Tolerance and Dependence

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs.

Dependence on benzodiazepines, as evidenced by a withdrawal syndrome, can develop to large doses of drugs. Mild dependence is produced at therapeutic doses.

Individuals report some craving for drug during withdrawal from benzodiazepines, but the level is not as great as among those who abuse alcohol. Once the withdrawal syndrome has dissipated, the abusers of benzodiazepines are not as likely to resume drug consumption as are alcoholics. Withdrawal signs appear to be more likely following chronic exposure to short-acting benzodiazepines, such as alprazolam (half-life of less than 15 hours) or lorazepam than long-acting drugs. Despite gradual dose reduction, individuals may have anxiety attacks, confusion, agitation, restlessness, sweating, clouded sensorium, heightened sensory perception, perceptual disturbances, sleep disruption, muscle cramps, muscle twitches, and tremors; 2% of addicts may have a seizure during withdrawal. Withdrawal signs peak the second day after abrupt withdrawal and last for at least 5 to 7 days. Withdrawal symptoms following long-acting benzodiazepines (diazepam, clorazepate) peak during the second week of abstinence. In contrast to alcohol and the barbiturate sedatives, withdrawal from benzodiazepines is not life threatening.

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