Diazepam vs Lorazepam
## Overview
Diazepam and lorazepam are both benzodiazepines that enhance GABA-A receptor activity, but they differ markedly in pharmacokinetics. Diazepam is long-acting with active metabolites lasting days; lorazepam is intermediate-acting without active metabolites.
## Mechanism of Action
Both are positive allosteric modulators of GABA-A receptors, binding at the benzodiazepine site (between alpha and gamma subunits) and increasing the frequency of Cl- channel opening in response to GABA, thereby hyperpolarizing neurons and producing anxiolysis, sedation, muscle relaxation, and anticonvulsant effects.
## Pharmacokinetics
Diazepam: oral bioavailability ~100%, very high lipophilicity (rapid CNS penetration), half-life 20–100 h, metabolized by CYP2C19 and CYP3A4 to active desmethyldiazepam (nordazepam, half-life 36–200 h), then further to oxazepam. Total effect duration days-to-weeks with repeated dosing. Highly protein-bound (98%).
Lorazepam: bioavailability ~90% oral (85% IM — one of few BZDs with reliable IM absorption), half-life 10–20 h, no active metabolites (glucuronidation only), protein-bound ~90%.
## Status Epilepticus
For acute status epilepticus, IV lorazepam is the first-line BZD in most guidelines (longer CNS residence time despite similar initial anticonvulsant effect to IV diazepam). IV diazepam reaches CNS faster due to higher lipophilicity but redistributes away from CNS faster.
## Hepatic Impairment
Lorazepam is preferred in hepatic impairment (conjugation not affected by liver disease; no active metabolites that accumulate). Diazepam is metabolized by CYP enzymes and can accumulate in cirrhosis. The LOT rule: Lorazepam, Oxazepam, Temazepam do not require hepatic Phase I metabolism.
## Key Takeaways
- Lorazepam: no active metabolites, preferred in elderly and liver disease, reliable IM route
- Diazepam: long-acting, useful for alcohol withdrawal (covers with active metabolites), muscle spasm
- Both first-line for status epilepticus (lorazepam IV preferred by most guidelines)
结论
Lorazepam is preferred for status epilepticus (IV), procedural sedation, and use in hepatic impairment or elderly patients. Diazepam is preferred for alcohol withdrawal (self-tapering with active metabolites) and muscle spasm. Both are effective anxiolytics but chronic use carries dependence risk.