Uric Reabsorption

The process of reabsorption depends on the HpophiHc—hydrophiHc balance of the molecule. Charged and ioni2ed molecules are reabsorbed slowly or not at all. Reabsorption of acidic and basic metaboHtes is pH-dependent, an important property in detoxification processes in dmg poisoning. Both passive and active carrier-mediated mechanisms contribute to tubular dmg reabsorption. The process of active tubular secretion handles a number of organic anions and cations, including uric acid, histamine, and choline. Dmg metaboHtes such as glucuronides and organic acids such as penicillin are handled by this process. 

Anti-gout Drugs. Figure 2 Reabsorption and secretion of uric acid in the proximal renal tubulus. (a) Normal situation. Uric acid is completely reabsorbed in the proximal segment of the renal tubulus and secreted more distally. (b) Situation in untreated hyperuricemia. 

Uricosuric dtugs increase the renal excretion of uric acid by inhibiting its renal reabsorption. Therapeutically used uricosuric dtugs are benzbromarone, probenecid and sulfinpyrazone. 

Probenecid is a uricosuric agent that blocks the tubular reabsorption of uric acid, increasing its excretion. Because of its mechanism of action, probenecid is contraindicated in patients with a history of uric acid stones or nephropathy. Probenecid loses its effectiveness as renal function declines and should be avoided when the creatinine clearance is 50 mL/minute or less. Its uricosuric effect is counteracted by low aspirin doses, which many patients receive for prophylaxis of coronary heart disease. 

The answer is e. (Katzung, p 254.) Furosemide affects the re absorption of uric acid in the proximal tubule. It increases uric acid reabsorption... 

Probenecid and sulfinpyrazone increase the renal clearance of uric acid by inhibiting the renal tubular reabsorption of uric acid. They should only be... 

The filtered marker undergoes tubular reabsorption and secretion. The clearance of such markers depends on the relative rates of filtration, reabsorption, and secretion. Determination of renal function by these markers, typified by uric acid, is cumbersome. 

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. 

Pharmacokinetics Allopurinol is approximately 90% absorbed from the Gl tract. Effective xanthine oxidase inhibition is maintained over 24 hours with single daily doses. Allopurinol is cleared essentially by glomerular filtration oxipurinol is reabsorbed in the kidney tubules in a manner similar to the reabsorption of uric acid. 

Most drugs act by reducing active transport rather than by enhancing it. Thus, drugs that promote uric acid loss (uricosuric agents, such as probenecid and sulfinpyrazone) probably inhibit active urate reabsorption, while pyrazinamide, which reduces urate excretion, may block the active tubular secretion of uric acid. A complicating observation is that a drug may primarily inhibit active reabsorption at one dose and active secretion at another, frequently lower, dose. For example, small amounts of salicylate will decrease total urate ex-... 

The thiazides have a variable effect on elimination of uric acid, which also is secreted by the renal acid secretory mechanism. Administration of thiazide diuretics, especially at low doses, may elevate serum uric acid levels and cause goutlike symptoms. Following large doses, thiazides may compete with uric acid for active reabsorption and thereby may promote uric acid elimination rather than impair it (see Chapter 37). 

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. 

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. 

A) By inhibiting proximal tubular reabsorption of uric acid... 

A. Probenecid blocks active reabsorption of uric acid in the proximal tubules following glomerular filtration. It does not inhibit uric acid synthesis (B), stimulate tubular secretion (C), or inhibit the metabolism of purines (D). 

Mechanism of Action An antigout agent that competitively inhibits reabsorption of uric acid at the proximal convoluted tubule. Also, inhibits renal tubular secretion of weak organic acids, such as penicillins. Therapeutic Effect Promotes uric acid excretion, reduces serum uric acid level, and increases plasma levels of penicillins and cephalosporins. 

It increases the excretion of uric acid (by inhibiting its reabsorption from kidney tubules) and hence causes reduced serum levels of uric acid. 

Loop diuretics can cause hyperuricemia and precipitate attacks of gout. This is caused by hypovolemia-associated enhancement of uric acid reabsorption in the proximal tubule. It may be prevented by using lower doses to avoid development of hypovolemia. 

The uricosuric drugs(having uric acid in the urine) prevent reabsorption of... 

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). 

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