Flashcards in Pharm - NSAIDS - Kisby Deck (19):
What is the MOA of all NSAIDs?
Inhibit COX-1 and COX-2 by binding to COX in hydrophobic channel
Where is COX-1 found?
Digestive system, kidney, hematological system
Where is COX-2 found?
Brain, bone, kidney, pancreas, female reproductive tract
How do most current NSAIDs inhibit COX-1 and COX-2?
What are the 3 major actions of NSAIDs?
1. Analgesic - reduced PG levels = less sensitization of nociceptive nerve endings and less PG-mediated vasodilation
2. Anti-inflammatory - less PG-mediated vasodilation and inhibition of adhesion molecules
3. Antipyretic - due to a decrease in PGs that is responsible for elevating the hypothalamic set-point for temp control in fever
What is the MOA of gastric and intestinal ulceration SE of NSAIDs?
Local irritation leads to acid back diffusion & tissue damage; stimulates acid secretion and reduces mucus production → increased GI injury
What is the MOA of nausea and vomiting SE of NSAIDs?
Stimulate the chemotrigger zone (CTZ)
• Low dose aspirin
• MOA: IRREVERSIBLY binds to COX-1 & COX-2
• Uses: mild to moderate pain, antipyretic, anti-inflammatory, anticoagulant
• Metabolism: plasma & liver
• SE: hypersensitivity (in pts w/asthama & nasal polyps), GI irritation and bleeding ulcers, salicylism, liver toxicity, acute renal failure, Reye's syndrome
What is salicylism, how does it present and what is its tx?
• Overdose of salicylates
• Presents with dizziness, nausea/vomiting, tinnitus, hyperventilation (respiratory alkalosis in adults; metabolic & respiratory acidosis in infants), hyperthermia
• Tx - lavage, correct acid-base balances, promote elimination of drug (using NaHCO3 infusions to alkalinize the urine)
What is Reye's syndrome?
• Severe SE seen when children & teens take salicylates while sick w/chickenpox or flu
• Sxs: hepatitis & cerebral edema (encephalopathy)
• MOA: damage to mitochondria → ATP & cell death
• Not used much because of SEs such as severe frontal HAs, hypersensitivity and GI bleeding
• Caution: increases closure of patent ductus arteriosus
• Incidence of SEs are low (better tolerated)
• Uses: mild to moderate pain, fever, rheumatoid arthritis
• Long half-life (1x/day dosing)
• Relatively selective COX-2 inhibitor
• Caution: possible severe renal toxicity
• Contraindication: pts w/impaired renal function
• Only selective COX-2 inhibitor
• Does not inhibit platelet aggregation & fewer GI SEs
• Caution: may be pro-thrombotic
• Use: may reduce risk of colon cancer b/c COX-2 is high in cancer cells & angiogenesis
• Para-aminophenol derivative
• Weak inhibitor of COX-1 & COX-2 in peripheral tissue
• No anti-inflammatory or anti-platelet effects
• No GI SEs
• SE: potentially fatal hepatotoxicity
What is the MOA and tx or acetaminophen induced hepatotoxicity?
• MOA: binding of the reactive metabolite → hepatic necrosis
• Tx: oral or IV n-acetylcysteine (replenishes intracellular GSH levels to bind reactive intermediate)
• Use: acute tx of migraines
• MOA: vasoconstriction
• SE: nausea, vomiting, weakness, muscle pain
• Caution: numbness & tingling of digits = Ergot poisoning
• Advantage over ergots is anti-emetic properties
• Use: acute tx of migraines
• MOA: stimulate 5-HT-1 receptors to vasoconstrict vessels in brain & relieve swelling
• Caution: risk of serotonin syndrome when used w/SSRI or SSNI