Pharm 101: Diazepam

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 (UWA) CCPU Emergency Medicine Trainee with interests in medical education, ECG interpretation, and the use of point-of-care ultrasound in the undifferentiated patient. Co-author of the LITFL ECG Library | Twitter

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