Treatment of gout

Treatment of Gout

• Drug mostly Used are:

1. NSAIDs (Asprin should be avoided as it can increase plasma urate at some conc.)
2. Colchicine
3. Allopurinol
4. Uricosuric Agents
For Acute inflamation
1. Indomethacin
2. Colchicine
3. Cortiosteroid for resistant episodes of gouts
Prophylactic Treatment
1. Allopurinol
2. Uricosuric Agents
Colchicine
Colchicine is an anti-inflamatory drug without anelgesic properties.

• Mechanism of Action

It interferes with the functions of mitotic spindles & causes de-polymerization. As the result, inhibition of migration of granulocytes into the inflammed area and decreased metabolic and phagocytic activity occurs. These changes lead to reduction of lactic acid release and pro inflammatory enzyme that occurs during phagocytosis and breaks the cycle that leads to the inflammatory response. Colchicine prevents spindle formation in metaphase in cell division. High conc. may prevent cells to start mitosis. Other effects are, it inhibits the release of histamine containing granules from blast cells & insulin from pancreatic islets. All these processes may involve the translocation of granules by the micro-tubular system. It lowers the body temperature, depress respiratory centers, constrict blood vessels and induce hypertension by central vasomotor stimulation. It enhances gastrointestinal activity & alters neuromuscular functions.

• Pharmacokinetics

Colchicine is rapidly absorbed after oral administration. Peak conc. in plasma reaches in 0.5-2 hrs. It is metabolized to a number of compounds. Large amount of metabolites enter the intestinal tract, in the bile and spleen.

• Dose

Colchicine can be used prophylactically. Prophylactic dose is 0.5mg 2-4 times in a week. Prophylactic medication depends upon the frequency & severity of attack. A single dose of 2 mg is used to relieve acute attack of gout.

• Adverse Effects

Nausea, vomitting, diarrhoea and abdominal pain by inhibition of mucosal cell division.
In acute poisoning of colchicine, symptoms are nephrotoxicity, ascending paralysis of CNS, gastroenteritis, and vascular damage.

DRUGS

Allopurinol
Alopurinol is an analogue of hypoxanthine and completely inhibits the enzyme xanthine oxidase.
Allopurinol and its metabolite oxipurinol inhibit the biosynthesis of uric acid. Uric Acid is formed by xanthine oxidase catalyzed oxidation of hypoxanthine and xanthine. At low conc. allopurinol is a substrate for, and competitive inhibitor of, the enzyme. At high conc. it is non-competitive inhibitor. Oxipurinol , the metabolite of allopurinol formed by the action of xanthine oxidase is a non-competitive inhibitor of the enzyme. Inhibition of Uric Acid biosynthesis reduces its plasma conc. and renal excretion of the more soluble oxipurine precursors. During treatment urinary purines are divided among hypoxnthine, xanthine and uric acid. Each has independent solubility. The plasma conc. of Uric acid is reduced below its limit of solubility. Alopurinol facilitates the dissolution of monosodium crystals and prevents the formation uric acid stones and nephropathy.

• Pharmacokinetics

It is rapidly absorbed after oral administration and peak plasma conc. within 60-90 min. Half-life is 1-2 hrs. Allopurinol and its metabolites oxipurinol are distributed in total tissue fluid with exception of brain. Drug is excreted in urine.

• Therapeutic Uses

Allopurinol is used for the treatment of primary hyperuricemia of gout and polycythemia vera, myeloid metaphasia, gouty nephropathy, renal urate stone and impaired renal function. It is also used prophylactically to reduce hyperuricemia and to prevent urate deposition or renal clearance in patients with leukemias, lymphomas or malignancies.

• Adverse effects

Hypersensitivity reactions, Fever and muscular pain are among the adverse effects

• Contraindications

It inhibits enzymatic inactivation of mercaptopurines by xanthine oxidase, so dose of anti-neoplastic agents must be reduced to 1/4th – 1/3rd of usual dose.