Hyperuricemia Primary

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

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. 

Primary gout (hyperuricemia) is the form of the disease that is attributable to an inborn error of metabolism, such as overproduction of uric acid. 

Therapeutic uses Allopurinol is effective in the treatment of primary hyperuricemia of gout and hyperuricemia secondary to other conditions, such as that associated with certain malignancies (those in which large amounts of purines are produced) or in renal disease. 

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. 

Tacrolimus may induce tubular dysfunction characterized as an increased excretion of urinary enzymes, decreased urinary concentrating ability, increased fractional excretion of magnesium in the presence of hypomagnesemia, hyperkalemia, hyperuricemia and fubular acidosis [12,260,645,647,705,736,737. In vitro sfudies showed fhat TAC inhibit Na/K - ATPase in rat microdissected cortical collecting duct and medullary thick ascending limb [738], and that high TAC doses added to primary human proximal tubules cultures decreased cell proliferation after 72 hours of incubation... 

Uric acid, an end product of protein catabolism, was identified as the cause of gout in the middle of the 19th century. Patients with primary hyperuricemia have elevated serum uric acid levels because of increased production of uric acid or impaired renal excretion of uric acid. 

Measurement of plasma uric acid is predominantly used in the investigation of gout, either as a result of a primary hyperuricemia or caused by other conditions or treatments that give rise to secondary hyperuricemias. It is also used in the diagnosis and monitoring of pregnancy-induced hypertension (preeclamptic toxemia). 

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. 

ADVERSE EFFECTS AND PRECAUTIONS Adverse effects of diuretics see Chapter 28) determine tolerance and adherence. Erectile dysfunction is a troublesome adverse effect of thiazide diuretics physicians should inquire specifically regarding its occurrence. Albeit uncommon, gout may be a consequence of the hyperuricemia induced by these diuretics. Either of these adverse effects is reason to consider alternative therapies. Hydrochlorothiazide may cause rapidly developing, severe hyponatremia in some patients. Thiazides inhibit renal Ca " excretion, occasionally leading to hypercalcemia although generally mUd, this can be more severe in patients subject to hypercalcemia, such as those with primary hyperparathyroidism. The thiazide-induced decreased Ca excretion may be used therapeutically in patients with osteoporosis or hypercalciuiia. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis, usually monoarticular, and is associated with abnormal levels of uric acid in the body, particularly the presence of monosodium urate crystals in synovial fluid. Primary gout is a hereditary disease in which hyperuricemia is caused by an error in uric acid metabolism—either overproduction or an inability to excrete uric acid. Secondary gout refers to those cases in which hyperuricemia is caused by an acquired disease or disorder, such as chronic renal disease, lead poisoning, or myeloproliferative disorders. Gout generally occurs in... 

HYPERURICEMIA IN PRIMARY HYPERPARATHYROIDISM INCIDENCE AND EVOLUTION AFTER SURGERY... 

Hyperuricemia was first found to be associated with primary hyperparathyroidism (PHP) by Mintz (1) in 1961. 

Table 1. Factors contributing to hyperuricemia in 23 cases o primary hyperparathyroidism...

Allopurinol has been used for 16 years at doses ranging from 200 to 800 mg/day for the control of primary and secondary hyperuricemia. At the most commonly used doses of allopurinol (300-400 mg/ day) about 70% of the allopurinol is oxidized to oxipurinol, which is excreted in the urine. Urinary allopurinol and allopurinol riboside each account for about 10% of the dose. Since the degree of xanthine oxidase inhibition is dose-related, not only the oxidation of hypoxanthine and xanthine to uric acid, but also the oxidation of allopurinol to oxipurinol might be expected to be strongly inhibited at high doses of allopurinol. This would lead to increased levels of allopurinol, as well as allopurinol riboside, in plasma and urine. The extent to which this phenomenon occurs was investigated in several laboratory animal species and in man. 

CEMIC YOUNG SONS, THE MEAN PLASMA GLUTAMATE LEVEL WAS SIGNIFICANTLY LOWER, 56+ I5 M/L, not distinguishable FROM THE NORMAL CONTROLS. The data indicate that HYPERGLUTAMATEMIA IS NOT ONLY A FREQUENT ACCOMPANIMENT OF HYPERURICEMIA IN PRIMARY GOUT, BUT appears early in the COURSE OF THE DISEASE, BEFORE THE ONSET OF SYMPTOMS AND APPARENTLY IN CONJUNCTION WITH THE ONSET OF HYPERURICEMIA AT ABOUT THE TIME OF PUBERTY. 

The fact that glycine uptake in leucocytes in patients with primary gout is excessive is merely symptomatic of the disease, just as the hyperuricemia is an epiphenomenon. The factor(s) leading to enhanced glycine uptake remain completely unresolved just as the reasons for the increased incorporation of glycine into uric acid in vivo in most cases of primary gout remain obscure. 

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