Gout, colchicine

Allopurinol (Zyloprim) reduces the production of uric acid, thus decreasing serum uric acid levels and the deposit of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. This probably accounts for its ability to relieve the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. 

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. 

Although NSAIDs are now the first-line drugs for acute gout, colchicine was the primary treatment for many years. Colchicine is an alkaloid isolated from the autumn crocus, Colchicum autumnale. Its structure is shown in Figure 36-6. 

For patients with chronic gout, colchicine has established value as a prophylactic agent, especially when there is frequent recurrence of attacks. Prophylactic medication also is indicated upon initiation of long-term medication with allopurinol or the uricosuric agents, because acute attacks often increase in frequency during the early months of such therapy. 

Drugs used in the treatment of gout Colchicine Allopurinol Uricosuric agents... 

The options available are allopurinol, probenecid (named patient only) and sulfinpyrazone. Allopurinol is the drug usually chosen as a first line agent for the prevention of gout. Colchicine may be given at a dose of 500 micrograms twice or three times daily when allopurinol or uricosuric drugs are initially commenced in order to prevent an attack of gout. NSAIDs may also be used but this would not be an appropriate option for Mr KT. 

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). 

The active principle of the autumn crocus (Colchicum autumnale), colchicine (48), is one of the very few drugs that have remained in reputable medical use since ancient times. This drug was the only useful treatment available for the excruciating pain associated with crystallization of uric acid in the joints characteristic of gout until the advent of allopurinol. Although the precise mechanism by which colchicine gives this dramatic relief remains undefined, the antimitotic activity of this agent is... 

In addition, the alkaloid colchicine (from Colchicum autumnale) blocks tubulin polymerization by binding to heterodimeric (3-tubulin between amino acids 239 and 254. Since it inhibits the MT-dependent migration of granulocytes into areas of inflammation and their MT-dependent release of proinflammatory agents, it is used to treat attacks of gout. Its antimitotic effect in the gastrointestinal system induces diarrhoea. Nocodazole competes for the binding site of colchicine and has similar effects on heterodimeric (3-tubulin. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

The drugp used for gout are contraindicated in patients with known hypersensitivity. Probenecid is contraindicated in patients with blood dyscrasias or uric acid kidney stones and in children younger than 2 years. Sulfinpyrazone is contraindicated in patients with peptic ulcer disease and gastrointestinal inflammation. Colchicine is contraindicated in patients with serious gastrointestinal, renal, hepatic, or cardiac disorders and those with blood dyscrasias. 

Colchicine for acute gout—Take this drug at the intervals prescribed by the primary health care provider and stop taking the drug when the pain is relieved or when diarrhea or vomiting occurs. If the pain is not relieved in about 12 hours, notify the primary health care provider. 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

Colchicine (a drug used in treatment of gout) and vinblastine (a cancer chemotherapy agent) may decrease liver uptake of americium. In rats that received an intraperitoneal injection of either colchicine and vinblastine prior to an intravenous or intramuscular injection of americium citrate, liver uptake of americium was lower, relative to controls, and kidney and skeletal americium uptake were higher (Seidel 1984, 1985). The effect is thought to involve disruption of hepatic microtubule formation, which is critical to the formation and intracellular processing of lysosomes, the initial site of accumulation of americium in the liver. 

Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. 

Colchicine (6) is used in the treatment of a broad range of diseases including acute gout and Mediterranean fever [28] and induces depolymerization of tubulin. This compound (6) distorts the tubulin/microtubule equilibrium by binding to the tubulin dimer and halting mitosis in the metaphase. The reason this approach is such a successful target in cancer therapy is that... 

Colchicine Antimitotic gout anti-inflammatory Inhibits migration of granulocytes leukopenia agranulocytosis... 

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

Management of an acute attack of gout involves the use of high doses of nonsteroidal anti-inflammatory agents (NSAIDs). Colchicine is useful in patients with heart failure where the use of NSAIDs is contraindicated because of water retention. Allopurinol and other uricosuric agents are not indicated for acute attacks as they may aggravate the condition. The use of an intra-articular corticosteroid injection in gout is unlicensed. 

Colchicine (9) Colchicum autumnale L. (autumn crocus), Gloriosa superha L. (glory lily) Anti-gout... 

Gout Do not start therapy until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid may be continued. Give full therapeutic doses of colchicine or other appropriate therapy to control the acute... 

Exacerbation of gout Exacerbation of gout following therapy with probenecid may occur in such cases, colchicine or other appropriate therapy is advisable. Salicylates Use of salicylates is contraindicated in patients on probenecid therapy. Salicylates antagonize probenecid s uricosuric action. 

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