Gout

Question 1

2 main strategies for the treatment of gout:

Answer 1

1. Management of acute attacks of gouty arthritis
2. Long-term management of chronic gout.

Question 2

AGENTS THAT SUPPRESS LEUKOCYTE RECRUITMENT AND ACTIVATION

Answer 2

• NSAIDs
• COLCHICINE
• GLUCOCORTICOIDS

Question 3

NSAIDs for Gout Rx

Answer 3

• First-line drugs for acute gout.
• Indomethacin is the most popular.
• Other NSAIDs are also effective.
• Aspirin is contraindicated, because it competes with uric acid for the organic acid secretion mechanism in the proximal tubule of the kidney.

Adverse

• Bleeding, salt and water retention, and renal insufficiency.
• COX-2 selective inhibitors may decrease the risk of GI bleeding, but concerns about adverse CV effects limit their long-term use.

Question 4

AGENTS THAT LOWER PLASMA URATE CONCENTRATION

Answer 4

AGENTS THAT DECREASE URIC ACID SYNTHESIS: ALLOPURINOL

AGENTS THAT ENHANCE URIC ACID EXCRETION (URICOSURIC AGENTS)

• PROBENECID
• SULFINPYRAZONE

AGENTS THAT ENHANCE URIC ACID METABOLISM: RASBURICASE

Question 6

ALLOPURINOL

Answer 6

• Purine analog.
• Inhibits xanthine oxidase.
• An NSAID or colchicine is coadministered during the first 4-6 months of allopurinol therapy to reduce the chance of an acute attack of gout.

Adverse

• Well tolerated by most patients.
• Hypersensitivity reactions, especially skin rashes, are the most common adverse reactions.
• In rare instances the rash may progress to
• Steven-Johnson syndrome.
• All patients who develop a cutaneous reaction to allopurinol should discontinue the drug.

Drug interactions

• anticancer drug mercaptopurine and the immunosuppressant azathioprine are purine analogues which are metabolized by xanthine oxidase.
• Inhibition of xanthine oxidase by allopurinol can result in toxic levels of coadministered mercaptopurine or azathioprine.
• Therefore, a dose reduction of these drugs is required.

Question 7

URICOSURIC AGENTS

Answer 7

• Urate is filtered, secreted, and reabsorbed by the kidneys.
• Reabsorption predominates: the amount excreted is 10% of that filtered.
• This process is mediated by a specific transporter.
• The transporter exchanges urate for an anion.
• Uricosuric drugs compete with urate for the
• transporter, thereby inhibiting its reabsorption.

Question 8

PROBENECID

Answer 8

• Colchicine or NSAIDs are given early in the therapy to avoid precipitating an attack of gout.
• Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid.

Adverse

• Mild GI irritation.
• Hypersensitivity reactions; usually mild. Serious hypersensitivity is extremely rare.
• A liberal fluid intake should be maintained to minimize risk of renal stones.

Question 9

SULFINPYRAZONE: ADVERSE EFFECTS

Answer 9

• GI irritation.
• Hypersensitivity reactions, usually a rash with fever, occur less frequently than with probenecid.
• Depression of hematopoiesis.
• Should not be used by patients with underlying blood dyscrasias.
• A liberal fluid intake should be maintained to minimize the risk of renal stones.

Drug Interactions

• Sulfinpyrazone inhibits warfarin metabolism.

Question 10

RASBURICASE

Answer 10

• AGENTS THAT ENHANCE URIC ACID METABOLISM
• Most mammals other than humans express the enzyme uricase.
• This enzyme oxidizes uric acid to allantoin, a soluble compound that is easily excreted by the kidney.
• In cancer chemotherapy, the rapid lysis of tumor cells can release free nucleotides and increase plasma urate levels.
• This can lead to massive renal injury.
• Exogenous uricase can reduce plasma urate levels and prevent renal damage.
• Allopurinol can also be used to prevent this component of tumor lysis syndrome.