Gout Drugs

Question 1

the aim of therapy in acute vs. chronic gout

Answer 1

acute: control pain using drugs that limit joint inflammation
chronic: achieve normal con of plasma urate by decreasing its production or increasing its excretion

Question 2

drugs used to treat acute gout

Answer 2

NSAIDs: especially indomethacin
Colchine
Glucocorticoids

Question 3

drugs used to treat chronic gout

Answer 3

RAPS

Rasburicase
Allopurinol
Probenecid
Sulfinpyrazone

Question 4

which NSAID is contraindicated in gout and why

Answer 4

aspirin because it competes with the same mechanism of excretion as uric acid in the proximal tubule of the kidney

Question 5

adverse of NSAIDs

Answer 5

bleeding
salt and water retention
renal insufficiency

Question 6

mechanism of colchine

Answer 6

binds to tubulin –> inhibits polymerization and formation of microtubules –> uric acid can’t migrate to affected area

Question 7

adverse effect of colchine

Answer 7

nausea, vomiting, abdominal pain, diarrhea

MAAN
myopathy, aplastic anemia, alopecia, neutropenia

Question 8

colchine is more specific for gout so why then has NSAIDs replaced it as therapy for gout

Answer 8

troublesome diarrhea that comes with therapy of colchine

Question 9

what can be used in acute gout as treatment when unresponsive to NSAIDs and colchine

Answer 9

glucocorticoids

Question 10

mechanism of allopurinol

Answer 10

inhibits xanthine oxidase hence inhibiting the synthesis of uric acid

Question 11

why are colchine and NSAIDs used in first 4-6 months of therapy with allopurinol

Answer 11

to prevent acute on chronic attack of gout

Question 12

adverse effect of allopurinol

Answer 12

hypersensitivity skin rash that can lead to Steven Johnson syndrome

Question 13

drug interaction with allopurinol

Answer 13

azathioprine and mercaptopurine are purine analogues and are metabolized by xanthine oxidase so if allopurinol is inhibiting the enzyme, you can have toxic levels of these drugs

Question 14

agents that lower uric acid synthesis vs. increase uric acid secretion name them vs. agent that enhance uric acid metabolism

Answer 14

lower uric acid synthesis: allopurinol
increase uric acid excretion: Probenecid, Sulfinpyrazole
enhance uric acid metabolism: Rasburicase

Question 15

how do the uricosuric agents aka agents that increase uric acid excretion work

Answer 15

they compete with urate for the brush border transporter that exchanges urate for an organic/inorganic anion which essentially reabsorbs urate while excreting the anions

hence with this competition more urates are excreted

Question 16

what patients do you not use probenecid in

Answer 16

gouty patients with nephrolithiasis
those with overproduction of uric acid
those with renal insufficiency

Question 17

what NSAID can antagonize probenecid action

Answer 17

aspirin

Question 18

adverse effect of probenecid

Answer 18

mild GI irritation

Question 19

adverse effect of sulfinpyrazone

Answer 19

GI irritation more than probenecid
rash with fever
Depression of hematopoiesis (do not give to those with blood dyscrasia)

Question 20

drug interaction of sulfinpyrazone

Answer 20

it inhibits warfarin metabolism –> increases bleeding

Question 21

mechanism of rasburicase

Answer 21

metabolizes uric acid to allantoin which can be easily excreted by kidney