MSK Pharm Flashcards
lipoxygenase produces
Leukotriens
cyclooxygenase produces
Prostacyclin (PGI2), Prostaglandins (PGE2, PGF2alpha), Thromboxane (TXA2)
LTB4 function
Neutrophil chemotaxis [PMNs arrive B4 others]
LTC4, D4, and E4
BRONCHOCONSTRICTION, vasoconstriction, contraction of smooth muscle, inc. vascular permeability
PGI2
Prostacyclin, inhibits platelet aggregation and promotes vasodilation. [Platelet-Gatherin Inhibitor]
What are the intermediates for lipo and cyclooxygenases
Hydroperoxides (HPETEs for Lip-), Endoperoxides (PGG2, PGH2 for Cyclo-)
What does Zileuton block
lipoxygenase
What does Zafirlukast, montelukast MOA
Blocks actions of LTC4,D4,E4
What is the substrate for all oxygenases
Arachidonic acid made via. phospholipase A2 from e.g. phosphatidylinositol
PGE2, PGF2alpha actions
inc. uterine tone
dec. bronchial tone
TXA2 actions
inc. platelet agg.
inc. vascular ton
inc. bronchial tone
Lifetime of platelets
Around 7 Days
Dosage range uses for aspirin
Low dose <300 is dec. platelet aggregation, intermediate dose 300-240 is antipyretic and analgesic. high dose (2400-4000 mg/day) is anti-inflammatory
Aspirin toxicity
Gastric ulceration, tinnitus (CN VIII). Chronic use: acute renal fialure, interstitial nephritis, upper GI bleeding.
Aspirin block of COX
irreversible inhibits COX-1 and COX-2.
COX-1 product
TXA2, PGI2 (in gut) (Platelet action and Gut Mucosa, hence why aspirin (low Km for COX-1) messes these up)
COX-2 product
PGI2 in blood vessels (much more than COX-1), this inhibition of PGI2 leads to the CV effects. Also produces prostaglandins in inflammatory cells, vascular endothelium, and mediates inflammation and pain.
COX-2 is found where
Found in inflammation, not constitutively active like COX-1. Hence why stopping it reduces inflammation. But when you block it’s anticoagulant properties without blocking the procoagulant properties of COX-1, you get an MI!
Celecoxib specific moeity
Sulfa drug, so sulfa allergy possible.
Acetaminophen MOA
inhibits reversibly cyclooxygenase mostly in CNS. inactivated peripherally
Acetaminophen uses
Antipyretic, analgesic, but not anti-inflammatory. Use in children instead of aspirin in viral infection.
Acetaminophen toxic metabolite and antidote
NAPQI: depletes glutathione and forms toxic adducts in liver.
N-acetylcysteine: regenerates glutathione
Bisphosphonates MOA
pyrophosphate analogs, binds hydroxyapatite in bone, inhibiting osteoclast activity
Bisphosphonates use
Osteoporosis, hypercalcemia, Paget disease of bone
