NSAIDS - Pharmacology Flashcards
main actions of NSAIDs (3)
anti inflammatory, anti pyretic, analgesic
side effects of NSAIDs
- prolonged use = irritation of GI tract
- ulcer complications can lead to death
- renal complications
- bleeding
mechanism of action of NSAIDs
inhibit COX enzyme.
COX is responsible for the conversion of phospholipids into porstonoids - for prostoglandin and thromboxane synthesis
describe the prostaglandin synthesis pathway
membrane phospholipid>AA>PGG2>PGH2>(prostoglandins and thromboxane)
how does inhibition of certain prostaglandins lead to analgesia
NSAIDs inhibit PGE2
PGE2 is made in macrophages, fibroblasts and endothelial cells - these cells are all involved in inflammation
PGE2 is an inflammatory mediator that has a role in the genesis of neuropathic and inflammatory pain
how are prostaglandins transported out of the cell
ABC transporters
why does inhibition of PGE2 have an effects on the GI system
PGE2 (prostaglandin) binds to the EP1-4 receptors which are located on cells in the GI tract
When this binds gastric acid secretion is inhibited
what is the main difference between the two COX enzymes 1&2 structures
different residues - cox 1 has Ile resiudes where cox 2 has val residues
cox 2 is larger and has a more flexible substrate access channel
differences in expression of cox enzymes 1 and 2
cox 1 - expressed continuously, always in body, expressed in most tissues
- role in gastric cytoprotection, renal blood flow autoregulation
- role in platelat aggregation through thromboxane and inhibited by PGI2
cox 2 - produced in response to inflammatory stimuli
which enzyme is iburpofen and aspirin selective to
weakly cox 1 selective but can also inhibit cox 2
which NSAID is highly selective of COX 1
Ketorolac
what are coxibs
new type of inhibitor which is selective to cox 2 enzymes
what is the main side effect of coxibs and what does this mean in the body
inhibit cox 2 enzymes which play a key role in regulation of platelet aggregation. cox 2 enzymes are involved in the prostaglandin synthesis which is involved in the production of PGI2. PGI2 decreced platelet aggregation so by inhibiting its production we risk the formation of blood clots which can block blood vessels. = CV EFFECT
how do NSAIDs increase bleeding risk (particularly aspirin)
NSIADS inhibit cox 1
decreased thromboxane = less platelet aggregation = inc bleeding risk
