Colchicine Medinova Mechanism of Action

PHARMACOLOGY: The mechanism of the relief afforded by colchicine in acute attacks of gouty arthritis is not completely known, but studies on the processes involved in precipitation of an acute attack have helped elucidate how this drug may exert its effects. The drug is not an analgesic, does not relieve other types of pain or inflammation, and is of no value in other types of arthritis. It is not a diuretic and does not influence the renal excretion of uric acid or its level in the blood or the magnitude of the "miscible pool" of uric acid. It also does not alter the solubility of urate in the plasma.
Colchicine is not a uricosuric agent. An acute attack of gout apparently occurs as a result of an inflammatory reaction to crystals of monosodium urate that are deposited in the joint tissue from hyperuric body fluids; the reaction is aggravated as more urate crystals accumulate. The initial inflammatory response involves local infiltration of granulocytes that phagocytize the urate crystals. Interference with these processes will prevent the development of an acute attack. Colchicine apparently exerts its effect by reducing the inflammatory response to the deposited crystals and also by diminishing phagocytosis. The deposition of uric acid is favored by an acid pH. In synovial tissues and in leukocytes associated with inflammatory processes, lactic acid production is high; this favors a local decrease in pH that enhances uric acid deposition. Colchicine diminishes lactic acid production by leukocytes both directly and by diminishing phagocytosis, thereby interrupting the cycle of urate crystal deposition and inflammatory response that sustains the acute attack. The oxidation of glucose in phagocytizing as well as in nonphagocytizing leukocytes in vitro is suppressed by colchicine; this suppression may explain the diminished lactic acid production. The precise biochemical step that is affected by colchicine is not yet known. The antimitotic activity of colchicine is unrelated to its effectiveness in the treatment of acute gout, as indicated by the fact that trimethylcolchicinic acid, an analog of colchicine, has no antimitotic activity except in extremely high doses.