Drug Intoxication and Withdrawal
John C. M. Brust
INTRODUCTION
There are two kinds of drug dependence. Psychic dependence leads to craving and drug-seeking behavior. Physical dependence produces somatic withdrawal symptoms and signs. Depending on the particular drug and the circumstances of its administration, psychic and physical dependence can coexist or occur alone. Addiction is psychic dependence.
In the United States, dependence of one or both types is encountered with a variety of agents, licit and illicit (Table 127.1). Different classes of drugs produce diverse symptoms of intoxication and withdrawal as well as medical and neurologic complications.
DRUGS OF DEPENDENCE
OPIOIDS
Opioids include agonists, antagonists, and mixed agonist-antagonists (Table 127.2). Heroin, the opioid most often abused, is illegal in the United States. During the past decade, however, escalation in the use of prescription opioids for noncancer pain resulted in an epidemic of prescription opioid recreational use, especially oxycodone, hydrocodone, methadone, morphine, fentanyl, and hydromorphone. During the same period, heroin use also increased sharply, in many cases representing escalation from prescription opioid use.
Desomorphine, a reduction of codeine that is more potent but also often contains more impurities, is termed crocodile for the green-black skin lesions found on parenteral users.
At desired levels of intoxication, agonist opioids produce drowsy euphoria; analgesia; cough suppression; miosis; and often nausea, vomiting, sweating, pruritus, hypothermia, postural hypotension, constipation, and decreased libido. Taken parenterally or smoked (often in combination with alkaloidal crack cocaine), heroin produces a “rush,” a brief ecstatic feeling followed by euphoria and either relaxed “nodding” or garrulous hyperactivity. Overdose causes coma, respiratory depression, and pinpoint (but reactive) pupils. For adults with respiratory depression, treatment consists of respiratory support and naloxone, 2 mg intravenously, repeated as needed up to 20 mg; for those with normal respirations, smaller doses (0.4 to 0.8 mg) are given to avoid precipitation of withdrawal signs. Naloxone is short acting, and so patients receiving it require admission and close observation.
TABLE 127.1 Drrugs off Dependence | ||||||||||
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Opioid agonist withdrawal symptoms include irritability, lacrimation rhinorrhea, sweating, yawning, mydriasis, myalgia, muscle spasms, piloerection, nausea, vomiting, abdominal cramps, fever, hot flashes, tachycardia, hypertension, and orgasm. In adults, seizures and delirium are not features of opioid withdrawal, which is rarely life threatening and can usually be prevented or treated with 20 mg of methadone taken once or twice daily. By contrast, untreated opioid withdrawal in newborns is severe and protracted, probably causes seizures, and is often fatal. Treatment is with titrated doses of methadone or paregoric; a barbiturate can be added if additional drug withdrawal is suspected or if seizures require treatment.
Effective pharmacotherapy for opioid dependence consists of substitution with oral methadone or buprenorphine. Treatment failure is usually attributable to inadequate dosage. Antagonist therapy with naltrexone proved disappointing.
TABLE 127.2 Commonly Used Opioids | ||||||||||||||||||
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TABLE 127.3 Commonly Used Psychostimulants | ||||||||||||
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PSYCHOSTIMULANTS
Psychostimulants include amphetamine-like agents and cocaine (Table 127.3). 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) appears to combine the psychostimulant properties of amphetamine with the hallucinogenic properties of lysergic acid diethylamide (LSD). An East African-Arabian shrub, khat (Catha edulis), is chewed for the effects of its psychoactive ingredient cathinone. A related and easily manufactured compound, methcathinone, as well as numerous designer analogs, are marketed as “bath salts” in Europe and North America. Also available are designer psychostimulants chemically characterized as aminoindanes, piperazines, and pipradol.
Desired effects of psychostimulants include alert euphoria with increased motor activity and physical endurance. Taken parenterally or smoked as alkaloidal cocaine (“crack”) or methamphetamine (“ice”), psychostimulants produce a rush clearly distinguishable from that of opioids. With repeated use, there is stereotypic activity progressing to bruxism or other dyskinesias and paranoia progressing to frank hallucinatory psychosis. Overdose causes headache, chest pain, tachycardia, hypertension, flushing, sweating, fever, and excitement. There may be delirium, cardiac arrhythmia, myoclonus, seizures, myoglobinuria, shock, coma, and death. Malignant hyperthermia and disseminated intravascular coagulation are described. Treatment includes benzodiazepine sedation, oxygen, bicarbonate for acidosis, anticonvulsants, cooling, an antihypertensive (preferably an α-blocker such as phenoxybenzamine or a direct vasodilator such as sodium nitroprusside), respiratory and blood pressure (BP) support, and cardiac monitoring.
Psychostimulant withdrawal produces fatigue, depression, and increased hunger and sleep. Objective signs are few, but depression or somnolence can require treatment or even hospitalization.
An effective pharmacotherapy for psychostimulant dependence does not exist.
SEDATIVES
Sedative agents include barbiturates, benzodiazepines, and miscellaneous products (Table 127.4). Desired effects and overdose both resemble ethanol intoxication, although respiratory depression is much milder with benzodiazepines. Treatment is supportive; for severe benzodiazepine poisoning, there is a specific antagonist, flumazenil. Withdrawal causes tremor and seizures, which can be prevented or treated with titrated doses of a benzodiazepine such as lorazepam 5 mg every 4 hours. Delirium tremens is a medical emergency requiring intensive care.
γ-Hydroxybutyric acid (GHB) and two of its precursors, γ-butyrolactone and 1,4-butanediol, are notorious as “date rape” drugs. Often taken with ethanol, they cause sedation and respiratory depression. Treatment is supportive. Dependence occurs and withdrawal signs resemble those of other sedatives and ethanol, including seizures and delirium tremens.
MARIJUANA
Marijuana, from the hemp plant Cannabis sativa, contains many cannabinoid compounds, of which the principal psychoactive
agent is δ-9-tetrahydrocannabinol (THC). Hashish refers to preparations made from the plant resin, which contains high concentrations of psychoactive cannabinoids. δ-9-THC acts at cannabinoid receptors in the brain, and the pharmaceutical development of synthetic receptor agonists was soon followed by their availability as recreational agents. Marketed as “Spice” or “K2,” they are often many times more potent than δ-9-THC.
agent is δ-9-tetrahydrocannabinol (THC). Hashish refers to preparations made from the plant resin, which contains high concentrations of psychoactive cannabinoids. δ-9-THC acts at cannabinoid receptors in the brain, and the pharmaceutical development of synthetic receptor agonists was soon followed by their availability as recreational agents. Marketed as “Spice” or “K2,” they are often many times more potent than δ-9-THC.
TABLE 127.4 Sedative//Hypnotic Drugs | ||||||||||||||||||||||||||||||||||
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