Pharm 101: Thiopentone

Class

Barbiturate

Pharmacodynamics

• Facilitate actions of GABA in CNS
• Bind to specific GABA-A receptor subunits at CNS neuronal synapses
• In contrast to benzodiazepines, increase duration of GABA-gated chloride channel openings
• At high concentrations, may be GABA-mimetic, directly activating chloride channels

Organ system effects

• CNS:
  • Dose-dependent depression ranging from sedation to general anaesthesia
  • Decreased CMR, blood flow and ICP
  • Decreased cerebral oxygen consumption
  • No analgesic effect, possible hyperalgesia
• CVS:
  • Hypotension due to vasodilatation (less than that of propofol)
  • Negative inotrope
  • Compensatory tachycardia
• Respiratory depression

Pharmacokinetics

• Highly lipid soluble
• 83% protein bound
• Distribution to highly vascular tissue and rapidly crosses BBB, then rapid redistribution to body fat
• Distribution half-life 2-4 mins
• Elimination half-life 11 hours
• Hepatic metabolism
• < 1% excreted unchanged in urine

Clinical uses

• Rapid Sequence Induction (RSI):
  • Induction dose 3-5 mg/kg
  • Onset within 30 seconds
  • Duration of action 5-10 mins

Adverse effects

• Extension of organ system effects including hypotension, respiratory depression
• Pain on injection
• Hyperalgesia
• Rarely, porphyric crisis due to induction of ALA synthase in liver
• Severe tissue injury +/- gangrene in accidental intra-arterial injection

Precautions/contraindications

• Acute porphyria
• Hypovolaemia
• Cardiovascular disease
• Rapid administration of neuromuscular blocking drugs may result in precipitation of insoluble thiopentone acid

Further reading

• Buttner R. Pharm 101: Diazepam. LITFL

References

• Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 383-389, 450-454 p.