Drugs for gout

Question 1

Management of acute gout: Agents that suppress leukocyte recruitment and activation

Answer 1

NSAIDS
COLCHICINE
GLUCOCORTICOIDS

Question 2

First line drugs for acute gout:
Which is the most popular?
Which drug is contraindicated?

Answer 2

NSAIDS

• Indomethacin Most popular
• Aspirin–> competes with uric acid in the proximal tubule of the kidney for organic acid secretion mechanism.

Question 3

NSAIDs adverse effects:

Answer 3

• bleeding
• salt and water retention
• renal insufficiency

COX-2 selective inhibitor may decrease the risk of GI bleeding but concerns of adverse cardiac effects due to COX-1 dorminance limit their long term use

Question 4

Colichicine MOA

Answer 4

Colichicine binds to tubulin inhibiting its polymerization and preventing formation of microtubules.

disrupts mobility of granulocytes decreasing their migration into the affected area.

also blocks cell division by dirupting mitotic spindle (disrupts mitotically active brush border cells–>diarrhea)

also inhibits synthesis and release of leukotrienes.

Question 5

Colichicine AE:

What drug has replaced Colichicine and whats the reason?

Answer 5

• Nausea/ vomiting/ abdominal pain/ and DIARRHEA*.
• chronic administration may cause myopathy neutropenia/ aplastic anemia and aloplecia (AI hairloss)
• should not be used in pregnancy
• careful use in patients with hepatic/ renal/ or CV disease.

NSAIDs have replaced Colichicine due to it associated diarrhea.

Question 6

When do you use glucocorticoids and what special way can they be administered?

Answer 6

When acute attack of gout cannot be relieved by NSAIDs or Colichicine.

Depot preparations of NSAIDs can be injected directly into the site of inflammation*

Question 7

Management of acute gout: Agents that lower plasma Urate Concentation

Answer 7

Agents that decrease uric acid synthesis:
- Allopurinol

Agents that enhance uric acid excretion (Uricosuric agents):

• Probenecid
• Sulfinpyrazone

Question 8

Allpurinol MOA

Answer 8

Pure analogue
Inhibits xanthine oxidase
- Facilitates the dissolution of tophi by lowering uric acid concentration.

Question 9

During initial months of allopurinol use what happens?
Reason for this?
How is it fixed?

Answer 9

1. Acute attacks of gouty arthritis increase
2. This is due to mobilization of tissue stores of uric acid
3. Coadministration of NSAIDs or colchicine during first 4-6 months.

Question 10

Allopurinol AE:

Answer 10

well tolerated by most
hypersensitivity reactions especially skin rashes
- Rare but rash mat progress to STEVEN-JOHNSON SYNDROME

Question 11

Allopurinol Drug interactions

Answer 11

Increases levels of cancer drugs Azathiopurine and Mercaptopurine which are both metabolized by xanthine oxidase.

Question 12

Uricosuric drugs?

MOA?

Answer 12

Probenecid
Sulfinpyrozone

Inhibit uric acid reabsorption.

Question 13

Probenecid AE

Answer 13

should not be given to pt.s with nephrolithiasis.
Mild GI Irritation
mild hypsensitivity reactions
Fluids to minimize renal stones

Question 14

Sulfinpyrazone AE

Answer 14

GI irritation
Hypersensitivity reactions
Depression of hematopoiesis*
should not be used by patients with underlying blood dyscrasias
Drink fluids to reduce stone formation

Question 15

Sulfinpyrazone inhibits

Answer 15

Warfarin

Question 16

Agents that enhance uric acid metabolism

MOA

Answer 16

Rasburicase (recombinant aspergillus uricase)

• Oxidizes uric acid to allantoin a soluble compound that is easily excreted by kidneys.
• Used in cancer chemo. Lysis of tumor cells releases free nucleotides and increases free plasma urate.