2- NSAIDS Flashcards
Which mediators of acute inflammation have the greatest vasodilatory effects?
Bradykinin, prostaglandins
Which mediators of acute inflammation have the greatest vascular permeability effects?
Histamine, leukotrienes
Which mediators of acute inflammation have the greatest chemotaxis effects?
Prostaglandins, leukotrienes
Which mediator of acute inflammation has the greatest pain effects?
Bradykinin
The following is the MOA for what drug?
Nonselective, irreversible inhibitor of COX-1 and COX-2
Aspirin
How does aspirin cross the placental barrier and blood-brain barrier?
Readily crosses placental barrier
Slowly crosses BBB
What drug competes with thyroxin T3, PenG, thiopental, bilirubin, phenytoin, sulfinpyrazone, and naproxen for protein plasma binding sites, causing drug interactions?
Aspirin
How is aspirin metabolized at low and high doses?
Low- 1st order kinetics
High- zero order kinetics
How is aspirin excreted?
Renally (alkalinization of the urine)
What are the uses for acetylsalicylic acid?
Analgetic, antipyretic, antiinflammatory, antiplatelet
ONLY irreversible (used for long-term effects, prevention of MI/ stroke)
What are the uses of NSAIDs?
Analgetic, antipyretic, antiinflammatory
What are the uses of acetaminophen?
Analgetic, antipyretic
Adverse effects of aspirin?
Respiratory alkalosis, GI effects, aspirin asthma (lungs), kidney damage
A single dose of 650mg of aspirin has what effect on bleeding time?
Doubles it
Pt with hypothrombinemia, vit K def, hemophilia, gastric ulcer or severe hepatic damage should avoid taking what drug?
Aspirin
In what circumstances should aspirin be avoided?
Prior to labor (3 mos), 1 week before elective surgery
What drug competes for excretion of uric acid (at low doses) and in what population should it be avoided?
Aspirin, pts with gout
(high doses enhances excretion but poorly tolerated- GI effects)
What is the DOC for analgesic and antipyretic effects in children?
Acetaminophen
(lower risk of Reye’s syndrome)
What is the fatal dose for aspirin or methyl salicylate (oil of Wintergreen)?
Aspirin ~ 20g
Methyl salicylate (oil of Wintergreen) ~ 4-5mL (children)
Magnesium choline salicylate, sodium salicylate, and salicyl salicylate are all what drug class?
Nonacetylated salicylates
Anti-inflammatory drugs, NO irreversible COX inhibition
What drugs are used for removal of warts, corns, fungal infections and eczematous dermatitis and have analgesic, antipyretic, and anti-inflammatory effects?
Nonacetylated salicylates
(magnesium choline salicylate, sodium salicylate, and salicyl salicylate)
What drug is a salicylic acid derivative but NOT metabolized to salicylic acid (not a pro-drug) and does not have significant antipyretic effects (poor CNS penetration)?
Diflunisal
What drug is a selective, reversible COX-2 inhibitor and has the potential to cause less gastropathy and risk of GI bleeding (due to no inhibitory effect on platelet aggregation)?
Celecoxib
(Valdecoxib, Rofecoxib)
Aside from GI effects, what is the adverse effect a/w Celecoxib?
Increased risk of CV disease
What are the contraindications for Celecoxib?
(selective, reversible COX-2 inhibitor)
GI disease, asthma, breast feeding/ pregnancy, renal failure
What is the first choice NSAID that is a nonspecific reversible inhibitor of COX-1 and COX-2 and is used in combo with ASA to decrease the effect on platelet aggregation?
Ibuprofen (fewest SEs)
What are the most potent NSAIDs that are nonspecific reversible inhibitors of COX-1 and COX-2?
Indomethacin, phenylbutazone
(serious SEs- GI, BM)
What AI AR agent is used to tx patent ductus arteriosus and reduce PMN migration via inhibition of phospholipase A?
(AI AR = anti-inflammatory, anti-rheumatic)
Indomethacin
What potent COX inhibitor is used in combination with misoprostol to decrease GI side effects?
Diclofenac
What drug should be used as an analgesic in postsurgical pain and may be combined with opiates?
Ketorolac
(> 5 days of use = GI effects)
How is ibuprofen excreted?
Renally
(overall toxicity is low, GI effects)
What NSAID should be used for once a day dosing due to half life ~ 13 hours?
Naproxen
What NSAID is largely excreted in the urine, is c/i’d in pregnancy and causes adverse drug reactions with oral anticoagulants and hypoglycemic agents?
Naproxen
(toxicity = GERD-like, mild GI bleed)
What NSAIDS inhibit PMN migration and lymphocyte function, decrease oxygen radical production, and have a long half life with high incidence of GI SEs?
Piroxicam, Meloxicam
Acetaminophen overdose (dose dependent, ~25g) can lead to what fatal SE?
Fatal hepatic necrosis
(encephalopathy/ coma > death)
What drug is preferred over aspirin due to absence of SEs such as PUD, inhibition of clotting, acid-base imbalance, and auditory toxicity?
Acetaminophen
What drug has dose dependent free radical production with antipyretic and analgesic action but NO anti-inflammatory action and NO platelet effects?
Acetaminophen
What NSAID can be combined with codeine, sedatives, cough suppressants, tramadol, diphenhydramine, and caffeine?
Ibuprofen
Ibuprofen has the potential to cause cross-sensitivity with what drugs?
Salicylates
What drug toxicity is a result of circulating toxic metabolites exceeding the available reduced glutathione in the body (no longer able to neutralize) and what increases this toxicity?
Acetaminophen
Chronic alcohol consumption increases toxicity
Pt presents with acetaminophen intoxication should be tx with what?
N-acetylcysteine (specific antidote, administered parenterally asap, w/i 10-12 hrs after intoxication)
If pt has NO hx of PUD, are there any restictions with type of NSAID given?
No
Pt has hx of PUD but it is NOT currently active. What is the tx?
Celecoxib +/- antacids
(some NSAIDs w/ misoprostol or “prazols”)
Pt with active PUD should be given what analgesic?
Acetaminophen and/ or opioids (codeine) only
How do antacids affect aspirin absorption?
Decrease absorption
