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Harrison’s Manual of Medicine



Clinical Features

Narcotics, or opiates, bind to specific opioid receptors in the CNS and elsewhere in the body. These receptors mediate the opiate effects of analgesia, euphoria, respiratory depression, and constipation. Endogenous opiate peptides (enkephalins and endorphins) are natural ligands for the opioid receptors and play a role in analgesia, memory, learning, reward, mood regulation, and stress tolerance.
The prototypic opiates, morphine and codeine, are derived from the juice of the opium poppy, Papaver somniferum. The semisynthetic drugs produced from morphine include hydromorphone (Dilaudid), diacetylmorphine (heroin), and oxycodone. Purely synthetic agents are meperidine (Demerol), propoxyphene (Darvon), and methadone. All of these substances produce analgesia and euphoria as well as physical dependence when taken in high enough doses for prolonged periods of time.
1% of the U.S. population meets criteria for narcotic abuse or dependence at some time in their lives. 70% of narcotic-addicted individuals have another psychiatric disorder (usually major depression, alcoholism, or a personality disorder). Three groups of abusers can be identified: (1) “medical” abusers—pts with chronic pain syndromes who misuse their prescribed analgesics; (2) physicians, nurses, dentists, and pharmacists with easy access to narcotics; and (3) “street” abusers. The street abuser is typically a higher functioning individual who began by using tobacco, alcohol, and marijuana and then moved on to opiates.
Clinical Features
Acutely, all opiates have the following CNS effects: sedation, euphoria, decreased pain perception, decreased respiratory drive, and vomiting. In larger doses, markedly decreased respirations, bradycardia, pupillary miosis, stupor, and coma ensue. Additionally, the adulterants used to “cut” street drugs (quinine, phenacetin, strychnine, antipyrine, caffeine, powdered milk) can produce permanent neurologic damage, including peripheral neuropathy, amblyopia, and myelopathy. The shared use of contaminated needles is a major cause of brain abscesses, acute endocarditis, hepatitis B, AIDS, septic arthritis, and soft tissue infections. At least 25% of street abusers die within 10–20 years of starting active opiate abuse.
Chronic use of opiates will result in tolerance (requiring higher doses to achieve psychotropic effects) and physical dependence. With shorter-acting opiates such as heroin, morphine, or oxycodone, withdrawal signs begin 8–12 h after the last dose, peak at 2–3 days, and subside over 7–10 days. With longer- acting opiates such as methadone, withdrawal begins 2–4 days after the last dose, peaks at 3–4 days, and lasts several weeks.
Withdrawal produces diarrhea, coughing, lacrimation, rhinorrhea, diaphoresis, twitching muscles, piloerection, fever, tachypnea, hypertension, diffuse body pain, insomnia, and yawning. Relief of these exceedingly unpleasant symptoms by narcotic administration leads to more frequent narcotic use. Eventually, all of the person’s efforts are consumed by drug-seeking behavior.

Overdose High doses of opiates, whether taken in a suicide attempt or accidentally when the potency is misjudged, are frequently lethal. Toxicity occurs immediately after IV administration and with a variable delay after oral ingestion. Symptoms include miosis, shallow respirations, bradycardia, hypothermia, stupor or coma, and pulmonary edema. Treatment requires cardiorespiratory support and administration of the opiate antagonist naloxone (0.4 mg IV repeated in 3–10 min if no or only partial response). Because the effects of naloxone diminish in 2–3 h compared with longer-lasting effects of heroin (up to 24 h) or methadone (up to 72 h), pts must be observed for at least 1–3 days for reappearance of the toxic state.
Withdrawal or Abstinence Syndromes Clonidine is effective in decreasing the sympathetic nervous system hyperactivity observed in opiate withdrawal. Doses of 0.3–0.5 mg/d are used for the 2–3 weeks of the withdrawal period. Although it is highly unpleasant, opiate withdrawal is not physically dangerous or life-threatening per se in adults (unlike alcohol withdrawal). However, withdrawal syndromes in newborns of street abusers are fatal in 3–30% of cases.
Methadone maintenance (to avoid withdrawal or abstinence syndromes) is a widely used treatment strategy in the management of opiate addiction. Long-acting oral methadone is most convenient: 1 mg methadone is equivalent to 3 mg morphine, 1 mg heroin, or 20 mg meperidine. Most patients receive 10–25 mg methadone bid, with higher doses given if withdrawal symptoms break through. Although methadone has mood-elevating effects in some individuals, maintenance nevertheless leads to reduced opiate and nonopiate drug use, reduced criminal behavior, and decreased symptoms of depression.
L-Alpha-acetylmethadol (LAAM) is a long-acting synthetic narcotic that may be given only 3 times a week; however, some pts experience nervousness and stimulation on LAAM. Buprenorphine is a partial receptor agonist that blocks some of the subjective effects of narcotics and may be as effective as low-dose methadone in maintenance treatment.
To help prevent relapses in the abstinent pt, the oral antagonist naltrexone is used in doses of 50–150 mg/d. It blocks the euphoric and analgesic effects of the opiate when a pt relapses and uses narcotics.
Chronic Pain Syndromes   Physicians should avoid encouraging narcotic addiction in pts with established chronic pain syndromes (this is to be distinguished from prescribing adequate analgesia in pts with acute pain). Once tolerance and physical dependence are established in the pt with a chronic pain syndrome, withdrawal and abstinence syndromes will intensify the pt’s pain and confuse the management of an already difficult problem. Pts should be educated that medications will be used to minimize the effects of pain on their physical function but that they will not abolish the pain entirely. Nonpharmacologic approaches to pain management should also be part of the treatment plan.
Identification of the Chronic Narcotic User Blood and urine screens for opiates, or the naloxone challenge test, can be used to identify chronic narcotic users. In the naloxone challenge test, 0.4 mg is given slowly IV over 5 min, and the pt is observed for 1–2 h for signs of withdrawal.
Realistic expectations for rehabilitation are possible only when the pt is motivated to make a long-term commitment to a drug-free lifestyle. Specialized counseling and peer programs, including Narcotics Anonymous, are a mainstay of treatment. In many cases, adjunctive pharmacologic management is helpful, either to block the euphoric effects of opiates or to impede withdrawal/abstinence syndromes (discussed above). Any co-morbid psychiatric diagnoses (the “dual diagnosis” pt) must be evaluated and treated vigorously.
Special issues exist for medical staff. Physicians should never prescribe opiates for themselves or members of their families. Medical organizations need to be prepared to identify and rehabilitate substance-impaired physicians as quickly as possible.


For a more detailed discussion, see Shuckit MA, Segal DS: Opioid Drug Abuse and Dependence, Chap. 388, p. 2567, in HPIM-15.

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