Pharmacology: Drugs Used in Gout

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What is the timing for the administration of colchicine?

Colchicine must be administered within 24 to 48 hours of the onset of the attack to be effective. It usually alleviates the pain of the attack within 12 hours.

In which patients is colchicine contraindicated?

Colchicine should not be used in pregnancy and it should be used with caution in patients with hepatic, renal or cardovascular disease

What are the adverse effects of sulfinpyrazone?

GI irritation more frequent that with probenecid. Hypersensitivity reactions, usually a rash with fever, occur lass frequently than with probenecid. Depression of hematopoiesis occurs; periodic blood cell counts are advised during prolonged therapy. A liberal fluid intake should be maintained during therapy to minimize the the risk of renal stones.

How are glucocorticoids used in the treatment of gout?

Glucocorticoids inhibit several steps in the inflammatory response during an acute attack. They are used in the treatment of polyarticular gout or when there are contraindications to other effective therapies.

In which patients is rasburicase used for?

Rasburicase is indicated for the initial management of elevated plasma uric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and significant hyperuricemia.

What NSAID is contraindicated in the treatment of acute gout?

*Aspirin* is contraindicated because it competes with uric acid for the organic secretion mechanism in the proximal tubule of the kidney.

What are the two main strategies for the treatment of gout?

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

How does allopurinol alleviate the symptoms of gout?

Allopurinol facilitates the dissolution of tophi and prevents development or progression of chronic gouty arthritis by lowering the uric acid concentration in the plasma below the limit of its solubility. It also prevents the formation of uric acid stones.

What is the mechanism of action of allopurinol?

Allopurinol is a purine analog. It reduces the production of uric acid by competitively inhibiting the last two steps in uric acid biosynthesis that are catalyzed by xanthine oxidase.

What are the side effects of allopurinol?

Allopurinol may cause hypersensitivity reactions, especially skin rashes, are the most common adverse reactions, occurring in approximately 3 percent of patients. In rare instances, the rash may progress to Steven's Johnson syndrome. For this reason all patients who develop a cutaneous reaction to allopurinol should discontinue the drug.

What are the adverse effects of colchicine?

Colchicine may cause nausea, vomiting, abdominal pain, and diarrhea. Chronic administration may lead to myopathy, neutropenia, aplastic anemia, and alopecia.

What do you have to keep in mind when administering probenecid with other drugs?

Because probenecid inhibits the secretion of most anions, the dose of other drugs excreted by this pathway should be reduced when probenecid is coadministered. Low dose aspirin may antagonize the action of probenecid.

What drugs increase the risk of gout?

Certain drugs, particularly thiazde diuretics and immunosuppressant agents (especially cyclosporine) may impair urate excretion and thereby increase the risk of gout.

What is the mechanism of action of colchicine?

Colchicine binds to tubulin inhibiting its polymerizatio and preventing the formation of microtubules. This disrupts cellular functions , such as the mobility of granulocytes, thus decreasing their migration into the affected area. It also blocks cell division by disrupting the mitotic spindle. Colchicine inhibits synthesis and release of leukotrienes.

What should be given along with probenecid?

Concommittant colchicine or NSAIDs are indicated early in the course of therapy to avoid precipitating an attack of gout which may occur in 20% of patients treated with probenecid alone.

What is the mechanism of action of probenecid?

In patients with gout, probenecid is useful for the treatment of chronic hyperuricemia. Probenecid shifts the balance between renal excretion and endogenous formation of urate thereby lowering plasma urate, dissolving urate crystals, and reversing the crystal deposition in synovial joints.

What is the mechanism of sulfinpyrazone?

In patients with gout, probenecid is useful for the treatment of chronic hyperuricemia. Sulfinpyrazone shifts the balance between renal excretion and endogenous formation of urate thereby lowering plasma urate, dissolving urate crystals, and reversing the crystal deposition in synovial joints. But it is rarely used today.

What are the adverse effects of probenecid?

Mild GI irritation, the risk increases at higher doses. Caution should be used in patients with a peptic ulcer. Hypersensitivity reactions are usually mild. Liberal fluid intake should be maintained to minimize the risk of renal stones.

What drugs are the first line drugs for acute gouty attacks?

NSAIDs are currently the first line drugs for acute gout. *Indomethacin* is used most often.

In which patients is probenecid contraindicated?

Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid. Probenecid is also ineffective in patients with renal insufficiency.

What is the mechanism of action of rasburicase?

Rasburicase is a recombinant version of aspergillus uricase, an enzyme that oxidizes uric acid to allantoin, a soluble compound that is easily secreted by the kidney.

What are the drug interactions with sulfinpyrazone?

Sulfinpyrazone inhibits warfarin metabolism. The anticoagulant effects of warfarin are markedly increased by sulfinpyrazone and serious bleeding has occured.

What are some drug interactions with allopurinol?

The anticancer drug mercaptopurine and the immunosuppressant azathioprine are purine analogs 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.

What is the goal of acute gout management?

The goal of acute gout management is to control pain using drugs that limit joint inflammation.

What is the goal of chronic gout management?

The goal of chronic gout management is to acheive normal concentrations of plasma urate. Drugs used for the treatment of chronic gout either decrease synthesis of urate or increase excretion of urate.

What are the side effects of allopurinol within in the first few months of administration?

The incidence of acute attacks of gouty arthritis may increase during the early months of therapy with allopurinol as a consequence of the mobilization of tissue stores of uric acid. Therefore, an NSAID or colchicine is coadmisistered during the first 4-6 months of allopurinol therapy to reduce the chance of precipitating an acute attack of gout.

What is a uricosuric agent?

Urosuric agents increase the rate of excretion of uric acid.


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