Aspirin/NSAIDS Flashcards
What are the general indications for NSAIDS?
Pain Relief
Reduce Inflammation
Fever REduction
What are Aspiring specific indications?
Stroke/MI prevention
How do NSAIDs work?
Block COX enzymes -> prevent prostaglandin production -> dec inflammation, pain, fever
How do NSAIDs block COX enzymes?
All NSAIDS except Aspirin act as competitive inhibitors for the COX enzyme
Aspirin blocks as an irreversible non-competitive COX enzyme inhibitor via covalent modification of the active site
Where are COX1 enzymes found and what do they do?
Constitutively expressed in most tissues
General housekeeping role
Where are COX2 enzymes found and what do they do?
Induced in macrophages, monocyte
Constitutive in kidney and endothelium at low levels
Pro inflammatory responses
What are the housekeeping functions of COX1 in the GI tract?
PG production provides cytoprotective functions to stomach Dec acid secretion Inc gastric bicarb production Inc gastric mucous production Vasodilate-> gastric blood flow inc
How do NSAIDS reduce fever?
Blocking PG production and thus no action on CNS at the thermoregulatory center of the hypothalamus for fever
What are the housekeeping functions of COX1 i the CV system?
Platelets expresss only COX-1 => produce TXA2 (thromboxane) => vasoconstriction + platelet aggregation
Endothelial cells => COX1 and COX2 => no TXA2 synthase => produce PGI2 (prostacyclin) => vasodilation and inhibit platelet aggregation
Balance between the two can have differing results
What are hte functions of COX enzymes in the kidney?
Both COX1 and COX2 => PGs promote vasodilation to prevent renal ischemia
*Important in diseased state to counter vasoconstrictors
How can NSAIDs be used during labor?
It would delay it as PG production stimulates uterine contraction and NSAIDs would block this
What can happen if a women is treated with NSAID during pregnancy?
Premature closure of hte ductus arteriousus -> deleterious to fetal circulation
What can be done with patent ductus?
Treat with NSAID to inhibit fetal PGs that are keeping hte ductus open
How are Coxibs differnt from Aspirin/NSAIDs?
Coxib only inhibits COX-2
Why does aspirin block COX1 better than COX2?
COX2 has a larger binding site so it can partially bind arachidonic acid
How does aspirin block the COX enzymes?
Irreversibly acetylates a serine residue in the actie site
What is the unique indication for aspirin?
prophylactc prevention of CV events via low dose (81mg) aspirin
Why should you not give more aspirin for the protective CV effects?
At high doses the anti platelet effect of inhibiting TXA2 in platelets is offset by increased inhibition of PGI2 from the endothelium
Why don’t other NSAIDs show the same protective effects of low dose aspirin?
They are reversible inhibitors while aspirin is irreversible
How does low dose aspirin help treat CVD?
Aspirin acetylates COX1 in platelets permanently -> dec TXA2 (Platelets have no nucleus so more permanent)
Endothelial cells have nucleus -> COX1 inhibition is minimal -> produce PGI2
Result: More Anti thrombotic environment with PGI2>TXA2
What are some other salicylates and their unique properties?
Diflusinal: does not cross BBB -> no anti fever properties
Methyl Salicylate: bengay/icy hot
What kind of inhibitors are hte salicylates (except for aspirin)
Competitive inhibtor
When should salicylates be used over aspirin?
Pts at inc risk for GI problems or bleeding
Why do we see aspirin/salicylate toxicities?
At low dose its fine with 1st order kinetics
High dose -> metabolic enzymes in liver are overwhelmeed -> get 0 order kinetics
What are the sx of salicylate intoxication?
COMA, DEATH, hyperthermia, hyperventilation, acidosis, eetc
What is the treatment for salicylate toxicity/OD
Alkalinization of urine with sodium bicarb => inc ionized form in urine -> prevents reabsorptionand inc excretion
What is an indication for traditional NSAIDs but not Aspirin/salicylates?
Treatment of Gout
What is unique about ibuprofen as a NSAID?
Equipotent to Aspirin and better tolerated
Rapid onset of action (15-30mins)
What is unique about Naproxen as an NSAID?
More potent than aspirin
Rapid onset of action (60 mins)
Long serum half life -> allows 2x daily dosing
What is unique about oxaprozin as an NSAID?
Slow onset of action
Very long serum half life -> allows 1x daily dosing
What is unique about indomethacin as an NSAID
10-40x more potenet than Aspirin for antiinflammatory
Not tolerated as well as ibuprofen
used to promote closure of patent ductus
What is Ketorolac used for?
Weak anti inflammatory NSAID
Used as IV analgesic for post surgery pain
Can be used as replacement for opioid analgesics
What is unique about Diclofenac as an NSAID?
More selective for COX2
Increasesd heart and stroke risk
What are the adverse effects seen with Aspirin and tNSAIds?
Gi toxicity Kidney Impairment Risk of bleeding Exacerbate HTN and heart disease NSAID hypersensitivity Pregnancy issues
What are adverse effects only specific for Aspirin?
Increased Gout
Reye’s Syndrome
How does NSAID induce GI toxicity?
Direct damage to gastric epithelial cells via ion trapping of aspirin/NSAIDs
Inhibiton of COX1 in stomach -> losss of gastric proective PG effects
Can lead to GI bleesd and ulcers
How can the sx of NSAID induced GI toxicity be relieved?
Misprostol
Omeprazole
How does NSAID induce adverse effects on kidney funciton?
Usually caused in pts with underlying kidney disease -> NSAIDS block production of vasodilatory PGs -> vasoconstriciton of renal arteries > ischemia
Only seen with sick ppl but not in normal
Also dec GFR and H2O/Na+ excretion
Exacerbate HTN and HF
What is another effect that NSAIDs can have on the kidney?
Acute interstitial Nephritis and NEphrotic syndrome due to prolonged exposure -> recover with drug removal
Analgesic Nephropathy/Chronic Interstitial Nephritis: due to chronic daily overuse over years -> can lead to end stage renal disease from renal ischemia
What are the CV adverse effects of NSAIDs
Increased risk of heart attack and stroke (NOT ASPIRIN)
Exacerbate HTN and HF due to vasoconstriciton promotion
What hemodyanmic adverse effects are possible with NSAIDs?
Increased risk of bleeding
Avoid in pts with preexisting platelet deficiency
Avoid in pts prior to surgery
What happens if a patient shows hypersensitivity to NSAID?
Probably will be reactive to other NSAIDs as well
What is REye’s Syndrome?
Rare, fatal liver degenerative disease associated with aspirin given to children during febrile viral infections
What should be given and not given with rEye’s syndrome?
DO NOT GIVE ASPIRING
Use NSAID or acetaminophen
Does Aspirin or NSAId lead to increased risk of gout?
Aspirin
what are COXIBs?
Selective COX-2 Inhibitors that do not exhbiti adverse effects of inhibiting COX-1
What is Celecoxib?
COXIB that competitively inhibits COX-2
What are hte indications for Celecoxib?
Rheumatoid Arhtritis and Osteoarthritis
Pts with increased risk of GI problems
Pts with increased risk of bleeding
What are the side effects of Celecoxib?
Increased CVD risk!!!
As a result dont want to use this as 1st choice med
How does Celecoxib promote CVD problems?
Inhibits COX2 -> dec level of PGI2 -> TXA2 > PGI2 -> pro thrombotic state along with vasoconstrictions
What are general contraindications for NSAIDs?
GI Ulcers Renal Disorders Bleeding Disorders/Anticoagulants History of CVD/HTN/HF Pregnancy Hypersensitivity to NSAID
How does NSAIDs interact with lithium, methotrexate, and aminoglycosides?
NSAIDs impair renal function -> decreased renal clearance -> lithium, methotrexate, or aminoglycoside toxicity seen
Why should you not take both NSAIDs and Anti HTN drugs together?
NSAIDs promote vasoconstriction -> counteract anti HTN effects
What happens when NSAIDs are given with anti coagulants?
NSAIDs displace warfarin from albumin -> NSAIDs prevent platetelet COX1 -> inc risk for bleeding
