Jatelka
25-08-2007, 06:24
Nitrazepam is 9-nitro-6-phenyl-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one.
It has the chemical formula C (http://en.wikipedia.org/wiki/Carbon)15H (http://en.wikipedia.org/wiki/Hydrogen)11N (http://en.wikipedia.org/wiki/Nitrogen)3, and a molecular weight of 281.3.
http://www.drugs-forum.com/photopost/data/533/Nitrazepamstructure.jpg
It is a yellow crystalline powder which is insoluble in water, and soluble in alcohol, ether and chloroform. It has a melting point of 226-229 C.
Pharmacokinetics
It is well and fairly rapidly absorbed from the GI tract, when taken orally. Peak plasma concentrations occur at 2 hours (0.5 – 5 hours). Peak plasma levels following an oral dose of 10mg are 68-108ng/ml. 12 hours after oral administration levels are 12 – 38 ng/ml.
Bioavailability varies from 54% (oral) to 94% (iv). It is 87% protein bound.
It is metabolised I the liver to 7-aminonitrazepam and then to 7-acetamidonitrazepam, and is then hydroxylated. The metabolites are not thought to have significant pharmacological activity. Nitrazepam does not cause liver enzyme induction or inhibition with long term treatment.
Clearance is 4.1+/- 2 L/ hour , and 4.7 +/- 1.5 L/hour in the over 65’s.
It is mainly excreted as urinary metabolites, aprox 70% of a dose is excreted this way. Less than 1% is excreted unchanged.
Half life is 16-48 hours (mean 27).
From clinical studies: Nitrazepam is absorbed at variable rates, and there is a lot of inter-individual variation in peak plasma levels. It crosses the blood brain barrier, and is excreted in breast-milk.
Indications
It is licensed for use in (the short-term) the treatment of insomnia. Usual therapeutic dose is 5-10mg at night.
Contraindications
Hypersensitivity, Chronic/Severe respiratory disease, severe hepatic impairment. Caution is advised in renal impairment.
Interactions
There is an additive sedative effect with other CNS depressants (including alcohol). Because Nitrazepam undergoes oxidative metabolism drugs which reduce this (such as cimetidine and disulfiram) increase plasma levels. The anti-cholinergic effects of drugs such as antihistamines and some antidepressants are potentiated by Nitrazepam. Niytrazepam also interacts with some anticonvulsants.
Adverse effects
Anterograde amnesia (including complex behaviours such as sleep-driving and sleep-sex) have been reported. This can occur with normal therapeutic doses, and is more likely when the maximum dose is exceeded, or when it is combined with other CNS depressants. Somnolence and dizziness are common.
There have been rare reports of angioedema and anaphylaxis.
As with all benzodiazepines, physical dependence and withdrawal can occur with as little as 14 days continuous use. Nitrazepam should not be discontinued abruptly.
Other rare side effects include low blood counts and deranged liver function tests. Periodic blood monitoring is advised.
Nitrazepam (and other benzodiazepines) may increase depression, and are not recommended as first line treatment. They can also worsen confusion and psychotic symptoms in schizophrenia and mania. Suicidal tendencies may be unmasked.
Paradoxical reactions (agitation, hallucination and aggression) may occur.
Use in Pregnancy
Is not recommended, and neonatal withdrawal symptoms have been reported. Foetal abnormalities have been demonstrated in studies with other benzodiazepines in the first trimester. Nitrazepam is excreted in breast milk, and should not be used by nursing mothers.
It has the chemical formula C (http://en.wikipedia.org/wiki/Carbon)15H (http://en.wikipedia.org/wiki/Hydrogen)11N (http://en.wikipedia.org/wiki/Nitrogen)3, and a molecular weight of 281.3.
http://www.drugs-forum.com/photopost/data/533/Nitrazepamstructure.jpg
It is a yellow crystalline powder which is insoluble in water, and soluble in alcohol, ether and chloroform. It has a melting point of 226-229 C.
Pharmacokinetics
It is well and fairly rapidly absorbed from the GI tract, when taken orally. Peak plasma concentrations occur at 2 hours (0.5 – 5 hours). Peak plasma levels following an oral dose of 10mg are 68-108ng/ml. 12 hours after oral administration levels are 12 – 38 ng/ml.
Bioavailability varies from 54% (oral) to 94% (iv). It is 87% protein bound.
It is metabolised I the liver to 7-aminonitrazepam and then to 7-acetamidonitrazepam, and is then hydroxylated. The metabolites are not thought to have significant pharmacological activity. Nitrazepam does not cause liver enzyme induction or inhibition with long term treatment.
Clearance is 4.1+/- 2 L/ hour , and 4.7 +/- 1.5 L/hour in the over 65’s.
It is mainly excreted as urinary metabolites, aprox 70% of a dose is excreted this way. Less than 1% is excreted unchanged.
Half life is 16-48 hours (mean 27).
From clinical studies: Nitrazepam is absorbed at variable rates, and there is a lot of inter-individual variation in peak plasma levels. It crosses the blood brain barrier, and is excreted in breast-milk.
Indications
It is licensed for use in (the short-term) the treatment of insomnia. Usual therapeutic dose is 5-10mg at night.
Contraindications
Hypersensitivity, Chronic/Severe respiratory disease, severe hepatic impairment. Caution is advised in renal impairment.
Interactions
There is an additive sedative effect with other CNS depressants (including alcohol). Because Nitrazepam undergoes oxidative metabolism drugs which reduce this (such as cimetidine and disulfiram) increase plasma levels. The anti-cholinergic effects of drugs such as antihistamines and some antidepressants are potentiated by Nitrazepam. Niytrazepam also interacts with some anticonvulsants.
Adverse effects
Anterograde amnesia (including complex behaviours such as sleep-driving and sleep-sex) have been reported. This can occur with normal therapeutic doses, and is more likely when the maximum dose is exceeded, or when it is combined with other CNS depressants. Somnolence and dizziness are common.
There have been rare reports of angioedema and anaphylaxis.
As with all benzodiazepines, physical dependence and withdrawal can occur with as little as 14 days continuous use. Nitrazepam should not be discontinued abruptly.
Other rare side effects include low blood counts and deranged liver function tests. Periodic blood monitoring is advised.
Nitrazepam (and other benzodiazepines) may increase depression, and are not recommended as first line treatment. They can also worsen confusion and psychotic symptoms in schizophrenia and mania. Suicidal tendencies may be unmasked.
Paradoxical reactions (agitation, hallucination and aggression) may occur.
Use in Pregnancy
Is not recommended, and neonatal withdrawal symptoms have been reported. Foetal abnormalities have been demonstrated in studies with other benzodiazepines in the first trimester. Nitrazepam is excreted in breast milk, and should not be used by nursing mothers.