Urate/uric acid, formation

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. 

Fig. 14-39 Formation of urate/uric acid from inosine and guanine.

The low solubility of uric acid has unfortunate consequences since at higher than normal concentrations it can crystallise in the body. For example, when the urine is unusually acid, calcium urate stones can form in the kidney and bladder. High levels of uric acid in the blood can result in the formation of urate crystals in the joints, which causes a very painful condition, since it results in inflammation in these joints. Gout is unlikely to develop if the urate concentration remains low (<0.4 mmol/L) but any factor that increases the rate of production or decreases that of elimination by the... 

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... 

Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the size of the urate pool. The more soluble xanthine and hypoxanthine are increased. 

Febuxostat is a potent and selective inhibitor of xanthine oxidase, and thereby reduces the formation of xanthine and uric acid. No other enzymes involved in purine or pyrimidine metabolism are inhibited. In clinical trials, febuxostat at a daily dose of 80 mg or 120 mg was more effective than allopurinol at a standard 300 mg daily dose in lowering serum urate levels. The urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion. 

An alternative to thiazides is allopurinol. Some studies indicate that hyperuricosuria is associated with idiopathic hypercalcemia and that a small nidus of urate crystals could lead to the calcium oxalate stone formation characteristic of idiopathic hypercalcemia. Allopurinol, 300 mg daily, may reduce stone formation by reducing uric acid excretion. 

Gout is a familial metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Formation of uric acid calculi in the kidneys... 

Probenecid and sulfinpyrazone are uricosuric drugs employed to decrease the body pool of urate in patients with tophaceous gout or in those with increasingly frequent gouty attacks. In a patient who excretes large amounts of uric acid, the uricosuric agents should be avoided so as not to precipitate the formation of uric acid calculi. 

During initial therapy a fluid intake of at least 2 1/d should be ensured to prevent urate crystall-uria. If the uric acid load is high, consider rendering the urine alkaline with Potassium Citrate Mixture 12-24 g/d with water p.o. or sodium bicarbonate powder 5-10 g/d with water p.o., again to prevent uric acid crystal formation in the renal tract. Other adverse effects are mainly gastrointestinal sulfinpyrazone is contraindicated in peptic ulcer. 

Ascorbic acid 4 g/day increases uric acid clearance in volunteers (23), although it does not reduce protein-bound uric acid in blood. Ascorbic acid 4-12 g/day causes acidification of the urine, which can cause precipitation of urate and cystine and consequently formation of urate stones or cystinuria. Ascorbic acid is excreted largely as oxalate, and hyperoxaluria results when large doses are... 

In a commercially available assay, serum NTP catalyzes the hydrolysis of IMP to yield inosine, which is then converted to hypoxanthine by purine-nucleoside phosphorylase (EC 2.4.2.1). Hypoxanthine is oxidized to urate with xanthine oxidase (EC 1.2.3.2). Two moles of hydrogen peroxide are produced for each mole of hypoxanthine liberated and converted to uric acid. The formation rate of hydrogen peroxide is monitored by a spectrophotometer at 510nm by the oxidation of a chromogenic system. The effect of ALPs on IMP is inhibited by p-glycerophosphate. This material is substrate for ALP but not for NTP, and by forming substrate complexes with the former enzyme, it reduces the proportion of the total ALP activity that is directed to the hydrolysis of the NTP substrate, IMP. ... 

Lower primates and mammals other than humans carry purine metabolism one step further with the formation of aUantoin from uric acid, a step mediated by uricase ([urate oxygen] oxidoreductase, EC 1.7.3.3). In humans, approximately 75% of uric acid excreted is lost in the urine most of the remainder is secreted mto the gastrointestinal tract, where it is degraded to allantoin and other compounds by bacterial enzymes. 

Hyperuricemia (gout) is a clinical condition characterized by elevated levels of uric acid that lead to the formation of sodium urate crystals that are found primarily in the joints of the extremities. Which of the following factors contributes most to the formation of urate crystals in the extremities ... 

B. Uric acid has a pKa of 5.4 and is ionized in the body to form urate. Urate is not very soluble in an aqueous enviromnent, and the quantity of urate in human blood is very close to the solubility range. Therefore, situations that lead to excessive degradation of purine bases can increase the urate concentration past the solubihty point and lead to the formation of urate crystals. The decreased body temperature found in the joints contributes to the formation of urate ays-tals under these conditions. 

Intratubular obstruction due to crystal formation with acetazolamide and stone formation with triamterene has been reported. In addition, uric acid stones, although rare, can result from the administration of those diuretics, which compete with uric acid for secretion, but also from any diuretic that causes severe volume depletion, thus enhancing urate reabsorption and compromising excretion. 

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