Allopurinol is a structural isomer of hypoxanthine. Allopurinol inhibits xanthine oxidase, an enzyme that converts oxypurines to uric acid. By blocking the production of uric acid, this agent decreases serum and urine concentrations of uric acid, thereby providing protection against uric acid-mediated end-organ damage in conditions associated with excessive production of uric acid, i.e. the massive cell lysis associated with the treatment of some malignancies.
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones, and for the high uric acid levels that can occur with chemotherapy.It is taken by mouth or injected into a vein.A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Allopurinol is considered a standard treatment of hyperuricemia associated with gout. In August 2017, an oral combination agent Duzallo was approved by FDA as a dual-mechanism treatment of hyperuricemia in patients with uncontrolled gout. Duzallo contains allopurinol and Lesinurad, a recently FDA-approved URAT1 inhibitor indicated for the treatment of hyperuricemia associated with gout.
Mechanism of action
Allopurinol is a purine analog; it is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an inhibitor of the enzyme xanthine oxidase.Xanthine oxidase is responsible for the successive oxidation of hypoxanthine and xanthine, resulting in the production of uric acid, the product of human purine metabolism.In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine. While xanthine cannot be converted to purine ribotides, hypoxanthine can be salvaged to the purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides may cause feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol, therefore, decreases uric acid formation and may also inhibit purine synthesis.
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Accompanying the decrease in uric acid produced by allopurinol is an increase in serum and urine concentrations of hypoxanthine and xanthine. Plasma concentrations of these oxypurines do not, however, rise commensurately with the fall in serum urate concentrations and are often 20-30% less than would be expected in view of urate concentrations prior to allopurinol therapy. This discrepancy occurs because renal clearance of the oxypurines is at least 10 times greater than that of uric acid. In addition, normal urinary purine output is almost exclusively uric acid, but after treatment with allopurinol, it is composed of uric acid, xanthine, and hypoxanthine, each having independent solubility. Thus, the risk of crystalluria is reduced. Alkalinization of the urine increases the solubility of the purines, further minimizing the risk of crystalluria. Decreased tubular transport of uric acid also results in increased renal reabsorption of calcium and decreased calcium excretion.
Indications
- For the treatment of hyperuricemia associated with primary or secondary gout. Also indicated for the treatment of primary or secondary uric acid nephropathy, with or without the symptoms of gout, as well as chemotherapy-induced hyperuricemia and recurrent renal calculi.
- Allopurinol is indicated in the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)
- Allopurinol is indicated in the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Treatment with allopurinol should be discontinued when the potential for over production of uric acid is no longer present
- Allopurinol is indicated in the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks.
- Allopurinol has been used to reduce hyperuricemia secondary to glucose-6- phosphate dehydrogenase deficiency, Lesch-Nyhan syndrome, polycythemia vera, sarcoidosis, and secondary to the administration of thiazides or ethambutol.
The drug must be avoided due to its major side effects. For better option for gout patients , use the fabuxostat .
