NSAIDs Flashcards
How do NSAIDs work?
inhibition of cyclo-oxygenase enzyme (COX)
What does COX enzyme do?
metabolizes arachidonic acid (fatty acid component of membranes) to ultimately prostanoids (PGD2, PGE2, PGF2a, PGI2, and TXA2)
What is COX-1?
found in stomach, colon, kidney, vascular smooth m, and platelets (involved in “housekeeping” functions of prostanoids
What is COX-2?
involved in inflammatory responses, fever, and algesia. also expressed in blood vessels, kidney, heart, and brain
What’s significant about the actions of prostanoids and leukotrienes?
tend to cause opposing effects (vasodilation/vasoconstriction, promotoe or inhibit platelet aggregation, etc)
What can the anti-inflammatory effects of NSAIDs be attributed to?
inhibition of COX-2
Which prostanoids have inflammatory effects?
all of them
How do NSAIDs combat inflammation?
reduce vasodilation, edema, and pain, ACUTE phase (vs, corticosteroids that inhibit all stages)
What sort of dosage do the anti-inflammatory effects of NSAIDs require?
significantly higher doses
What does the low pH of inflammatory milieu lead to?
increased intracellular concentrations of NSAIDs (ion trapping of an acidic drug)
What causes the analgesic effects of NSAIDs?
inhibition of COX-2 which prevents formation of prostaglandins (PGE2) at peripheral sites
What types of pain are NSAIDs effective vs?
chronic post-operative, pain from inflammation, integumental pain, PMS HA, myalgia) achieved with “ordinary” doses of NSAIDs
What don’t NSAIDs do?
not effective against some types of pain, don’t alter sensory perceptions, don’t cause physical dependence.
What are NSAIDs used in combo with?
opioids to achieve greater analgesic effect
Anti-pyresis?
COX-2, PGE2. NSAIDs reduce elevated body temp with “ordinary” doses
What do NSAIDs do to CV system?
inhibit platelet COX-1 derived TxA2 - inhibit platelet aggregation! also COX-2 derived PGI2
What’s unique about aspirin?
irreversibly inhibits platelet COX. achieved at very low dose. selective inhibition of COX-1 due to impact on platelets.. antagonized by reversible COX-1 inhibitors. Therefore therapeutic efficacy in stroke and MI.
What are two other CV considerations?
1) NSAIDs can elevate blood pressure via COX-2
2) COX-2 is upregulated in athersclerotic plaques, but role in athersclerosis is unclear
Which prostanoids act on kidneys and what do they do?
PGE2 and PGI2, COX-1 and COX-2 generated. increase and decrease sodium retention (natriuresis predominates)
What do NSAIDs do in the kidneys?
promote sodium retention and can therefore increase BP. can counteract effects of many anti-hypertensives.
Who is at risk of renal ischemia with NSAIDs?
elderly and volume depleted.
GI effects of NSAIDs?
COX-1 inhibition: gastric distress, gastric bleeding/ulcers, sudden acute hemorrhage. (prostaglandins PGE1 inhibit stomach acid secreation, enhance mucosal blood flow, and promote intestinal secretion of ctopreotective mucus)
effect on gestation?
prolong via COX-2 inhibition
effects on respiratory system?
COX-independent effects! increased CO2 production -> hyperventilation with high doses. even higher doses cause depression of respiration
