by nitrazepam. Estazolam was found to be more potent however. Nitrazepam increases the slow wave light sleep (SWLS) in a dose-dependent manner whilst suppressing deep sleep stages. Less time is spent in stages 3 and 4 which are the deep sleep stages, when benzodiazepines such as nitrazepam are used. The suppression of deep sleep stages by benzodiazepines may be especially problematic to the elderly as they naturally spend less time in the deep sleep stage. Pharmacokinetics Nitrazepam is largely bound to plasma proteins. Benzodiazepines such as nitrazepam are lipid-soluble and have a high cerebral uptake. The time for nitrazepam to reach peak plasma concentrations following oral administration is about 2 hours (0.5 to 5 hours). The half-life of nitrazepam is between 16.5 and 48.3 hours. In young people, nitrazepam has a half-life of about 29 hours and a much longer half-life of 40 hours in the elderly. Both low dose (5 mg) and high dose (10 mg) of nitrazepam significantly increases growth hormone levels in humans. Nitrazepam's half-life in the cerebrospinal fluid, 68 hours, indicates that nitrazepam is eliminated extremely slowly from the cerebrospinal fluid. Concomitant food intake has no influence on the rate of absorption of nitrazepam nor on its bioavailability. Therefore, nitrazepam can be taken with or without food. Overdose Nitrazepam overdose may result in stereotypical symptoms of benzodiazepine overdose including intoxication, impaired balance and slurred speech. In cases of severe overdose this may progress to a comatose state with the possibility of death. The risk of nitrazepam overdose is increased significantly if nitrazepam is abused in conjunction with opioids, as was highlighted in a review of deaths of users of the opioid buprenorphine. Nitrobenzodiazepines such as nitrazepam can result in a severe neurological effects. Nitrazepam taken in overdose is associated with a high level of congenital abnormalities (30 percent of births). Most of the congentital abnormalities were mild deformities. Severe nitrazepam overdose resulting in coma causes the central somatosensory conduction time (CCT) after median nerve stimulation to be prolonged and the N20 to be dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, III-V and I-V. Toxic overdoses therefore of nitrazepam cause prolonged CCT and IPLs. An alpha pattern coma can be a feature of nitrazepam overdose with alpha patterns being most prominent in the frontal and central regions of the brain. Benzodiazepines were implicated in 39% of suicides by drug poisoning in Sweden, with