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Pharmacology
Valium is a benzodiazepine with CNS depressant properties and a somewhat flatter dose-response slope than the sedative-hypnotic drugs. In laboratory animals, it produces, in varying doses, taming, disinhibitory, sedative, anticonvulsant, muscle relaxant, ataxic and hypnotic effects. Valium is relatively devoid of autonomic effects and does not significantly reduce locomotor activity at low doses, or depress amphetamine-induced excitation. In high doses, it activates the drug metabolizing enzymes in the liver. Valium also possesses dependence liability and may produce withdrawal symptoms, but has a wide margin of safety against poisoning. Metabolism studies in animals and man have indicated that oral diazepam is rapidly absorbed from the gastrointestinal tract. Peak blood levels are reached within 1-2 hours after administration. The acute half-life is 6-8 hours with a slower decline thereafter, possibly due to tissue storage. In humans, comparable blood levels of diazepam were obtained in maternal and cord blood indicating placental transfer of the drug. Valium may appear in human breast milk. With the parenteral form, peak blood levels are reached within 15 minutes after i.v. administration and are of the same magnitude as after oral administration. The respective half-life is approximately 2-3 hours. The distribution and fate of tritium-labeled Valium in man has indicated that the drug has a rapid and extensive uptake by tissues. Although the radioactivity in the blood appears to represent mainly the intact drug, Valium was shown to be excreted exclusively in the form of its metabolites. The two major metabolites are oxazepam glucuronide and N-desmethylated diazepam.
IndicationsThe short-term symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions and anxiety states with somatic expression.In acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor and impending acute delirium tremens. As an adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare stiff man syndrome.
ContraindicationsMyasthenia gravis, known hypersensitivity to benzodiazepines. Not recommended for children under 6 months of age.
WarningsPregnancy:Several studies have suggested an increased risk of congenital malformations associated with the use of Valium, chlordiazepoxide and meprobamate during the first trimester of pregnancy. Therefore, the administration of diazepam is rarely justified in women of childbearing potential. If the drug is prescribed for a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant.
PrecautionsGeriatrics:Elderly and debilitated patients or those with organic brain disorders have been found to be prone to CNS depression following even low doses. For these patients it is recommended that the dosage be limited to the smallest effective amount to preclude development of ataxia, oversedation or other possible adverse effects. Use in emotional disorders: Use in epileptic patients: Potentiation of drug effects: Drug dependence: Occupational Hazards: The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If Valium is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable.
Adverse EffectsThe most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, changes in libido.The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions. Paradoxical reactions such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, as well as sleep disturbances and stimulation, have been reported; should these occur, the drug should be discontinued. Minor changes in EEG patterns have been observed in patients on Valium therapy. These changes consist of low to moderate voltage fast activity, 20 to 30 cycles/second and are of no known significance.
OverdoseSymptoms:Drowsiness, oversedation and ataxia. When the effects of drug overdosage begin to wear off, the patient exhibits some jitteriness and overstimulation. The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimum effects on respiration, pulse and blood pressure unless the overdosage is extreme. Treatment:
DosageMust be individualized according to diagnosis, severity of symptoms and degree of response. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In the first few days of administration a cumulative effect of the drug may occur, and therefore the dosage should be increased only after stabilization is evident.Adults: Symptomatic relief in acute alcohol withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed. Adjunctively for relief of skeletal muscle spasms: 2 to 10 mg, 3 to 4 times daily. Elderly and debilitated patients, or in the presence of debilitating disease: Children (Because of varied responses, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months): Do not prescribe or administer diazepam for periods in excess of 6 weeks, unless a definite need for utilizing this medication has been established by a follow-up medical examination.
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