Mar22 M2-Antipyretics Flashcards
3 drugs discussed in fever
- NSAIDs
- aspirin
- acetaminophen
cytokines of fever and end result
IL-1B, IL-6, TNF-a, INF. regulate secretion of PGs
initial fever response
ceramide release from the anterior hypothalamus neurons
late fever response
induction of COX-2 and microsomal PGE synthase-1 in endothelium of blood vessels in preoptic hypothalamic area to form PGE2
What’s the effect of PGE2 (from blood vessels of preoptic area)?
- binds EP3 and EP1 Rs on thermosensitive neurons of hypoth.
- more heat gen and less heat loss
steps to PGE2 synthesis
- phospholipase A2 cleaves phospholipid membrane of the cell to make AA
- AA made into PGH2 by COX1 and COX2
- PGH2 can become diff things depending on tissue specific enzymes (one of these is PGE2)
how NSAIDs work
block reversibly COX enzymes. so inhibit PG synthesis
3 major NSAIDs (and anti-pyretics) actions
- analgesia
- anti-pyretic
- anti-inflammatory (exept acetaminophen)
how aspirin has an anti-pyretic action
blocks COX1 and COX2 irreversibly (NSAIDs and acetaminophen DON’T DO THAT) so blocks PG synthesis
other thing aspirin can do
- anti-platelet, anti-thrombotic effect
- decreases platelet prod of TXA2 bc blocks COX-1 (this is with low dose aspirin).
main worries with aspirin and NSAIDs (adverse effects)
- pregnancy
- GI bleeding
- renal problem (will block EA of nephron and reduce water, NA, K excretion but not bad in healthy kidney. bad in HF, dehydration, older people)
anti-pyretics that can cause sensitivity reactions
- aspirin (ASA, salicylate)
- NSAID
- acetaminophen doesn’t*
charact. of anti-pyretic sensitivity rx
- because of histamine release (not immuno mediated)
- rhinitis, asthma, urticaria (hives), laryngeal edema, bronchospasm
why anti-pyretics (NSAIDs and aspirin) can cause hypersensitivity rx
inhibit COX so more AA shunted to leukotriene pathway. leukotrienes cause these symptoms
tx of febrile pt with anti-pyretic hypersensitivity
acetaminophen for the fever
3 effects that antipyretics can have (each is better at some things)
- analgesia
- anti-pyretic
- anti-inflammatory (exept acetaminophen)
naproxene best thing it does
anti-inflammatory (less for fever or pain relief)
risk factors for GI effects (bleeding) of aspirin and NSAIDs
- age over 65
- multiple NSAID use
- peptic ulcer or bleeding hx
- high dose
- alcohol
- anticoagulant use
how NSAID effect on PGs affects GIT (bleeding)
loss of protection from PGs in stomach
- less inhibition of acid secretion
- less protective mucus
- less mucosal blood flow
how NSAID anti-platelet effect affects GIT (bleeding)
lose TXA2 actions
- harder to coagulate (platelet aggreg inhibited)
- loss of vasoconstriction
people in whom you can’t use an anti-pyretic with anti-coag effect
people that don’t have CV (healthy people with normal coag and CV health)
*bc will disturb coagulation
one thing aspirin doesn’t do well
pain relief
active ingredient in aspirin
salicylate (ASA becomes salicylate)
half life of ASA before it becomes salicylate (the active ingredient)
15 min
