Pharm 101: Aspirin

Class

Antiplatelet

Pharmacodynamics

• Irreversible non-selective COX inhibitor (COX-1 and COX-2)
• In platelets, irreversible inhibition of COX-1 results in reduction of thromboxane A2 and inhibition of platelet aggregation for life of platelet (10 days)
• In tissues, inhibits PG synthesis (COX-2), resulting in antiinflammatory, antipyretic and analgesic effects:
  • Duration of action 6-12 hours before synthesis of new COX enzyme

Pharmacokinetics

• Weak acid, pKa 3.5
• Rapid absorption from stomach and upper small intestine
• Peak plasma level 1-2 hours
• High protein binding
• Metabolism:
  • Rapid hydrolysis to acetic acid and salicylate by esterases in tissue and blood
  • Salicylate is non-linearly bound to albumin
  • Saturable metabolism and excretion with increasing dose, switch from first to zero order kinetics at higher doses
  • Serum half-life 15 minutes
• Excretion:
  • Renal – pH dependent reabsorption
  • Urinary alkalinisation increases excretion of free salicylate and its water-soluble conjugates

Clinical uses

• Secondary prevention of IHD
• Reduces incidence of TIA, unstable angina, coronary artery thrombosis with MI, and thrombosis after CABG

Adverse effects

• Adverse effects are similiar to those of all NSAIDs
• Main adverse effects at antithrombotic doses are GI upset, and gastric and duodenal ulcers
• Hepatotoxicity, asthma, rashes, GI bleeding and renal toxicity are very rare at antithrombotic doses
• Salicylism:
  • Hyperthermia/fever
  • Vomiting
  • Headache, tinnitus, dizziness
  • Hyperventilation and respiratory alkalosis due to medullary stimulation
  • HAGMA (high lactate, low bicarbonate)
  • ABG reveals mixed respiratory alkalosis and metabolic acidosis
  • Seizures, APO, cardiovascular collapse, coma

Precautions/contraindications

• Haemophilia
• Gout: aspirin and serum uric acid level:
  • Aspirin has a bimodal effect on renal handling of uric acid
  • High doses > 3 g / day are uricosuric thus reduce uric acid levels
  • Low doses 1-2 g / day cause uric acid retention and increase levels
  • Therefore aspirin is contraindicated in treatment of pain and inflammation associated with gout
• Drug interactions:
  • Warfarin, phenytoin and probenecid can displace aspirin from plasma proteins

Further reading

• Long N. Salicylate Toxicity. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 619-620