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Prescription and illicit opiates and opioids (eg, morphine, heroin, codeine, oxycodone, fentanyl, hydromorphone) are popular drugs of misuse and abuse and the cause of frequent hospitalizations for overdose. These drugs have widely varying potencies and durations of action; for example, some of the illicit fentanyl derivatives are up to 2000 times more potent than morphine. Poisonings and fatalities have been reported due to the illicit use of fentanyl and the presence of fentanyl and its derivatives in counterfeit medications. Overdose deaths involving synthetic opioids have accelerated during the COVID-19 pandemic and are a significant public health concern. All of these agents decrease CNS activity and sympathetic outflow by acting on opiate receptors in the brain. Tramadol is an analgesic that is unrelated chemically to the opioids but acts on opioid receptors. Buprenorphine is a partial agonist-antagonist opioid used for the outpatient treatment of both chronic pain and opioid addiction (see Table 5–7). Kratom (Mitragyna speciosa) is an herbal supplement with agonist activity at mu opioid receptors. While it has been marketed as a “safe” and natural treatment for patients with opioid use disorder, overdose is associated with both agitation and drowsiness and in severe cases seizures, hallucinations, and respiratory depression.


Mild intoxication is characterized by euphoria, drowsiness, and constricted pupils. More severe intoxication may cause hypotension, bradycardia, hypothermia, coma, and respiratory arrest. Pulmonary edema may occur. Death is usually due to apnea or pulmonary aspiration of gastric contents. Methadone may cause QT interval prolongation and torsades de pointes. While the duration of effect for heroin is usually 3–5 hours, methadone intoxication may last for 48–72 hours or longer. Tramadol, dextromethorphan, and meperidine also occasionally cause seizures. With meperidine, the metabolite normeperidine is probably the cause of seizures and is most likely to accumulate with repeated dosing in patients with CKD. Wound botulism has been associated with skin-popping, especially involving “black tar” heroin. Buprenorphine added to an opioid regimen may precipitate acute withdrawal symptoms. Many opioids, including fentanyl, tramadol, oxycodone, and methadone, are not detected on routine urine toxicology “opiate” screening.


A. Emergency and Supportive Measures

Protect the airway and assist ventilation. Administer activated charcoal for recent large ingestions.

B. Specific Treatment

Naloxone is a specific opioid antagonist that can rapidly reverse signs of narcotic intoxication. Although it is structurally related to the opioids, it has no agonist effects of its own. If no intravenous access is available, administer naloxone 4 mg intranasally, otherwise administer 0.2–2 mg intravenously and repeat as needed to awaken the patient and maintain airway protective reflexes and spontaneous breathing. Large doses (up to 10 mg) may be required for patients intoxicated by some opioids (eg, codeine, fentanyl derivatives). Caution: The duration of effect of naloxone is only about 2–3 hours; repeated doses may be necessary for ...

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