Gout and Hyperuricemia

Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin. 

Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin. In most cases, these drugs block uric acid secretion in the kidney. Long-term consequences of gout and hyperuricemia include joint destruction, tophi, and nephrolithiasis. 

AHopurinol inhibits xanthine oxidase and also can reduce purine synthesis by inhibiting PRPP amidotransferase (provided HPRT is active). Hyperuricemia and gout often accompany the following conditions ... 

Becker M, Schumacher H, Wortmann R, MacDonald P, Eustace D, Palo W et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005 353(23) 2450-61. 

Burack DA, Griffith BP, Thompson ME, Kahl LE. Hyperuricemia and gout among heart transplant recipients receiving cyclosporine. Am J Med 1992 92(2) 141-6. 

Ben Hmida M, Hachicha J, Bahloul Z, Kaddour N, Kharrat M, Jarraya F, Jarraya A. Cyclosporine-induced hyperuricemia and gout in renal transplants. Transplant Proc 1995 27(5) 2722 1. 

Studies by CJifford ft /if. 197ft) revealed the effect of purine consumption on uric acid levels. The purines were supplied to human subjects in the form of ribonucleic acid (RNA) 4g/day). Purine consumption resulted in a near doubling of plasma levels of uric acid and a 2.5-fold increase in urinary uric acid, Thi.s demonstrates the need for avoiding purine rich foods in treating hyperuricemia and gout, it has been recommended that the maximal safe limit of RMA in the diet is 2,0 g/day (Clifford ef ai, 1976). 1)115 amount of RNA can be supplied by 340 g cf sardines, 415 g of dried lentils or pinto beans, or 500 g of chicken liver. As few people consume, or would be willing to consume, 500 g of liver per day the limitation of dietary RNA to safe levels would not be expected to be a common concern,... 

Horwitz LR, Liebman JA, Cavolo DJ. Thiazide-induced hyperuricemia and gout. J Am Podiatry Assoc 1982 72(10) 511-6. 

Rundles RW, Wyngaarden JB, Flitchings GFI, Elison B, Silberman FIR. Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia, and gout.Trans Assoc Am Physicians 1963 76 126-140. 

Hyperuricemia and gout are common among individuals with excessive exposure to lead, apparently the result of decreased excretion and increased production of uric acid. Although hyperuricemia invariably accompanies azotemia, gout is uncommon in patients with renal failure except in those with lead nephropathy. Half of uremic patients with lead nephropathy have clinical gout [18] but in the absence of renal failure, gout cannot usually be attributed to lead despite coexisting hypertension [23, 37]. 

These studies seem to indicate that the uric acid production found in cases of hyperuricemia and gout occurs by the usual biosynthetic pathways. 

TABLE 91—2. Drugs Capable of Inducing Hyperuricemia and Gout... 

The oxidation of the endobiotic, hypoxanthine, to uric acid also requires XO, and can be inhibited by aUox-anthine, an XO-mediated metabolite of allopurinol. Thus, allopurinol is, in essence, a pro-drug intended to inhibit XO in the treatment of hyperuricemia and gout. The oxidation of 6-mercaptopurine to thiouric acid is also mediated by XO. Folic acid and tetrahydrofolic acid are among the most potent inhibitors known for mammalian XO, exhibiting Ki values between 0.5 and 1.0 pM. 

Aspirin, acetaminophen, the other nonnarcotic nonsteroidal antiinflammatory drugs (NSAIDs) used to treat pain and inflammation, and the drugs used for hyperuricemia and gout. 

Becker MA. Hyperuricemia and gout. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, vol II, 8th Ed. New York McGraw-Hill, 2001 2513-2535. 

Nephrotoxic effects include reversible acute tubular dysfunction (Including Fanconi-like aminoaciduria in children) and chronic interstitial fibrosis. Hyperuricemia and gout may ooour. 

There was a different response to RNA in gouty patients compared with normals. Characteristically patients with familial hyperuricemia and gout have higher serum uric acid levels at the same renal excretion, and a lower renal excretion at the same serum level. Accordingly, with RNA added to the diet, serum uric acid levels increased more in gouty patients than in normals (Nugent et al, 1964 Griebsch and Zollner, 1970). 

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