Adverse Effects and Toxicities

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Most adverse effects associated with use of the benzodiazepines are related to their ability to produce central nervous system depression. These include drowsiness, excessive sedation, impaired motor coordination, confusion, and memory loss.These effects are most troublesome during the initial week or two of treatment. Subsequently, the patient becomes tolerant and these effects produce less difficulty. Although for most individuals these symptoms are mild, patients should be cautioned against engaging in potentially dangerous tasks such as operating machinery or driving a car during the initial treatment period.

Less common adverse effects include blurred vision, hallucinations, and paradoxical reactions consisting of excitement, stimulation, and hyperactivity. Also, a variety of gastrointestinal complaints occur, and blood dyscrasias have been reported, but these are rare. Benzodiazepine administration during pregnancy, delivery, or lactation has the potential to have adverse effects on the fetus or newborn.

As with other central nervous system depressants, the effects of benzodiazepines are additive with those of ethanol. Patients should be warned that ethanol-containing beverages may produce a more profound depression when taken simultaneously with a benzodi-azepine.

One of the major reasons for the popularity of the benzodiazepines is their relative safety. Overdoses with the benzodiazepines occur commonly, but fatal toxic occurrences are rare. Fatal intoxications are more likely in children, in individuals with respiratory difficulties, and in individuals who have consumed another central nervous system depressant, such as alcohol. After an overdose, the patient begins a deep sleep that may last for 24 to 48 hours, depending on the dose. However, even with large overdoses, the patient can usually still be aroused.

Tolerance and dependence do occur with the use of benzodiazepines. Discontinuation of drug administration, particularly abrupt withdrawal, can be associated with a variety of symptoms, including rebound insomnia and rebound anxiety. The level of insomnia or anxiety may even exceed that which preceded the treatment. Usually, a gradual tapering of the dose until it is eventually discontinued lessens the likelihood of a withdrawal reaction, although in some individuals even this method of drug removal can result in anxiety, apprehension, tension, insomnia, and loss of appetite. More severe symptoms may occur when an individual withdraws from a supratherapeutic dose, particularly if the drug has been taken for months or years. These symptoms can include, in addition to those already mentioned, muscle weakness, tremor, hyperalgesia, nausea, vomiting, weight loss, and possibly convulsions.

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