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Assessing compliance
Monitoring for appropriate therapeutic level
Assessing toxicity
Diazepam, a benzodiazepine derivative, is an anxiolytic agent that reduces neuronal depolarization resulting in decreased action potentials. It enhances the action of gamma-amino butyric acid (GABA) by tightly binding to A-type GABA receptors, thus opening the membrane channels and allowing the entry of chloride ions. It is also used as a muscle relaxant, procedural sedation agent, and sedative-hypnotic agent to treat withdrawal states (ie, ethanol), along with other conditions (seizures).
Diazepam is metabolized to several metabolites in the liver including temazepam, oxazepam, and nordiazepam (desmethyldiazepam) and the clearance of the drug is reduced considerably in the elderly and in patients with hepatic disease.
Therapeutic assessment typically includes measurement of both the parent drug (diazepam) and the active metabolite (nordiazepam).
Diazepam and Nordiazepam: 200-2,500 ng/mL
For seizures:
Serum concentrations are not usually monitored during early therapy because response to the drug can be monitored clinically as seizure control. If seizures resume despite adequate therapy, another anticonvulsant must be considered.
Toxicity is commonly seen when diazepam plus nordiazepam concentrations exceed 3,000 ng/mL. Adverse effects of benzodiazepines in therapeutic doses usually reflect the drug's pharmacology and include sedation, slurred speech, and ataxia. Respiratory depression/arrest may occur with large overdoses or following rapid IV injection with short-acting benzodiazepines.
No significant cautionary statements
1. Langman LJ, Bechtel L, Holstege CP: Chapter 35: Clinical Toxicology, In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, Philadelphia, PA, 2011, pp 1109-1188
2. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Edited by CA Burtis, ER Ashwood, DE Bruns, WB Saunders Company, Philadelphia, PA, 2011, Table 60.2, pp 1109-1188