NSAIDS Flashcards
what type of activities do NSAIDs have
antipyretic, analgesic, anti inflammatory activities
mechanism of NSAIDs
inhibitor of COX so both inhibition of both prostaglandins and thromboxanes
difference between COX-1 and COX-2
- COX-1 is a constitutively active enzyme that is expressed in most tissues and is main source of cytoprotective prostaglandin formation
- COX-2 is inducible and is main source of prostanoids in inflammation and cancer
where in the body is COX-2 constitutively active
kidney and brain as it is the main source of vascular prostacyclin
why has there been a search for selective COX-2 inhibitors versus COX-1 inhibitors
inhibition of COX-1 causes inability to form protective prostaglandin leading to gastric damage as a side effect
What are the non selective COX inhibitors
PINK AID
Piroxicam Ibuprofen Naproxen Ketorolac Aspirin Indomethacin Diclofenac
what are the COX-2 inhibitors
Celecoxib
Meloxicam
how do NSAIDs produce their analgesic action
they decrease PGE2 synthesis hence repressing the sensation of pain
dominant source of prostaglandins that mediate the rise in temperature
COX-2 hence why both selective and non selective are consistent with antipyretic clinical efficacy of both subclasses of NSAIDs
therapeutic effects of NSAIDs
- antipyretic, anti inflammatory, analgesic
- tx for mild to moderate pain
- pain arising from inflammation (usually not visceral pain with exception to menses)
- tx of musculoskeletal disorders
- rheumatoid arthritis, gout, osteoarthritis, ankylosing spondylitis, dysmenorrhea
NSAIDs used to treat gout
- Indomethacin
- Other NSAIDs excluding AST (Aspirin, Salicylates, Tolmetin) used for acute gout
NSAIDs that decreases the risk of colon cancer
Aspirin
how do NSAIDs help with tolerating Niacin
- with increased dose or first dose, Niacin causes flushing which is mediated by release of PGD2 from the skin
- this release can be inhibited by COX inhibitor NSAIDs
NSAID used for closure of ductus arteriosus
Indomethacin
FUN FACT: Alprostadil is used to keep patent ductus arteriosus from closing
what are the GI effects caused by using NSAIDs
- inhibition of COX-1 in gastric epithelial cells depresses mucosal cytoprotective prostaglandins (PGI2 and PGE2)
- local irritation from contact of NSAIDs with gastric muxosa
what does PGI2 and PGE2 do
inhibit acid secretion by the stomach, enhance mucosal blood flow, promote secretion of cytoprotective mucus in the intestine
this is all inhibited by blocking COX-1
less side effects with selective COX-2 inhibitor
which one of the NSAIDs has the lowest risk and which has highest risk of GI adverse effects
lowest - Celecoxib
highest - Piroxicam
adverse effects of NSAIDs other than GI adverse effects
- increase cardiovascular risk
- decrease in renal blood flow
- analgesic nephropathy from long term use
- aspirin hypersensitivity
- hypersensitivity to sulfa since Celecoxib is a sulfonamide
what do COX-1 and COX-2 produce and inhibition of which one has more of a cardiovascular risk and why?
- COX-1 produces vasoconstricting, platelet aggregating thromboxane A2
- both COX-1 and COX-2 produce vasodilating, platelet inhibiting prostacyclins
-COX-2 selective inhibitors have more of a cardiovascular risk because COX-1 is left to produce vasoconstriction, platelet aggregation, and thrombosis
how do NSAIDs cause a decrease in renal blood flow
- it only affects persons with CHF, chronic kidney failure, or those with hypoperfusion to the kidney
- they rely on the vasodilative effects of COX to maintain the GFR so its inhibition leads to decreased GFR, sodium and water retention, edema, high BP, hyperkalemia, and acute renal failure
what is aspirin hypersensitivity associated with
increased synthesis of leukotrienes reflecting diversion of arachidonate to LOX metabolism due to COX inhibition
NSAIDs interaction with other drugs
- ACEIs prevent breakdown of bradykinin which stimulates PG production and NSAIDs prevent PG production. Together they decrease antihypertensive effect of ACEIs
- diuretics effects reduced
- with corticosteroids, increases severity GI ulceration
- increases bleeding with warfarin
what is triple whammy when it comes to NSAIDs
use of ACEIs (or ARBs) with NSAIDs and diuretics
NSAIDs constrict the afferent arteriole and reduce GFR. ACEIs (or ARBs) dilate the efferent arteriole and reduce GFR. Diuretics decrease plasma volume and GFR. Together, they all lead to acute renal failure.
contraindication of NSAIDs
- Pregnancy close to term
- Reye’s syndrome –> aspirin and other salicylates are contraindicated in children or those less than 20 with fever and viral illnesses (give them acetaminophen or ibuprofen)
