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More about Nitrazepam

What is/are Nitrazepam?

Nitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Nitrosun, Ormodon, Paxadorm, Remnos, and Somnite. It is a hypnotic drug used in the treatment of moderate to severe insomnia which has sedative and motor impairing properties, as well as anxiolytic, amnestic, anticonvulsant, and skeletal muscle relaxant properties. As with other benzodiazepines, tolerance, dependence, and withdrawal can occur, and there is a potential for drug abuse and overdose. Nitrazepam is not suitable for use in the elderly, children, pregnant women, or those with chronic obstructive pulmonary disease, and should be used with caution in individuals with comorbid psychiatric disorders or those who are driving or operating machinery. Nitrazepam is available in 5 mg and 10 mg tablets. In the Netherlands, Australia, Israel, and the United Kingdom it is only available in 5 mg tablets. In Denmark it is available as 2.5 mg and 5 mg tablets under the name Pacisyn.

Medical uses

itrazepam is used to treat short-term sleeping problems (insomnia), namely difficulty falling asleep, frequent awakening, early awakenings, or a combination of each.

Nitrazepam is sometimes used for refractory epilepsies. However, long term prophylactic treatment of epilepsy has considerable drawbacks. Most importantly the loss of antiepileptic effects due to tolerance which renders prolonged nitrazepam therapy ineffective. Nitrazepam also has the drawback of significant side effects such as sedation, which is why nitrazepam and benzodiazepines in general are only prescribed in the acute management of epilepsies. Nitrazepam has been found to be more effective than clonazepam in the treatment of West syndrome which is an age dependent epilepsy, affecting the very young. However, as with other epilepsies treated with benzodiazepines, long term therapy becomes ineffective with prolonged therapy and the side effects of hypotonia and drowsiness are troublesome with nitrazepam therapy, other antiepileptic agents are therefore recommended for long term therapy, possibly Corticotropin (ACTH) or vigabatrin. In uncontrolled studies nitrazepam has shown effectiveness in infantile spasms; nitrazepam is sometimes considered as a treatment option for this indication when other drugs fail to control infantile spasms.

Nitrazepam along with diazepam, oxazepam, and temazepam in 1993 represented 82% of the benzodiazepine market in Australia. The rate of benzodiazepine prescribing in Tasmania is higher than in other Australian states; according to one 1992 study, nitrazepam and flunitrazepam prescribing levels in Tasmania were disturbingly high. Prescribing of hypnotics in Norway is quite restrictive with only 3 hypnotics which are prescribable; nitrazepam, zolpidem and zopiclone. The usage of benzodiazepine hypnotics in local authority homes for the elderly in Edinburgh, 1982, established via a clinical survey, was that 34% of residents were taking sleeping medication. However, the number varied between the homes, with some homes reporting only 2.3% of residents to be on hypnotic medication and others up to 56.5% on hypnotic drugs. Nitrazepam was the most frequently prescribed hypnotic medication accounting for a third of hypnotic use in Edinburgh residential homes in 1982.

Adverse effects

Common side effects

Central nervous system depression including, somnolence, dizziness, depressed mood, rage, violence, fatigue, ataxia, headache, vertigo, impairment of memory, impairment of motor functions, hangover feeling in the morning, slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, double vision and inattention have been reported. Unpleasant dreams and rebound insomnia have also been reported. High levels of confusion, clumsiness also occurs after administration of nitrazepam. Increased reaction time, co-ordination problems and impaired learning and memory.

Impaired learning and memory occurs due to the action of the drug on benzodiazepine receptors which causes a dysfunction in the cholinergic neuronal system. Nitrazepam causes a reduced output of serotonin which is closely involved in regulating mood and may be the cause of feelings of depression in users of nitrazepam or other benzodiazepines.

Nitrazepam is a long acting benzodiazepine with an elimination half-life of 15-38 (mean elimination half-life 26 hours).[1] Residual "hangover" effects after nighttime administration of nitrazepam such as sleepiness, impaired psychomotor and cognitive functions may persist into the next day which may impair the ability of users to drive safely and increases the risk of falls and hip fractures. Significant impairment of visual perception and sedative effects persisting into the next day typically occurs with nitrazepam administration as was demonstrated in a human clinical trial assessing the effect of nitrazepam on peak saccade velocity.

Impairment of psychomotor function may especially occur after repeated administration, with the elderly being more vulnerable to this adverse effect. Overall accuracy of completing tasks is impaired after repeated administration of nitrazepam and is due to drug accumulation of nitrazepam. The elderly are more vulnerable to these side effects.

Less common side effects

Hypotension, faintness, palpitation, rash or pruritus, gastrointestinal disturbances, changes in libido. Very infrequently, paradoxical reactions may occur, for example, excitement, stimulation, hallucinations, hyperactivity and insomnia. Also depressed or increased dreaming, disorientation, severe sedation, retrograde amnesia, headache, hypothermia, delirium tremens. Acroparaesthesia has been reported as a side effect from nitrazepam with symptoms including, pins and needles in hands and loss of power of fingers and clumsiness of the fingers. Severe liver toxicity has also been reported.[

Mechanism of action

Nitrazepam interacts with the antibiotic erythromycin which is a strong inhibitor of CYP3A4, which affects concentration peak time. This interaction is not to believed to be clinically important. However, anxiety, tremor and depression have been documented in a case report following administration of nitrazepam and triazolam. Following administration of erythromycin to the patient, repetitive hallucinations and abnormal bodily sensations developed. The patient had however acute pneumonia and renal failure. Co-administration of benzodiazepine drugs at therapeutic doses with erythromycin may cause serious psychotic symptoms especially in those with other significant physical complications. Oral contraceptive pills, reduce the clearance of nitrazepam which may lead to increased plasma levels of nitrazepam and accumulation. Rifampin increases the clearance of nitrazepam significantly and probenecid decreases the clearance of nitrazepam significantly. Cimetidine slows down the elimination rate of nitrazepam leading to more prolonged effects of nitrazepam and increased risk of accumulation. Alcohol (ethanol) in combination with nitrazepam may cause a synergistic enhancement of the hypotensive properties of both benzodiazepines and alcohol. Benzodiazepines including nitrazepam may inhibit the glucuronidation of morphine leading to increased levels of and prolongation of the effects of morphine in rat experiments.

This article uses material from the Wikipedia article Nitrazepam, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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