Nitrazepam

Nitrazepam (中文:[[ ]])is a long-acting benzodiazepine. It is used as a hypnotic in the short-term management of insomnia. It is reported to act in 30 to 60 mionutes to produce sleep lasting for 6 to 8 hours.

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Nitrazepam Tablet 5 mg	NITR01	P1S1S3 & Part 1 Dangerous Drug

Mechanism of Action

• Nitrazepam is a benzodiazepine.
• Gama-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, acting on the GABA receptors in the central nervous system (CNS), inducing sleepiness, muscular relaxation, and control of anxiety and seizures.
• Nitrazepam acts on the benzodiazepine receptors in the brain and the spinal cord. Benzodiazepine receptors in the CNS are linked with GABA receptors as a complex.
• Nitrazepam by binding to the benzodiazepine receptors results in activation of the GABA-benzodiazepine receptor complex.
• Thus, Nitrazepam helps to promote muscle relaxation, reduce anxiety, control of convulsions and promote sleep.

Insomnia (short-term use	By mouth ADULT: 5 – 10 mg daily, to be taken at bedtime. ELDERLY: 2.5 – 5 mg daily, to be taken at bedtime

Benzodiazepines are sometimes used in the management of epilepsy, but their long-term use is limited by problems of sedation, dependence, and tolerance to the antiepileptic effects.

Nitrazepam has been used in the treatment of infantile spasms (as for example in West’s syndrome) and the so-called infantile myoclonic seizures.

Usual oral dose: 0.3 to 1 mg/kg daily in 3 divided doses.

Side Effects

Nitrazepam is an unsuitable hypnotic for the elderly as it causes:

• Impairments in body balance and standing steadiness in individuals who wake up at night
• As a result, leading to falls and hip fractures
• It induces general mental deterioration
• Inability to walk
• Incontinence
• Confusion and disorientation

The nitrazepam-induced symptoms can lead to a misdiagnosis of dementia.

Elderly are more likely to experience sedation and decreased coordination. The lowest effective dose of nitrazepam should be used for the shortest possible length of time.

Possible side effects include:

Very common (>10% of incidence) or Common (1-10% of incidence)	Shakiness and unsteady walk (especially in the elderly) Trembling, , impairment of muscle functions or coordination Confusion (especially in the elderly) Amnesia(impairment of memory) Drowsiness the next day Numbed emotions Reduced alertness Muscle weakness Paradoxical increase in aggression
Infrequent (0.1 -1% of incidence)	Dysarthria Hypotension hypothermia Gastro-intestinal disturbances Gynaecomastia Low blood pressure Incontinence Drooling, impaired swallowing and aspiration pneumonia Slurred speech Tremor Vertigo Visual disturbances
Rare (<0.1% of incidence)	Apnoea Blood disorders Jaundice Respiratory depression hypersensitivity reactions

Overdosage can produce CNS depression and coma.

Paradoxical reactions (the opposite of what is to be expected) may occur. Symptoms include

• aggression, rage
• mania, agitation, and restlessness
• hallucinations, inappropriate behavior
• twitches and tremor

Pharmacokinetics

Oral bioavailability	Nitrazepam is well absorbed after oral doses.
Onset of action	Peak plasma concentrations occur about 2 to 3 hours after ingestion
Metabolism	Nitrazepam is metabolized in the liver, mediated by the cytochrome P450 system.
Elimination half-life	Nitrazepam is excreted in the urine. Up to about 20% of an oral dose is found in the faeces. 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. Nitrazepam’s half-life in the cerebrospinal fluid, 68 hours, indicates its extremely slow elimination from the cerebrospinal fluid.