Acute Gout

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Chapter: Essential pharmacology : Antirheumatoid and Antigout Drugs

Acute gout manifests as sudden onset of severe inflammation in a small joint (commonest is metatarsophalangeal joint of great toe) due to precipitation of urate crystals in the joint space.



Acute gout manifests as sudden onset of severe inflammation in a small joint (commonest is metatarsophalangeal joint of great toe) due to precipitation of urate crystals in the joint space.

The joint becomes red, swollen and extremely painful: requires immediate treatment.




One of the strong anti-inflammatory drugs, e.g. indomethacin, naproxen, piroxicam, diclofenac or etoricoxib is given in relatively high and quickly repeated doses. They are quite effective in terminating the attack, but may take 12–24 hours, i.e. response is somewhat slower than with colchicine, but they are generally better tolerated; majority of patients prefer them over colchicine. Their strong anti-inflammatory (not uricosuric) action is responsible for the benefit. Naproxen and piroxicam specifically inhibit chemotactic migration of leucocytes into the inflamed joint. After the attack is over, they may be continued at lower doses for 3–4 weeks while drugs to control hyper-uricaemia take effect. They are not recommended for long term management due to risk of toxicity.


The NSAIDs have also substituted colchicine for covering up the period of initiation of therapy (6–8 weeks) with allopurinol or uricosurics in chronic gout.


2. Colchicine


It is an alkaloid from Colchicum autumnale which was used in gout since 1763. The pure alkaloid was isolated in 1820.


Colchicine is neither analgesic nor anti-inflammatory, but it especifically suppresses gouty inflammation. It does not inhibit the synthesis or promote the excretion of uric acid. Thus, it has no effect on blood uric acid levels.


An acute attack of gout is started by the precipitation of urate crystals in the synovial fluid. They start an inflammatory response, chemotactic factors are produced  granulocyte migration into the joint; they phagocytose urate crystals and release a glycoprotein which aggravates the inflammation by:


·        Increasing lactic acid production from inflammatory cells  local pH is reduced → more urate crystals are precipitated in the affected joint.


·        Releasing lysosomal enzymes which cause joint destruction.


Colchicine does not affect phagocytosis of urate crystals but inhibits release of the glycoprotein and the subsequent events. By binding to fibrillar protein tubulin, it inhibits granulocyte migration into the inflamed joint and thus interrupts the vicious cycle. Other actions of colchicine are:


·        Antimitotic: causes metaphase arrest by binding to microtubules of mitotic spindle. It was tried for cancer chemotherapy but abandoned due to toxicity. It is used to produce polyploidy in plants.


·        Increases gut motility through neural mechanisms.




Colchicine is rapidly absorbed orally, partly metabolized in liver and excreted in bile—undergoes enterohepatic circulation; ultimate disposal occurs in urine and faeces over many days.


Toxicity      is high and dose related.


Nausea, vomiting, watery or bloody diarrhoea and abdominal cramps occur as dose limiting adverse effects. Accumulation of the drug in intestine and inhibition of mitosis in its rapid turnover mucosa is responsible for the toxicity. In overdose, colchicine produces kidney damage, CNS depression, intestinal bleeding; death is due to muscular paralysis and respiratory failure.


Chronic therapy with colchicine is not recommended because it causes aplastic anaemia, agranulocytosis, myopathy and loss of hair.




(a)  Treatment of acute gout


Colchicine is the fastest acting drug to control an acute attack of gout; 1 mg orally followed by 0.25 mg 1–3 hourly till control of the attack is achieved (occurs in 4– 12 hour), or till total dose 6 mg is reached, or diarrhoea starts. The response is dramatic, so much so that it may be considered diagnostic. However, because of higher toxicity, most physicians prefer using a NSAID. Maintenance doses (0.5–1 mg/day) may be given for 4–8 weeks in which time control of hyperuricaemia is achieved with other drugs.


(b)  Prophylaxis


Colchicine 0.5–1 mg/day can prevent further attacks of acute gout, but NSAIDs are generally preferred.


Taken at the first symptom of an attack, small doses (0.5–1.5 mg) of colchicine abort it.




3. Corticosteroids


Intraarticular injection of a soluble steroid suppresses symptoms of acute gout. Crystalline preparations should not be used. It is indicated in refractory cases and those not tolerating NSAIDs/ colchicine.


Systemic steroids are rarely needed. They are very effective and produce nearly as rapid a response as colchicine, but are reserved for patients with renal failure/history of peptic ulcer bleed in whom NSAIDs are contraindicated or for cases not responding to or not tolerating NSAIDs. Prednisolone 40–60 mg may be given in one day, followed by tapering doses over few weeks.


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