Class

Benzodiazepine

Pharmacodynamics
  • Benzodiazepines binds to GABA-A receptor in neuronal membranes in CNS (y subunit of the pentamer). This receptor is a chloride ion channel.
  • Enhance inhibitory effect of GABA through membrane hyperpolarisation. This increases frequency of chloride channel opening
    • Do not substitute for GABA
    • Do not directly activate GABA-A receptor or open chloride channels
  • Cause sedation, hypnosis, anxiolysis, amnesia, anticonvulsant effect, muscle relaxation, and at higher doses, anaesthesia and cardiorespiratory depression
Pharmacokinetics
  • IV, PO, PR, IM (erratic bioavailability)
  • Bioavailability 100%
  • Hepatic metabolism to active metabolites desmethyldiazepam, and subsequently oxazepam
    • Undergo mirosomal oxidation (phase 1)
    • Subsequent conjugation (phase 2) by glucuronidation
  • Time to peak blood level 1-2 hours
  • Half-life 20-80 hours
  • Renal excretion
Clinical uses
  • Anxiety and sleep disorders
  • Sedative-hypnotic
    • Sedation of agitated patients
    • Procedural sedation (also has amnesic effect)
    • Anaesthesia adjunct
  • Seizure disorders
  • Alcohol withdrawal
  • Neuromuscular disorders
  • Treatment of various toxidromes
Adverse effects
  • Dependence and tolerance
  • Other are extension of CNS depressant effects
  • Excess sedation
  • Respiratory depression:
    • Can be profound even at therapeutic doses in patients with pulmonary disease
    • Effects are dose-related
    • Depression of medullary respiratory centre is usual cause of death in overdose
  • Cardiovascular depression:
    • May occur at normal dose in hypovolaemic states and heart failure
    • Toxicity causes depression of both myocardial contractility and vascular tone leading to circulatory collapse
Precautions/contraindications
  • Additive CNS depression with ethanol and other depressant drugs
  • Respiratory or cardiovascular disease due to depressant effects on these organ systems
  • Dose reduction in liver failure
References
  • Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 384-393 p.
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MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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