Diazepam
⚠️ Overdose (accidental or intentional):
– Manage ABCs, monitor O₂ sats, and give supplemental oxygen.
– Ensure ability to manage respiratory depression and airway issues.
– Respiratory and airway support as needed.
– Flumazenil may be given with caution (risk of seizures, esp. in mixed overdoses).
- 🔹 A long-acting benzodiazepine.
- ⏳ Active metabolites (e.g. desmethyldiazepam) have a half-life up to 100 hours → prolonged sedation.
⚙️ Mode of Action
- 📌 Binds to a specific site on the GABA(A) receptor–chloride ionophore complex (allosteric site, not the GABA site).
- 💡 Enhances the effect of GABA, the main inhibitory neurotransmitter in the CNS.
- ⚡ Increases the frequency of Cl⁻ channel opening → neuronal hyperpolarisation → CNS depression.
🎯 Indications
- 💤 Hypnotic for insomnia (short-term use only).
- 😟 Anxiolytic (anxiety disorders, premedication before procedures).
- 🧠 Anticonvulsant (status epilepticus, myoclonus).
- 💪 Muscle relaxant (spasms, tetanus).
- 🍺 Alcohol withdrawal (reduces agitation, tremors, seizures).
- 📝 Amnesia (for unpleasant procedures, e.g. endoscopy).
📊 Dose (BNF / specialist guidance)
- 😟 Anxiety / Sedation: 2–5 mg TDS PO (up to 30 mg/day in divided doses).
- ⚡ Status epilepticus: 5–10 mg slow IV (Diazemuls formulation less irritating).
May repeat up to 20 mg total.
⛔ Contraindications
- 🚫 Driving or operating machinery (due to sedation).
- 😴 Sleep apnoea syndrome.
- 💨 Respiratory depression or significant respiratory muscle weakness.
- ⚠️ Myasthenia gravis (risk of worsening weakness).
- ❌ Concomitant use with alcohol or other strong sedatives.
⚠️ Cautions
- 🚗 Warn about impaired driving/operating machinery.
- 📉 Reduce dose in elderly, renal or hepatic impairment (risk of accumulation).
- ⚠️ Avoid long-term use → dependence risk after 4–6 weeks.
⚠️ Side Effects
- 💤 Sedation, drowsiness, ataxia, impaired psychomotor skills.
- 🧠 Anterograde amnesia, confusion.
- ⬇️ Respiratory depression (esp. IV or with other sedatives).
- 🔄 Rebound insomnia/anxiety on withdrawal.
- 📉 Dependence & withdrawal syndrome (convulsions, agitation, insomnia).
- ⏳ Long half-life → “hangover” effects (daytime sedation).
🔄 Interactions
- 💉 Effects reversed by flumazenil, but caution: risk of rebound seizures, especially in mixed overdoses.
- ⚠️ Potentiated by other CNS depressants (opioids, antipsychotics e.g. olanzapine, antihistamines).
- 🔬 Metabolised by hepatic enzymes – levels ↑ with CYP450 inhibitors (e.g. erythromycin, cimetidine).
📚 References
