ASPIRIN

1. Also known as acetylsalicylic acid.

(Diagram retrieved from Katzung 12th edition pg. 639)

1. Aspirin is an irreversible inhibitor of platelet COX (this lasts 8-10 days, which is the lifespan of the platelet as the platelet cannot manufacture new COX).
2. In other tissues, synthesis of new COX replaces the enzyme so aspirin’s effects on other tissues last 6 to 12 hours.

1. PO
   • Aspirin is a weak acid with a pKa of 3.5. It is well absorbed in the GIT due to acid pH.

1. Aspirin is absorbed in the GIT as ASA. It has a T ½ of 15 minutes (rapidly broken down by red cell esterases). It is hydrolyzed to acetic acid and salicylate. Salicylate is bound to albumin and then undergoes glucuronidation in the liver.

1. At low doses, aspirin follows first order kinetics.
2. At higher doses, aspirin follows zero order kinetics. The T ½ is extended to 15 hours.

1. It is renally excreted.
   • Note that alkalinizing the urine will increase its excretion.

1. With other drugs that are highly protein bound (e.g. phenytoin).
2. It is a weak acid and therefore reduces the clearance of penicillins (like probenacid).
3. Decreases the activity of spironolactone.

1. Acute ingestion of >200mg/kg or chronic over medication will cause toxicity.
   • The mechanism of toxicity is uncoupling of oxidative phosphorylation and disruption of normal cellular metabolism.
   • Signs and symptoms as follows:
     1. CNS: vertigo, tinnitus and loss of hearing.
     2. First sign is respiratory alkalosis and hyperventilation. Metabolic acidosis then occurs (usually HAGMA). ABG will show mixed respiratory alkalosis and metabolic acidosis.
     3. Hyperthermia and vomiting may also occur – contributes to fluid loss and dehydration.
     4. Severe poisoning leads to profound metabolic acidosis, seizures, coma, pulmonary oedema and cardiovascular collapse.
   • Treatment
     1. Supportive care
     2. No specific antidote
     3. Enhanced elimination (activated charcoal, sodium bicarbonate to aid urinary excretion, and haemodialysis if salicylate levels >100)