relating to electronic reporting) (via the self-service Child Welfare Portal). 
• A mandated reporter making an oral report of suspected child abuse to the DHS via the Statewide toll-free telephone number under section 6332 (relating to establishment of Statewide toll-free telephone number) shall also make a written report (CY-47), which may be submitted electronically, within 48 hours to DHS or county agency assigned to the case in a manner and format prescribed by DHS. 
• The failure of the mandated reporter to file the written report (CY-47) described in the paragraph immediately above shall not relieve the county agency from any duty under the PA CPSL, and the county agency shall proceed as though the mandated reporter complied. 

This line is available 24/7 and will guide you through the reporting process specific to your scenario. Electronic submission will likely need to accompany your verbal report.  You can complete an online electronic submission through the Child Welfare portal. Oral reports are required to be followed up within 48 hours with an electronic report sent to the investigating agency through the portal. 

Reporting procedure (23 Pa.C.S. § 6313) section (b) 

(b) Contents of report — A written report of suspected child abuse, which may be submitted electronically, shall include the following information, if known: 

• The names and addresses of the child, the child’s parents, and any other person responsible for the child’s welfare. 
• Where the suspected abuse occurred 
• The age and sex of each subject of the report 
• The nature and extent of the suspected child abuse, including any evidence of prior abuse to the child or any sibling of the child. 
• The name and relationship of each individual responsible for causing the suspected abuse and any evidence of prior abuse by each individual. 
• Family composition 
• The source of the report 
• The name, telephone number and e-mail address of the person making the report. 
• The actions taken by the person making the report, including those actions taken under section 6314 (relating to photographs, medical tests, and X-rays of child subject to report), 6315 (relating to taking child into protective custody), 6316 (relating to admission to private and public hospitals) or 6317 (relating to mandatory reporting and postmortem investigation of deaths) 
• Any other information required by Federal law or regulation. 
• Any other information that DHS requires by regulation. 

Reporting procedure (23 Pa.C.S. § 6313) section (e) 

(e) Applicability of Mental Health Procedures Act – Notwithstanding any other provision of law, a mandated reporter who makes a report of suspected child abuse or who makes a report of a crime against a child to law enforcement officials shall not be in violation of the act of July 9, 1976 (P.L.817, No.143), known as the Mental Health Procedures Act, by releasing information necessary to complete the report. 

Release of Confidential Information 

Release of information in confidential reports (23 Pa.C.S. § 6340) section (c) 

(c) Protecting identity – Except for reports under section 6340(a)(9) and (10) of the PA CPSL and in response to a law enforcement official investigating allegations of false reports under 18 Pa.C.S. § 4906.1 (relating to false reports of child abuse), the release of data by DHS, county, institution, school, facility, or agency or designated agent of the person in charge that would identify the person who made a report of suspected child abuse or who cooperated in a subsequent investigation is prohibited. Law enforcement officials shall treat all reporting sources as confidential informants. 

Confidentiality of reports (23 Pa.C.S. § 6339)  

Except as otherwise provided in subchapter C of the PA CPSL (relating to powers and duties of department) or by the Pennsylvania Rules of Juvenile Court Procedure, reports made pursuant to the PA CPSL, including, but not limited to, report summaries of child abuse and reports made pursuant to section 6313 (relating to reporting procedure) as well as any other information obtained, reports written, or photographs or X-rays taken concerning alleged instances of child abuse in the possession of DHS or a county agency shall be confidential. 

ChildLine receives the report and determines who is to respond dependent upon the information reported, such as the identity, if known, of the person who allegedly acted to abuse or harm a child.  

ChildLine will immediately transmit oral or electronic reports that they receive to the appropriate county agency and or law enforcement official: 

• If a person identified falls under the definition of perpetrator, ChildLine would refer the report to the appropriate county agency for an investigation. 
• If the person identified is not a perpetrator and the behavior reported includes a violation of a crime, ChildLine will refer the report to law enforcement officials. 
• If a person identified falls under the definition of perpetrator and the behavior reported includes a criminal violation, ChildLine will refer the report to the appropriate county agency and law enforcement officials. 

If a report indicates that a child may need other protective services, ChildLine will refer the report to the proper county agency to assess the needs of the child and provide services, when appropriate. 

If a report was made by a mandated reporter, the department will notify the mandated reporter who made the report of DHS’s receipt of the results of the investigation. 

A child abuse investigation must be determined within 30 days whether the report is: 

• founded, indicated, unfounded or pending. 
• Any services provided, arranged for or to be provided by the county agency to protect the child. 

An investigation may take up to 60 days if there is a valid reason, such as when waiting for results from a medical report or from another evaluation. 

While mandated reporters are not able to remain anonymous, they are offered certain protections from legal action as long as the report was made in good faith. Mandated reporters are immune from litigation involving photographs taken during an investigation, medical exams performed, or backlash from family members or perpetrators in situations where abuse was or was not actually found to be occurring. Their names are also kept confidential unless the situation evolves to one where the reporter’s identity must be revealed, such as testifying in court (4).    

Immunity From Liability 

Immunity from liability (23 Pa.C.S. § 6318) section (a) 

(a) General rule – A person, hospital, institution, school, facility, agency, or agency employee acting in good faith shall have immunity from civil and criminal liability that might otherwise result from any of the following: 

• Making a report of suspected child abuse or making a referral for general protective services, regardless of whether the report is required to be made under the PA CPSL. 
• Cooperating or consulting with an investigation under the PA CPSL, including providing information to a child fatality or near-fatality review team. 
• Testifying in a proceeding arising out of an instance of suspected child abuse or general protective services. 
• Engaging in any action authorized under 23 Pa.C.S. § 6314 (relating to photographs, medical tests and X-rays of child subject to report), § 6315 (relating to taking child into protective custody), § 6316 (relating to admission to private and public hospitals), or § 6317 (relating to mandatory reporting and postmortem investigation of deaths). 

Immunity from liability (23 Pa.C.S. § 6318) section (b) 

(b) Departmental and county agency immunity – An official or employee of DHS or county agency who refers a report of suspected child abuse for general protective services to law enforcement authorities or provides services as authorized by the PA CPSL shall have immunity from civil and criminal liability that might otherwise result from the action. 

Immunity from liability (23 Pa.C.S. § 6318) section (c) 

(c) Presumption of good faith – For the purpose of any civil or criminal proceeding, the good faith of a person required to report suspected child abuse and of any person required to make a referral to law enforcement officers under the PA CPSL shall be presumed. 

Protection From Employment Discrimination 

Protection from employment discrimination (23 Pa.C.S. § 6320) section (a) 

(a) Basis for relief – A person may commence an action for appropriate relief if all of the following apply: 

• The person is required to report suspected child abuse or encouraged to report suspected child abuse. 
• The person acted in good faith in making or causing the report of suspected child abuse to be made. 
• As a result of making the report of suspected child abuse, the person is discharged from employment or is discriminated against with respect to compensation, hire, tenure, terms, conditions, or privileges of employment. 

Protection from employment discrimination (23 Pa.C.S. § 6320) section (b) 

(b) Applicability – This section does not apply to an individual making a report of suspected child abuse who is found to be a perpetrator because of the report or to any individual who fails to make a report of suspected child abuse as required and is subject to conviction for failure to report or to refer. 

Failure to Report  

Failing to report a suspected abuse case as a mandated reporter is an offense as a felony of the third degree if: 

• The person or officially willfully fail to report.  
• The child abuse constitutes as a felony of the first degree or higher AND.  
• The person has direct knowledge of the nature of the abuse.  

The offense not otherwise specified above is considered a misdemeanor of the second degree.  
 

Penalties for Not Reporting 

Penalties (23 Pa.C.S. § 6319) section (a) 

(a) Failure to report or refer 

1. A person or official required by the PA CPSL to report a case of suspected child abuse or to make a referral to the appropriate authorities commits an offense if the person or official willfully fails to do so. 

1. An offense under this section is a felony of the third degree if: 

• the person or official willfully fails to report. 
• the child abuse constitutes a felony of the first degree or higher; and 
• the person or official has direct knowledge of the nature of the abuse. 

1. An offense not otherwise specified above is a misdemeanor of the second degree. 

1. A report of suspected child abuse to law enforcement or the appropriate county agency by a mandated reporter, made in lieu of a report to DHS, shall not constitute an offense under this subsection, provided that the report was made in a good faith effort to comply with the requirements of the PA CPSL. 

Penalties (23 Pa.C.S. § 6319) section (b)  

(b) Continuing course of action – If a person’s willful failure to report an individual suspected of child abuse continues while the person knows or has reasonable cause to suspect a child is being subjected to child abuse by the same individual, or while the person knows or has reasonable cause to suspect that the same individual continues to have direct contact with children through the individual’s employment, program, activity, or service, the person commits a felony of the third degree…except that, if the child abuse constitutes a felony of the first degree or higher, the person commits a felony of the second degree. 

Penalties (23 Pa.C.S. § 6319) section (b) 

(c) Multiple offenses – A person who, at the time of sentencing for an offense under this section, has been convicted of a prior offense under this section commits a felony of the third degree…except that, if the child abuse constitutes a felony of the first degree or higher, the penalty for the second or subsequent offenses is a felony of the second degree. 

A child is not required to come before the mandated reporter for the mandated reporter to make a report of suspected child abuse. 

Penalties (23 Pa.C.S. § 6319) section (d) 

(d) Statute of limitations – The statute of limitations for an offense under this section shall be either the statute of limitations for the crime committed against the minor child or five years, whichever is greater. 

Case Study 

Case Study No. 5 – please read the following scenario and answer the questions below: 

A pediatric nurse is off duty and supervising her nine-year-old child and a few peers swimming in her backyard. She notices that one of the other children has a large fading bruise on his back. She is friends with this child’s mother, Katie, and asks her what happened when she comes to pick the child up. Katie gets very quiet and then admits that the child’s father sometimes is very rough when he gets angry and had grabbed the child by the arm a few nights ago and then hit him. Katie states not to worry, that the father has agreed to go to anger management, and she is hoping it won’t happen anymore.   

• Is the nurse in this scenario required to report? Yes/No 

Correct answer: 

Yes – even if the nurse is off duty, “A person makes a specific disclosure to the mandated reporter that an identifiable child is the victim of child abuse. This statement does not require you to be “on the clock.” 

• What category of child abuse is presented in this scenario? 
  • Neglect 
  • Physical  
  • Sexual 
  • Mental 

Correct answer: 

B – physical abuse includes corporal punishment that leaves bruises and has the potential to injure the child. 

Adverse Childhood Experiences 

Adverse Childhood Experiences or ACE is an umbrella term to describe events that had a potentially traumatic impact and that occurred before the individual turned 18 (2). 

The Centers for Disease Control and Prevention (CDC) reports that approximately 64% of adults in the United States have experienced an ACE (2). These experiences can have long lasting effects on health, overall wellbeing, access to higher education, and job opportunities. The impact reaches far beyond just the individual. It can affect their family dynamics and can have societal implications. This is why preventing childhood abuse and promoting family stability needs to be a community effort and not just the responsibility of a select few. 

Community Strategies to Prevent ACE: 

• Increasing opportunities for families to have financial stability. 
• Providing education on how to prevent violence and how to approach these situations as a person required to report or person encouraged to report. 
• Community youth activities. 
• Early intervention. 
• Affordable access to high quality childcare. 

Conclusion

Obviously, even one child being abused is too many. However, as community advocates, teachers, healthcare professionals, and others working on correcting and eliminating the societal conditions that lead to child abuse in the first place, it is important for nurses and other healthcare professionals to continue working diligently to identify potential victims of abuse and activate the system in place to help them as quickly and efficiently as possible. By having an ability to identify who is at risk, an understanding of the reporting system, and knowledge on what being a mandated reporter entails, nurses can play an active role in curtailing the number of children seriously harmed by these situations. Children are one of our most vulnerable populations because of their dependency on others to meet their many needs. Advocacy for their safety is one of the most important roles a nurse can take on.

Pennsylvania Pain Management and Identification of Addiction

Introduction   

Pain can vary according to the source and intensity, as well as an individual’s age, gender, culture, and interpretation by the individual. Unfortunately, everyone will eventually experience pain. The nurse's role is crucial in providing comprehensive patient care by evaluating and treating pain effectively.  

Pennsylvania allows a licensed and authorized advanced practice nurse to prescribe and monitor medications, including narcotics for pain management. The state requires mandatory completion of a course on safe narcotic prescription and identification of potential substance use disorder, which is discussed in this course.  

Pennsylvania Laws Regarding Safe Controlled Substance Prescriptions  

Pennsylvania state and federal laws govern the prescribing and monitoring of controlled substances including all narcotics. The Controlled Substances Act (CSA), administered by the Drug Enforcement Administration (DEA), regulates all aspects of controlled substance manufacturing, distribution, dispensing, prescribing and distribution. The DEA regulations offer healthcare providers specific guidelines regarding prescribing practices, record keeping practices and monitoring (39).  

At the federal level any prescriber of narcotics or scheduled drugs must apply for and be approved to be a prescriber, which includes physicians, nurse practitioners, and physician assistants. It is within the scope of practice for a nurse practitioner in the state of Pennsylvania to prescribe narcotics with an approved advanced practice license and prescribing authority.  

Pennsylvania developed its own Controlled Substance, Drug Device and Cosmetic Act to outline regulations surrounding the production, distribution and dispensing of controlled substances within the state. This law mandates requirements such as prescription writing, dispensing, and record-keeping. Pennsylvania has a Prescription Drug Monitoring Program (PDMP) to track the prescribing and dispensing of controlled substances to patients. Healthcare providers must check this database prior to prescribing them to patients.  

The Pennsylvania Department of Health may issue additional regulations related to controlled substances, prescribing practices, and monitoring. Healthcare providers administering narcotics must abide by federal and state laws regarding prescription issuance for legitimate medical purposes while keeping accurate records and meeting PDMP requirements.  

Healthcare providers in Pennsylvania must remain up to date with both federal and state regulations to ensure safe prescribing practices, compliance, and ensure patient and colleague communication regarding controlled substances such as narcotics. Regular review is key. 

Incidence And Prevalence of Substance Use Disorders 

By conducting a careful pain assessment, nurses can gain an understanding of a patient's subjective pain perceptions as well as its severity, causes, and symptoms. Nurses may implement both non-pharmacologic and pharmaceutical interventions to manage pain appropriately.  

The role of the nurse practitioner is to formally diagnose and order treatment, so a thorough understanding of pain management and identification of addiction risk factors is crucial. For DEA-registered practitioners, care should be given when choosing which pharmacological interventions to utilize, to minimize risks for substance abuse disorders and achieve maximum pain relief.  

Uncontrolled pain or the development of substance use disorders can disrupt functional living and complicate comorbidities. Collaboration among members of the health care team and patients themselves is also key, including setting realistic goals for managing pain effectively and actively participating in their plan of care. 

Pain, including abdominal, head, throat, and back pain, continues to be the top four most common patient complaints seen in primary care (1). In efforts to address and treat pain, both pharmacological approaches are given by nurse practitioners.  

Unfortunately, a result of prescribed pain medications is the possibility of substance use disorders, which is a continued important issue in the United States. The opioid epidemic continues to be a serious public health concern. Assessing, diagnosing, treating pain, and identifying risk factors for substance use disorder are important topics for every nurse practitioner.  

The most common substance use disorders in the United States are (2):  

• Alcohol use disorder (29.5 million) 
• Cannabis use disorder (16.3 million) 
• Methamphetamine use disorder (1.6 million) 
• Opioid Use disorder (5.0 million) 
• Tobacco use disorder (16 million) 

Types of Pain  

Pain can be an ordinary response to illness or injury and doesn't typically require medical intervention. Pain may be divided into various categories depending on its onset and duration, including acute, chronic or breakthrough (3).  

Acute pain is experienced from within minutes of an injury up to several months afterwards. Chronic pain is experienced beyond six months and usually due to a continuous medical issue or condition. Breakthrough pain occurs when pain that was controlled with medication begins to be felt beyond the pharmacological properties of the pain medication. Pain is divided further into neuropathic, nociceptive, and radicular (36). 

Pain Assessment 

Pain is considered the fifth vital sign and provides significant information about a patient’s lived experience.  

In 1995, it was proposed by a practicing physician James Campbell that pain should be considered the fifth vital sign, which was later supported by the American Pain Society as a standard practice guideline (6). In addition to blood pressure, heart rate, respiratory rate, temperature, and pulse oximetry, a pain assessment provides information necessary for holistic care.  

A regular pain assessment allows nurses to manage patient discomfort more effectively by creating personalized plans of action to effectively address pain management needs. Prior to ordering or administrating pain medications, nurses must perform an in-depth pain evaluation that includes gathering data from various sources, including the patient’s medical history, chief complaint, and a physical exam. A follow-up is important to evaluate any therapeutic results of prescribed medication.  

Components of a Pain Assessment 

A systematic pain assessment is key to correctly identifying all the components of pain (7). 

1. Assess risks for pain. For example, advanced age, cancer, anxiety, recent surgery/invasive procedures increase the likelihood of experiencing pain and discomfort. 
2. Assess pain using an approved pain scale to create a baseline for the current pain level (which will be discussed later). Remember pain is subjective and influenced by age, gender, and cultural factors.  
3. Identifying the pain source such as nociceptive, neuropathic, referred, somatic, visceral, or phantom pain. 
4. Assess the type of pain (acute or chronic) and contributory factors.  
5. Evaluate their past response to pharmacological interventions and analgesics, including any adverse reactions they experience.  
6. The assessment should include physical, behavioral, and emotional signs of pain including confusion, diaphoresis, moaning, decreased activity levels, irritability, guarding, clenched teeth, muscle tension, depression, insomnia, confusion, diaphoresis, moaning, and grimacing.  

Pain Assessment Mnemonics 

Nurses often use three mnemonics to remember standardized questions for conducting a comprehensive pain assessment: 

• COLDSPA 
• OLDCARTES 
• PQRSTU 

Each letter presents important questions to ask the patient about their pain.  

Nurses may ask any number of questions to obtain information for each category. Examples of each of these mnemonics can help the practitioner remember to ask important questions relevant to pain.  

The “OLDCARTES” mnemonic consists of the letter of each category of questions to ask. 

• O: Onset 
• L: Location 
• D: Duration 
• C: Characteristics 
• A: Aggravating factors 
• R: Radiating 
• T: Treatment 
• E: Effect 
• S: Severity 

The “PQRSTU” mnemonic also helps the clinician to ask about components of pain.   

• P: Provocative/Palliative 
• Q: Quality/Quantity 
• R: Region/Radiation 
• S: Severity 
• T: Timing/Treatment 
• U: Understanding 

Regardless of the pain assessment framework utilized, it is critical that open-ended questions allow patients to describe the pain in their own words. Closed-ended questions result in either yes/no responses or fail to capture an accurate account of the patient’s pain.  

It is also vitally important for the nurse to follow-up on initial responses by asking clarifying questions so they can create and implement an individualized pain treatment plan to address all aspects of pain. In completing a pain assessment with patients, the nurse practitioner gains better trust with the patient, which can result in better patient adherence to prescribed treatment.  

Pain is Subjective 

Given that everyone responds differently, each person's experience of pain will vary widely, even for stimuli with similar properties. For instance, some may feel considerable discomfort after receiving injections while others experience none, which means consequently we must treat pain according to whatever the individual claims it to be.  

Due to this completely subjective nature of describing pain, the evaluation of the response to pain medication is also subjective. Clinicians must recognize the biological, psychological, and social factors that affect the perception of pain as shown in the following table.  

Caption: The biological, psychological, and social influences on pain.  

(48) 

Pain Scales 

At the core of any pain assessment is determining the intensity. As pain cannot be objectively tested to pinpoint an individual's sensations, providers use pain scales as tools for objectively understanding each patient's discomfort and setting realistic pain goals. Nurses have access to numerous standardized pain scales.  

A popular one is numerical, in which patients rate their discomfort between zero and 10, with zero being no pain and 10 being the worst pain ever experienced. While simple and user-friendly, numerical pain scale cannot be used by children or other populations who cannot accurately quantify pain, therefore alternative pain scales such as FACES scale, FLACC scale comfort behavioral scale or PAINAD scale may be used. 

The FACES scale is a visual assessment tool for children and other people who cannot use numeric scales. When using it with children or others who cannot describe numbers accurately, explain to the patient that each face represents either no pain, some discomfort, or intense distress. For instance: Face 0 doesn't hurt at all while Faces 2-6 hurts just slightly more, while Face 8 hurts even further before reaching 10, which represents extreme suffering. Ask the individual which of those depictions best represents their discomfort. 

Caption: Wong Baker FACES Scale used to help score pain level 

The FLACC scale is used to assess pain in children aged two months to seven years and those unable to verbalize. It comprises five criteria such as face, legs, activity, cry, and consolability. Care providers assign each criteria a score between zero and two upon observation of their patient and then combine all five scores together into an overall pain score between zero (no pain) and 10 (10 severe) (8).  

The Pain Assessment in Advanced Dementia (PAINAD) Scale is used to assess pain in patients with advanced dementia (9). This scale has five criteria including breathing independent of vocalization, negative vocalization, facial expression, body language, and consolability.  

Like the FLACC scale, each of the five criteria are assigned a score of 0, 1, or 2. The provider observes the patient, assigns a score for each criterion, and adds the scores. The total pain score will be between 0 and 10, with 0 being no pain and 10 being severe pain. Like FLACC, the PAINAD scale is simple, valid, and reliable, but it may not always result in the most accurate pain assessment, as it requires the nurse to calculate the score based upon observed patient behaviors rather than the patient’s subjective pain rating. 

Online Resources  

• FACES scale: http://wongbakerfaces.org 
• FLACC scale: https://www1.health.gov.au/internet/publications/publishing.nsf/Content/triageqrg~triageqrg-pain~triageqrg-FLACC 
• PAINAD scale: https://geriatrictoolkit.missouri.edu/cog/painad.pdf 

Cultural Influence on Pain 

Culture plays an intricate role in how individuals express physical and emotional discomfort. Some cultures, such as those found in East Asia, place strong value on self-discipline and control and may choose not to show any emotions when in pain.  

Middle Eastern and Mediterranean societies emphasize open expressions of emotion and may easily express and verbalize their sensations of pain (10).  

Although culture may impact pain levels differently for each patient, nurses must understand its impact before creating an individual plan that best meets each person's specific needs. 

Pain Assessment on Special Populations 

The elderly, children, individuals who speak English as a second language, deaf, mute, limited English training, and people from different countries may require additional patience while completing a pain assessment.  

Chronic pain can be related to depression, anxiety, and sleep disturbances, which can complicate a clear report of pain. Using a multimodal approach for a pain assessment, a physical exam, and the pain scales identified above can be helpful.  

Reassessment After Intervention  

Pain must always be assessed again following implementation of an intervention to determine its effectiveness in relieving symptoms. Oral medications should be assessed within 1 hour while intravenous treatments within 15-30 minutes, and per facility protocol (40). 

For a primary care provider in an office clinic, reassessing pain should use the same pain scale used during initial assessment at the next visit. If their discomfort has not decreased to meet their established goal level, further interventions will be needed.  

Interventions may involve medications and/or nonpharmacological modalities like heat, ice, music therapy and repositioning to achieve the patient's ideal pain goal (41). Intervention and reassessments must continue until this goal has been attained. All reassessments and interventions must be documented in their medical record. 

Pain Management Care Plan  

In developing care plans for pain, nurse practitioners should provide a tailored approach to address each patient's unique pain management needs. Beginning with an in-depth evaluation, the nurse practitioner gathers information regarding medical history, current pain symptoms, functional status, psychosocial factors, and desired goals for treatment.  

Based on their evaluation, nurse practitioners collaborate with patients to set realistic expectations and goals for pain management care plans that integrate pharmaceutical interventions along with nonpharmacological interventions.  

Pharmacological interventions include using analgesic medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and any adjuvant medicines such as antidepressants or anticonvulsants as well as topical agents to relieve discomfort (42).  

Nurse practitioners carefully consider all risks and benefits when prescribing medications to their patients, tailoring individualized plans to optimize pain relief while mitigating adverse side effects as well as risks related to opioid misuse or addiction.  

Non-pharmacological interventions also play a vital part in pain management. These may include physical therapy, occupational therapy, acupuncture, and massage therapy as well as cognitive-behavioral therapy (CBT), relaxation techniques and mindfulness-based interventions.  

Nurse practitioners work collaboratively with other healthcare professionals such as physical therapists, psychologists, and pain specialists to coordinate and integrate interventions into a patient's care plan. Education and self-management strategies also play a pivotal role in pain management plans. Nurse practitioners provide patients with education about their pain condition, its causes, and possible solutions.  

Patients can become actively engaged in their care by learning self-management techniques such as pacing activities, maintaining proper posture, using heat or cold therapy, and practicing stress reduction methods.  

Additionally, patients receive guidance regarding medication adherence, potential side effects and the significance of regular follow up appointments to monitor progress. Furthermore, their pain management care plan incorporates strategies designed to address any psychosocial factors which might impact pain for an improved experience and treatment outcome. Screening may include depression, anxiety, sleep disturbances, substance use disorders and any additional coexisting conditions. 

Referrals may be made to mental health professionals, social workers, or support groups as a source of additional assistance and resources for the patient. Reassessment and monitoring should form integral parts of any pain management care plan. Nurse practitioners collaborate closely with patients to monitor pain levels, functional status, effectiveness of medication treatment plans and any adverse side effects. Treatment plans may be altered accordingly as needed based on response to therapy, changes to condition or evolving goals of care. 

Pharmacological Pain Management 

Pain medications are divided into two main groups, including analgesics and adjuvants. Analgesics are used to prevent or treat pain and can further be classified as opioids or nonopioids; the classification is based on whether their original source is from poppy plants, known as opioids (42).  

Nonopioids include medications not classified as opioids while adjuvants contain medication with both independent analgesic properties as well as additive properties when taken together with opioids. 

When taking analgesics, it is wise to start with those having minimal side effects in a smaller dose and using minimally invasive approaches. 

Developed by the World Health Organization, the following graphic demonstrates the stair-step ladder approach to guide the advancement of pain medication.  

Caption: The WHO pain ladder is a guide for using pain medications responsibly. 

Image Source: https://www.researchgate.net/figure/The-World-Health-Organization-WHO-pain-ladder-modified-for-Acute-Pain-Management-a_fig1_340312749 

Originally created to assist cancer patients, the pain ladder model can now be applied to all forms of discomfort. Nonopioids should generally be employed first in managing pain and if persistent or increasing discomfort continues then opioids or adjunct therapies should be added alongside nonopioids as appropriate (43).  

For severe, short-term pain that's expected to diminish gradually over time however, opioids, nonopioids and adjunct therapies might initially all be given before gradually withdrawing their presence so only nonopioids remain. 

Analgesic Medications  

Analgesic medications (nonopioids and opioids) are used to alleviate or manage pain. Nonopioids tend to work best at managing mild-to-moderate discomfort in most cases and are well tolerated by most users. Examples of such analgesics include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS).  

Acetaminophen 

Acetaminophen is a non-narcotic analgesic and fever reducer. It is available by prescription or over the counter (OTC). Acetaminophen (the active ingredient found in Tylenol) can help relieve mild pain in all age groups and is generally safe. As it can be administered orally, sublingually, or intravenously, it could also provide an ideal choice for people unable to take oral medications.  

The pharmacokinetics and mechanism of action of acetaminophen include the quick absorption from the gastrointestinal tract within 30-60 minutes. Delays of absorption to peak concentration in the circulatory system can be due to food in the stomach. It is then metabolized by the liver via the three main hepatic pathways including glucuronidation, sulfation, and CYP450 oxidation (44). The half-life is approximately 4 hours, however with hepatic injury or overdose the blood peak level can be accelerated to 2 hours.  

In patients suffering from liver failure, it should be used with caution as one potential adverse side effect could be hepatotoxicity. Therefore, it is crucial that daily dosage be closely monitored (12). Millions of people use over the counter (OTC) pain relievers every day to treat minor aches and pains.  

Usually, these medicines are safe and effective, but they can be dangerous and even deadly when they are not taken as directed (11). Acetaminophen, also called paracetamol in many other countries, is sold by many names including Tylenol, Panadol, Ofirmev, Acephn, and Mapap. 

It is used effectively for fever, muscle pain, neck pain, plantar fasciitis, sciatica and common body aches and pains.  It is abbreviated as APAP for acetyl-para-aminophenol, which is the chemical name and is known by 28 band names in the United States (12).  

It is very commonly used in combination drugs for pain as a nonnarcotic analgesic and known as Excedrin, Goody’s Body Pain, Saleto, Exaprin, Levacet, Painaid, Apadaz, Rhinocaps, Staflex, and included in over-the-counter medications for acute cold symptoms, respiratory conditions, and headaches (43) 

In addition, it is a component of some narcotic prescriptions. Acetaminophen can be used as a sole medication or as an active ingredient in many OTC and prescription medicines. Acetaminophen is generally safe at recommended doses, but if taken in larger dosages or frequency, it can cause serious and even fatal liver damage. In fact, acetaminophen poisoning is a leading cause of liver failure in this country (13). 

Safety guidelines include:  

• Older adults: limit to no more than 3,200 mg in 24 hours.  
• Healthy young adults: can take no more than 4,000 mg.  
• Alcoholism: should limit themselves to no more than 2,000 mg daily.  

Add all sources of acetaminophen into daily totals, including amounts found in combination medicines such as Percocet 5/325, which contains 5mg Oxycodone and 325 mg Acetaminophen. One Percocet 325 mg tablet should count toward the total daily acetaminophen dosage and should be included when prescribing individual dosages to avoid too close an administration of multiple medicines at once.  

As an illustration, if 500 mg of acetaminophen is prescribed every four hours to combat fever while 5/325 Percocet is intended as pain reliever, both medications should not be given together within four hours as it would increase intake significantly and cause too much acetaminophen.   

NSAIDs 

Nonsteroidal anti-inflammatories (NSAIDs) are nonprescription medicines prescribed to relieve mild to moderate discomfort and may also be combined with opioids for treating severe pain. The pharmacokinetics of NSAIDS is based on the absorption, distribution, metabolism, and elimination of the drug as all oral medications. NSAIDS inhibit both COX-1 and COX-2 enzymes and play a role in prostaglandin mediated pain from inflammation (45).  

Although they offer more gastrointestinal protection than aspirin, they do have cardio-nephrotoxic adverse effects. Due to the inhibition of prostaglandins and thromboxane, the desired actions are anti-inflammatory, antipyretic, and analgesic.  

Common examples of NSAIDs are Ibuprofen, Naproxen and Ketorolac. Ibuprofen should be taken every 6-8 hours for adults aged six months or over. Naproxen can be taken 2-3 times per day and provides longer-acting pain relief than Ibuprofen does. Ketorolac may be taken temporarily (up to five days) in cases of moderate-to-severe adult pain relief. Aspirin is often the last line of nonopioids before turning to opioids and may help treat breakthrough pain for patients already taking opioids.  

Side effects from taking an NSAID drug could include dyspepsia, nausea, and vomiting. To minimize risk, NSAIDs should always be taken with food. Long term or high dose use also increases risks such as heart attack, stroke, and heart failure; and must be prescribed carefully for people over 60 or those with liver or renal problems. One notable exception is aspirin, which when taken in low doses may reduce the risk of another heart attack in people who have already had one. NSAIDs may cause gastrointestinal bleeding when combined with warfarin or corticosteroids.  

Narcotic Pain Relief Categories  

Opioid Agonists 

• Codeine 
• Fentanyl 
• Heroin 
• Hydrocodone (Lortab, Vicodin, Percocet) 
• Hydromorphone and Oxymorphone 
• Meperdine 
• Morphine 
• Oxycodone (OxyContin, Percodan) 

Partial Opioid Agonists 

• Buprenorphine (Subutex) 
• Tramadol  

Pure Opioid Antagonists 

• Narcan 
• Naltrexone 
• Nalmefene 

Opioids  

Opioids include codeine, fentanyl, hydrocodone, meperidine, hydromorphone, methadone, morphine, oxycodone, and heroin. Drugs from the class of opioids are powerful analgesics and used for pain management. From 2000 to 2021, more than one million people in the United States died from opioid drug overdoses and over 80,000 died from opioids in 2021 (14).  

Opioids are categorized as schedule 1 or 2 drugs by the Drug Enforcement Agency (DEA). A schedule 2 drug, such as morphine, means that although it has been approved for medical treatment as an analgesic, it has high potential for strong psychological and physiological dependence.  

It has been used for over 100 years as an analgesic. Heroin is made by taking morphine, from the opium plant, and adding a chemical reagent that makes it more potent and potentially dangerous. Heroin is a schedule 1 drug and is not approved for any medical use as it is highly addictive.  

So how did we get to this point of millions of Americans using and abusing opioids? The documented use of opioids began as early as the 3400 BC in Mesopotamia, which they called the “joy plant.” Opium was used for every medical malady from diarrhea, cholera, rheumatism, fatigue and even diabetes by early Egyptians.  

Opium was then regularly traded by Turkish and Arab traders in the 6th century. Opioid use became much more available in the early 1700’s as the British refined the production from the Asian poppy plant grown in the British providence of India and sold in China. What became helpful as analgesia quickly became popular for treating every malady and even used as entertainment in historical records of opium parties (15). British ships filled 1,000 chests of opium into China in the 1760’s and ships gradually increased it to 4,000 chests in 1800 to eventually 40,000 chests in 1838. Opium was so popular in China and the desire for porcelain, silk and tea was equally in demand in the West, so the trading continued.  

Because of its powerful addicting properties to the Chinese citizens, the Chinese emperor Yongzheng (1722-1735) eventually prohibited the sale and smoking of opium, which resulted in two infamous Opium Wars (Britannica). Opium trading eventually became more regulated and slowed during the communist reign in China. Unfortunately, the opium trading continued with new players such as tropical growers and illegal importers from Central and South America to the United States. 

In the late 1800’s Bayer created heroin and misuse was rampant causing regulations and taxes to thwart its use (15). Then after WWII and Vietnam another wave of use and abuse crossed America with the resultant reflex to regulate and tax its use. The war on drugs has continued.  

Opioids are prescribed to manage moderate to severe pain by blocking the neurotransmitter that sends pain signals. Opioids can be administered via oral, intramuscular, intravenous, subcutaneous rectal or transdermal means. Oral opioids such as codeine, hydrocodone and oxycodone are typically prescribed to manage moderate pain.  

Stronger opioids like fentanyl hydromorphone or morphine may be utilized if necessary for more intense discomfort. Morphine is often prescribed for cancer and end-of-life pain treatment because its impact does not reach a plateau point where increasing dosage won't have any more of an impact.  

Opioid drugs include: 

Natural Opioids: 

• Morphine 
• Codeine (Only Available in Generic Form) 
• Thebaine 

Semi-Synthetic 

• Hydrocodone (Hysingla Er, Zohydro Er) 
• Hydrocodone/Acetaminophen (Lorcet, Lortab, Norco, Vicodin) 
• Hydromorphone (Dilaudid, Exalgo) 
• Oxycodone (Oxycontin) 
• Heroin 

Fully Synthetic/Manmade 

• Fentanyl (Actiq, Duragesic, Fentora) 
• Meperidine (Demerol) 
• Methadone (Dolophine, Methadose) 
• Tramadol 
• Levorphanol 
• Pethidine 
• Dextropropoxyphene 

Pharmacokinetics and Pharmacodynamics of Opioids  

Analgesics are a drug class that helps relieve the body from the sensation of pain by blocking chemicals in the neurons throughout the brain that sense pain. Neurons send messages of stimuli from the body to the brain and include different types of neurons that sense different things in the body from temperature, pressure, and even blood acidity and alkalinity.  

The metabolism of opioids occurs through the Cytochrome (CYP-450 enzymes), which blocks the nerves from relaying messages to the brain (46).  

Nociceptors, the nerve receptors for pain, send messages from noxious stimuli to the brain from the skin, walls of organs, and deep within the body such as muscles that something is hurting the tissues. Nociceptors send messages such as pressure, sharp objects, noxious smells, tastes and pain and the brain interprets those for immediate response to protect the body.  

There are several neurotransmitters involved in pain signals, but the main ones are glutamine and substance P. When noxious stimuli trigger the primary neuron through the skin or muscle, the message is relayed by a secondary neuron to the spinal cord’s dorsal root ganglion towards the brain for interpretation.  

These chemicals are relayed to the thalamus in the brain and then onto the limbic system for an emotional response. Ideally the message to the limbic area of the brain promotes learning to avoid the cause of the noxious substance in the future. Opioids inhibit pain signals at multiple areas in this pathway. 

Opioids affect the brain, spinal cord, and even the peripheral nervous system. Opioids work on both directions of messages in the nervous system including the ascending pathways in the spinal cord, which are inhibited and the descending pathways, which block inflammatory responses to noxious stimuli. In the brain, opioids cause sedation and decrease the emotional response to pain.  

Heroin, like morphine, passes through the liver and then is released back into the blood where it passes the blood-brain barriers. Heroin is then converted to morphine where it connects with mu receptors, but only faster and heroin is three times more potent than morphine (18).  

Opioid receptors are found on both the primary and secondary neurons and when an opioid binds to these receptors no other pain signals are sent up to the brain, making opioids very effective against pain. Naturally these endogenous analgesic receptors include human endorphins, which comes from the name endogenous morphine.  

Our bodies have three receptors called mu, kappa and delta which can be activated by opioid agonists like morphine, hydrocodone, or heroin. When mu receptors are activated, dopamine, a natural brain chemical, is also increased, which is the brain’s chemical for pleasure. Pleasurable feelings are inherently worth repeating, which drives the user to repeat the drug use (18).  

Short term sensations of opioids include the following:  

• Warmth sensation through skin and body 
• A feeling of heaviness in arms and legs 
• Pain relief 
• Dry mouth 
• Itchiness 
• Possible dry mouth 
• Drowsiness 
• Slow heart functioning. 
• Slow breathing. 
• Relaxation 
• Sense of well being 

Opioid agonists come with additional noxious side effects. When a kappa receptor is stimulated it can also produce hallucinations, anxiety, and restlessness. The Delta and mu receptors can cause respiratory depression because as the midbrain is stimulated it suppresses the body’s ability to detect carbon dioxide levels in the body, which is the main stimulus for breathing. Other negative side effects include constipation, sedation, nausea, dizziness, urinary retention, and tolerance.  

Tolerance is the requirement of the body to need increased amounts of the drug to reach its desired effects, which is why opioids can become addictive as the person requires more of the drug to achieve the desired pain relief (18). The key ingredient in opium is morphine, which began to be produced formally by the pharmaceutical company Merck. It was also discovered that when administered by IV, morphine is 3 times more potent than administered by other methods such as smoking or snorting.   

Long term use of opioids has been shown to cause the deterioration of the brain’s white matter and include long term effects of insomnia, chronic constipation, sexual dysfunction, irregular menstrual cycles in women, kidney disease and physical damage as a result of the administration technique such as snorting, smoking or IV drug use.  

Although cocaine and morphine both have effects on the neurotransmitter dopamine, they work in different ways. Whereas the opioids increasing dopamine stimulation, cocaine blocks the reuptake of existing dopamine and makes it last longer producing a longer state of pleasure. Both opioids and cocaine drugs influence the brain’s interpretation of the pleasure drive reinforcing the drive for repeated behavior to get the drug.  

In addition to the short-term withdrawal symptoms, long term opioid use causes:  

• Decreased ability in decision making. 
• Decreased ability for self-reflection and discipline. 
• Decreased ability to effectively respond to stress. 

Opioids can be effective pain relievers yet can become highly addictive if used improperly. Of the potential adverse reactions associated with opioid use, respiratory depression is the most serious. Those taking opioids must monitor for decreased respiratory rate, oxygen saturation, and heart rate after receiving them. Those taking opioids for the first time or receiving increased doses, taking concurrent benzodiazepine use such as alcohol consumption or other sedatives may experience a more significant respiratory depression.  

Treating opioid-induced respiratory depression requires treatment with Naloxone, which binds the mu receptors that opioids act on. Naloxone comes in a variety of preparations, including nasal spray, auto-injectors, and injectables. 

(49) 

Online Resource:  

• The American Medical Association video on how to use Naloxone: https://www.ama-assn.org/delivering-care/overdose-epidemic/how-administer-naloxone 

The Pain of Opioids 

The Center of Disease Control has declared the overuse and abuse of opioids an epidemic (14). Ninety-one (91) Americans die every day from an opioid overdose (14). The US consumes 99% of all the world’s hydrocodone, 80% of the world’s oxycodone, and 65% of the world’s hydromorphone prescription opiate supply. 25% of all workers’ compensation costs relate to opioids and $56 billion/year is spent on opioid abuse costs. Trends of opioid overdose related deaths have increased 5.5% annually from 6 deaths per 100,000 people in the US in 1999 to 16.3 in 2015.  

In adults aged 45-54 the death rate from drug overdose was the highest of all age populations showing a constant trend upward of 10% annual increase in abuse and deaths (16). Clearly, America has an opioid epidemic that is claiming lives and lifestyles. Additional statistics, not as easily identified but very real, include lost productive work hours and loss of meaningful lives, families, and marriages due to opioid abuse (17). 

Patients taking opioids must also be monitored for less severe side effects, such as constipation, nausea and vomiting, urinary retention, and itching. Opioids slow peristalsis and increase reabsorption of fluid into the large intestines, thereby slowing the passing of stool and removing the fluid from the stool so that it becomes concrete-like. It is important for the nurse to assess bowel functioning and encourage fluid and fiber intake and ambulation throughout the course of opioid treatments.  

The provider can prescribe a bowel management program that includes a stool softener (such as docusate) and a stimulant laxative (such as sennoside, bisacodyl, or milk of magnesia). Should nausea and vomiting occur, antiemetics (such as prochlorperazine or ondansetron) may be prescribed. Antihistamines (such as diphenhydramine) may be prescribed for subsequent itching; however, they may cause drowsiness and exacerbate the potential for opioid-induced respiratory depression. 

Fentanyl 

The Centers of Disease Control has estimated that over 20,000 Americans died from fentanyl overdose in 2016 and that rate continues to climb in America. Fentanyl production in China has surged with the high demand for it in America and it has been called the new nuclear narcotic in the Opium War Against America (19).  

Names of Fentanyl 

Prescription Street Names 

• Abstral: China Girl or China Town 
• Actiq: Dance Fever 
• Duragesic: Friend 
• Fentora: Goodfellas 
• Instanyl: Great Bear 
• Lazandal: He-Man 
• Sublimaze: Jackpot, King Ivory, Murder 8, Tango and Cash, Per-a-Pop (berry flavored Fentanyl lozenge)  

One danger of fentanyl use is when fentanyl is mixed in with street drugs such as heroin and the user is unaware of what they are receiving. The quantity of fentanyl in street products also varies widely and can become quickly fatal as doses exceed what would have been carefully prescribed. Illegal street use without guidance, monitoring and education have created the dangerous opioid epidemic. The fully synthetic drugs such as fentanyl are much more potent and have the higher potential for abuse and death (19).  

As an analgesic, fentanyl is 100 more potent than morphine and 50 times more potent than heroin (20). Ohio forensic testing in 2017 revealed 99% of their narcotic overdose deaths were fentanyl related and often due to combinations of synthetic fentanyl products including 25 fentanyl analogs such as acryl fentanyl, nor fentanyl and furanyl fentanyl.  

The state also determined that males accounted for 64% of overdose deaths and 92% were white (21). Over half of the deaths in Ohio were in persons aged 25-44 years (22).  Trends continue to rise and causes point to the increased prescriptions of opioids for chronic pain and the availability of these drugs in non-prescription form.  

Route and Administration of Fentanyl 

Opioids can be administered by FDA approval through the subcutaneous, intramuscular, and intravenous and oral routes but due to variations in first-pass liver metabolism there are variations of response by users. Non-prescription drug users often speed the delivery by nasal and intravenous administration.  

The potency of fentanyl and carfentanil have been demonstrated by the rapid deleterious effects on police officers who have come in contact with the powder through their skin during drug investigations and raids. One police officer overdosed just by brushing power off his uniform with his hand (23). 

Subcutaneous fentanyl is commonly used to address chronic local pain, such as in a transdermal fentanyl patch that has a slow-release action. When fentanyl is delivered through more rapid routes such as IV or intranasal, the response is much quicker and therefore potentially fatal.  

Fentanyl is usually administered by injection or topical patch in the hospital setting. It may be prescribed through the intradermal route for chronic pain and is classically used for chronic lower back pain. 

Contraindications 

It should not be used by someone who is allergic to the drug, has any type of breathing problem, a history of head or brain injury, liver or kidney disease, slow heart rhythms, concomitant use of sedatives like Valium or if a MAO inhibitor has been used in the recent 14 days or the client is already taking another narcotic.  

There are no adequate studies to confirm safety or danger in pregnancy or breastfeeding so providers must be notified, and careful clinical decision making must be considered to weigh benefits from any possible damage to infants and mothers as it is a Category C claiming risk cannot be ruled out (24).  

Patient Education and Support 

Online and face-to-face support groups are available to help with effective and appropriate use of fentanyl. Often the only information provided is about the serious opioid epidemic and potential risk for addiction and abuse, however when used properly and within the clear instructions given by a medical provider who is monitoring for adverse reactions, it can be a helpful option for people in very real chronic pain.  

Using any medications as directed is important because the route has been chosen for a specific reason. Unfortunately, a dangerous practice of chewing on a transdermal patch can speed up the delivery of the drug and create addiction and possibly respiratory depression or death. Mental and physical dependence can still occur even at prescribed doses so patients must be carefully monitored.  

Supporting patients in their quest for relief from pain and judgement is extremely important. In the national conversation about opioid abuse, patients who have a real need for chronic pain continue to suffer as physicians are attempting to prescribe less, and pharmacies are blocking repetitive refilling of narcotics.  

The dialog for effective pain management and effective systems to prevent opioid abuse must continue in creative, non-judgmental, and respectful ways. Encouraging support groups who can speak freely about issues and concerns can be helpful. Not all people who use fentanyl are drug addicts and should not be treated as such.  

The pain blocking effects of intradermal fentanyl often takes from 12-48 hours and often up to 72 hours and may require a breakthrough alternative to pain relief until the full effect is in action. Titrating carefully for pain relief is required based on individualized patient needs. Variations in the need for higher dosages depends on the location of a transdermal patch, the quantity of fat on the body area and dryness of the skin it is applied to.  

All patients should be taught to avoid alcohol consumption if using fentanyl. Patients also need to be aware that the narcotic may remain in the blood stream for up to three days and can be in hair and urine. Drug testing for abuse or employer requirements is most commonly done on hair and urine.  

Patient-Controlled Analgesia 

Patient-controlled analgesia (PCA) allows a patient to self-administer opioid medications such as morphine, hydromorphone, and fentanyl without requiring a nurse to give each injection, by using an automatic pump programmed with their dosage amount and rate/volume settings (37). A locked computerized pump connects directly to their IV line where medication syringes can be safely locked inside ready for an infusion at scheduled rates/volume settings; its programming ensures medication infusion occurs at its intended rate/volume setting without exceeding prescribed amounts. 

Doses of medication can be self-administered on an as-needed basis by pressing a button. Patients may give themselves doses according to an adjustable schedule that includes preset interval times and dose limits per hour, up to four in total per hour limit. If these criteria are fulfilled, the PCA button illuminates to alert patients that doses can be administered when needed. Even when not illuminated, pressing it still delivers medication.  

PCAs may only be used for patients who are alert, oriented, and can independently press the button. Because small doses of opioids are administered frequently, it is important to monitor patients for oversedation and respiratory depression. To reduce the risk of these adverse events, the patient and all caregivers should understand that no one should press the PCA button except the patient. Nurses should also ensure that the PCA button is easily within the patient’s reach, as patients on PCAs are at a high risk for falling. 

Given the potential risk associated with PCA medication errors, both incoming and outgoing nurses should independently double check to verify correct drug, concentration, and dose (loading dose, PCA demand dose, continuous dose), lockout interval and 4-hour limit settings of their pump settings (37). When providing bonuses or changing any settings or replacing medication syringes two nurses will always be needed to verify results accurately. 

As part of their PCA treatment, it is vital that patients carefully monitor their vital signs to detect possible indicators of respiratory depression such as decreased respiratory rate, oxygen saturation levels or heart rate. Nurses must follow organizational protocols when administering PCA medications - usually including taking baseline vital signs prior to commencing administration, for an extended period post administration and then every two hours for its duration.  

Co-Analgesic Medications 

Co-analgesics, commonly referred to as adjuvants, are medications with analgesic properties; however, their primary purpose is not pain relief. For instance, antidepressants are usually taken for treating depression but may also help manage chronic pain symptoms, like sleep issues and muscle spasms. Anxiolytics may help relieve anxiety symptoms but could potentially also treat chronic pain-related anxiety as well as relax muscles. Anticonvulsants used for seizures also block pain receptors and help with providing relief from certain forms of neuropathic pain while corticosteroids reduce inflammation while simultaneously managing this kind of discomfort from injured nerves. 

Patient Education 

Prescribers have an obligation to educate patients appropriately on pharmacological pain interventions, in a culturally and linguistically sensitive manner. Drug education should help the patient comprehend the treatment plan, improve adherence to the treatment plan, alleviate fears while setting realistic expectations and discussing concerns openly, all to ultimately contribute to improved health, well-being, and patient outcomes. 

Education should start when treatment commences and continue throughout the duration of therapy. A personalized approach tailored specifically for each individual should include considering the primary language spoken by the patient as well as culture, age, cognitive function, and health literacy level.  

Simple language with clearly defined technical terms used along with open-ended questions as well as visual materials like demonstration videos/pictures or handouts may prove highly useful during education sessions. It is crucial not to wait until severe discomfort before seeking medication as once pain becomes extreme it becomes much harder to control and may require stronger medications.  

Nurses should help patients understand the typical progression of pain medication prescribed through the pain ladder model. Patients need to comprehend why nonopioids need to come first before adding opioids or adjuvants into the regimen. Acute surgical pain patients, in particular, must know that although opioids might initially provide relief, their ultimate aim should be reducing dependency through intravenous, oral, and then nonopioids prescription. 

Patients must also be educated on the need to use only as much pain relief medication as necessary to reach the intended pain goal. If their provider prescribes two tablets every four to six hours, for instance, it's wiser for them to start with just one and gradually add on additional pain relievers as required. They should be advised against exceeding prescribed amounts as soon as they start feeling any relief. Before initiating any medication treatment plan, patients must receive proper instruction about its name, dose, route, and frequency of administration.  

It's also essential that any special instructions regarding when it should be taken such as with or without food, be written for the patient as well as storage tips to protect medications safely away from children by either keeping out of reach or locking up safely. 

Every time they receive medication, patients should be educated on its potential adverse side effects as well as when to report them. When opioids are prescribed, patients should understand the potential risk for constipation, respiratory depression and addiction and also be advised that taking opioid medication could make them feel sleepy. Additionally, they must not consume alcohol, drive heavy machinery, take any unapproved drugs while on such medicines or take other drugs not approved by their prescriber at that time. 

Patients often hold incorrect assumptions about pain management that require being addressed. Therefore, it's crucial that an assessment be completed of each individual and any misconceptions discovered. For instance, they might fear taking opioids due to concerns they will become dependent. Although long-term opioid usage could potentially lead to dependence issues, short-term use should still be weighed against its benefits regarding being tapered as quickly as possible. 

Non-Pharmacological Pain Alternatives 

Nonpharmacological interventions may be combined with or without pharmaceutical medicines as they often provide tremendous benefits. As with all treatments, nonpharmacological interventions must be documented within a plan of care to determine their ability to fulfill pain relief goals effectively. Non-pharmacological pain management techniques may fall under either complementary or alternative medicine categories. Though sometimes interchanged, there is a distinct distinction: complementary therapies work alongside pharmaceutical pain treatments while alternative therapies are practiced as an alternative from standard pharmaceuticals. 

Substance Use Disorder 

According to the Centers for Disease Control and Prevention (CDC), one out of every seven Americans reports having experienced some form of substance use disorder in the last month (25).  

Defining Substance Use Disorder (SUD) 

Substance Use Disorder, according to the Centers for Disease Control (CDC), is defined as any pattern of substance abuse which leads to clinically significant impairment or distress, from substances including alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, stimulants, and tobacco (25). A substance use disorder (SUD) may range in severity between mild, moderate, or severe cases. 

Addiction, which is one of the more serious forms of substance use disorder (SUD), refers to continued drug consumption despite negative consequences, and should be seen as a medical disease rather than character description. Therefore, people living with SUDs should not be labeled abusers, addicts, alcoholics, or "medication seekers," since such language can be stigmatizing and isolating.  To reduce the stigma surrounding substance use disorders we focus instead on medical diagnoses of each specific case and offer effective solutions. 

Though Substance Use Disorder (SUD) is considered treatable, recovering can still be challenging for many. Individuals suffering from an SUD often cannot stop taking the substance in question without experiencing excruciating withdrawal symptoms. Sometimes another drug may help wean patients off problematic opioids, such as methadone, buprenorphine or naltrexone which are all widely prescribed to treat opioid addictions. Patients may benefit from participating in programs like 12-Step Facilitation Therapy, outpatient counseling to better understand addiction and triggers, or inpatient rehabilitation at full-time facilities that offer supportive environments without distractions or temptations for recovery.  

Definitions of Use and Abuse 

Understanding the differences between dependence and addiction is paramount for understanding opioid misuse and abuse. Dependence refers to physical tolerance that requires increased doses to produce desired responses. Addiction occurs when that threshold has been passed and greater amounts must be administered for desired responses to be realized. Withdrawal from drugs will often bring on physical symptoms like shaking, tremors, nausea, and vomiting.  

Addiction refers to an emotional need for drugs with desirable effects that leads to strong drug seeking behavior. Opioid dependent individuals will tend to oscillate between feeling sick without taking their prescribed dose and experiencing the desired high after taking it. Being addicted is the driving force for individuals trying to obtain and take more opioids in order to avoid withdrawal symptoms. 

Withdrawal symptoms include the following (16):  

• Intense drug cravings 
• Depression, withdrawal fears, anxiety 
• Sweating, watery eyes, runny nose 
• Restlessness, yawning 
• Diarrhea 
• Fever and chills 
• Muscle spasms 
• Tremors and joint pain 
• Stomach cramps 
• Nausea and vomiting 
• Elevated heart rate and blood pressure  

Populations at Risk 

People at risk for opioid dependence and addiction are seen in every age, gender, ethnicity, and culture. Physical dependence varies as a genetic component has been identified, which influences how quickly a person may slide from occasional use to physical need and addiction to the drug (26). Susceptible populations have typically included the homeless, alcoholics and those with personality or mental health disorders who look for opiates to block the emotional pain of life stressors.  

Healthcare professionals who also experience great work stress have a higher risk of becoming dependent or addicted to opiates due to back injuries and easier access to narcotics in their work setting (26).  

How Pain Control Becomes SUD 

Scheduled drugs such as narcotics, and even alcohol have the potential to become an addictive substance. Opioid abuse may lead to opioid Use Disorder, or OUD for short. OUD occurs due to problematic patterns of opioid usage. Opioids work by stimulating endorphin release in the brain, producing feelings of pleasure that make them highly addictive. Opioid use disorder (OUD), however, often leads to physical dependence, which is when someone believes they cannot function without using certain substance(s).  

Dependence should not be mistaken for tolerance, which occurs when your body requires increasing quantities of the drug to achieve similar pain relief over time. When someone who is dependent on drugs reduces or ceases taking it altogether, withdrawal symptoms could ensue. SUDs have become a serious public health risk in the U.S.  

Caption: These data, from 2019–2020, show the number of people in the United States affected in different ways by the opioid epidemic.  

(Image Source: https://www.hhs.gov/opioids/statistics/index.html) 

Prevention Strategies 

The best treatment for any drug overdose is prevention. Because of the national attention to the opioid epidemic and harsh statistics of deaths caused by fentanyl overdose, political, federal, state and even pharmaceutical companies have made efforts to address the problem. One strategy is to decrease the availability of prescriptions for opioids and fentanyl, however that makes it difficult for those with real pain to receive the medication.  

Monitoring drug prescription use, and public education are additional strategies. The Food and Drug administration has produced guidelines for effective pharmacological use of opiates, which includes the identification of persons at risk, assessing a patient’s benefit vs. risk, developing, and using tools to decrease risks of opiate prescription use such as contracts for pain management and standards of required 30-day physician visits before new prescriptions can be refilled.  

The CDC Clinical Practice Guidelines for Prescribing Opioids for Pain advises healthcare providers to review a patient's history with controlled substance prescriptions prior to prescribing opioids (28).  

Providers can gain insight into a patient’s history of opioid prescribing via an electronic database tracking-controlled substance prescriptions known as Prescription Drug Monitoring Program (PDMP). PDMPs also alert healthcare providers of other medications a patient is taking that might increase his/her risk for opioid overdose, making PDMPs particularly helpful when transitioning between providers or when medication histories cannot be provided by patient themselves. Prior to prescribing opioids and at least once every three months when continuing therapy, the database should be reviewed.  

• Online Resource: https://www.cdc.gov/phlp/publications/topic/prescription.html 

CDC Public Health Law Program: provides resources regarding state laws on prescription drug misuse and abuse.  

Prevention strategies include:  

• Patient education regarding use of opiates 
• Pain contract signed by patient to agree to terms of drug use 

• Prescription monitoring programs to detect multiple use of pharmacies and physicians for opiates. 
• Detection of inappropriate prescribing of opioids 
• Photo identification to pick up opioid prescriptions 
• Urine toxicology screening for employees 
• Safe disposal of unused opioids 
• Referrals to pain and addiction specialists 
• Use of semi-synthetic opioid alternatives 

Patient education regarding the use of opiates, and truly all prescription medications, is essential to understand the need for the drug, its side effects, and adverse effects. An additional pain contract should be included with the patient education, which outlines the parameters for the use of the drug. Especially when used for chronic pain management, patients should be partners with the prescriber to outline when the drug will be used and for how long.  

Prescription monitoring programs include detection systems in pharmacies and the local district that identify patients who have filled a narcotic prescription. In many states, photo ID is already required for the purchase of cigarettes or alcohol and could become a beginning point to dissuade unauthorized and high frequency prescription use.  

According to the National Alliance for Model State Drug Laws, currently 85% of states require ID for narcotic prescription use (27). Some drug stores even run the name of a client picking up a narcotic prescription through a drug monitoring data system for alerts. The challenge is for busy pharmacists to take the time to use the monitoring system and for patients to be patient as the process is completed.  

Possible “red flags” that could lead to prescription denial:  

• A pain medication not previously filled the pharmacy. 
• A new doctor is writing a prescription for the same pain medication. 
• A doctor writing a prescription who is not in a “reasonable geographic location” near the pharmacy. 
• A patient paying for a prescription in cash. 
• A patient seeking an early refill of a prescription. 
• A patient seeking an “excessive” number of pills. 
• A patient taking the same pain medication for more than 6 months. 

Another strategy includes receiving prior authorization before opiates can be filled. In 2007 the FDA passed an amendment to create a patient registry for opioids. In 2012, Blue Cross Blue Shield began to require prior authorization for more than a one-month supply of opioids in a two-month period. By this simple process alone in the state of Massachusetts, the number of opioid prescriptions decreased by more than 6,500,000 pills in one year (29,31). 

Safe disposal of opioids is a challenging issue as many people believe that flushing them down the toilet is appropriate, which it is not. Public education and awareness programs should also include safe medication disposal such as mixing with used coffee grounds, dirt or kitty litter and placing in a sealed container to then dispose of in the garbage. Used opioid patches should be folded in half on the sticky sides and disposed of in a sealed container in the garbage.  

Patient Screening Tools 

Several screening tools are available to help clinicians identify when a patient taking opioids may be experiencing dependence or addiction.  

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based practice used to identify, reduce, and prevent problematic use, abuse, and dependence on alcohol and illicit drugs” (30). The SBIRT model was inspired by a recommendation from the Institute of Medicine to increase community-based screening for health risk behaviors, including substance use. SBIRT is an early and brief intervention of 15-30 minutes and billable to Medicare/Medicaid. The screening and referral to treatment includes a patient encounter, history, physical exam, clinical diagnosis, and plan for care specific to the concern of substance abuse other than for those patients already identified with severe substance abuse. The SBIRT screening tool can be as simple as asking several key questions of patients receiving narcotics and opioids at every doctor’s office visit.  

The Opioid Risk tool is another brief screening tool of questions to help identify a patient at increased risk for dependence and abuse. Currently no one tool has been identified to be better than any others, nor is any one tool sufficient to identify drug behaviors of chronic pain patients using opioids (31, 32).  

Here is an example of an opioid screening tool:  

(50) 

Treatment for SUD 

Managing pain for those living with substance use disorder can be challenging. Everyone deserves respect and to have their pain appropriately managed, which requires taking an integrated, patient-centric approach to include both pharmaceutical and nonpharmaceutical interventions. Before medicating with opioids for pain management in those suffering from OUDs, nonpharmacological therapies and nonopioid medications must first be explored as effective options. Such nonpharmacological approaches might include therapeutic exercise, physical therapy, cognitive-behavioral therapy (CBT), complementary and alternative medicines as well as complementary and alternative remedies (CAMs).  

Nonopioid medications that could be useful include nonsteroidal anti-inflammatory drugs (NSAIDs), topical analgesics and adjuvant medicines like serotonin-norepinephrine reuptake inhibitors, CBT, and combination SSRI/SSNI or tricyclic antidepressants.  

If pain levels necessitate opioid use, opioids should not be withheld from patients with OUDs. As with any patient, it's essential that shared goals and risks are established along with an agreed upon treatment agreement and close monitoring via scheduled follow-up visits in order to reassess pain levels regularly. In general, starting off with a low dose and gradually increasing as needed is the standard. Creating a pain agreement with the patient is required.  

Reducing Stigma Against SUD 

In addition, working to decrease the stigma of SUD can be helpful for those seeking medical assistance (33). Pain clinics are a newly developed specialty, which allow patients suffering from chronic pain to work with a pain specialist for more effective management using a variety of modalities. It is estimated that at least 100 million Americans live with chronic pain. Pain clinics can offer help focusing on procedures that deal with specific pain such as neck and lower back pain.  

They can also approach pain through an interdisciplinary approach involving psychologists, physical therapists, nutritionists, occupational and vocational therapists in addition to physicians and nurses. Other modalities such as acupuncture, biofeedback, cognitive behavioral therapy, water therapy, massage and meditation can be options for chronic pain in lieu of just relying on opioids. Patient education as well as for the prescriber needs to include these alternative treatment strategies.  

Recognition of opioid use within healthcare professionals has been addressed by the National Council of State Boards of Nursing. A free educational webinar for understanding substance use disorder in nursing is available to nurses and managers to help identify signs of opioid use and abuse. It also outlines the system of helping professionals with therapy and recovery. It can be accessed at https://www.ncsbn.org/5127.htm 

Acute Treatment for Overdose 

Treatment for opioid abuse generally starts with treatment of withdrawal in the acute phase. Managing symptoms of overdose and preventing death are the first objective. Securing an airway and supporting the patient during the tremors, seizures, hypertension, nausea, vomiting, and pain are often handled in an ER and medical/surgical setting.  

Naloxone (Narcan) can be used for reversal of opioid overdose and is available in IV, SQ, IM and nasal routes. If a patient is unconscious, follow the ABCs of emergency response such as calling 9-1-1, checking for a pulse, securing an open airway, and providing rescue breaths. Give the first full dose of naloxone and continue rescue breaths. If the patient doesn’t respond give the second full dose of naloxone.  

Patients will often respond quickly and be confused and possibly combative. Monitor the patient after recovery with naloxone to prevent another dose of an opioid and follow up medical attention.  

Using pharmacological blocking agents is helpful in stopping opioid overdose. Antagonist medications block opioid receptors so that the desired effect is no longer active. Two opiate substitution medications are currently available in the United States and include methadone and levomethadyl acetate but are only available in strictly regulated environments where medication is received under clinical observation and limited out-patient use.  

Methadone and buprenorphine are synthetic opioid agonists and act on the same mu receptors that opioids activate and therefore has been a popular treatment for addiction, known as Opioid Substitution Therapy (OST). Methadone has a slow onset of action and long elimination half-life of about 24 hours. A longer acting opioid receptor agonist is Buprenorphine, a partial opioid agonist and can reduce cravings and symptoms of withdrawals. These drugs can be taken less frequently and can help wean a patient from the more fatal opioids. Control trials show that it is more effective than a placebo and can help decrease fatalities from opioids. Access to these drugs is still dependent upon physician-controlled prescribing or treatment programs.  

Getting into approved treatment programs where these drugs can be given and monitored closely, in combination with behavioral therapy is often difficult, expensive, and not approved by insurance companies. The strict control of these opiate-substitution drugs is necessary because they do produce a euphoric sensation like the opiates and the tight regulation is due to the fear of creating a new market of illicit use for these. These medications can be given in sublingual, oral and even intranasal forms. By giving these opioid antagonist drugs, they act as competition for the mu receptors and ideally block the effectiveness of other opiates.  

Future of SUD Efforts 

Our nation’s opioid epidemic and increase in SUD prevalence is complicated and concerning. Thousands of lives are lost needlessly due to SUD addiction and overdose. Education of prescribers and patients is needed. Legislation is needed and debated for opioids available on the market and how to regulate their use.  

States must decide on the training and availability for the use of naloxone and opioid agonists for overdose and weaning. Healthcare professionals must learn to collaborate with pharmacists, nutritionists and behaviorists who work with those with chronic pain to offer more options for pain management. Schools and public officials such as police workers must be able to improve security to dissuade drug sales.  

Each of the proposed strategies to fight our national war on drugs is at various stages of development and implementation and take time. The cost to implement programs, educate stakeholders and evaluate any negative consequences to appropriate treatment plans for pain needs patience. In the meantime, small efforts can save lives. Your efforts to learn more about the substance use disorder and the opioid epidemic are a notable step for improvement.  

Key Terms  

Acute pain: short-term pain, typically lasting from minutes to up to three months. 

Acupuncture is a pain management technique that inserts thin steel needles into the skin to stimulate specific points throughout the body. 

Addiction is the most severe form of Sud, in which there is continued use of the substance despite negative consequences. 

Alternative therapies treatments used in place of pharmacological pain management. 

Animal-assisted therapy is a treatment that utilizes animals to reduce pain, anxiety, or depression. 

Aromatherapy is the inhalation or dermal application of essential oils. 

Breakthrough pain: sudden increase in pain that lasts for a short time. 
Chiropractic therapy is a pain management technique that manipulates the spine, joints, and skeletal system. 

Chronic pain: pain lasting longer than six months. 

Complementary therapies treatments used in combination with pharmacological pain management. 

Dependence inability to function without the use of a substance. 

Faces scale: a visual tool for assessing pain with children and others who cannot quantify the severity of their pain on a numerical scale. 

FLACC scale: a pain scale used to assess pain in children between the ages of 2 months and 7 years, as well as those unable to verbally communicate. 

Hypnosis is the creation of a trance-like state to enhance awareness of feelings, thoughts, and sensations. 

Imagery positive, relaxing images created in the mind. 

Massage is a pain management technique that manipulates the soft tissues of the body to relieve tension and create relaxation. 

Meditation is the practice of breathing and repeating certain words to reduce stress and put the mind at ease. 

Mindfulness is the practice of focusing on the present moment to create awareness of thoughts, feelings, the body, and the environment. 

Numerical scale: a pain scale that rates pain on a scale of 0 to 10. 

Neuropathic pain: pain caused by damage to nerves or other parts of the nervous system. 

Nociceptive pain: pain caused by damage to body tissue. 

Nociceptor: a type of sensory receptor that responds to potentially damaging stimuli by sending nerve signals to the spinal cord and brain. 

Normal pain: pain of the expected severity and duration, according to its cause. 

Pain is an uncomfortable or unpleasant sensation that typically signifies injury or illness. 

Opioid use disorder (oud) a type of Sud caused by a problematic pattern of opioid use leading to physical dependence. 

Pain assessment in advanced dementia scale: a pain scale used to assess pain in patients with advanced dementia. 

Phantom pain: pain perceived to be coming from a missing body part. 

Referred pain: pain in one part of the body that is caused by pain in a different location of the body. 

Reflexology is a pain management technique that applies massage to specific pressure points aligned with the body in the hands and feet. 

Reiki is a pain management technique in which one person uses lightly placed hands to guide energy throughout another person’s body. 

Somatic pain: pain experienced in the muscles, skin, or bone. 

Substance use disorder (SUD) is a problematic pattern of substance use leading to clinically significant impairment or distress. 

Tai chi is a practice that combines exercise and meditation with slow body movement and controlled breathing. 

Thermotherapy is the application of heat or cold to alter the cutaneous, intra-articular, and core temperature of soft tissues.  

Tolerance the state of requiring more of a drug over time to achieve the same level of pain relief yoga the practice of using specific stretches, poses, meditation, and controlled breathing to balance the mind and body. 

Visceral pain: pain experienced in the internal organs. 

Withdrawal physical and mental symptoms experienced when a person suddenly stops or decreases the use of an addictive substance. 

Controlled Substances

Introduction   

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

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

Definition of Pain

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

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

Their expansion is summarized below:

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

Types of Pain

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

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

Acute Pain

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

Chronic Pain

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

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

Nociceptive Pain

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

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

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

Neuropathic pain

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

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

Affective pain

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

Case Study

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

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

Assessment

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

Record Review

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

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

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

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

Case Study

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

Pain Assessment

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

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

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

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

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

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

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

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

(21).

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

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

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

(21).

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

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

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

Case Study

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

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

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

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

Opioid Classifications and Drug Schedules

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

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

(Pain Physician, 2008)

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

(41).

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

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

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

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

Hydrocodone

Mechanism of Action and Metabolism

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

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

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

Available Forms

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

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

Dosing and Monitoring

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

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

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

Side Effects and Contraindications

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

Other adverse effects of hydrocodone include:

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

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

The most common drug interactions are listed below:

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

Considerations

Use with caution in the following:

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

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

Oxycodone

Mechanism of Action and Metabolism

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

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

Available Forms

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

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

Dosing and Monitoring

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

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

Side Effects and Contraindications

Common side effects of oxycodone include:

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

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

It is also contraindicated with the following medications and classes:

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

Considerations

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

Morphine

Mechanism of Action and Metabolism

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

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

Available Forms

Morphine is available in various forms, including.

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

Dosing and Monitoring

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

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

Prescribe IR opioids instead of ER opioids.

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

Side Effects and Contraindications

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

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

Contraindications of morphine are:

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

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

Morphine interacts with the following medications:

• Ciprofloxacin
• Metoclopramide
• Ritonavir

Considerations for Nurse Practitioners

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

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

Fentanyl

Mechanism of Action and Metabolism

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

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

Indications for fentanyl are as follows:

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

Available Forms

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

Dosing and Monitoring

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

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

Fentanyl is most dosed as follows:

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

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

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

Side Effects and Contraindications

Common side effects of fentanyl include:

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

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

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

Considerations for Nurse Practitioners

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

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

Hydromorphone

Mechanism of Action and Metabolism

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

Hydromorphone is indicated for:

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

Available Forms

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

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

Dosing and Monitoring

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

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

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

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

Side Effects and Contraindications

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

Common side effects of hydromorphone include:

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

Caution should be exercised in patients with:

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

Considerations for Nurse Practitioners

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

Additional Considerations

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

Hydromorphone requires careful administration in cases of concurrent psychiatric illness.

Specific Patient Considerations:

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

Tramadol

Mechanism of Action and Metabolism

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

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

Tramadol is used for moderate to severe pain.

Available Forms of Tramadol include:

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

Dosing and Monitoring

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

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

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

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

Side Effects and Contraindications

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

Common Side Effects of Tramadol Include:

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

Serious side effects include:

• respiratory depression
• serotonin syndrome
• seizures

Contraindications

Tramadol is contraindicated in patients with:

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

Additionally, the following can be observed in tramadol intoxication:

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

Poisoning leads to:

• multiple organ failure
• coma
• cardiopulmonary arrest
• death

Considerations for Nurse Practitioners

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

Tramadol poisoning can affect multiple organ systems:

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

Cannabis

Mechanism of Action and Metabolism

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

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

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

Available Forms

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

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

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

Dosing and Monitoring

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

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

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

Side Effects and Contraindications

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

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

Contraindications include:

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

Case Study

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

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

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

Opioid Use, the Opioid Epidemic, and Statistics

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

History of Opioid Use

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

The Opioid Epidemic

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

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

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

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

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

Statistics on the Opioid Epidemic

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

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

Federal Regulations on Opioid Prescribing

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

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

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

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

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

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

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

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

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

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

The 2022 CDC guidelines are summarized below (13):

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

Safe Prescribing and Prescription Monitoring Program

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

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

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

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

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

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

Case Study

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

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

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

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

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

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

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

Preventing Opioid Use Disorder

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

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

Physical Symptoms

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

Behavioral Changes

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

Social Isolation

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

Psychological Changes

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

Tolerance and Withdrawal Symptoms

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

Opioid Overdose

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

Naloxone

Mechanism of Action and Metabolism

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

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

Available Forms

Naloxone is available in various formulations:

• Intranasal
• Intramuscular
• Intravenous
• auto-injectors.

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

Dosing and Monitoring

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

Side Effects and Contraindications

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

Common side effects of naloxone include

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

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

Considerations for Nurse Practitioners

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

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

Methadone

Mechanism of Action and Metabolism

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

Available Forms

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

Dosing and Monitoring

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

Side Effects and Contraindications

Common side effects of methadone include:

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

Contraindications include:

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

Considerations for Nurse Practitioners

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

Buprenorphine

Mechanism of Action and Metabolism

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

Available Forms

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

Dosing and Monitoring

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

Side Effects and Contraindications

Common side effects of buprenorphine include:

• Constipation
• Nausea
• Headache
• Insomnia
• Sweating

Serious side effects are rare but can include:

• Respiratory depression
• Allergic reactions

Buprenorphine is contraindicated in individuals with:

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

Considerations for Nurse Practitioners

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

Clonidine + Lofexidine

Mechanism of Action and Metabolism:

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

Available Forms

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

Dosing and Monitoring

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

Side Effects and Contraindications:

Common side effects of both medications include:

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

Both medications are contraindicated in patients with:

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

Considerations for Nurse Practitioners:

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

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

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

Emerging Therapies for Withdrawal

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

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

Medication-Assisted Treatment (MAT):

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

Examples of medications used:

• Methadone
• Buprenorphine:
• Naltrexone:

Adjunctive Pharmacotherapies:

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

Anticonvulsants:

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

Other Substance Use Disorders

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

Alcohol Use Disorder (AUD):

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

Cannabis Use Disorder (CUD):

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

Cocaine Use Disorder:

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

Methamphetamine Use Disorder:

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

Drug Diversion and Illegal opioids

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

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

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

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

Patient Teachings and Considerations

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

Safe Storage and Disposal:

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

Medication Adherence:

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

Potential Side Effects:

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

Risk of Dependence and Addiction:

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

Avoiding Alcohol and Other Central Nervous System Depressants:

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

Driving and Operating Machinery:

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

Case Study

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

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

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

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

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

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

Conclusion

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

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

Tirzepatide for Type 2 Diabetes and Weight Management

Introduction   

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

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

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

Drug Classification

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

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

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

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

Indications of Usage

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

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

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

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

Use of Tirzepatide with Diabetic Patients

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

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

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

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

Case Study

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

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

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

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

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

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

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

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

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

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

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

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

Use of Tirzepatide for Weight Loss Management

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

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

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

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

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

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

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

Common Side Effects and Contraindications

Side Effects

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

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

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

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

Contraindications

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

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

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

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

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

Safe Prescribing Practices, Guidelines, and Considerations for Providers

Safe Prescribing Practices

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

Guidelines

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

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

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

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

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

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

Inclusion Criteria for Weight Loss

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

Considerations for Providers

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

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

How long does it take for tirzepatide to begin working?

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

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

Safe Administration

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

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

Does the tirzepatide injection hurt when administered?

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

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

Alternatives to Tirzepatide for Weight Loss Management

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

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

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

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

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

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

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

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

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

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

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

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

Conclusion

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

Semaglutide and Type 2 Diabetes

Introduction   

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

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

Diabetes Overview

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

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

Types of Diabetes

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

There are three main types of diabetes:

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

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

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

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

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

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

Diabetes Signs and Symptoms, Diagnostic Testing

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

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

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

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

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

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

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

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

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

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

The hallmark signs/symptoms of diabetes

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

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

Lifestyle Interventions and the Diabetes Prevention Program

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

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

Additional Resources on Diabetes Prevention

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

Semaglutide

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

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

GLP-1 receptor agonist: Hormone Review

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

Ghrelin and Leptin (6)

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

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

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

Glucagon-like peptide-1 receptors

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

What is meant by receptor agonist and antagonist?

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

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

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

Semaglutide mechanism of action (7)

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

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

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

Side Effects of Semaglutide

Common side effects of semaglutide (8)

Common side effects may include any of the following:

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

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

Serious side effects of semaglutide

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

Black Box Warning (9)

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

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

Contraindications

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

Cautions

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

Dosing

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

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

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

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

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

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

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

Missing Dose Guidelines

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

Administration Day Guidelines (10).

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

Dose Availability (packaging)

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

Treatment Goals- Effects on A1C and Weight (11)

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

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

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

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

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

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

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

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

Examples of this include the following:

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

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

Cost Concerns

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

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

Semaglutide Cost Savings Programs

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

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

Emerging Concerns: Semaglutide and gastroparesis

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

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

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

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

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

Diabetes and gastroparesis

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

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

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

Diabetes Lifestyle changes: Patient education (16)

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

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

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

Diet

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

Activity (17)

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

Sleep hygiene (18)

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

Medication adherence/ literacy

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

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

Ozempic Case Study

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

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

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

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

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

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

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

Your patient decides to go ahead with the semaglutide regimen.

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

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

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

Medication Assisted Treatment

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

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.