Allopurinol, 319

Allopurinol is a drug used primarily to treat hyperuricemia, which means excess uric acid in blood plasma and its complications, including chronic gout. It should be noted that allopurinol is not a uricosuric which means that it does not increase the excretion of uric acid in the urine so it can be used in patients with poor kidney function. Allopurinol has been marketed in the United States since 1966 under the trade name of Zyloprim. After it becomes 

FIGURE 24.2 Allopurinol reduces the pool of uric acid. 

Allopurinol is used not only in treating the hyperuricemia associated with gout, but also in the secondary hyperuricemia associated with the use of antineoplastic agents. However, allopurinol may interfere with the metabolism of antineoplastic agents such as azathioprine and 6-mercaptopurine. 

Gout is a metabolic disease in which there is a overproduction of purines. It is characterized by intermittent attacks of acute arthritis produced by the deposition of sodium urate crystals in the synovial tissue of joints. Drugs used for treating gout are allopurinol, probenecid, colchicine, and NSAIDs. 

Colchicine is an alkaloid obtained from various Colchicum species. It is used for the relief of acute gout and as a prophylaxis of acute attacks. Colchicine is used in several other conditions including amyloidosis, Behcet s syndrome, pyoderma, and gangrenosis. 

Most common adverse effects include nausea, vomiting, diarrhea, abdominal pain, bone marrow depression with agranulocytosis, thrombocytopenia, and aplastic anemia. Cumulative toxicity is possible in elderly patients, hence it should be used cautiously. Care also should be exercised in patients with cardiac, hepatic, and renal dysfunctions. Colchicine causes teratogenicity in animals, and there are evidences of the risk of fetal chromosomal damage in humans. Colchicine should not be administered by the parenteral route as it causes severe local irritation. 

Allopurinol is used in the treatment of hyperuricemia, which is associated with chronic gout and in cancer chemotherapy. Allopurinol has been used in renal calculi caused by the deposition of calcium oxalate and of 2,8-dihydroxy-adenine. Allopurinol treatment does cause hypersensitivity reaction, which may be fatal. 

The special risk is observed in patients with hepatic or renal impairment. It is not advised to use allopurinol in acute attacks of gout, but it is useful in chronic gout. Excretion of allopurinol and its active metabolite oxypurinol is primarily via the kidneys and therefore the dosage should be reduced if renal function is impaired. The adverse effects have been reported in patients receiving allopurinol with thiazide diuretics, particularly in patients with impaired renal function. The metabolism of azathioprine and mercaptopurine is inhibited by allopurinol and their doses should be reduced to one-quarter to one-third of the usual dose when either of them is given with allopurinol to avoid potentially life-threatening toxicity.27-29 

Therapeutic Function Xanthine oxidase inhibitor gout therapy Chemical Name 1 H-pyra2olo[3,4-d] pyrimidin4-ol Common Name — 

Trade Name Manufacturer Country Year Introduced 

3-Morpholino-2 yanoacrylamide A stirred mixture of cyanoacetamide (63 g), triethylortho-formate (134 g), morpholine (82.5g) and acetonitrile (37.5 ml) was heated under reflux for 4 hours. The initial reflux temperature was 117°C and the final reflux temperature was 82°C. 

At the end of the reflux period the mixture was cooled to 30°C and the heavy crystalline precipitate was collected and washed with 2 X 75 ml of ethanol. The product was dried in vacuo at30°C. Wt = 111g. Yield = 82%, MP 173°-175°C. 

3- Aminopyrazole-4-carboxamidehemisulfate To water (253 ml) at 60°C was added 3-morpho-lino-2-cyanoacrylamide (63.4g) and 85% technical hydrazine hydrate (22.7 g). The mixture was rapidly heated to 95°Cand the temperature was maintained at 90°C for 20 minutes. The mixture was then cooled to 60°C and the pH carefully adjusted to 1.5 by the addition of a mixture of suifuric acid (45.7 g) and ice (45.7 g). The acidified reaction was cooied to 5 and the crystaiiine product collected and washed with cold water (2 X 100 ml) and acetone (2X50 ml). The product was dried in vacuo at 80°C. Wt = 5.8g. Yield 95%, MP 237°-239°C. 

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Allomaltol, methyl — see Pyran-4-one, 5-methoxy-2-methyl-Allopurinol applications, 5, 343 metabolism, 1, 237 synthesis, 5, 316, 340 tautomerism, 5, 308 xanthine oxidase inhibition by, 1, 173 Allopurinol, oxy-applications, 5, 343 synthesis, 5, 316 Alloxan... 

The active principle of the autumn crocus (Colchicum autumnale), colchicine (48), is one of the very few drugs that have remained in reputable medical use since ancient times. This drug was the only useful treatment available for the excruciating pain associated with crystallization of uric acid in the joints characteristic of gout until the advent of allopurinol. Although the precise mechanism by which colchicine gives this dramatic relief remains undefined, the antimitotic activity of this agent is... 

As an inhibitor of xanthine oxidase, allopurinol also markedly decreases oxidation of both hypoxanthine and xanthine itself to the sole source of uric acid (19) in man. This metabolic block thus removes the source of uric acid that in gout causes the painful crystalline deposits in the joints. It is of interest that allopurinol itself is oxidized to the somewhat less effective drug, oxypurinol (21), by xanthine oxidase. 

Dimethyl tubocurarine Iodide Cyanacetamid Ethionamide Protionamide Cyanamide Albendazole Butalamine HCl Cimetide Cyanoacetamide Allopurinol Cyanoacetic acid Aminometradine Amisometradine Cyclopentamine HCl Sulindac... 

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