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 (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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