Uric acid levels

Allopurinol (Zyloprim) reduces the production of uric acid, thus decreasing serum uric acid levels and the deposit of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. This probably accounts for its ability to relieve the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

Niacin can raise uric acid levels, and in diabetics can raise blood glucose levels. However, several clinical trials have shown that niacin can be used safely and effectively in patients with diabetes.33 Due to the high cardiovascular risk of patients with diabetes, the benefits of improving the lipid profile appear to outweigh any adjustment in diabetic medication(s) that is needed.33... 

Select an appropriate drug to reduce serum uric acid levels in patients with gout, and outline a plan for monitoring efficacy and toxicity. 

The serum uric acid level often is elevated but may be normal during an acute attack. 

Allopurinol Starting dose CrCI greater than 90 mL/minute = 300 mg/day CrCI 60-90 mL/minute = 200 mg/day CrCI 30-60 mL/minute = 100 mg/day CrCI less than 30 mL/minute = 50 mg/day Adjust dosage based on follow-up uric acid levels maximum 800 mg/day... 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

Serum uric acid levels must be monitored periodically, with the first follow-up level obtained 6 months (or sooner) after starting therapy. The target serum uric acid level is less than 6 mg/dL (less than 357 ptmol/L). The dose should be titrated upward (to a maximum of 800 mg/day) or downward as these levels dictate. 

Obtain the first follow-up serum uric acid level within 6 months of starting therapy. Then monitor levels at least every 6 to 12 months, and adjust the dose to achieve a target serum uric acid level of less than 6 mg/dL (less than 357 pmol/L). 

Serum uric acid level greater than 8 mg/dL (476 pmol/L)... 

The primary goals of management of tumor lysis syndrome are (1) prevention of renal failure and (2) prevention of electrolyte imbalances. Thus the best treatment for tumor lysis syndrome is prophylaxis to enable delivery of cytotoxic therapy for the underlying malignancy. For patients who present with or develop tumor lysis syndrome despite prophylaxis, treatment goals include (1) decrease uric acid levels, (2) correct electrolyte imbalances, and (3) prevent compromised renal function. These goals should be achieved in a cost-effective manner. 

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. 

Administration of urate oxidase to humans suffering from hyperuricaemia results in the reduction of serum uric acid levels through its conversion to allantoin. Urate oxidase purified directly... 

Fed diets containing 50 mg/kg for 10 weeks with no effect on serum uric acid levels... 

Oral administration of 1.2 mg/kg BW daily for 6 weeks reduced uric acid levels in plasma by 67%... 

Jauge, P. and L.M. Del-Razo. 1985 Uric acid levels in plasma and urine in rats chronically exposed to inorganic As(III) and As(V). Toxicol. Lett. 26 31-35. 

Allopurinol and its major metabolite, oxypurinol, are xanthine oxidase inhibitors and impair the conversion of hypoxanthine to xanthine and xanthine to uric acid. Allopurinol also lowers the intracellular concentration of PRPP. Because of the long half-life of its metabolite, allopurinol can be given once daily orally. It is typically initiated at a dose of 100 mg/day and increased by 100 mg/day at 1-week intervals to achieve a serum uric acid level of 6 mg/dL or less. Serum levels can be checked about 1 week after starting therapy or modifying the dose. Although typical doses are 100 to 300 mg daily, occasionally doses of 600 to 800 mg/day are necessary. The dose should be reduced in patients with renal insufficiency (200 mg/day for CLcr 60 mL/min or less, and 100 mg/day for CLcr 30 mL/min or less). 

Because of comorbidity with diabetes, dyslipidemia, hypertension, and stroke, the presence of increased serum uric acid levels or gout should prompt evaluation for cardiovascular disease and the need for appropriate risk reduction measures. Clinicians should also look for possible correctable causes of hyperuricemia (e.g., medications, obesity, and alcohol abuse). 

And since high uric acid levels were associated with migraine as well, there appeared to be a positive relation between acid in the blood and blood pressure. Finally, Haig had already observed that test tube solutions of urates could be chemically manipulated to form gelatinous colloids, and supposed it was "quite possible" a like phenomenon might occur in the blood. 

A recent study in our laboratories 13 involved the determination of the blood levels of 11 items in 11 "normal" young men. In most cases 5 specimens, drawn at about weekly intervals under basal conditions, were analyzed from each individual. The uric acid levels in the two extreme individuals were as follows (mg. per cent) ... 

Initial dose 100 mg qd, increase by 100-mg increments/vi k until uric acid levels <6.5 mg/dL max 800 mg/d. Usual maintenance dosage 300 mg/d reduce in renal insufficiency rash, Gl intolerance common. Marrow suppression, hepatitis. 

Workers at a molybdenum-roasting plant with time-weighted average (TWA) exposures of approximately 9.5mgMo/m to soluble dusts had increased plasma and urine levels of molybdenum the only adverse biochemical findings were large elevations in serum ceruloplasmin levels and some increase in serum uric acid levels. ... 

Uric acid levels are also reduced by drugs that interfere with tubular... 

Gout Elevated uric acid levels have occurred. 

Drug/Lab test interactions Thiazides may decrease serum PBI levels without signs of thyroid disturbance. Thiazides also may cause diagnostic interference of serum electrolyte, blood, and urine glucose levels (usually only in patients with a predisposition to glucose intolerance), serum bilirubin levels, and serum uric acid levels. In uremic patients, serum magnesium levels may be increased. Bendroflumethiazide may interfere with the phenolsulfonphthalein test due to decreased excretion. In the phentolamine and tyramine tests, bendroflumethiazide... 

Diarrhea nausea vomiting jaundice liver enzyme abnormalities. Azotemia elevated BUN/creatinine increased serum uric acid levels (in patients predisposed to gouty arthritis) thrombocytopenia megaloblastic anemia weakness dizziness Hypokalemia headache dry mouth anaphylaxis. ... 

Serum uric acid - Serum uric acid levels are elevated by salicylate levels less than 10 mg/dL and decreased by levels more than 10 mg/dL. 

Urinary alkalinization- Urates tend to crystallize out of an acid urine therefore, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g/day) or potassium citrate (7.5 g/day) to maintain an alkaline urine continue alkalization until the serum uric acid level returns to normal limits and tophaceous deposits disappear. Thereafter, urinary alkalization and the restriction of purine-producing foods may be relaxed. 

Maintenance therapy- Continue the dosage that maintains normal serum uric acid levels. When there have been no acute attacks for 6 months or more and serum uric acid levels have remained within normal limits, decrease the daily dosage by 0.5 g every 6 months. Do not reduce the maintenance dosage to the point where serum uric acid levels increase. 

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. 

Another suggested dose is 1 mg/kg/day divided every 6 hours, to a maximum of 600 mg/day. After 48 hours of treatment, titrate dose according to serum uric acid levels. 

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