NSAIDs Flashcards
NSAIDs GI adverse
Due to inhibition of COX-1 and ulceration of the mucosa
TX: misoprostol, PPI’s, H2 blockers
Lowest risk = COX-2 (celecoxib)
High risk = Piroxicam
NSAID cardiovascular adverse
Imbalance between TXA2 and PGI2 -> vasoconstriction, platelet aggregation and thrombosis
Selective COX-2 inhibitors have higher CV risk, but fewer GI adverse effects
NSAID Renal adverse
Decrease renal blood flow, AIN, analgesic nephropathy
Decrease PGE2 -> Na+ and H2O retention (via a decrease in GFR)
Decrease PGI2 -> hyperkalemia and ARF
NSAIDs & ABx are most common cause of AIN (Type 1HS)
Chronic use-> analgesic nephropathy & papillary necrosis
NSAID adverse other
*Uricosuric effects** are dose dependent -> low dose reduces secretion while high dose inhibits reabsorption
Aspirin hypersensitivity (NSAIDs)
Rhinitis, edema, asthma, etc
Due to excess LT synthesis
NOT a typical HS reaction
NSAID drug interactions
ACE-I’s -> have vasodilator effects due to increased kinin -> increase PG synthesis which is blocked by NSAIDs
Corticosteroids-> when combined with NSAIDs may increase frequency and severity of GI ulcers
Warfarin and NSAID use can increase the risk of bleeding
Aspirin/Salicylates
Irreversible acetylation of COX (other NSAIDs are reversible)
Uncouple oxidative phosphorylation -> increase CO2 and increased respiration
High dose stimulates respiratory center -> hyperventilation
Toxic levels-> respiratory paralysis
Decrease TXA2 platelets (lack nuclei), but endothelial PGI2 is unaffected -> increased bleeding time -> cardioprotective due to decrease aggregation
High dose-> zero order elimination by kidney
Chronic use can cause hepatic injury
Salicylism -> HA, confusion, Tinnitus, dizziness
Respiratory alkalosis and metabolic acidosis
NSAIDs and colon cancer
Aspirin decreases risk by 50%
Fun fact: aspirin also inhibits the flushing associated with niacin used to lower serum cholesterol (PGD2)
NSAIDs and GOUT
DOC -> Indomethacin
- *Do NOT use aspirin** because it inhibits urate excretion and may increase risk for stones
- *Tolmetin** is also ineffective
NSAID contraindications
Aspirin use in children -> Reye’s syndrome (use acetaminophen or ibuprofen instead)
Pregnancy is a relative contraindication
Aspirin is Category D in 3rd trimester
Fun fact: Acetaminophen -> DOC in OA & pregnancy but is not antiplatelet or anti inflammatory
NSAID Nonselective Drugs
Aspirin Diclofenac Ibuprofen Indomethacin Ketorolac Naproxen Piroxicam Tolmetin Acetaminophen (not technically an NSAID)
NSAID COX-2 selective
Celecoxib
Etoricoxib
Meloxicam (not as selective as coxibs)
NSAID mechanism
- Antipyretic, Analgesic and Anti-inflammatory* properties
- *Inhibition of COX -> decrease PG and TXA synthesis**
COX-1 = constitutive enzyme involved in homeostasis (cytoprotective PG formation in gastric cells)
COX-2 = induced by growth factors, tumor promotors and cytokines -> inflammation and cancer
Constitutive in Kidney and brain
Endothelial COX-2 -> source of vascular prostacyclin
Most NSAIDs inhibit both isozymes; most antiinflammatory effects are due to inhibition of COX2 while gastric damage is due to blockade of COX-1
PGE2 sensitizes nerve endings to pain -> NSAIDs are better than opioid for inflammatory pain
PGE2 also responsible for fever, mainly from COX-2
NSAID uses
Better than opioids for inflammatory pain
Useful in treatment of RA, OA and acute gouty arthritis
Indomethacin -> DOC for closure of ductus arteriosis
Celecoxib is a sulfonamide that may cause HS reactions
Celecoxib adverse NSAID
Is a sulfonamide -> may cause HS reaction
Cardiovascular imbalance between TXA2 and PGI2 -> vasoconstriction, platelet aggregation and thrombosis
