Nitrazepam - Tolerance Dependence and Withdrawal - Tolerance

Tolerance

Tolerance to a drug's effects occurs after regular exposure to a drug. The mechanism of nitrazepam tolerance may be due to down-regulation of benzodiazepine receptors (observed in rats). When tolerance and habituation occurs to nitrazepam its pharmacokinetic profile changes with absorption of the drug slowing down, elimination increasing and brain concentration of nitrazepam increasing significantly. Increased levels of GABA in cerebral tissue and alterations in the activity state of the serotoninergic system occurs as a result of nitrazepam tolerance.

Tolerance to the sleep inducing effects of nitrazepam occurs after about seven days; tolerance also frequently occurs to the anticonvulsant effects of nitrazepam. A benzodiazepine dependence can develop with a benzodiazepine withdrawal syndrome occurring when the drug is stopped or the dose lowered. Common withdrawal symptoms include; anxiety, insomnia, concentration problems and fatigue. Long-term effects of benzodiazepines such as nitrazepam include worsening mental and physical health as well as cognitive deficits; and immunological disturbances.

After six days of use, tolerance to nitrazepam's but not temazepam's sleep-inducing effects and performance-impairing effects occurred in a study. One study demonstrated tolerance to the sleep promoting effects of nitrazepam and temazepam after seven days nightly administration in 19 elderly inpatients. Self reported quality of sleep was found to be increased after the first nights administration of either nitrazepam or temazepam but by day seven self reported quality of sleep was found to have returned to baseline in these patients, suggesting the development of tolerance after seven days use. The effect was more pronounced in patients of lower intelligence. In mice tolerance to the anticonvulsant properties of nitrazepam developed profoundly and rapidly over six days, and then did not proceed. Some anticonvulsant effects were still apparent after six days administration. In humans tolerance to the anticonvulsant effects of nitrazepam is a frequent occurrence.

Read more about this topic:  Nitrazepam, Tolerance Dependence and Withdrawal

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