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Although phenylbutazone and oxyphenbutazone are used Post Date: Sat, 11 Oct 2008 19:03:49 +0000
The degree to which these drugs may complement or antagonize the effects of probenecid and sulfinpyrazone has yet to be established.INHIBITORS OF TUBULAR TRANSPORT OF ORGANIC COMPOUNDS.Although phenylbutazone and oxyphenbutazone are used during acute attacks of gout primarily for their anti-inflammatory and analgesic effects, it should be remembered that they are also potent uricosuric agents.

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For details of the role Post Date: Sat, 11 Oct 2008 18:53:07 +0000
THE CLINICAL USE OF URICOSURIC AGENTSAbnormalities in the rate of formation or renal excretion of uric acid, or both, are the primary etio-logical factors in gout and other hyperuricemic states. Current knowledge of urate production has been reviewed by Wyngaarden (1974). For details of the role of the kidney in the development of hyperuricemia, see Rieselbach and Steele (1974).

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In about two thirds Post Date: Sat, 11 Oct 2008 18:37:25 +0000
In the clinical use of the available uricosuric drugs, it must be kept in mind that they can alter the plasma binding, distribution, and renal excretion of other organic acids (as discussed above), whether these be naturally occurring substances or drugs and drug metabolites. The use of probenecid and sulfinpyrazone for the mobilization of uric acid in chronic gout is well established. In about two thirds of patients, these agents cause uric acid to be excreted at a rate sufficient to exceed that of formation and thereby promptly lower the plasma uric acid concentration.

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In gouty arthritis, there Post Date: Sat, 11 Oct 2008 18:18:21 +0000
Although the intravenous administration of large doses of these drugs can cause a fivefold to sevenfold increase in the renal clearance of urate, continuous oral administration to patients with tophaceous gout approximately doubles the daily excretion of urates. In such patients, continued administration prevents the formation of new tophi and causes gradual shrinkage, or even disappearance, of old tophi. In gouty arthritis, there is a reduction in the swelling of chronically enlarged joints and a dramatic degree of rehabilitation may be achieved in patients who suffer severe pain and limitation of joint movement.

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In patients with gouty nephropathy Post Date: Sat, 11 Oct 2008 18:05:31 +0000
The introduction of allopurinol, a drug that in-hibits the formation of uric acid, constitutes a very important addition to the therapeutic means of con-trolling hyperuricemia, regardless of its etiology (see Chapter 17). In those patients who do not respond well to uricosuric agents because of impaired renal function, allopurinol is especially useful. In patients with gouty nephropathy, it offers the additional ad-vantage over the uricosuric agents that the daily excretion of uric acid is reduced rather than in-creased.

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Indeed, the acute attacks may Post Date: Sat, 11 Oct 2008 17:47:54 +0000
Its administration is compatible with the simultaneous use of the uricosuric agents if necessary (see Chapter 17).Neither the uricosuric agents nor allopurinol alters the course of acute attacks of gout or supplants the use of colchicine and anti-inflammatory agents in their management. Indeed, the acute attacks may increase in frequency or severity during the early months of therapy when urate is being mobilized from affected joints.

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When an acute attack occurs Post Date: Sat, 11 Oct 2008 17:34:34 +0000
Therefore, therapy with uri-cosuric agents should not be initiated during an acute attack but may be continued if already begun. Col-chicine in small doses (0,5 to 2 mg per day) may be administered at this period (or at any time) to reducethe frequency of attacks. When an acute attack occurs, it is treated with full doses of colchicine or whatever agent has proven most satisfactory in the management of previous attacks (phenylbutazone or oxyphenbutazone, corticosteroids, indomethacin, etc).

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Later in the course Post Date: Sat, 11 Oct 2008 17:19:19 +0000
The use of salicylates is contraindicated be-cause they antagonize the action of probenecid and sulfinpyrazone. However, for analgesia, acetamino-phen may be used. Later in the course of therapy, acute attacks become less frequent or may cease altogether.

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This precaution is essential Post Date: Sat, 11 Oct 2008 17:00:42 +0000
In the treatment of gout, the uricosuric drugs are given continually in the lowest dose that will main-tain satisfactory plasma uric acid concentrations. Since the pKa of uric acid is 5,6 and the solubility of the undissociated form is very low, maintaining the output of a large volume of alkaline urine minimizes its intrarenal deposition. This precaution is essential during the early weeks of therapy when uric acid excretion is large, especially in patients with a history of renal disease associated with the passage of urate stones or gravel.

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The use of allopurinol permits Post Date: Sat, 11 Oct 2008 16:47:27 +0000
It is believed that renal disease of any etiology is a predisposing factor in the development of gouty nephropathy. Eventual improvement in renal function in patients with gouty nephropathy has been reported, but it is uncommon. The use of allopurinol permits a more favorable prognosis in such patients.

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