Pharm 101: Ethanol

Class

Alcohol

Pharmacodynamics

• Multiple signalling pathways affected, mainly:
  • Enhances GABA action at GABA-A receptors
  • Inhibits NMDA receptors
• Multiple organ system effects, mainly CNS depression, CVS depression and smooth muscle relaxation (see below)

Pharmacokinetics

• Rapid absorption from GIT (water soluble), peak levels within 30 minutes
• Rapid distribution, Vd approximates TBW ~0.5-0.7L/kg
• Hepatic metabolism undergoes zero-order kinetics* with two major pathways to produce acetaldehyde:
  1. Alcohol dehydrogenase (ADH) pathway is primary pathway and forms NADH as co-product
  2. Microsomal ethanol-oxidising system (MEOS) pathway is induced in chronic alcohol consumption
• Acetaldehyde is oxidised to acetate by enzyme ALDH, forms NADH as co-product. Disulfiram inhibits this reaction.
• Excretion: lungs, liver
• Induces CYP2E1 enzyme

*Elimination occurs at a constant rate independent of drug concentration. Other drugs that have zero order kinetic metabolism include aspirin, and phenytoin (at higher doses)

Clinical uses

• Severe methanol poisoning
• Topical antiseptic

Adverse effects

• CNS depression:
  • Sedation and anxiolysis
  • Disinhibition, impaired judgment, impaired motor skills
  • Ataxia, slurred speech
  • Respiratory depression and coma
• CVS depression:
  • Depression of myocardial contractility
• Smooth muscle:
  • Vasodilation –> hypothermia
  • Uterine relaxation

Further reading

• Buttner R. Pharm 101: methanol

References

• Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 396-404 p.