Analgesics Flashcards
How is aspirin unique among the NSAIDs?
It irreversibly acetylates, and thus inactivates, cyclo-oxygenase
What happens to aspirin in the body?
It is rapidly deacetylated by esterases in the body, thereby producing salicylate
What effects does salicylate have?
Anti-inflammatory, antipyretic, and analgesic
What are the antipyretic and anti-inflammatory effects of salicylate due to?
Primarily due to blockade of prostaglandin synthesis at the thermoregulatory centres in the hypothalamus and at peripheral target sites.
How does aspirin achieve it’s anti-inflammatory action?
It diminishes the formation of prostaglandins, and thus modulates those aspects of inflammation in which prostaglandins act as mediators.
How does aspirin achieve its analgesic action?
PGE2 is thought to sensitise nerve endings to the action of bradykinin, histamine, and other chemical mediators released locally by the inflammatory process. Aspirin decreases PGE2 synthesis, and so represses the sensation of pain
How does aspirin achieve its antipyretic action?
Fever occurs when the set-point of the anterior hypothalamic thermoregulatory centre is elevated, which can be caused by PGE2 synthesis. Aspirin inhibits PGE2 synthesis, and so resets the thermostat to towards normal. This rapidly lowers the body temperature of febrile patients by increasing heat dissipation as a result of peripheral vasodilation and sweating.
In what conditions are the analgesic effects of aspirin utilised?
Gout, rheumatic fever, osteoarthritis, RA, headache, arthralgia, myalgia
What are the most common GI ADRs of aspirin?
Epigastric distress, nausea, and vomiting
How can dyspepsia caused by aspirin be minimised?
Should be taken with food and large volumes of fluid.
A PPI may be taken concurrently.
How long before surgery should aspirin be withheld?
At least a week
Why should aspirin be withheld for at least a week prior to surgery?
Because it can cause inhibition of platelet aggregation and a prolonged bleeding time
How has aspirin been related to Reye syndrome?
Aspirin given during viral infections have been associated with an increased incidence of Reye syndrome, especially in children
What is Reye syndrome?
An often fatal, fulminating hepatitis with cerebral oedema
What % of salicylate derived from aspirin is protein bound?
80-90%
What is the result of the high level of protein binding of aspirin?
It can be displaced from protein-binding sites by other drugs, thus increasing the concentration of free salicylate.
It can alternatively displace other highly protein bound drugs, such as warfarin, phenytoin, or valproic acid, resulting in higher free concentrations of the other agent.
In patients taking what drugs should aspirin use be avoided in?
Probenecid or sulfinpyrazone
Why should long-term aspirin use be avoided in patients taking probenecid or sulfinpyrazone?
Because these agents cause increased renal excretion of uric acid, whereas aspirin causes a reduced clearance of uric acid, so aspirin reduces their action
Why is concomitant use of ketorolac and aspirin contraindicated?
Because of increased risk of GI bleeding and platelet aggregation inhibition