Gout & Eicosanoid Pharm

Question 1

tx options for acute attacks of gout

Answer 1

naproxen po
colchicine po
prednisone po (or IV or intrarticular)

Question 2

tx options for long term uric acid lowering and gout management

Answer 2

allopurinol po
probenecid po
pegloticase iv

Question 3

where does uric acid come from?

Answer 3

breakdown of dietary purine and purines from pt’s DNA –> hypoxanthine –> xanthine –> uric acid

Question 4

lifestyle changes for gout

Answer 4

alter diet (lower purines, drink more water)
reduce alcohol intake

Question 5

colchicine

Answer 5

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

Question 6

allopurinol

Answer 6

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

Question 7

probenecid

Answer 7

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

Question 8

pegloticase

Answer 8

pegylated urate oxidase enzyme (produced by e coli) that catalyses uric acid –> allantoin (harmless metabolite cleared by kidney)
IV, expensive
ADR: antibodies develop in 92% of pts, making drug less effective; occasionally causes anaphylaxis, can precipitate acute attacks of gout

Question 9

drugs that imitate prostacyclin (PGI2)

Answer 9

epoprostenol, iloprost

Question 10

drugs that imitate PGE2

Answer 10

misoprostol, alprostadil, dinoprostone

Question 11

drug that imitates PGF2a

Answer 11

latanoprost

Question 12

MOA of montelukast and zafirlukast

Answer 12

leukotriene receptor antagonist

Question 13

MOA of zileuton

Answer 13

lipoxygenase inhibitor

Question 14

where do eicosanoids come from?

Answer 14

synthesized as needed (not stored)
derived from phospholipids in cell membranes - arachidonic acids
arachadonic acid –> eicosanoids via PLA2 - phospholipase A2 = rate-limiting step

Question 15

where do prostaglandins and leukotrienes come from?

Answer 15

arachidonic acids –> prostaglandins via COX

arachidonic acid –> leukotriene via LIPOXYGENASES

Question 16

how does prostaglandin signalling work?

Answer 16

GPCR –> variety of secondary messengers

Question 17

major areas effected by prostaglandins

Answer 17

1. airway
2. GI
3. vascular
4. uterine
   PGF2 always contracts
   PGI2 relaxes vascular and uterine tissue
   PGE2 usually contracts

Question 18

what prostacyclins are protective of GI tract?

Answer 18

PGE2 and PGI2: increase mucosal blood glow, increase mucus secretion + inhibit gastric acid secretion

Question 19

major mediators of asthma

Answer 19

leukotrienes: LTC4, LTD4

Question 20

major mediator of pain and fever

Answer 20

PGE2

Question 21

which prostaglandins mediate dysmenorhea?

Answer 21

PGE2 and PGF2

Question 22

which prostaglandin regulates intraocular eye pressure?

Answer 22

PGF2

Question 23

difference in MOA b/t glucocorticoids and NSAIDS

Answer 23

glucocorticoids inhibit levels/quantity of COX2, while NSAIDs inhibit enzyme activity

Question 24

counterbalance of thromboxane and prostacyclin in vascular system

Answer 24

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

Question 25

basis of adverse cardiac events assoc w/ COX2 inhibitors

Answer 25

tips the platelet function balance –> COX1 only –> vasoconstriction and platelet aggregation w/out counterbalance

Question 26

SRS-A

Answer 26

slow reacting substance of anaphylaxis: mix of leukotrienes, especially LTC4 and LTD4 –> contract respiratory muscle

Question 27

aspirin hypersensitivity asthma

Answer 27

block COX1 and COX2 –> more arachadonic acid diverted to make leukotrienes –> asthma

Question 28

misoprostol

Answer 28

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

Question 29

what type of drug can keep patent ductus open in infants w/ heart defects?

Answer 29

PGE2 and analogs

Question 30

how to close ductus arteriosus open in otherwise healthy infant?

Answer 30

NSAIDs - ibuprofen, indomethacin

Question 31

iloprost (ilomedin)

Answer 31

prostacyclin analog for pulmonary hypertension

Question 32

alprostadil

Answer 32

prostaglandin, PGE1 analog
vasodilator for erectile dysfunction that does not respond to PDE-5 inhibitors
admin: topical, injection, urethral suppository

Question 33

montelukast

Answer 33

leukotriene inhibitor for asthma (LTD4-receptor antagonist), oral

Question 34

zileuton

Answer 34

inhibitor of 5-lipoxygenase for asthma prophylaxis and chronic tx
po