Gout, Indomethacin

Acute attacks of gout are treated with colchicine or indomethacin to reduce the inflammation. 

In addition to the agents in this section, sulindac and indomethacin (see Nonsteroidal Anti-inflammatory Agents monograph) and phenylbutazone and oxyphenbutazone (see individual monographs) are indicated for the treatment of gout. 

Indomethacin was particularly popular for gout and ankylosing spondylitis. In addition, it has been used to accelerate closure of patent ductus arteriosus. Indomethacin has been tried in numerous small or uncontrolled trials for many other conditions, including Sweet s syndrome, juvenile rheumatoid arthritis, pleurisy, nephrotic syndrome, diabetes insipidus, urticarial vasculitis, postepisiotomy pain, and prophylaxis of heterotopic ossification in arthroplasty. 

All NSAIDs, including aspirin, are about equally efficacious with a few exceptions—tolmetin seems not to be effective for gout, and aspirin is less effective than other NSAIDs (eg, indomethacin) for ankylosing spondylitis. 

Although colchicine is more specific in gout than the NSAIDs, NSAIDs (eg, indomethacin and other NSAIDs [except aspirin]) have replaced it in the treatment of acute gout because of the troublesome diarrhea sometimes associated with colchicine therapy. Colchicine is now used for the prophylaxis of recurrent episodes of gouty arthritis, is effective in preventing attacks of acute Mediterranean fever, and may have a mild beneficial effect in sarcoid arthritis and in hepatic cirrhosis. Although it can be given intravenously, this route should be used cautiously because of increased bone marrow toxicity. 

Colchicine (an alkaloid obtained from meadow saffron or autumn crocus) may be used both diagnostically to ascertain the presence of gout and prophylactically to prevent its further occurrence. Usually, 0.5-mg oral doses of colchicine are given hourly until either the therapeutic effects appear or the side effects develop. In addition to colchicine, phenylbutazone, indomethacin, adrenocorticotropic hormone (ACTH), and steroidal anti-inflammatory agents may be used to treat the acute attack of gout. 

All NSAIDs, including aspirin, are about equally efficacious with a few exceptions—tolmetin seems not to be effective for gout, and aspirin is less effective than other NSAIDs (eg, indomethacin) for ankylosing spondylitis. Thus, NSAIDs tend to be differentiated on the basis of toxicity and cost-effectiveness. For example, the gastrointestinal and renal side effects of ketorolac limit its use. Fries et al (1993), using a toxicity index, estimated that indomethacin, tolmetin, and meclofenamate were associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen were least toxic. The selective COX-2 inhibitors were not included in this analysis. 

In addition to inhibiting prostaglandin synthase, indomethacin and other NSAIDs also inhibit urate crystal phagocytosis. Indomethacin is commonly used as initial treatment of gout as the replacement for colchicine. Three or four doses of 50 mg every 6 hours are given when a response occurs, the dosage is reduced to 25 mg three or four times daily for about 5 days. 

Adverse effects may be severe with abdominal pain, vomiting and diarrhoea which may be bloody. Renal damage may result and rarely, blood disorders. Large doses cause muscle paralysis. Many patients are unable to tolerate colchicine and use NSAIDs such as indomethacin or diclofenac for an acute attack of gout some patients require oral corticosteroid. 

Acute gout is usually treated with an NSAID in full dose. Any such drug which is tolerated may be used (except aspirin which in low dose promotes urate retention, see below) indomethacin is often chosen because of its strong anti-inflammatory action and efficacy. If treatment is started early, the attack may be terminated in a few hours. Colchicine is useful if NSAIDs are contraindicated. If neither colchicine nor NSAIDs are tolerated, oral prednisolone 40 mg/d and tapered over a week is also effective. It requires only a moment s thought to appreciate that the uricosurics and allopurinol will not relieve an acute attack of gout. 

D Indomethacin is a drug of choice for an acute gout attack. Because he has no history of ulcer disease, there is no evidence... 

When tolerated, indomethacin often is more effective than aspirin in the treatment of ankylosing spondylitis and osteoarthritis. It also is very effective in the treatment of acute gout, although it is not uricosuric. 

Recurrent attacks of gout can be prevented with the use of colchicine (e.g., 0.6 mg daily or on alternate days). Indomethacin (25 mg/day) also has been used. These agents are used early in the course of uricosuric therapy when mobilization of urate is associated with a temporary increase in the risk of acute gouty arthritis. 

Drugs used in gout Anti-inflammatory drugs Colchicine NSAIDs, eg, indomethacin, glucocorticoids... 

In the treatment of this woman s acute attack of gout, the advantage of using indomethacin instead of colchicine is that indomethacin is... 

Indomethacin and colchicine have equivalent efficacy in the treatment of acute gout. Colchicine is now more likely to be used chronically to prevent other attacks. Indomethacin is more—-not less— likely to precipitate sudden gastrointestinal bleeding and acute renal failure. In the dose used to treat acute gout, colchicine frequently causes significant diarrhea. The answer is (B). 

While colchicine has been used in acute gout, the drug often causes severe gastrointestinal distress. Consequently, many authorities now consider that the drug of choice for acute gout is (A) Acetaminophen Aspirin Indomethacin Methotrexate Sulfinpyrazone... 

Probenecid inhibits renal tubular reabsorption of water and by this meehanism enhanees the urinary excretion of uric acid. This lowers the level of urate in the serum. It thus serves as a potent uricosuric agent in the treatment of gout. Probenecid also blocks the renal tubular seeretion of penicillins and cephalosporins. It is, therefore, used as an adjuvant therapy with penicillin V or G, ampicillin, cloxacillin, oxacillin, methicillin and naficillin to increase and prolong their plasma levels. Besides it also enhances the plasma levels of anti-inflammatory agents like naproxen and indomethacin, and a host of medicinal compounds such as sulphonamides, sulphonylureas, dapsone, etc. 

The therapeutic approach differs depending upon whether the patient is in the acute or chronic phase. In acute gout, the drug of choice has for a long time been colchicine. The exact mode of action of colchicine is not known, but it is believed to inhibit leukocyte phagocytosis and thereby interfere with the inflammatory cycle. Phenylbutazone and indomethacin are also used in the treatment of the acute phase of gout. The administration of anti-inflammatory corticosteroids enhances the effect of colchicine. 

Indomethacin and Analogs - While the clinical application of indomethacxn in the treatment of spondylitis, gout, osteoarthrosis and rheumatoid arthritis remains widely accepted, its efficacy against rheumatoid arthritis has become a matter of some discussion in the recent literature.For medicinal chemists the inadequacy of existing animal models to simulate rheiimatoid arthritis should also be realized. 

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