Generic Name

Diazepam

Mechanism

• Diazepam is a benzodiazepine that potentiates the inhibitory neurotransmitter gamma‑aminobutyric acid (GABA).
• It binds to a specific allosteric site on the GABA_A receptor complex, increasing chloride ion influx.
• Resulting hyperpolarization diminishes neuronal excitability, producing anxiolytic, anticonvulsant, skeletal‑muscle relaxant, and hypnotic effects.

Pharmacokinetics

• Absorption: Rapid oral bioavailability (~70 %), peak plasma concentration in 1–2 h.
• Distribution: Large volume of distribution (~700‑1,000 L) due to high lipid solubility; plasma protein binding ~80‑95 %.
• Metabolism: Hepatic CYP2C19, CYP3A4, and CYP2E1 → primarily 3‑hydroxy‑diazepam and lorazepam.
• Elimination: Elimination half‑life ~20–60 h (active metabolites extend clinical effect).
• Excretion: Renal (~70 %) and biliary routes.

Indications

• Acute seizure disorders (e.g., status epilepticus).
• Alcohol withdrawal (agitation, tremor, seizures).
• Pre‑operative anxiolysis and sedation.
• Myoclonus and muscle spasm.
• Ethanol‑induced insomnia.

Contraindications

• Contraindicated in:
• Severe respiratory insufficiency or chronic obstructive pulmonary disease.
• Acute narrow‑angle glaucoma.
• Severe hepatic insufficiency (reduced metabolism).
• Known hypersensitivity to benzodiazepines.
• Warnings:
• Potential for respiratory depression when combined with opioids, alcohol, or other CNS depressants.
• Risk of dependence and withdrawal; taper slowly.
• Cognitive and motor impairment; caution in elderly.

Dosing

• Intravenous: 1‑2 mg; infusion over 2–5 min to mitigate hypotension.
• Intramuscular: 10 mg in thigh; onset in 5‑10 min.

Adverse Effects

• Common: drowsiness, dizziness, impaired coordination, blurred vision.
• Serious: respiratory depression, paradoxical agitation or aggression, seizures (rare in overdose), hypotension.
• Chronic use: tolerance, physical dependence, withdrawal syndrome (delirium, seizures, hallucinations).

Monitoring

• Vital signs: BP, HR, respiratory rate (especially after IV/IM).
• Neurologic: Glasgow Coma Scale, sedation score.
• Laboratory: LFTs if >7 days use; renal function if dialysis indicated.
• Behavior: Monitor for paradoxical reactions, especially in elderly or patients with a history of aggression.

Clinical Pearls

• Rapid induction for status epilepticus: Use 10 mg IV, repeat every 10 min up to 40 mg for 1 h before ICU transfer.
• Avoid cross‑tolerance with antiepileptic drugs that also modulate GABA; switch to ketamine or propofol for refractory cases.
• Elderly & pregnancy: Favor oral over IV if possible; consider lower starting dose due to increased sensitivity.
• Overdose signs: Look for myoclonus, opisthotonus, and paradoxical hyperactivity; treat with flumazenil (dose‑fractionated, monitor for recurrence).
• Drug interactions: CYP3A4 inhibitors (ketoconazole, clarithromycin) increase diazepam levels; adjust dose accordingly.

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• *End of Diazepam Drug Card*