Drug Management

The aims are to:

• suppress the symptoms (anti-inflammatory drugs) i.e. NSAIDs, colchicine, corticosteroids

• prevent urate synthesis i.e. allopurinol

• promote the elimination of urate (uricosurics) i.e. sulfinpyrazone.

Colchicine

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 contra-indicated. 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.

The dose in acute gout is 1 mg by mouth, followed by 500 micrograms 2-3-hourly until either relief or adverse effects develop. The total dose should not exceed 6 mg and the course should not be repeated within 3 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.

Allopurinol

Allopurinol inhibits xanthine oxidase, the enzyme that converts xanthine and hypoxanthine to uric acid. Patients taking allopurinol excrete less uric acid and more xanthine and hypoxanthine in the urine. These compounds are more soluble than uric acid (renal stones are rarely xanthine) and are more readily excreted in renal failure.

Allopurinol (t\ 2 h) is readily absorbed from the gut, metabolised in the liver to alloxanthine (t'/2 25 h) which is also a xanthine oxidase inhibitor, and is excreted unchanged by the kidney.

Allopurinol is indicated in recurrent gout, when at least three attacks occur per year, in blood diseases where there is spontaneous hyperuricaemia, and during treatment of myeloproliferative disorders where cell destruction creates a high urate load. Allopurinol prevents the hyperuricaemia due to diuretics and may be combined with a uricosuric agent. The dose is usually 300 mg/d by mouth but some patients may need as much as 600 mg daily.

Adverse effects include precipitation of an acute attack of gout (see below), and allergic reactions which are uncommon but may be severe e.g. exfoliative skin rash, arthralgia, fever, lympha-denopathy, vasculitis and hepatitis. Deaths have been reported. For this reason, allopurinol should not be commenced unless the diagnosis is certain, and attacks of gout are frequent despite life-style changes (see below). Allergy to allopurinol can be managed by desensitisation, using very small doses of the drug initially, and continuing over a long period.

Allopurinol prevents the oxidation of mercap-topurine to an inactive metabolite; if an ordinary dose of mercaptopurine is given to a patient whose gout is being treated with allopurinol, dangerous potentiation occurs (see also azathiopurine, p. 292).

Sulfinpyrazone

Sulfinpyrazone competitively inhibits the active transport of organic anions across the kidney tubule, both from the plasma to the tubular fluid and vice versa. The effect is dose-dependent for at low dose sulfinpyrazone prevents secretion of uric acid into tubular fluid, and at high dose, and more powerfully, it prevents reabsorption, increasing its excretion in the urine. A net beneficial uricosuric action is obtained with an initial dose of 100-200 mg/d by mouth with food, increasing over 2-3 weeks to 600 mg/d which should be continued until the serum uric acid level is normal. The dose may then be reduced for maintenance, and may be as little as 200 mg/d.

During initial therapy a fluid intake of at least 2 1 /d should be ensured to prevent urate crystall-uria. If the uric acid load is high, consider rendering the urine alkaline with Potassium Citrate Mixture 12-24 g/d with water p.o. or sodium bicarbonate powder 5-10 g/d with water p.o., again to prevent uric acid crystal formation in the renal tract. Other adverse effects are mainly gastrointestinal; sulfinpyrazone is contraindicated in peptic ulcer.

Fenofibrate is an antihyperlipidaemic drug with added uricosuric action.

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