Learning Outcomes
By the end of this section, you should be able to:
- 15.2.1 Discuss the pathophysiology of opioid use disorder disorder.
- 15.2.2 Identify clinical manifestations of opioid use disorder.
- 15.2.3 Identify the etiology and diagnostic studies related to opioid use disorder.
- 15.2.4 Identify the characteristics of drugs used to treat opioid use disorder.
- 15.2.5 Explain the indications, actions, adverse reactions, and interactions of drugs used to treat opioid use disorder.
- 15.2.6 Describe the nursing implications of drugs used to treat opioid use disorder.
- 15.2.7 Explain the client education related to drugs used to treat opioid use disorder.
Opioid Use
Opioids are a class of drugs that activate the opioid receptors in the CNS. Opioids have been widely used for thousands of years and are derived from the opium poppy, Papaver somniferum. Opioids include many agents, including naturally occurring opioids such as heroin, codeine, and morphine, along with synthetically derived agents such as hydrocodone, oxycodone, and fentanyl. Opioids are well known to be powerful analgesics and antitussive agents but have also been shown to carry risk for physical dependence and opioid use disorder (OUD).
The United States is dealing with one of the biggest health crises that it has ever faced—the opioid epidemic. It is estimated that OUDs affect more than 16 million people worldwide, with over 2.1 million of those individuals residing in the United States. The biggest risk seen with use of opioids is the chance of overdose and death, which accounts for 120,000 deaths annually worldwide (Dydyk et al., 2023). This is true despite the fact that opioids are tightly regulated by the U.S. Drug Enforcement Administration (DEA). Most prescription opioids (e.g., morphine, hydrocodone) are designated as Schedule II (CII) medications, meaning they carry a substantial risk for misuse but still have an acceptable medical use. Heroin, on the other hand, is used illicitly, as it is scheduled as Schedule I (CI), meaning that it has a high abuse potential and no acceptable medical use. This means that if clients with an OUD are using CII medications without a valid prescription or any CI medications, there may be legal complications (e.g., felony arrest), which can further complicate their road to long-term recovery.
Opioid Intoxication
Opioids produce many of their desired therapeutic effects and potentially life-threatening adverse effects via the opioid receptors, including the mu, delta, and kappa receptors. Opioid intoxication is classically described as a triad of symptoms consisting of reduced consciousness, slow and/or shallow breathing, and miosis (i.e., pinpoint pupils). In addition, opioids will cause analgesia and euphoria depending on the dose and route used. Tolerance will rapidly develop to the analgesic and euphoric properties of the opioids, which leads to a rapid dose escalation to achieve the same effects that the client had been experiencing at lower doses. Clients receiving treatment for an OUD that includes abstention from opioids (e.g., stays at rehabilitation facilities) may lose tolerance over time. It is vital to educate clients about this, since clients who go on to relapse and use opioids at their previous doses may experience more opioid effects than they were intending, leading to accidental overdose and risk for death due to respiratory depression.
The presence of opioids in a client is not routinely measured in the blood but rather is detected using urine drug screens. Most traditional urine drug screens will test reliably for naturally occurring opioids such as heroin, codeine, and morphine but will potentially miss opioids that do not share the same chemical resemblance. Specific tests must be performed to detect the presence of agents such as oxycodone or fentanyl. For the clinician, it is important to keep in mind that a negative urine opioid screen does not always rule out the possibility that someone is experiencing opioid intoxication.
Opioid Withdrawal
Opioid withdrawal occurs in clients using opioids for a chronic period who have abruptly discontinued the drug, or from rapid reversal of the drug’s effect with an opioid antagonist (e.g., naloxone). The onset of opioid withdrawal will vary from a few seconds to minutes after administration of a dose of a reversal agent like naloxone, or from hours to days if using an agent with a longer half-life (e.g., methadone).
The effects of opioid withdrawal may include a variety of symptoms that may be present in some clients but not others. These effects fit into several categories. Gastrointestinal effects of opioid withdrawal include severe abdominal cramping, diarrhea, nausea, and vomiting. Flu-like symptoms can occur including rhinorrhea, shivering, myalgias, and piloerection (i.e., goosebumps). Symptoms of excessive sympathetic and CNS activation include dilated pupils, tachycardia, anxiety, irritability, agitation, and tremor. Fortunately, withdrawal from opioids is rarely life-threatening, but there are rare reports of seizures occurring, so health care providers should be prepared in case these consequences arise.
Drugs Used to Treat Opioid Use Disorders
There are several drugs available to assist in the management of opioid use disorders. They include medications to reduce withdrawal symptoms and to help reduce clients’ desire to begin using opioids again, such as methadone and buprenorphine. It is also important to be able to rapidly reverse the life-threatening effects of opioids in case of overdose; thus opioid antagonists, such as naloxone, are also used.
Naloxone
Naloxone is the prototypical mu opioid receptor antagonist used to rapidly reverse the life-threatening effects of opioid overdose. While naloxone is not used directly in the treatment of opioid use disorders, it is important that clients at risk for opioid overdose have quick and easy access to naloxone in case of accidental or intentional overdoses. This was made easier when naloxone was designated as an over-the-counter drug in March 2023.
Naloxone may be administered in several ways but will most commonly be given intravenously in the hospital setting and intranasally when administered by non-health care practitioners (e.g., family members, law enforcement agents). Because of the nature of opioid overdoses, clients will be too sedated to administer naloxone to themselves. Those who are most likely to be around the client should an overdose occur (e.g., family members, roommates) need to be educated on proper recognition of an opioid overdose and how to administer naloxone should the need arise. See this video for a demonstration of intranasal naloxone administration.
A key limitation of naloxone is its short duration of action. While naloxone rapidly reverses the effects of opioids within seconds to minutes, it only lasts approximately 20–30 minutes, which is less than the duration of action of many opioids. It is imperative that whoever administers naloxone to a client should promptly call emergency services to provide definitive treatment to the client prior to the re-sedating effects of the opioid.
Naltrexone
Naltrexone is like naloxone in that it is a pure mu opioid receptor antagonist. The key difference between the two is that naltrexone is orally bioavailable. Because of this, naltrexone is not used as a rescue medication in case of opioid overdose but is used as a preventative agent. Once a client is abstinent from opioids for 5–7 days, they can then begin taking naltrexone daily. The purpose of this waiting period is to prevent an immediate withdrawal syndrome. Naltrexone will prevent the euphoric effects of opioids should the client relapse and begin using opioids again. As there are concerns about client compliance with taking a daily medication, naltrexone also comes as a long-acting, once-monthly injectable form to ensure compliance for this period.
Buprenorphine-Naloxone
Buprenorphine is a partial mu opioid receptor agonist that is designed to reduce the symptoms of opioid withdrawal and cravings in clients abstaining from opioid use. The inclusion of naloxone with oral preparations of buprenorphine may seem nonsensical given that naloxone has poor oral bioavailability, but this is done to discourage intravenous abuse of buprenorphine, as the naloxone would cancel out the euphoric effects of buprenorphine upon injection. The inclusion of naloxone in these oral dosages is a form of abuse deterrence. Buprenorphine by itself also comes in a variety of dosage forms, including long-acting injectables and transdermal patches. Buprenorphine has a high affinity for the opioid receptor and can displace other opioids that can cause opioid withdrawal to occur. Because of this, buprenorphine should be initiated once withdrawal symptoms begin to occur to reduce these symptoms to aid in opioid abstention.
Methadone
Methadone is a full mu opioid receptor agonist that has been used for many years to wean clients off opioids. Being a full agonist, methadone can help reduce or prevent opioid withdrawal symptoms and allow for a gradual tapering down of the methadone dose until the client no longer requires it. Methadone is used over other opioids because it has a long half-life of up to 59 hours. Since methadone is a full opioid agonist and carries the same risk for abuse as other opioids (e.g., morphine, heroin), clients are not given a full month’s worth of methadone at a time like a typical prescription. Instead, methadone must be given in a monitored setting as a part of direct observed therapy. The long half-life of methadone allows for levels of the drug to build up in the client’s body throughout the week. When the clinic where the client receives their methadone is closed on the weekend, they still have high enough drug levels in the body to reduce or prevent withdrawal symptoms until the clinic opens again on Monday. This is the most traditional way for methadone to be used, but in recent years, clinicians have realized the potential for methadone to be an effective agent to treat chronic pain, so it is important for health care providers to not assume that all clients using methadone have an OUD.
Table 15.1 lists common medications used to treat opioid use disorders and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Buprenorphine-naltrexone (Suboxone) |
Maintenance treatment (sublingual): Buprenorphine 2 mg/naloxone 0.5 mg once daily with titrations up to a target dose of buprenorphine 16 mg/naloxone 4 mg once daily. |
| Buprenorphine (Buprenex) | Sublingual: 2–4 mg once daily. Subcutaneous: 100 mg once monthly after induction and dose stabilization. |
| Methadone (Dolophine) |
Induction/initial dosing: 20–30 mg orally once daily; titrate to a dose sufficient to suppress withdrawal symptoms. |
| Naloxone (Narcan) |
Opioid overdose (known or suspected): Intravenous (IV): 0.4–2 mg as needed. Intranasal: 4–8 mg as needed in one nostril every 2–3 minutes until medical assistance is available. |
| Naltrexone (Vivitrol) |
Oral: 25–50 mg daily. Intramuscular: 380 mg every 4 weeks. |
Adverse Effects and Contraindications
The primary adverse effect of opioid antagonists like naloxone and naltrexone is the risk of inducing opioid withdrawal in clients chronically taking opioids. Clients generally should be abstaining from opioids prior to initiation of naltrexone therapy and should be under medical supervision in the case of severe withdrawal reactions.
Since buprenorphine is a partial opioid receptor agonist, it can still cause symptoms of opioid intoxication including CNS and respiratory depression. This is especially true for accidental ingestions of buprenorphine by children and animals. Like other full opioid agonists, methadone carries the same risk for problematic use and risk for overdose causing life-threatening CNS and respiratory depression. Methadone can prolong the QTc interval on an electrocardiogram (ECG, EKG), and clients should be monitored if taking multiple medications that prolong the QTc interval due to risk for the ventricular dysrhythmia torsades de pointes.
Table 15.2 is a drug prototype table for medications used to treat opioid use disorders featuring buprenorphine-naloxone. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Partial opioid agonist/opioid antagonist Mechanism of Action Used as a partial agonist at the mu opioid receptor. Naloxone is an opioid antagonist and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally |
Drug Dosage Maintenance treatment (sublingual): Buprenorphine 2 mg/naloxone 0.5 mg once daily with titrations up to a target dose of buprenorphine 16 mg/naloxone 4 mg once daily. |
| Indications Maintenance treatment of opioid dependence Therapeutic Effects Reduces opioid withdrawal symptoms |
Drug Interactions Benzodiazepines Cytochrome P450 3A4 inhibitors Cyclobenzaprine Diphenhydramine Food Interactions Ethanol |
| Adverse Effects Diaphoresis (excessive sweating) Abdominal pain Constipation Headache Pain Withdrawal syndrome Vasodilation Vomiting Hepatocellular injury |
Contraindications Hypersensitivity Caution: Substance abuse and misuse Respiratory depression CNS depression Hepatic dysfunction |
Nursing Implications
The nurse should do the following for clients who are taking a medication for OUD:
- Determine the client’s last use of an opioid prior to starting naltrexone or buprenorphine-naloxone to avoid withdrawal reactions.
- Advise the client and those close to them how to recognize an opioid overdose and how to administer intranasal naloxone.
- Advise the client and those close to them to call emergency services any time that naloxone is given.
- Observe for withdrawal symptoms, including anxiety, diarrhea, piloerection, and sweating.
- Assess for changes in level of consciousness and respirations.
- Provide client teaching regarding the drug and when to call the health care provider. See below for additional client teaching guidelines.
Safety Alert
Methadone
Methadone can have variable pharmacokinetics in clients based on their individual genetics, along with interacting medications that can affect its metabolism. Prior to adding any new medications to a client’s regimen, it is imperative to check for any interactions and monitor for increased or reduced effects of methadone and adjust its dose accordingly. Clients should be educated to disclose that they are on methadone to prescribing health care providers to ensure that these interactions are monitored. This information should include the indication for the client’s methadone use and current dose. Most current dosing information should be obtained from the clinic where the client receives methadone. Methadone can also prolong the client’s QTc interval as measured on an ECG and can increase the risk of fatal dysrhythmias. Use cautiously in clients with a history of congenital prolonged QT syndrome or who are taking multiple medications that prolong the QTc interval.
Client Teaching Guidelines
The client taking a medication for OUD should:
- Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert their health care provider about any recent opioid medication use prior to starting therapy.
- Alert other health care providers that they are taking these OUD medications, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take a missed dose as soon as they remember; however, they should not take double doses.
- Avoid abrupt discontinuation of medications used to treat OUD to avoid withdrawal symptoms.
- Seek out care from their health care provider if they notice dark urine, light-colored stools, right upper quadrant pain, nausea, or yellow sclera.
- Seek out community services to aid in SUD treatment, including organizations such as Narcotics Anonymous.
- Increase intake of fluid to prevent constipation.
Trending Today
X-Waiver Requirement
In the United States, there is a severe lack of specially trained health care practitioners able to provide OUD treatment with agents such as methadone. There has been a push recently to increase the ability for health care practitioners to treat clients with OUD in the primary care setting with agents such as buprenorphine. Buprenorphine has a greater safety margin than methadone, so it can be prescribed with relative safety by physicians, nurse practitioners, and physician assistants. In the past, nurse practitioners and physician assistants who wanted to prescribe buprenorphine needed a DEA license in addition to specialized training to receive authorization to prescribe buprenorphine. This authorization was known as an X-waiver. As of 2023, this X-waiver requirement has been removed, opening the door to a much wider number of prescribers who can manage OUDs and increasing access for those clients with an OUD. Thus, you may see a wider adoption of buprenorphine for treatment of OUDs.
Clinical Tip
Assess for Most Recent Opioid Use
When initiating therapy with buprenorphine or naltrexone, it is important to assess the client’s most recent opioid use. If therapy is initiated and the client has recently used an opioid, it is likely the client will experience moderate to severe withdrawal symptoms. This can be difficult due to clients commonly being hesitant to share recent drug use, so fostering an open and nonjudgmental environment will help to promote honest communication with the client.
Unfolding Case Study
Part A
Read the following clinical scenario to answer the questions that follow. This case study will evolve throughout the chapter.
Daniel Nguyen is a 34-year-old client who presents to his health care provider’s office stating that he wishes for help with his prescription opioid use.
History
Opioid use disorder: takes prescription oxycodone when he can acquire it
Cigarette smoking: smokes 1 pack per day for 7 years
Major depressive disorder
Chronic back pain—developed after a workplace injury at his construction job 5 years ago
Current Medications
Duloxetine 40 mg orally daily
Oxycodone 20 mg orally as needed for pain
| Vital Signs | Physical Examination | |
|---|---|---|
| Temperature: | 98.4°F |
|
| Blood pressure: | 126/75 mm Hg | |
| Heart rate: | 78 beats/min | |
| Respiratory rate: | 16 breaths/min | |
| Oxygen saturation: | 99% on room air | |
| Height: | 5'8" | |
| Weight: | 175 lb | |
FDA Black Box Warning
Benzodiazepines and Opioids
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for clients for whom alternative options are inadequate. Limit dosages and durations to the minimum required.
Buprenorphine
Serious, life-threatening, or fatal respiratory depression may occur with the use of buprenorphine.