Benzodiazepines

Benzodiazepines and information for nurses and pharmacy students.

1. Benzodiazepines Diazepam, Midazolam, Temazepam etc.

2. Why ? The most common substance present in drug-induced deaths in 2018 were benzodiazepines, identified in 883 deaths (51%). The rate of drug-induced deaths in 2018 was higher in  Regional and remote  areas (7.2 per 100,000 population) compared with  Major cities  (6.8 per 100,000 population). Reference: https://www.aihw.gov.au/reports/alcohol/alcohol-tobacco-other-drugs-australia/contents/impacts/health-impacts

3. Mechanism and use Benzodiazepines potentiate the inhibitory effects of GABA throughout the CNS, resulting in: 1) anxiolytic 2) sedative 3) hypnotic 4) muscle relaxant 5) antiepileptic effects.

4. Reference: Australian Medicines Handbook (AMH 2021)

5. diazepam Indications Short-term management of anxiety, agitation Acute alcohol withdrawal Muscle spasm or spasticity Premedication Procedural sedation (see Practice points below) Status epilepticus Accepted Benzodiazepine withdrawal Acute behavioural disturbance

6. diazepam 20 mg orally, every 2 hours until symptoms subside. A cumulative dose of 60 mg daily is usually adequate. Do not exceed 100 mg daily without seeking specialist advice. Acute alcohol withdrawal Anxiety, agitation Oral , 2–5 mg as a single dose. Dose may be repeated, if necessary, up to a maximum of 10 mg daily. ( Maximum 30mg for acute severe anxiety, agitation, behaviour disturbance) Dosage – Diazepam

7. midazolam Indications Procedural sedation Induction of anaesthesia Sedation during ventilation Premedication Accepted Status epilepticus

8. Dosage – Midazolam Conscious sedation. Endoscopic or cardiovascular procedures. the initial dose is approximately 2.5 mg, Total doses greater than 3.5 mg are not usually necessary. Induction of anaesthesia. 0.15-0.2 mg/kg (10-15 mg), administered at a rate of approximately 2.5 mg/10 sec. Intravenous sedation in intensive care units (ICU). the recommended infusion rate is 0.03-0.2 mg/kg/hour. Dilution and admixture. Hypnovel may be mixed in the same syringe with frequently used premedicants : morphine sulphate, pethidine, atropine sulphate or scopolamine. Hypnovel is compatible with normal saline, glucose 5% and 10% in water, fructose IV infusion ( levulose 5%), potassium chloride, sodium chloride and calcium chloride IV infusion (Ringer's solution) and compound sodium lactate IV infusion (Hartmann's solution). Onset of clinical effect may be delayed; there is a danger of overdosage if midazolam is given rapidly without waiting to assess its effects. Reference: Australian Medicines Handbook (AMH 2021)

9. temazepam Indications Short-term treatment of insomnia Dosage – Temazepam Adult: Oral , 10–20 mg at night. Elderly: Oral , 5–10 mg at night. Reference: Australian Medicines Handbook (AMH 2021)

10. Practice points Reserve for short-term (2–4 weeks) or intermittent use only; they should be part of a broader treatment plan, not a first or sole treatment Benzodiazepines are occasionally used short term (up to 2 weeks) to manage agitation or insomnia when starting antidepressants ( eg in panic disorder) Benzodiazepines are sometimes misused for their euphoric and sedative effects, both alone and with other drugs Some data suggest that cognitive dysfunction associated with long-term use may not be fully reversible Reference: Australian Medicines Handbook (AMH 2021)

11. Withdrawal symptoms Suddenly stopping treatment (or reducing or tapering the dose too quickly) in dependent people may produce withdrawal symptoms, including anxiety, dysphoria, irritability, insomnia, nightmares, sweating, memory impairment, hallucinations, hypertension, tachycardia, psychosis, tremors and seizures After stopping short-acting benzodiazepines, eg alprazolam, these may occur within a few hours; for those that are longer acting, eg diazepam, they may take days or weeks; they can last for several weeks or longer after prolonged use Reference: Australian Medicines Handbook (AMH 2021)