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

References

Pharm 101 700

Pharmacology 101

Top 200 drugs

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

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.