Oxazepam
Oxazepam
Generic Name
Oxazepam
Mechanism
- Oxazepam is a benzodiazepine that potentiates GABAA receptor activity by increasing the frequency of chloride channel opening.
- The result is a hyperpolarization of neuronal membranes, leading to reduced excitability in the CNS.
- It lacks a strong affinity for the benzodiazepine site in the presence of high GABA levels, which accounts for its shorter half‑life and lower risk of withdrawal compared to longer‑acting analogs.
Pharmacokinetics
| Parameter | Value |
| Absorption | Rapid oral absorption; peak plasma concentration in 2–4 h. |
| Bioavailability | ~80 % (good oral bioavailability). |
| Distribution | Widely distributed; plasma protein binding 60–70 %. |
| Metabolism | Hepatic conjugation via glucuronidation (CYP3A4 & UGT enzymes). |
| Elimination | Renal excretion of inactive conjugates. |
| Half‑life | 11–27 h (average 17 h), allowing once‑daily dosing in most patients. |
| Drug interactions | Potentiated by CNS depressants, CYP3A4 inhibitors (e.g., ketoconazole), and alcohol. |
Indications
- Generalized anxiety disorder (short‑term).
- Acute alcohol withdrawal (to prevent seizures and delirium tremens).
- Pre‑operative sedation or anxiolysis.
- Adjunct in insomnia when used short‑term (<2 weeks) and at low doses.
Contraindications
- Absolute contraindications:
- Severe respiratory insufficiency (COPD, sleep apnea).
- Acute narrow-angle glaucoma.
- Pregnancy (Category D; avoid unless benefits > risks).
- Warnings:
- Hepatic or renal impairment → dose reduction.
- Elderly patients: increased sensitivity → lower starting dose.
- Potential for sedation, cognitive impairment, and falls.
- Risk of abuse, dependence, and withdrawal.
Dosing
| Population | Dose | Route | Frequency |
| Adults | 15–30 mg/day | Oral | 1–3 divided doses |
| Elderly / renal impairment | 7.5–15 mg/day | Oral | 1–2 divided doses |
| Acute alcohol withdrawal | 15–30 mg every 8 h | Oral/IV (if needed) | 3–4 d (taper) |
| Adolescents (≥12 y) | 15 mg/day | Oral | 1–2 divided doses |
> Note: Initiate at the lower end and titrate up based on response and tolerability.
Adverse Effects
- Common: somnolence, dizziness, muscle weakness, impaired coordination, dry mouth, constipation.
- Serious: respiratory depression (especially with opioids or alcohol), paradoxical agitation, severe bradycardia in susceptible patients.
- Rare: anaphylactoid reactions, hepatotoxicity (in high doses or with hepatic disease).
Monitoring
- CNS status: sedation level, psychomotor function.
- Respiratory rate: especially with polypharmacy.
- Renal function: serum creatinine, BUN.
- Liver enzymes: AST/ALT for patients with hepatic disease or prolonged use.
- Blood alcohol level if alcohol withdrawal management.
Clinical Pearls
- Tapering is essential: abruptly stopping >12 h after the last dose can precipitate rebound anxiety or seizures.
- Use the lowest effective dose: due to its intermediate duration, even modest doses can cause significant sedation in the elderly.
- Avoid in COPD patients: benzodiazepines can exacerbate hypoventilation and worsen chronic obstructive lung disease.
- Monitor for withdrawal in patients who have taken it >4 weeks: discontinue over 7–10 days to minimize rebound.
- Drug interaction check: co‑administration with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) can raise serum oxazepam levels, increasing CNS depression.
- Pregnancy consideration: animal studies indicate fetal risk; human data limited – use only if benefits clearly outweigh risks.
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• *Prepared for medical students and clinical professionals seeking an evidence‑based, concise reference on Oxazepam.*