Uric acid urinary excretion

Since allopurinol blocks xanthine conversion to uric acid, urinary xanthine excretion is increased, creating a risk of xanthine crystal formation in the urinary system or even in muscles this can result in nephrolithiasis (12). It is still an open question whether a predisposition to renal disease or renal disease itself is required to precipitate these adverse effects. It is also not known whether increased excretion of orotic acid, due to an interaction of allopurinol with pyrimidine formation, has any consequences for these adverse effects or for its role in reducing glucose tolerance. 

Xanthine oxidase does not act on biopterin (Forrest et al., 1956). The pattern of urinary excretion of biopterin might be expected, therefore, to differ not only from that of xanthopterin, but also from uric acid. The excretion of uric acid is elevated in leukemia, perhaps reflecting (Krakoff, 1957) an acceleration of nucleic acid ssmthesis. If this acceleration entailed parallel increases in the folic acid and other cofactors for making nucleic acid, then it would account for the increased excretion of xanthopterin in leukemia noted earlier. The turnover of biopterin in leukemia and in normal subjects is, one must emphasize, entirely unknown. 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

DRUGS USED FOR GOUT. The nurse encourages a liberal fluid intake and measures the intake and output. The daily urine output should be at least 2 liters. An increase in urinary output is necessary to excrete the urates (uric acid) and prevent urate acid stone formation in the genitourinary tract. 

Uric acid - Normal urinary excretion in humans ... 

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

Uric acid nephrolithiasis occurs in 10% to 25% of patients with gout. Predisposing factors include excessive urinary excretion of uric acid, acidic urine, and highly concentrated urine. 

Prophylactic treatment can be withheld if the first episode of acute gouty arthritis was mild and responded promptly to treatment, the patient s serum urate concentration was only minimally elevated, and the 24-hour urinary uric acid excretion was not excessive (less than 1,000 mg/24 hours on a regular diet). 

If the patient had a severe attack of gouty arthritis, a complicated course of uric acid lithiasis, a substantially elevated serum uric acid (greater than 10 mg/dL), or a 24-hour urinary excretion of uric acid of more than 1,000 mg, then prophylactic treatment should be instituted immediately after resolution of the acute episode. 

Pharmacology Thiazide diuretics increase the urinary excretion of sodium and chloride in approximately equivalent amounts. They inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henie and the early distal tubules. Other common actions include Increased potassium and bicarbonate excretion, decreased calcium excretion and uric acid retention. At maximal therapeutic dosages all thiazides are approximately equal in diuretic efficacy. 

Pharmacology A uricosuric and renal tubular blocking agent, probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum uric acid levels. 

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. 

Allopurinol is especially indicated in the treatment of chronic tophaceous gout, since patients receiving it show a pronounced decrease in their serum and urinary uric acid levels. Because it does not depend on renal mechanisms for its efficacy, allopurinol is particularly beneficial for patients who already have developed renal uric acid stones, patients with excessively high urate excretion (e.g., above 1,200 mg in 24 hours), patients with a variety of blood disorders (e.g., leukemia, polycythemia vera), patients with excessive tophus deposition, and patients who fail to respond well to the uricosuric drugs. 

Mechanism of Action A uricosuric that increases urinary excretion of uric acid, thereby decreasing blood urate levels. Therapeutic Effect Promotes uric acid excretion and reduces serum uric acid levels. 

As the urinary excretion of uric acid increases, the size of the urate pool decreases, although the plasma concentration may not be greatly reduced. In patients who respond favorably, tophaceous deposits of urate are reabsorbed, with relief of arthritis and remineralization of bone. With the ensuing increase in uric acid excretion, a predisposition to the formation of renal stones is augmented rather than decreased therefore, the urine volume should be maintained at a high level, and at least early in treatment the urine pH should be kept above 6.0 by the... 

In patients affected with GAMT deficiency, GA is elevated in urine, plasma and CSF. In addition, Cr is decreased or in the low-normal range in urine, plasma and CSF. Creatinine in urine (expressed as excretion per 24 h) and plasma is decreased. This low urinary creatinine results in increased concentration of other metabolites (e.g. amino acids, organic acids, uric acid) when expressed per mol creatinine. During treatment by Cr supplementation, GA in plasma decreases, but does not normalise. Cr in plasma and urine becomes increased. 

Gout is caused by the deposition of crystals of monosodium urate hydrate which are ingested by leucocyctes and trigger the inflammatory response. The biosynthesis of uric acid involves the oxidation of the more soluble compound xanthine (2,6-dihydroxypurine) by xanthine oxidase, and this enzyme is inhibited by allopurinol (187). The treatment of gout also relies on uricosuric drugs to accelerate urinary excretion of uric acid and antiinflammatory drugs to ease the pain and inflammation. 

The nucleoside formed from hypoxanthine and ribose is known as inosine (Ino or I) and the corresponding nucleotide as inosinic acid. Further substitution at C-2 of -H by -OH and tautomerization yields xanthine (Xan). Its nucleoside is xanthosine (Xao, X). A similar hydroxylation at C-7 converts xanthine to uric acid, an important human urinary excretion product derived from nucleic acid bases. 

In six healthy subjects, ampicillin caused an increase in urinary uric acid excretion this effect was attributed to competition for active renal tubular reabsorption of urate (SEDA-13, 212). 

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. 

Fanconi syndrome (metabolic acidosis secondary to malfunction of proximal renal tubules, resulting in urinary excretion of amino acids, glucose, phosphate, bicarbonate, uric acid, and other substances) secondary to longterm valproic acid has been described in an 8-year-old boy with severe developmental disability (1170). In a review of 10 previous reports of Fanconi syndrome secondary to long-term valproic acid therapy the authors found that all occurred at 4-14 years, all had taken valproic acid for 10 months to 10 years, and symptoms were fully reversible within 2-14 months after withdrawal of valproic acid. Most of the patients (9 of 11) were severely disabled, bedridden, or wheelchair-bound. 

Uric acid, cystine, and some other weak acids are relatively insoluble in, and easily reabsorbed from, acidic urine. Renal excretion of these compounds can be enhanced by increasing urinary pH with carbonic anhydrase inhibitors. In the absence of continuous bicarbonate administration, these effects of acetazolamide are of relatively short duration (2-3 days). Prolonged therapy requires bicarbonate administration. 

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... 

Uricosurics, such as probenecid or benz-bromarone (100 mg/day), promote renal excretion of uric acid. They saturate the organic acid transport system in the proximal renal tubules, making it unavailable for urate reabsorption. When underdosed, they inhibit only the acid secretory system, which has a smaller transport capacity. Urate elimination is then inhibited and a gout attack is possible. In patients with urate stones in the urinary tract, uricosurics are contraindicated. 

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