Flashcards in Gout & Eicosanoid Pharm Deck (34):
tx options for acute attacks of gout
prednisone po (or IV or intrarticular)
tx options for long term uric acid lowering and gout management
where does uric acid come from?
breakdown of dietary purine and purines from pt's DNA --> hypoxanthine --> xanthine --> uric acid
lifestyle changes for gout
alter diet (lower purines, drink more water)
reduce alcohol intake
for both acute attacks and prevention of gout
MOA: not clear, reduces WBC response to uric acid crystals
ADRs: nausea, vomiting, diarrhea often dose limiting
MOA: xanthine oxidase inhibitor
for gout prevention
ADRs: rare bad things like hypersensitivity, vasculitis, agranulocytosis, hepatic necrosis, TENs/Steven Johnson, can precipitate and acute attack
interactions: dramatic increase in toxicity of azathioprine and 6-MP
MOA: increases renal excretion of uric acid (competitively inhibits reabsorption of uric acid in PCT) + competitively inhibits active tubular secretion of Pen antibiotics
ADRs: avoid in pts w/ previous allergy or uric acid kidney stones, may precipitate acute gout attack
pegylated urate oxidase enzyme (produced by e coli) that catalyses uric acid --> allantoin (harmless metabolite cleared by kidney)
ADR: antibodies develop in 92% of pts, making drug less effective; occasionally causes anaphylaxis, can precipitate acute attacks of gout
drugs that imitate prostacyclin (PGI2)
drugs that imitate PGE2
misoprostol, alprostadil, dinoprostone
drug that imitates PGF2a
MOA of montelukast and zafirlukast
leukotriene receptor antagonist
MOA of zileuton
where do eicosanoids come from?
synthesized as needed (not stored)
derived from phospholipids in cell membranes - arachidonic acids
arachadonic acid --> eicosanoids via PLA2 - phospholipase A2 = rate-limiting step
where do prostaglandins and leukotrienes come from?
arachidonic acids --> prostaglandins via COX
arachidonic acid --> leukotriene via LIPOXYGENASES
how does prostaglandin signalling work?
GPCR --> variety of secondary messengers
major areas effected by prostaglandins
PGF2 always contracts
PGI2 relaxes vascular and uterine tissue
PGE2 usually contracts
what prostacyclins are protective of GI tract?
PGE2 and PGI2: increase mucosal blood glow, increase mucus secretion + inhibit gastric acid secretion
major mediators of asthma
leukotrienes: LTC4, LTD4
major mediator of pain and fever
which prostaglandins mediate dysmenorhea?
PGE2 and PGF2
which prostaglandin regulates intraocular eye pressure?
difference in MOA b/t glucocorticoids and NSAIDS
glucocorticoids inhibit levels/quantity of COX2, while NSAIDs inhibit enzyme activity
counterbalance of thromboxane and prostacyclin in vascular system
COX1 makes platelets and TXA2 --> vasoconstriction, platelet aggregation
COX1+2 make endothelial PGI2 --> vasodilation and anti- platelet aggregation
results in physiological balance of platelet function
basis of adverse cardiac events assoc w/ COX2 inhibitors
tips the platelet function balance --> COX1 only --> vasoconstriction and platelet aggregation w/out counterbalance
slow reacting substance of anaphylaxis: mix of leukotrienes, especially LTC4 and LTD4 --> contract respiratory muscle
aspirin hypersensitivity asthma
block COX1 and COX2 --> more arachadonic acid diverted to make leukotrienes --> asthma
for ulcer prevention during long-term NSAID therapy
stim mucus and bicarb secretion, inhibits gastric acid secretion; heals gastric ulcers as effectively as H2 blockers
adverse effects: diarrhea, abdominal discomfort
contraindicated in pregnancy
what type of drug can keep patent ductus open in infants w/ heart defects?
PGE2 and analogs
how to close ductus arteriosus open in otherwise healthy infant?
NSAIDs - ibuprofen, indomethacin
prostacyclin analog for pulmonary hypertension
prostaglandin, PGE1 analog
vasodilator for erectile dysfunction that does not respond to PDE-5 inhibitors
admin: topical, injection, urethral suppository
leukotriene inhibitor for asthma (LTD4-receptor antagonist), oral