Hyperuricemia allopurinol therapy

Urinary tract A case report was published on anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immxme glomerulonephritis during febuxostat treatment. A 63-year-old African started treatment with febuxostat (dose not reported) because he had a history of chronic asymptomatic hyperuricemia which was not adequately controlled by allopurinol therapy. After 6 months of febuxostat therapy he developed AKI, characterised by acute renal failure, nephritic syndrome, proteinuria, microscopic haematuria and aseptic leukocyturia. Within 48 h after discontinuation of febuxostat, serum creatinine levels improved, although nephritic syndrome remained. ANCA-positive pauci-immune glomerulonephritis was confirmed by renal biopsy revealing diffuse crescentic necrotizing glomerulonephritis [60 ]. 

Allopurinol is an xanthine oxidase inhibitor. It reduces urate production and is used in primary and secondary urate overproduction. Therapy of hyperuricemia prevents recurring attacks of acute gouty arthritis. Allopurinol dosages are 300 mg/day for serum creatinine < 1.5 mg/dl and 100 mg/day for serum creatinine between 1.6-2.0 mg/dl. Reduction of tophi is slow with allopurinol, particularly in patients with giant tophi and renal insufficiency where drug dosage is limited. 

MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation reaction catalyzed by xanthine oxidase, whereas 6-TG undergoes deamination. This is an important issue because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used as a supportive care measure in the treatment of acute leukemias to prevent the development of hyperuricemia that often occurs with tumor cell lysis. Because allopurinol inhibits xanthine oxidase, simultaneous therapy with allopurinol and 6-MP would result in increased levels of 6-MP, thereby leading to excessive toxicity. In this setting, the dose of mercaptopurine must be reduced by 50-75%. In contrast, such an interaction does not occur with 6-TG, which can be used in full doses with allopurinol. 

Mercaptopurine is used in the treatment of acute lymphoid leukemia. Maintenance therapy makes use of both methotrexate and 6-mercaptopurine. Mercaptopurine is absorbed well from the gastrointestinal tract. It is metabolized through (1) methylation of the sulfhydryl group and subsequent oxidation, and (2) conversion to 6-thiouric acid with the aid of xanthine oxidase, which is inhibited by allopurinol. Mercaptopurine may cause hyperuricemia. Its chief toxicities are hepatic damage and bone marrow depression. 

Allopurinol (4-hydroxypyrazolo [3, 4-d] pyrimidine) is an inhibitor of xanthine oxidase that was successfully introduced in the treatment of primary gout about 45 years ago [171]. Allopurinol continues to be accepted as standard therapy in the treatment of primary and secondary hyperuricemia. Adverse reactions occur in about 10% of patients treated with allopurinol and are relatively mild and self-limited [171,172]. A mild maculopapular eruption or gastrointestinal disorders are usually noted, which promptly regress with cessation of therapy. Isolated instances of allopecia [173], bone marrow depression [174], ocular lesions [175], acute cholangitis [176], various types of hepatic injuries [177,178] temporal arthritis [179], and xanthine stones [180] have been reported. Recently, LaRosa et al [180a] have reported a case of xanthine nephropathy during treatment of childhood T-cell ALL. 

Note Five to 10% of people taking ampicillin develop eruptions between the 5th and 14th day following initiation of therapy. Also, there is a 95% incidence of exanthematous eruptions in patients who are treated for infectious mononucleosis with ampicillin. The allergenicity of ampicillin appears to be enhanced by allopurinol or by hyperuricemia. Ampicillin is clearly the more allergenic of the two drugs when given alone... 

K20. Krakoff, I. H., and Balls, M. E., Allopurinol in the prevention of hyperuricemia secondary to the treatment of neoplastic diseases with alkylating agents, adrenal steroids and radiation therapy. Ann. Rheumatic Diseases 26, 651-654, 1966. 

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. Therefore, allopurinol may be used in the management of patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer therapy that causes elevations of serum and urinary uric acid levels. Allopurinol may interfere with the metabolism of antineoplastic agents such as azathioprine and 6-mercaptopurine. 

Rasbnricase (Elitek) is a recombinant urate-oxidase that catalyzes the enzymatic oxidation of uric acid into the sol-nble and inactive metabolite allantoin. It has been shown to lower nrate levels more effectively than allopurinol. It is indicated in the initial management of elevated plasma nric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and significant hyperuricemia. 

Isolated hyperuricemia is not necessarily an indication for therapy, as not all of these patients develop gout. Persistently elevated uric acid levels, complicated by recurrent gouty arthritis, nephropathy, or subcutaneous tophi, can be lowered by allopurinol, which inhibits the formation of urate, or by uricosuric agents. Some physicians recommend measuring 24-hour urinary urate levels in patients who are on a low-purine diet to distinguish underexcretors from overproducers. However, tailored and empirical therapies have similar outcomes. 

AUopurinol inhibits xanthine oxidase and prevents the synthesis of urate from hypoxanthine and xanthine. It is used to treat hyperuricemia in patients with gout and to prevent it in those with hematological malignancies about to undergo chemotherapy (acute tumor lysis syndrome). Even though underexcretion rather than overproduction is the underlying defect in most gout patients, allopurinol remains effective therapy. 

Allopurinol (zyloprim, aloprim, others) is available for oral use and provides effective therapy for the primary hyperuricemia of gout and the hyperuricemia secondary to polycythemia vera, myeloid metaplasia, other blood dyscrasias, or acute tumor lysis syndrome. 

Allopurinol. a xanthine oxidase inhibitor, is given to control the hyperuricemia that occurs as a result of large cell kills in the successful drug therapy of malignant diseases. The antimetabolite mercaptopurine is metabolized by xanthine oxidase and, in the presence of an inhibitor of this enzyme (eg, allopurinol), toxic levels of the drug may be reached rapidly. The answer is (J). 

The clinical manifestations of gout, i.e. articular and renal disease, are intimately connected with hyperuricemia and/or particularities of renal handling of uric acid. It is well established that normalization of plasma uric levels will cure the joint disease. The diminution of renal uric acid excretion by administration of allopurinol will cure nephrolithiasis in its uncomplicated forms. One may presume that the other manifestations of the gouty kidney (i.e. parenchymal renal disease, hypertension and azotemia) will also be influenced by a therapy reducing urinary uric acid however no reliable reports exist as yet on this point. 

In uric acid stone patients with hyperuricemia, we principally combined a conservative therapie with Uralyt-U and Allopurinol. 

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