Pharmacology of Gout and Hyperuricemia

Question 1

Tx of pain and inflammation when UA crystals deposit in joint (three drugs).

Answer 1

Anti-inflammatories - NSAIDs, colchicine, corticoids

Question 2

UA reputake inhibitor (enhanced secretion)

Answer 2

probenecid (Uricosuric agent)

Question 3

UA synthesis inhibitor (blocks XO)

Answer 3

allopurinol

Question 4

UA uricosolytics (increase UA breakdown)

Answer 4

rasburicase, pegloticase

Question 5

gout specific anti-inflammatory

Answer 5

colchicine within 24 hours of attack

Question 6

MOA of colchicine

Answer 6

Binds to tubulin, depolymerizes microtubules, and impairs migration of granulocytes/neuts, thereby blunting inflammation.

Question 7

CS are CI in a pt with…

Answer 7

uncontrolled DM

Question 8

1st line Urate Lowering Therapy - drugs and MOA

Answer 8

XO inhibitors - allopurinol and febuxostat

Used for acute gout attacks and reduction of tophi

Question 9

difference between allopurinol and febuxostat

Answer 9

• Allopurinol is a purine analog (febuxostat is not).

- Febuxostat can be used in renal disease and less effects on liver function

Question 10

NSAIDs and ULT paradox

Answer 10

ULT initiation can cause acute gout attacks, so administer colchicine when beginning ULT to decrease the attacks.

Question 11

Drug interaction with allopurinol and febuxostat.

Answer 11

Metabolism of chemo drugs (6-mercaptopurine, azathioprine, theophylline) is inhibited.

Question 12

Black box warning for allopurinol (sx and genetics)

Answer 12

skin rash/sever hypersensitivity to allopurinol - if they have HLA-B*5081 genotype (screen in Chinese and Thai)

Question 13

Target serum urate

Answer 13

less than 6mg/dl

Question 14

Why is it recommended ot administer Oral ULT + Oral Uricosuric agent.

Answer 14

oral ULT + (probenecid) = enhance urate excretion in renal tubules from 10% up to 20%.

Question 15

MOA of probenecid (uricosuric agent)

Answer 15

blocks urate transporter - URAT 1

Question 16

Uricosuric agnts are CI in ___pts

Answer 16

Risk or PMH of nephrolithiasis or uric acid nephropathy.

Question 17

When should ULTs NOT be initiated?

Answer 17

During an acute attack.

Question 18

Explain aspirin paradox

Answer 18

During acute gout attacks, only very high doses will beneficially lower urate levels. Standard doses will increase urate level by blocking tubular secretion, aggravating hyperuricemia.

Question 19

Give loops or thiazides during acute gout attack?

Answer 19

no

Question 20

Name the drug and MOA of urate oxidase recombinant enzyme

Answer 20

Pegloticase and rasburicase

Question 21

Peglodicase is used for:

Rasburicase is used for:

Answer 21

Pegloticase: hyperuricemia associated with MALIGNANCY (tumor lysis syndrome)
Rasburicase: gout associated hyepruricemia