Drugs used in the treatment of gout

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Chapter: Medicinal Chemistry : Analgesics, Antipyretics, and NSAIDs

i. Allopurinol (Zyloprim) ii. Probenecid (Benemid) iii. Sulphinpyrazone (Anuturane) - Synthesis and Drug Profile

Drugs used in the treatment of gout

An acute attack of gout occurs as a result of anti-inflammatory reaction to crystals of sodium ureate (the end product of purine metabolism in human beings) that is deposited in the joint tissues. Drugs used to treat gout may act in the following ways:

·By inhibiting uric acid synthesis: Allopurinol.

·By increasing uric acid excretion: Probenecid, Sulphinpyrazone.

·Miscellaneous: Colchicines (alkaloid obtained from Colchicum autumnale).


i. Allopurinol (Zyloprim)


Mode of action: In human beings, uric acid is formed primarily by the xanthine oxidase-catalyzed oxidation of hypoxanthine and xanthine. At low concentrations, allopurinol is a substrate for and competitive inhibitor of the enzyme at high concentrations; it is a noncompetitive inhibitor.

Metabolism: It is rapidly metabolized via oxidation and numerous ribonucleoside derivatives are formed. The major metabolites are alloxanthine or oxypurinol.

Properties and uses: Allopurinol is a white powder, very slightly soluble in water, in alcohol and in dilute solutions of alkali hydroxides. It is used in the treatment of gout and prevention of urate deposition in patients with leukaemia receiving anticancer drugs, which cause increasing serum uric acid levels.

Assay: It is assayed by adopting liquid chromatography technique.

Dose: Usual adult oral dose for gout is 100–200 mg two or three times a day.

Dosage forms: Allopurinol tablets I.P., B.P.


ii. Probenecid (Benemid)


Metabolism: The metabolite is glucuronide conjugates of carboxylic acid, ω oxidation of N-propyl side chain, and subsequent oxidation, resulting in alcohol to carboxylic acid derivative. ω Oxidation of N-propyl side chain and N-dealkylation are the process steps in the metabolism of probenacid.

Properties and uses: Probenecid exists as white crystalline powder or small crystals, practically insoluble in water, soluble in acetone, and sparingly soluble in ethanol. Probenecid is uricosuric agent that increases the rate of excretion of uric acid and used in the treatment of chronic gout. The oral administration of probenecid in conjugation with penicillin G results in higher and prolonged concentration of the antibiotic in the plasma than when penicillin is given alone.

Assay: Dissolve the sample in alcohol, shaking and heating slightly, if necessary, and titrate against 0.1 M sodium hydroxide. Determine the end point potentiometrically.

Dose: Adult oral dose is 500 mg–2 g per day; usually 250 mg two times a day for one week, then 500 mg twice a day thereafter.

Dosage forms: Probenecid tablets I.P., B.P.


iii. Sulphinpyrazone (Anuturane)


Metabolism: The metabolic product results from sulphoxide reduction, sulphur, and aromatic oxidation and C-glucuronidation of heterocyclic ring. The metabolite resulting from para hydroxylation of phenyl ring posseses uricosuric effect.

Properties and uses: Sulphinpyrazone is a white powder, very slightly soluble in water, sparingly soluble in alcohol, soluble in dilute solutions of alkali hydroxides and used as uricosuric agent.

Assay: Dissolve the sample in acetone and titrate against 0.1 M sodium hydroxide using bromothymol blue as an indicator, until the colour changes from yellow to blue.

Dose: Initial oral dose is 100–200 mg per day, taken with meals or milk.

Dosage forms: Sulphinpyrazone tablets B.P.

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