Plasma uric acid

The enzyme urate oxidase has also found medical application for the treatment of acute hype-ruricaemia (elevated plasma uric acid levels), associated with various tumours, particularly during their treatment with chemotherapy. 

Side-effects of thiazide diuretics predominantly consist of metabolic changes, such as hypokalaemia and rise of plasma uric acid levels, glucose, and lipids (total cholesterol and triglycerides). These metabolic changes are clearly less pronounced when... 

When probenecid (ColBENEMID) is given in sufficient amounts, it will block the active reabsorption of uric acid in the proximal tubules following its glomerular filtration, thereby increasing the amount of urate eliminated. In contrast, low dosages of probenecid appear to compete preferentially with plasma uric acid for the proximal tubule anionic transport system and thereby block its access to this active secretory system. The uricosuric action of probenecid, however, is accounted for by the drug s ability to inhibit the active reabsorption of filtered urate. 

Trimethoprim 15 mg/kg/day increased urinary uric acid excretion and reduced the plasma uric acid concentration in five healthy volunteers from 333 gmol/l (5.6 mg/dl) to 226 pmol/l (3.8 mg/dl) (1149). In 90 in-patients with hypouricemia co-trimoxazole was identified as the likely cause in four patients (1150). However, since the study was limited to patients with hypouricemia and since exposure rates for co-trimoxazole were not reported for hypouricemic or non-hypouricemic patients, no conclusions about the incidence and the relevance of trimethoprim-associated hypouricemia can be made. 

Normally dietary NA is hydrolyzed by pancreatic ribonucleases and absorbed in the small intestine. Guanine and adenine are metabolized further to uric acid before urinary excretion (2). Increased consumption of NA increased the uric acid levels above the urinary excretion rate, resulting in an increased plasma uric acid level. Uric acid has a pKa near 5.4. In the acidic urine, as much as half of the excreted compound may be in the form of the undissociated acid, which has a low solubility... 

Elitek Rasburicase Sanofi-Synthelabo 7/2002 Management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies 5. cerevisiae... 

The diuretic properties of indocrinone have been reported to improve by manipulation of the enantiomers rario (22) Although the diuretic property is predominantly ascribed to R(-)-indocrinone, both enantiomers possess urisocuric activity. The uricosuric effect is desirable as it counteracts the diuretic-induced rise in plasma uric acid concentration. However, this property of racemic indocrinone is transient. Examination of the overall pharmacodynamic profile of various formulations of indocrinone suggests that the patients remain isouricemic during a 7-day treatment period with an R S ratio of 10 40. 

In addition to a rise in serum potassium, timolol increases plasma uric acid concentrations (207). In the TOMHS study, acebutolol increased serum urate by 7 pmol/1 (196). 

Dietary purines are largely catabolized in the gut, rather than used by the body for the synthesis of nucleic acids. The end-product of purine catabolism in hvunans is uric acid. The diet accounts for less than half of the uric acid appearing in the bloodstream. Most of the plasma uric acid, or urate, originates from catabolism of the purines synthesized by the body (endogenous purines). The major purines are adenine and guanine. They occur mainly as nucleotides, such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), and as parts of nucleic acids. For example, the adenine in RNA occurs as adenosine monophosphate, and the adenine in DNA occurs as deoxyadenosine monophosphate. 

Normal serum uric acid is 0.025 to 0.080 mg/ml in males and 0.015 to 0.060 mg/ml in females. A uric acid level greater than 0.070 mg/ml is associated with an increased risk for gout. Purine-restricted diets can result in plasma uric acid levels of 0.005 to 0.015 mg/ml. About two-thirds of the uric acid in the body is excreted via the urine the rest is excreted in the feces. Uric acid accoimts for only about 5% of urinary nitrogen. 

Reduced plasma triglycerides, increased S-hydro-xybutyrate, and increased plasma uric acid were noted over 6 days of administration of DCA as a hypoglycemic agent. Although there is no conclusive evidence, DCA is proposed to cause neurotoxic effects in humans based on the fact that DCA inhibits its own metabolism. These effects are expected to occur at therapeutic doses, 25-100 mg kg... 

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). 

Preeclamptic Toxemia. This condition is associated with increasing plasma uric acid concentration, probably caused by uteroplacental tissue breakdown and decreased kidney perfusion. Plasma urate measurement can be used as an indicator of the severity of preeclampsia. Redman et al noted that concentrations in excess of 6.0mg/dL (0.36mmol/L) at 32 weeks gestation are associated with a high perinatal mortality rate. 

An alternative approach to the interpretation of plasma uric acid concentrations is to consider the degree of hyperuricemia in relation to the risk of developing gout men with plasma uric acid concentrations exceeding 9.0mg/dL (0.540 mmol/L) are approximately 150 times more hkely to have coexisting gouty arthritis than are men with uric acid concentrations less than 6.0mg/dL (0.360mmol/L). ... 

Meites S, Thompson C, Roach RW. Two ultramicroscale methods for plasma uric acid analysis with uricase. Clin Chem 1974 20 790-3. 

Biochemical diagnosis can be made by detection of excess sulfite in urme using the Merckoquant sulfite dipstick test (Merck KGaA, Darmstadt, Germany). Samples should not be evaluated until at least 10 days after birth and should be tested within 10 minutes of collection. Another type of molybdenum cofactor deficiency can be confirmed by finding a low plasma uric acid. Specialized centers... 

Allopurinol, which affects both the penultimate and ultimate steps in the production of uric acid, is used to lower plasma uric acid levels in conditions associated with excessive urate production (e.g., gout, hematologic disorders, and antineoplastic therapy). Sodium urate has a... 

B36. Buchanan, J. M., Sonne, J. C., and Delluva, A. M., Biological precursors of uric acid. II. The role of lactate, glycine, and carbon dioxide as precursors of the carbon chain and nitrogen atom 7 of uric acid. J. Biol. Chem. 173, 81-98 (1948). B37. Bulger, H. A., and Johns, H. E., The determination of plasma uric acid. J. Biol. Chem. 140, 427-440 (1941). 

In renal failure uric acid is also increased, its levels correlating poorly with creatinine (G16). Apparently there is an increase in the extrarenal uric acid elimination by uricolysis in the intestinal tract (B14, S29, S30). This becomes progressively important as plasma uric acid concentration rises (S30). Although hyperuricemia has been implicated in the precipitation of uremic pericarditis (CIO), most investigators believe that uric acid is innocuous, though clearly it may precipitate gout. 

Suppression of Plasma Uric Acid by Inhibiting Xanthine... 

Diuretics may also increase plasma lipid levels and cause glucose intolerance and insulin resistance, so they have to be used with caution in individuals with hyperlipi-daemia and/or diabetes. In addition, most diuretics produce an increase in plasma uric acid levels, which may lead to gout (see Chapter 7). 

Rasbnricase is an antimetabolite that catalyzes enzymatic oxidation of nric acid into an inactive and soluble metabolite (allantoin). It is indicated in initial management of plasma nric acid levels in pediatric patients with leukemia, lymphoma, and solid tnmor malignancies who are receiving anticancer therapy expected to result in tumor lysis and snbsequent elevation of plasma uric acid. 

The goal of therapy is to reduce the plasma uric acid concentration to <6 mg/dL (360 fjimol). 

Have maximal effects on blood pressure at doses below the maximal diuretic dose May cause an elevation of plasma uric acid and triglyceride levels Decrease the urinary excretion of calcium Cause ototoxicity... 

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