Gouty arthritis, acute prevention

The goals in the treatment of gout are to terminate the acute attack, prevent recurrent attacks of gouty arthritis, and prevent complications associated with chronic deposition of urate crystals in tissues. 

Clinical uses Anti-inflammatory, analgesic, antipyretic Anti-inflammatory for acute gout attack Anti-inflammatory for acute gout attack Prevent acute gouty arthritis hyperuricemia Prevent acute gouty arthritis hyperuricemia... 

Indomethacin is available for the short-term treatment of acute gouty arthritis, acute pain of ankylosing spondylitis, and osteoarthritis. An injectable form to be reconstituted also is available as the sodium trihydrate salt for IV use in premature infants with patent ductus arteriosus. Because of its ability to suppress uterine activity by inhibiting prostaglandin biosynthesis, indomethacin also has an unlabeled use to prevent premature labor. 

Tubulin is a major component of the cellular cytoskele-ton. Tubulin polymers (microtubules) are important for cell division (mitotic spindle) and the chemotaxis and phagocytosis of neutrophils. Prevention of tubulin polymerisation by colchicine accounts for the therapeutic effects of this drug in acute gouty arthritis and its anti-mitotic effects. 

Treatment of gout involves (1) acute relief of a gouty arthritis attack and (2) in some patients long-term maintenance treatment to prevent future attacks. 

Colchicine [Antigout Agent/Colchicum Alkaloid] Uses Acute gouty arthritis prevention of recurrences familial Mediterranean fever primary biliary cirrhosis Action -1- Migration of leukocytes X leukocyte lactic acid production Dose Initial 0.6—1.2 mg PO, then 0.6 mg ql-2h until rehef or GI SE develop (max 8 mg/d) do not r eat for 3 d /U 1-3 mg, then 0.5 mg q6h until rehef (max 4 mg/d) do not rqjeat for 7 d Prophylaxis PO 0.6 mg/d or 3-4 d/wk ... 

Acute gouty arthritis interferes seriously with work, recreational activities and mobility. Between flare and intercritical gout 25% of patients still report pain most of the time for unexplained reasons. Therefore, maintaining low levels of serum uric acid (SUA) in chronic gout is important to prevent flare of acute gouty arthritis. 

Allopurinol is an xanthine oxidase inhibitor. It reduces urate production and is used in primary and secondary urate overproduction. Therapy of hyperuricemia prevents recurring attacks of acute gouty arthritis. Allopurinol dosages are 300 mg/day for serum creatinine < 1.5 mg/dl and 100 mg/day for serum creatinine between 1.6-2.0 mg/dl. Reduction of tophi is slow with allopurinol, particularly in patients with giant tophi and renal insufficiency where drug dosage is limited. 

Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area (Fig. 37.1).The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area. 

The major use of colchicine is as an antiinflammatory agent in the treatment of acute gouty arthritis it is not effective in reducing inflammation in other disorders. It also can be used to prevent attacks. Since colchicine is so rapidly effective in relieving the acute symptoms of gout (substantial improvement is achieved within hours), it has been used as a diagnostic aid in this disorder. 

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. 

Neutrophils exposed to urate crystals ingest them and produce a glycoprotein, which may be the causative agent of acute gouty arthritis. Injected into joints, this substance produces a profound arthritis that is histologically indistinguishable from that caused by direct injection of urate crystals. Colchicine appears to prevent the elaboration by leukocytes of this glycoprotein. 

This is an alkaloid derived from the autumn crocus (Colchicum). Colchicine rapidly relieves the pain and inflammation of an acute attack of gout. Such swift relief is considered to confirm the diagnosis because non-gouty arthritis is unaffected, though failure does not prove the patient is free of gout. It is most effective if given within 24 h of onset and is useful in patients in whom NSAIDs are contraindicated. It is also used in recurrent hereditary polyserositis (Familial Mediterranean Fever) when it may prevent attacks and the development of amyloid. The t) is 1 h. 

Recurrences of acute gouty arthritis may be prevented with continuous low-dose daily oral colchicine or by uric acid-lowering therapy with either uricosuric agents or inhibition of xanthine oxidase with allopurinol. Combination therapy consisting of colchicine plus a uricosuric agent or allopurinol may be employed in resistant cases. The choice of treatment depends on the serum urate concentration, the amount of uric acid excreted in a 24-hour period, and the renal function stams of the patient. 

Prophylactic therapy with low-dose oral colchicine, 0.5 to 0.6 mg twice daily, may be effective in preventing recurrent arthritis in patients with no evidence of visible tophi and a normal or slightly elevated serum urate concentration. Patients do not become resistant to or tolerant of daily colchicine, and if they sense the beginning of an acute attack, they should increase the dose to 1 mg every 2 hours in most instances the attack will abort after 1 or 2 mg of colchicine. If the serum urate concentration is within the normal range and the patient has been symptom-free for 1 year, maintenance colchicine may be discontinued. The patient should be advised, however, that discontinuation of the treatment program may be followed by an exacerbation of acute gouty arthritis. 

Questions are often raised regarding the indications for drug therapy for asymptomatic hyperuricemia. The purported heneflts from treatment include prevention of acute gouty arthritis, tophi formation, nephrolithiasis, and chronic urate nephropathy. The first three complications are easily controlled shonld they develop therefore antihyperuricemic therapy is not warranted to prevent these conditions. 

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. 

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