Makindo Medical Notes

💡 Key Safety Point: Oversedation and respiratory depression are the major concerns — particularly with IV or IM use. 🩺 Always ensure facilities for airway support, oxygen, and resuscitation are available before administration.

🧠 About

• Lorazepam is a short-acting benzodiazepine used for acute seizure control, sedation, and anxiety.
• Compared with diazepam, it has a slower onset but longer duration of CNS activity, as it binds more avidly to GABA_A receptors and redistributes more slowly.
• It is metabolised hepatically by conjugation (not oxidation), so preferred in liver impairment.

⚙️ Mechanism of Action

• Enhances the effect of gamma-aminobutyric acid (GABA) at the GABA_A receptor.
• Increases chloride ion influx, hyperpolarising neuronal membranes and reducing excitability.
• Produces anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects.

🎯 Indications

• ⚡ Status epilepticus (first-line benzodiazepine for IV use in the UK).
• 😠 Acute agitation or violent behaviour in psychiatric or medical settings.
• 😟 Acute anxiety or pre-operative sedation.
• 💤 Insomnia associated with anxiety.

💉 Typical Doses

• Status epilepticus: Lorazepam 2–4 mg slow IV over 1 minute into a large vein; may repeat once after 10–15 minutes if seizures persist. Flush line with 0.9% saline before and after to avoid precipitation.
• Acute agitation: Lorazepam 1–2 mg IV or IM; slower absorption by IM route, duration 4–6 hours.
• Anxiety / sedation: 1–2 mg PO/IM/IV up to BD; elderly start at 0.5–1 mg BD.
• Insomnia (short-term): 1–2 mg PO at bedtime.

📊 Dose Range (Always Check BNF or Datasheet)

🔗 Interactions

• 🔹 Sodium valproate: reduce lorazepam dose by 50% (valproate impairs lorazepam clearance).
• 🔹 Other CNS depressants (alcohol, opioids, antihistamines): additive sedation and respiratory depression.
• 🔹 Flumazenil reverses effects but may provoke rebound seizures in epileptic patients — use with extreme caution.

⚠️ Cautions

• Ensure resuscitation and airway equipment are available before parenteral use.
• Use lower doses in elderly and hepatic impairment.
• Risk of dependence and withdrawal phenomena with prolonged use.
• Avoid long-term use for insomnia or anxiety unless under specialist supervision.

🚫 Contraindications

• Severe respiratory depression or sleep apnoea.
• Unstable myasthenia gravis (worsens muscle weakness).
• Severe COPD with CO₂ retention.
• Chronic psychosis or untreated depression (may exacerbate).
• Acute intoxication with alcohol or CNS depressants.

💥 Adverse Effects

• 🫁 Respiratory depression — most serious risk (esp. with IV).
• 🧠 Amnesia (anterograde), confusion, drowsiness, fatigue, ataxia.
• 💓 Hypotension, bradycardia (with rapid IV administration).
• 🌀 Vertigo, headache, paradoxical agitation (esp. in elderly or children).
• 💊 Dependence and withdrawal symptoms with chronic use.

🧾 Monitoring

💡 Teaching Tip

• Contrast lorazepam’s **pharmacokinetics** with diazepam: lorazepam redistributes more slowly and is metabolised by conjugation → **longer clinical effect** despite shorter half-life.
• In **status epilepticus**, it’s the drug of choice due to prolonged CNS activity and lower fat solubility (less redistribution out of the brain).
• Always emphasise airway safety — the best anticonvulsant is useless if the patient becomes hypoxic.
• Review dependence risk after 2–4 weeks in chronic use; switch to SSRIs or CBT for persistent anxiety disorders.

📚 References

• BNF: Lorazepam
• NICE NG185 (2020): Epilepsies: diagnosis and management
• MHRA Drug Safety Update (2022): Benzodiazepines and respiratory depression
• Stahl SM. Prescriber’s Guide, 7th ed. Cambridge University Press, 2022