Name: Diazepam (Valium)
Class: Antianxiety-Sedative-Hypnotic Agent (Benzodiazepine) (Antiepileptic-Status)
Mechanism: Acts on BZD receptors closely coupled to GABAA receptors ® enhancement of GABA inhib. action via freq. of Cl- channel opening.
Absorption: Oral ® rapid absorption (large variability in indiv. responsiveness). IV for seizures & conscious sedation, but may cause pain & phlebitis. IM ® poor bioavailability (avoid).
Dist.: Protein binding 99%. High lipid solubility. Rapid CNS dist. Accum. in fat.
Metabolism.: Liver microsomal N-dealkylation/hydroxylation, then conjug ® inactive glucuronides. No induction of hepatic microsomal enzymes.
Excretion, t½: Urine—mostly Metabolismolized. Long—50-150 hr. Active Metabolismolites.
Toxicity/S.E.s: All dose-related. Acute—excessive depression of CNS fxns (drowsiness, sleep, confusion, disorientation, ataxia, slurred speech, nystagmus, mild amnesia, dementia). May also cause aggression, hyperactivity, delirium, insomnia. Large doses or mixture w/depressants (e.g., EtOH) may cause resp. depression, coma, hallucinations, nightmares, confusion. Chronic—impaired thinking/memory, weight gain/loss. May exacerbate depression. Habituation & physical dependence ® w/drawal syndrome. Abrupt discontinuation ® risk for convulsion (but less risk than w/newer BZDs). Symptoms have long latency (5+ days). Metabolism. ¯ in elderly and by cimetidine. Overdose ® serious resp. depression (rarely fatal w/support). Psych & phys depend.
BZDs are DOCs for sedation. Anticonvulsant—a DOC (IV) for status epilepticus or drug-induced seizures. Skeletal muscle relaxation—spasms, tetanus, orthopedic manipulations.