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Opioids: Addiction, Overdose Prevention, and Patient Education

INTRODUCTION

The Centers for Disease Control and Prevention (CDC) has officially declared prescription drug overdose deaths epidemic in the United States (U.S.).1 The 2013 National Survey on Drug Use and Health estimated that 1.9 million Americans were living with prescription opioid use disorder and 517,000 were addicted to heroin.2 In addition to opioids available by prescription, synthetic opioids — particularly illicitly made fentanyl and fentanyl analogs — are increasingly implicated in overdose deaths.2 The opioids most often used nonmedically include controlled-release oxycodone, oxycodone plus acetaminophen, hydrocodone plus acetaminophen, and codeine with promethazine.1-3 Table 1 lists common street names for often-abused opioids. In addition, a nonprofit education and harm reduction web site (www.erowid.org), Erowid, provides information about psychoactive drugs, plants, chemicals, and common illicit substances.

Table 1. Common Prescription and Illicit Opioid Street Names
Opioid Street Names
Codeine Captain Cody, Syrup, Schoolboy
Fentanyl (Actiq, Duragesic) Apache, China Girl, Dance Fever, Friend
Heroin Smack, Dope, Junk, Black Tar, Dragon, China White
Hydrocodone (Vicodin, Lortab)   Vikes, Watson-387, Norco, Hydro
Hydromorphone (Dilaudid) Juice, Smack, Dillies
Morphine Black Mollies, Black Pill, Tango and Cash, TNT, Murder 8, Morph
Oxycodone (OxyContin, Percocet)   Oxy, Ox, OC, Hillbilly Heroin, Percs, Oxycotton
Oxymorphone (Opana) Blue Heaven, Blues, Octagons, Stop Signs, Pink, Pink Heaven, The O Bomb

Daily, local, and national news reports document the rise in prescription drug misuse, and describe opioids’ toll, including addiction, overdoses, and death. The CDC reports that 46 Americans die each day from prescription drug overdoses, and 72% of deaths involve opioid analgesics.1,2 The number of women who lost their lives to opioid overdoses rose 415% between 1999 and 2010.1,2 Even more concerning, estimates indicate that around 75% of people with addictions to prescription opioids later switch to heroin as a cheaper, more accessible alternative. The rate of heroin overdose deaths tripled from 1999 to 2014.4

This article introduces the reader to the neurobiology of addiction and opioid use disorder. Next, the article discusses how to identify individuals at risk for opioid use disorder and overdose. The health care team, and specifically pharmacists, can play an important role in reducing prescription and heroin overdose deaths. This article reviews key issues surrounding access, education, and treatment with naloxone rescue therapy, allowing pharmacists to become comfortable with this treatment modality.

PATHOPHYSIOLOGY OF OPIOID ADDICTION

To address the opioid epidemic effectively in the U.S., pharmacists must understand the neurobiology of addiction. Patients diagnosed with substance use disorders may abuse or be addicted to caffeine, alcohol, cannabis, hallucinogens, inhalants, sedative–hypnotics/anxiolytics, stimulants, nicotine, or opioids. They may abuse several of these substances concurrently.5 Opioid use disorder is specifically a problematic pattern of opioid use. Like all substance use disorders, it can be mild, moderate, or severe in intensity.

Substance use disorders are complex health conditions with etiologies that often include a combination of genetic vulnerability and psychosocial or developmental dysfunction. For example, consider an adolescent with a family history of addiction who experiences childhood trauma. This youth is much more likely to develop an addictive disorder when exposed to a substance of abuse than a peer who has no underlying risk factors. Similar to other chronic disease states, substance use disorders are life-long illnesses with periods of recovery and relapse. Without proper treatment, quality of life can diminish dramatically because of chronic substance use's impact on overall physical and mental health.5

To understand opioid use and opioid use disorder, we first briefly review receptor activity. Opioid receptors are located throughout the central nervous system (CNS) and in peripheral tissues. Opioid receptors are stimulated endogenously in response to externally inflicted pain and exogenously when an opioid agonist is ingested. Three opioid receptors have clinically relevant actions: mu (μ), kappa (κ), and delta (δ).6

  • Mu receptors are responsible for analgesic effects, respiratory depression, sedation, decreased bowel motility, euphoria, and potentially physical dependence.
  • Kappa receptors are predominately responsible for analgesia, sedation, dyspnea, dysphoria, respiratory depression, and potentially physical dependence.
  • Delta receptors are less well studied but may be more likely to trigger psychiatric symptoms and dysphoria.

Depending on the opioid consumed, a patient will not only feel pain relief, but also feelings of pleasure and reward.6,7

Opioids elicit positive reinforcing effects when they interact with individual neurotransmitter systems within the brain’s general reward circuitry. Dopamine is the primary neurochemical involved; it has been identified as the main component of dependence. Dopamine’s receptors span the ventral tegmental area of the brain to the basal forebrain (nucleus accumbens).7 Dopamine regulates movement, emotion, motivation, feelings of pleasure, and reward. Activation of mu-opioid receptors triggers release of dopamine into the reward pathway.

Individuals who are genetically predisposed to addiction may have an innately lower expression of dopamine receptors, leading to reward deficiency and increased impulsivity. An individual may in turn “self-medicate” with a drug of abuse to compensate for this deficiency. After repeated exposure to opioids, basal levels of dopamine progressively increase, the user begins to develop a tolerance, and subsequently he or she needs a higher dose to obtain the same initial rewarding effect.5,7

Opioid addiction should not be confused with physical dependence. Physical dependence, a normal response to opioid use, is a state of adaptation in which withdrawal occurs when the drug is stopped.

Opioid Use, Intoxication, and Withdrawal

Opioid use disorder is defined as a pattern of use leading to clinically significant impairment where at least 2 of the following are present:5

  • The individual has taken an opioid in larger amounts than prescribed.
  • The individual tried unsuccessfully to cut down or control use.
  • The individual spends a significant amount of time obtaining or using opioids.
  • The individual craves opioids.
  • The individual’s opioid use negatively affects work, school, or home life.
  • The individual’s social, occupational, and recreational activities are reduced because of use.
  • The individual’s use continues despite negative consequences.
  • The individual presents with tolerance and/or withdrawal.

As the disorder progresses, individuals may begin to show patterns of compulsive drug-seeking behaviors, such as lying, stealing, or manipulating to obtain more drug. Most individuals with opioid dependence will show signs of both intoxication and withdrawal, described in Table 2, upon stopping use. Opioid withdrawal after long-term use can be so intense that it triggers the need to use again. In fact, individuals may go to extremes to obtain their next opioid dose, which can lead to social discord, loss of work or school function, legal issues, and chronic financial struggles. The clinical course of opioid use disorder often waxes and wanes between periods of abstinence (recovery) and relapse. Only 20% to 30% of individuals achieve long-term abstinence.5

Table 2. Signs of Opioid Intoxication, Withdrawal, and Overdose5,8
Opioid Intoxication Opioid Withdrawal Opioid Overdose
Euphoria or dysphoria Irritability or dysphoria Slow and shallow breathing (< 8 breaths/minute)
Apathy Rhinorrhea Lethargic, unable to talk
Psychomotor slowing Muscle aching, sweating Blue or grayish skin, lips, fingernails
Sedation Insomnia Choking or gurgling
Slurred speech Piloerection Cessation of breathing
Slowed cognition Nausea, vomiting, fever Unresponsive to sternal rub
Miosis (pinpoint pupils) Mydriasis (pupil dilation), lacrimation Unconscious
Respiratory depression Yawning  
Constipation (with long-term use) Diarrhea  

Overdose risk is the most concerning component of opioid use. An opioid overdose can occur2,9:

  1. Intentionally in an effort to abuse a drug
  2. Unintentionally in an effort to gain better control of pain
  3. When a prescription opioid dose is miscalculated
  4. When a drug or dose is dispensed incorrectly
  5. When the patient misunderstands opioid treatment
  6. When the patient has a chronic medical condition that may affect respiratory rate (chronic obstructive pulmonary disorder, asthma, sleep apnea) or whose pharmacotherapy may alter drug metabolism (human immunodeficiency virus [HIV], hepatitis infections)
  7. When the patient’s tolerance to the opioid changes because of cessation of use (e.g., hospitalization, incarceration, change in prescriber)

The risk of fatal overdose increases when the opioid user takes other CNS depressants—e.g., benzodiazepines, or muscles relaxants—concurrently. Signs and symptoms of opioid overdose go beyond the symptoms of intoxication. A patient’s respiratory rate may fall below 8 breaths per minute, the patient may make choking or gurgling sounds as he or she struggles to breathe, and the patient may not respond to a sternal rub.2,9 The fatal component of an opioid overdose–respiratory depression–eventually leads to cessation of breathing.

Populations at Risk of Opioid Use Disorder

Several factors can increase a person’s risk for opioid exposure and use disorder. Any patient experiencing acute or chronic pain (e.g., dental, following an accident, postpartum, cancer) is at risk for exposure to an opioid medication. Opioid use exposure, coupled with genetic vulnerability and psychosocial and environmental risk factors, increases the risk for the development of opioid use disorder.

For adolescents and young adults the following are risk factors for the development of a substance use disorder: lower socioeconomic status, exposure to physical or sexual abuse, undiagnosed and untreated depression, anxiety, attention deficit/hyperactivity disorder, a family history of addiction/genetic predisposition, and a diagnosis of conduct disorder.2,10 Opioid use and abuse at a younger age increases dependence severity and morbidity.

Adult patient populations with the highest risk for opioid use disorder are white men between the ages of 25 and 54; those who reside in rural communities with lower socioeconomic status; individuals of Native American decent; soldiers and veterans; those with occupational injuries; those with a genetic predisposition for addiction; and individuals diagnosed with serious mental illnesses or HIV.2,10

Those at higher risk for heroin use include white men aged 18 to 25 years; individuals residing in urban areas with low income; and those with a history of alcohol, marijuana, cocaine, and prescription drug abuse. In addition to these well-defined high-risk groups, overall heroin use rates have increased significantly across all patient populations, including women and those who are privately insured with higher economic status.4

Psychologic or behavioral symptoms that are often present with opioid use disorder include irritability, frequent mood shifts, hostility or violence, chronic dysphoria or depression, and psychosomatic symptoms. Case 1, described below, identifies a patient attempting to obtain refills too soon. He takes a benzodiazepine concurrently with an opioid and a muscle-relaxing agent. This is a warning sign for the pharmacist, indicating potential prescription overuse or abuse, and may suggest opioid use disorder. Pharmacists may observe other warning signs of opioid use disorder, including11-13 :

  • Frequently running out of medication too soon
  • Reporting lost or stolen prescriptions
  • Presenting with prescriptions from multiple prescribers
  • Having prescriptions filled at multiple pharmacies
  • Negative urine drug screens for opioids
  • Reporting allergies to all other drugs but opioids
  • Frequently demonstrating signs and symptoms of intoxication
Patient Case 1: Refill Too Soon

Jason is a 35-year-old man who arrives at the pharmacy 2 weeks early to refill his alprazolam. His medication profile also indicates an active prescription for oxycodone–acetaminophen 7.5–325 mg, quetiapine 600 mg, and cyclobenzaprine 10 mg. He reports that a friend stole the rest of his Xanax; thus, he is requesting an early refill.

The patient described in Case 1 may suffer from opioid use disorder. The pharmacist could suggest an assessment by a trained clinician. Whether or not opioid use disorder is present, Case 1 is an opportunity for the pharmacist to evaluate this patient’s risk of opioid overdose, and assess the need for an opioid overdose rescue therapy. Individuals at the highest risk for opioid overdose and subsequent death include patients who are prescribed multiple prescription opioid medications; co-prescribed opioids and CNS depressant medications; identified as “doctor shopping” to obtain opioids or other CNS depressant medications; and who present with concomitant serious mental illness, HIV, and cardiovascular disease. An additional risk factor is Medicaid eligibility. Medicaid-insured patients are prescribed pain medications twice as often as others and are 6 times more likely to overdose.11

In Case 2, Sarah has many risk factors, including several chronic diseases and a mental health diagnosis. She is also co-prescribed CNS depressants and opioid medications that increase her likelihood for unintended opioid overdose. The pharmacist, as part of an integrated care team, can often bridge the gap between multiple prescribers, thereby reducing polypharmacy and overdose risk.

Patient Case 2: Too Many Providers

Sarah is a 50-year-old woman who has been diagnosed with lupus, Crohn disease, fibromyalgia, and depression. She receives treatment from her primary care physician, rheumatologist, and psychiatrist—all at different practice locations. She is prescribed duloxetine 90 mg daily, aripiprazole 20 mg daily, diazepam 10 mg at bedtime, hydrocodone plus acetaminophen 5–325 mg every 6 hours for pain, and prednisone 10 mg daily.

Opioid Overdose Prevention Strategies

Numerous national organizations, including the Substance Abuse and Mental Health Services Administration (SAMSHA), the CDC, the American Pharmacists Association, and the American Medical Association are embracing and advocating for improved opioid overdose prevention strategies. Pharmacists play a critical role in this movement at the national, state, and individual patient level. First, it is critical to promote collaboration between state licensing boards, public health agencies, pharmacy associations, and health professionals who are involved in pain management and behavioral health. A comprehensive approach that focuses on patient, provider, and public education and advocacy, proper screening for addiction, monitoring and enforcement for poor opioid prescribing, safe disposal of prescription opioids, and access to life-saving treatments, such as naloxone, is necessary to reduce heroin and prescription medication overdose-related deaths.2,10

Education and Advocacy

Pharmacists have numerous opportunities for public and provider education. Pharmacists can provide in-service training to pain management specialists, psychiatric care providers, family medicine specialists, professionals practicing in emergency departments, and advanced practice nurses in the area of prescription drug abuse and naloxone rescue kit awareness. In states where pharmacists can prescribe naloxone or provide it under a standing order or collaborative practice agreement, pharmacists can directly support naloxone access to patients at risk of overdose and their caregivers. In states without such provisions, pharmacists can advocate that providers prescribe naloxone to patients at risk of overdose. Pharmacists may also help educate providers on the safe prescribing of opioid medications. The Substance Abuse and Mental Health Services Administration (SAMHSA) and the National Institute on Drug Abuse provide free continuing medical education courses that highlight how to prescribe opioids safely and effectively for chronic pain (http://www.opioidprescribing.com).

Pharmacists are widely viewed as one of the most trusted and accessible health care providers. Overdose prevention efforts start with becoming proactive in the community and reaching out to patients at high risk of opioid overdose. These activities should include providing education and resources that promotes harm reduction and safe opioid prescription use. All patients who are considered at risk for opioid overdose (Table 3) should be educated on risk-reduction strategies, prescription opioid adherence, medication safety, and how to attempt to reverse an opioid overdose. Organizations such as health departments and university researchers have designed user-friendly opioid overdose handouts that pharmacists can distribute to patients in the community pharmacy setting.14 Training and education on the use and administration of naloxone rescue therapy should be provided to both the patient and, ideally, to a friend or caregiver who may be able to respond to the patient’s overdose. Prescribe to Prevent (www.prescribetoprevent.org), a web site specifically for prescribers and pharmacists, provides information about the logistics of providing and dispensing naloxone. The web site also contains educational materials for patients and advocacy groups on naloxone rescue treatment and overdose prevention strategies.

Table 3. Risk Factors That Suggest Naloxone Rescue Readiness
All patients exposed to opioids are candidates for naloxone rescue therapy. Patients who are considered at higher risk and should be offered naloxone include those who:10
  1. Are prescribed long-term opioid therapy, especially in doses greater than 50 mg of morphine equivalent per day
  2. Are prescribed rotating opioid medication regimens
  3. Are prescribed or taking an opioid plus other CNS depressants (benzodiazepines)
  4. Are prescribed or taking an opioid and have concomitant renal or hepatic dysfunction, cardiovascular disease, respiratory disorders (sleep apnea, COPD), or HIV/AIDS
  5. Use heroin
  6. Were recently discharged from a substance abuse treatment facility or from an acute medical center following opioid intoxication or poisoning
  7. Were recently released from incarceration or have a history of opioid abuse
  8. Have previously overdosed


If abuse or opioid addiction is suspected, pharmacists may offer the patient resources on substance abuse treatment services and recovery resources in the community. SAMHSA offers resources on their web site, which directs patients and providers to behavioral and substance abuse services in their area (http://findtreatment.samhsa.gov). State and local behavioral health authorities may have additional resources.

All health professionals, including pharmacists, should advocate within their states to increase access and funding for substance abuse treatment services. Substance use disorder treatments are often not integrated with other aspects of treatment, including pain management. Additionally, treatment outcomes are less successful when substance use disorders and psychiatric disorders are treated separately. More than 30 states are participating in Medicaid expansion, which will allow for the growth of substance abuse services and better integration of overall care.15 Pharmacists are also encouraged to lobby local and state representatives for evidence-based programs that reduce drug diversion, abuse, and overdose.

Screening

Before providers prescribe any opioid, they should obtain the patient’s drug use history (including illicit substances and prescribed medications with abuse potential). Pharmacists and other health professionals involved in caring for patients with chronic pain conditions and mental health disorders should obtain training on the proper screening for drug abuse and addiction.

Screening tools frequently used by pain specialists include the Opioid Risk Tool and the Current Opioid Misuse Measure.16,17 Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based practice clinicians use to identify, decrease, and prevent problematic use and abuse of alcohol, illicit drugs, and prescription medications. Clinicians use series of standardized screening questions such as, “How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?” with the patient. Based on the patient's responses, clinicians conduct a brief, time-limited, and patient-centered intervention focused on enhancing insight and awareness of substance use (through motivational interviewing [MI]).18

Depending on the work environment, pharmacists may have access to clinicians who are SBIRT-trained. Screening results can be used when making medication and treatment decisions in outpatient clinical settings. Pharmacists who provide substance use disorder or pain management treatment are encouraged to obtain MI training. MI is a person-centered communication style intended to elicit behavior change by helping patients to explore and resolve ambivalence.

Patients such as Stacy in Case 3, who have long periods of recovery from opioid use, are at elevated risk for overdose when presented with an opioid again. The risks for Stacy are multi-fold. The new oxycodone prescription for pain and the possible trauma from her car accident may trigger a relapse of her addiction. She may also be at risk for an unintentional overdose due to tolerance changes while in recovery. Other factors increase Stacy’s risk: she has been prescribed several other CNS depressing agents (trazodone, lorazepam, prazosin) and a medical condition (sleep apnea) that could impair her breathing. All of these increase overdose risk. The case presents an opportunity for a pharmacist to screen for opioid abuse potential, closely review the medication profile, and provide pharmacotherapy recommendations, including naloxone, that may reduce overdose risk.

Patient Case 3: In Recovery

Stacy is a 45-year-old woman with generalized anxiety disorder, posttraumatic stress disorder, diabetes, and sleep apnea. She is in recovery from heroin addiction and is 5 months clean. She was recently in a car accident and is receiving care in the emergency department for a headache and neck pain. Her ongoing prescriptions include citalopram 40 mg daily, metformin 500 mg twice daily, prazosin 4 mg at bedtime, and trazodone 50 mg at bedtime. She receives prescriptions for lorazepam 1 mg twice daily #14 and oxycodone 5 mg 3 times daily as needed for pain #21.

Monitoring

Pharmacists should use prescription drug monitoring programs (PDMPs) routinely and encourage other providers to use them. PDMPs are state-run electronic databases used to track controlled substance prescribing and dispensing. All health professionals who prescribe (physicians, dentists, advance practice nurses, physician assistants, and clinical pharmacists) or dispense controlled substances (community pharmacists) can access PDMP databases.19,20 In many states, regulatory and law enforcement agencies involved in drug-related investigations may access the database to help identify individuals involved in illegal trafficking or misuse of prescription drugs. California was the first state to establish a PDMP in 1939. In 2002, in an effort to better standardize PDMPs, the National Alliance for Model State Drug Laws drafted a model program, outlining common goals that should be shared among all state PDMPs. Currently, 49 states have operational PDMPs. Missouri is the most recent state to pass a law implementing PDMP.19,20

Although PDMPs are unique to each state, the CDC recommends that each PDMP focus resources on the number of (1) prescription opioid dosages, (2) controlled substance prescriptions per patient, (3) different prescribers per patient, (4) prescribers who deviate from accepted medical practices with regard to drug dosages, and (5) controlled substance prescriptions.1,19 In many states, the PDMP links to patients' electronic health record, allowing health professionals to use the PDMP routinely in clinical environments. Prescribers and pharmacists dispensing controlled substances should be encouraged to use PDMPs as an aid to make safe and effective treatment decisions (not as a punitive measure to catch patients doing wrong). Unfortunately, access to PDMPs by health professionals is low, averaging between 5% and 39%.2,20 Barriers to use continue to be lack of awareness or education surrounding the use of PDMPs, lack of access to technology to use the database, time restraints, and lack of up-to-date programs.10

When pharmacists use PDMPs, they should review all active prescriptions and look for multiple psychotropic or sedating medications, and patients' use of multiple prescribers as indicators of overdose risk and naloxone provision.

Disposal

Almost all prescription drugs involved in overdoses originate from real prescriptions, not from pharmacy theft or forged precriptions.2,3 Primary care and internal medicine physicians and dentists, not pain specialists, write most of these prescription. Roughly 20% of prescribers prescribe 80% of all prescription opioids.2,3

Once dispensed, opioid medications are at risk of being diverted to people using them without active prescriptions. Adolescents and young adults may also obtain medications from old prescription bottles not used by parents, grandparents, or other loved ones. Community pharmacists should promote and become actively involved in locally hosted controlled substance take-back programs, and educate patients about proper storage and disposal of controlled substance medications (Table 4). Up and away (http://upandaway.org/) is an excellent online resource offering education on medication safety and storage. A public fact sheet regarding the DEA disposal act can be found on the DEA website (http://www.deadiversion.usdoj.gov/drug_disposal/index.html).

Table 4. Tips on Safe Storage of Prescription Medications
  1. 1. Try to keep all medications in 1 location in the home
  1. 2. Store medications securely and out of reach of children and teenagers (consider keeping controlled substances in a locked area)
  1. 3. Store medications in a cool, dry place (preferably not the bathroom)
  1. 4. Make sure safety caps are always locked
  1. 5. Keep medication in the bottle it came in
  1. 6. Properly dispose of expired medications

Pharmacists may also direct patients to the DEA website to locate authorized collectors in their community. Some states require that pharmacies display a DEA-developed sign highlighting when local take-back programs will occur. The DEA no longer hosts national prescription take-back events; however, local law enforcement officials offer these throughout the year and community pharmacists can collaborate with these local events.

Enforcement

The community pharmacist is often the first to identify problem prescribers or unsafe prescribing practices. Recognizing and reporting “pill mill” providers helps keep patients safe and prevent future medication overdoses. All states have laws prohibiting “doctor shopping” for opioid prescription drugs. Thirty-two states have laws requiring or permitting a pharmacist to request proper identification before dispensing a controlled substance.

The most abused opioid prescriptions—oxycodone and hydrocodone—have been moved to DEA schedule II.21 Community pharmacists can actively enforce schedule II legal prescription requirements, such as requiring the physician DEA number on all schedule II prescriptions. Pharmacy benefit managers can implement formulary restrictions that promote step therapy for pain management or limit prescription quantities.

Clinical pharmacists may have opportunities to review insurance claim data to evaluate prescribing patterns and opioid use.2,10 It is important to be mindful that excessive restriction placed on opioid access may cause undertreatment of patients with to true pain. These patients may seek alternative methods of pain relief.

NALOXONE RESCUE THERAPY

There is a national movement promoting use of naloxone rescue therapy as a risk mitigation and harm reduction strategy, especially for individuals at risk for opioid overdose. This can include the prescribing of naloxone as a standard of care to all patients prescribed an opioid medication.

Naloxone (Narcan) is a competitive antagonist at all opioid receptor sites. Its primary use is to reverse respiratory depression associated with an opioid overdose.22-24 Emergency medical services personnel and emergency department clinicians have used it for more than 40 years to for this purpose, saving patient lives.22 It is available for use intravenously (IV), intramuscularly (IM), subcutaneously (SQ), and intranasally (IN).10,24

Naloxone for home use is prescribed IN or IM, as an injection kit or auto-injector. The established IM dose is 0.4 mg/mL, with the option of repeating this dose in 2 to 3 minutes if necessary. It should be injected intramuscularly at a 90° angle into the upper arm, thigh, or outer buttocks.16,22,23 The intranasal administration is dosed as 2 mg (1 mg per nostril), with the option to repeat the same dose in 3 to 5 minutes if necessary. Naloxone products have a shelf life of 12 to 18 months and should be stored at room temperature to maintain proper stability.16,24

Insurance coverage and access to the various naloxone products may differ by patient and by state. The community pharmacist can often perform real-time claim submissions to determine individual patient naloxone coverage.10 It is important for the pharmacist to be familiar with all available naloxone products and be ready to advise patients on which product bests fits their individual needs. Patient preference, cost, hand strength, and literacy level all influence naloxone product selection. In addition to educating patients on proper naloxone use, the pharmacist can provide user-friendly brochures on overdose prevention and naloxone rescue therapy.

Prescribing and dispensing naloxone rescue therapy for use in suspected opioid overdose situations is consistent with the drug’s FDA-approved indication. Prescribers or pharmacists who provide naloxone as a risk mitigation and harm reduction treatment incur no legal risk.

Harm Reduction Strategies

The practice of harm reduction follows a patient-centered philosophy of care with the primary goal that focuses on harm reduction rather than complete opioid use cessation. This philosophy aligns with the biologic understanding of substance use disorders, underscoring the fact that an addiction cannot be “shut off” at will. Clinicians communicate nonjudgmentally and empathically, while actively assessing the patient’s readiness to quit or decrease substance use.

In addition to prescribing and dispensing naloxone rescue therapy, syringe (and needle) exchange programs are another harm reduction initiative. These offer clean syringes for individuals actively injecting heroin. When offering patients naloxone rescue therapy and/or access to clean syringes, health professionals may discuss opioid use, safety concerns, and overdose risk. Ultimately, naloxone is only 1 part of the overall treatment of opioid abuse, and it should be administered at the first sign of opioid overdose.25,26

Before initiating or dispensing naloxone rescue therapy, pharmacists should educate the patient and a friend, family member, or caregiver on the signs and symptoms of opioid overdose: slow and shallow breathing (fewer than 8 breaths/minute), sleepiness, lethargy, inability to talk, lack of consciousness, blue or grayish skin color, and/or dark lips and fingernails. If symptoms of an overdose are present, they should then follow 5 essential steps2,10,23:

  1. Lightly tap, shake, and shout at the person to get a response. If there is still no response, rub knuckles on the breastbone.
  2. Call 911 for help.
  3. If breathing is shallow or nonexistent, or if the skin is blue or grayish, with dark lips and fingernails, perform mouth-to-mouth rescue breathing by tilting head back and lifting up chin until mouth opens, clearing airway. Give 2 quick breaths to start and then a strong breath every 5 seconds.
  4. Administer naloxone by IM or IN delivery.
  5. Stay with the person. If you have to leave the person alone or vomiting occurs, place the person in the recovery position–on his or her side, hand supporting the head, mouth facing downward, and leg on the floor to keep the person from rolling onto stomach.

Within 3 minutes (IM delivery) to 5 minutes (IN delivery) after naloxone administration the patient will begin to experience opioid withdrawal.22,23 These symptoms may include an elevation in blood pressure and pulse, sweating, body aches, abdominal cramping, nausea and vomiting, and severe agitation. These withdrawal symptoms are not an adverse effect of naloxone, but the direct effect of opioid reversal.22,23 Opioid withdrawal, while extremely uncomfortable, is not life threatening.

If adequate breathing does not resume within 3 minutes, a second dose of naloxone may be administered. If there is no response after 2 doses of naloxone, it is likely that the patient has ingested nonopioid substances. The duration of effect after naloxone administration is 30 to 90 minutes, depending on the type and amount of opioid taken. With a longer-acting opioid such as methadone, fentanyl, extended-release morphine, or controlled-release oxycodone, overdose symptoms may return after 90 minutes. A patient who receives naloxone should be monitored in an emergency care setting for at least 3 to 4 hours to ensure safe recovery.2,22,23

The Pharmacist’s Role

As part of an integrated care model, the pharmacist is a critical team member. With advanced pharmacotherapy knowledge, the pharmacist can perform extensive medication reviews, identifying patients at risk for opioid overdose, dangerous medication combinations, or opioid medications from multiple providers. The pharmacist should also actively provide ongoing education to the community, patients, and providers on methods to reduce prescription drug abuse and opioid overdose.

Pharmacists should provide the following information to patients who are prescribed opioids and their caregivers: (1) only take prescription opioids prescribed to you and take as directed, (2) ensure that all of your prescribers are aware of the medications you take, (3) do not mix opioids with other sedating medications or alcohol, (4) store your prescription opioids in a safe and secure place and dispose of unused medication properly, (5) understand that your tolerance to opioid medications will change if you stop taking them for an extended period of time, and (6) consider naloxone rescue therapy as an emergency, life-saving treatment that can be administered in the event of an opioid overdose. You can obtain naloxone to take home with you, just in case.2,10

Numerous states allow collaborative practice agreements with a standing order for pharmacists to dispense naloxone without a prescription.2,10,17,27,28 California, Rhode Island, and New Mexico have paved the way for many other states with their proactive initiatives giving patient access to naloxone directly from the pharmacy through a collaborative agreement with a physician. In Rhode Island, a physician has collaborated with the Board of Pharmacy to implement a program allowing direct naloxone access without a prescription from Walgreens, Rite Aid, and CVS pharmacies, and several independent and hospital pharmacies. For pharmacists to dispense naloxone under the collaborative agreement, they must complete advanced training on naloxone treatment (this varies from 1 to 4 hours, online or in person). 2,10,17,27

Laws related to naloxone access and use change frequently. The Network for Public Health Law (www.lawatlas.org) provides the most up-to-date resources on individual state laws and initiatives with regard to naloxone access.17

CONCLUSION

Prescription drug abuse is a crisis in the U.S. Pharmaceutical drug overdoses are a leading cause of death among Americans.1,2 Substance use disorders–long-term use, abuse, and resulting premature death–can devastate the lives of patients, their family, and friends. This problem also challenges communities. States are rapidly developing laws to expand and implement access to naloxone therapy. Pharmacists must be at the forefront of state and national initiatives that focus on opioid safety and naloxone use. Prescribe to Prevent  (http://prescribetoprevent.org/wp-content/uploads/2012/11/naloxoneCEU_vURI_CE.pdf) and the College of Psychiatric and Neurologic Pharmacists (https://cpnp.org/_docs/guideline/naloxone/naloxone-access.pdf) offer updated resources for pharmacists regarding the treatment of substance use disorders and naloxone distribution programs. Naloxone is a user-friendly harm reduction treatment with minimal risk to the patient. Pharmacists can help reduce the number of opioid deaths by expanding naloxone use, educating patients, and providing naloxone at local pharmacies.

REFERENCES

  1. Centers for Disease Control and Prevention (CDC). National Vital Statistics System. Multiple cause of death file. Atlanta: CDC, 2012.
  2. Jones CM, Einstein EB, Compton WM. Changes in synthetic opioid involvement in drug overdose deaths in the United States, 2010-2016. JAMA. 2018;319(17):1819-1821.
  3. Jones CM, Paulozzi LJ, Mack KA. Sources of prescription opioid pain relievers by frequency of past-year nonmedical use United States, 2008-2011. JAMA Intern Med. 2014;174(5):802-803.
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