Thiazides Allopurinol

Allopurinol, barbiturates, carbamazepine, cephalosporins, cyclophosphamide, ethambutol, fluconazole, ibuprofen, lamotrigine, macrolides, nitrofurantoin, penicillins, phenytoin, propranolol, quinolones, sulfonamide antimicrobials, sulindac, tetracyclines, thiazides, valproic acid, and vancomycin... 

Drugs that may affect allopurinol include ACE inhibitors aluminum salts thiazide diuretics uricosuric agents. 

Drugs that may affect penicillins include allopurinol, aminoglycosides (parenteral), aspirin, beta blockers, chloramphenicol, erythromycin, ethacrynic acid, furosemide, indomethacin, phenylbutazone, probenecid, sulfonamides, tetracycline, and thiazide diuretics. Drugs that may be affected by penicillins include aminoglycosides (parenteral), anticoagulants, beta blockers, chloramphenicol, cyclosporine, oral contraceptives, erythromycin, heparin, and vecuronium. 

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. 

Allopurinol is used to lower uric acid levels in the treatment of primary gout, as a prophylaxis in myeloproliferative neoplastic disease, for investigational purposes in Lesch-Nyhan syndrome, and as an adjunct with thiazide diuretics or ethambutol (see Chapter 24). Allopurinol acts by inhibiting xanthine oxidase, which converts hypoxanthine into xanthine and in turn becomes oxidized into uric acid. 

The special risk is observed in patients with hepatic or renal impairment. It is not advised to use allopurinol in acute attacks of gout, but it is useful in chronic gout. Excretion of allopurinol and its active metabolite oxypurinol is primarily via the kidneys and therefore the dosage should be reduced if renal function is impaired. The adverse effects have been reported in patients receiving allopurinol with thiazide diuretics, particularly in patients with impaired renal function. The metabolism of azathioprine and mercaptopurine is inhibited by allopurinol and their doses should be reduced to one-quarter to one-third of the usual dose when either of them is given with allopurinol to avoid potentially life-threatening toxicity.27-29... 

Aspirin, salicylates, and thiazide diuretics should not be used with allopurinol. The dose of mercaptopurine should be reduced one-third or one-fourth when used with allopurinol. Acute poisoning of colchicine should be treated with gastric lavage and activated charcoal administration. Supportive maintenance measures for blood pressure and respiration should be provided. Probenecid is used by athletes to inhibit the urinary excretion of banned anabolic steroids.85... 

THIAZIDES ANTIGOUT DRUGS Possible t risk of severe allergic reactions when allopurinol is given with thiazides in the presence of renal impairment Uncertain Caution in co-administering allopurinol with thiazides in the presence of renal insufficiency... 

Allergic interstitial nephritis, caused by penicillins (especially), thiazides, allopurinol, phenytoin, sulphonamides... 

Erectile dysfunction (ED), the inability to achieve or maintain a penile erection sufficient to permit satisfactory sexual intercourse, is estimated to affect over 100 million men worldwide, with a prevalence of 39% in those of 40 years. Its numerous causes include cardiovascular disease, diabetes mellitus and other endocrine disorders, alcohol and substance abuse, and psychological factors (14%). While the evidence is not conclusive, drug therapy is thought to underlie 25% of cases, notably from antidepressants (SSRI and tricyclic), phenothiazines, cypro-terone acetate, fibrates, levodopa, histamine H -receptor blockers, phenytoin, carbamazepine, allopurinol, indomethacin, and possibly adrenoceptor blockers and thiazide diuretics. 

Thiazides enhance the excretion of orotic acid, which is already increased during allopurinol treatment, but the implications for the frequency of adverse effects are not known. 

Adverse reactions to allopurinol, particularly toxic epidermal necrolysis and a hypersensitivity syndrome, are reputed to be more common in patients taking thiazides, but evidence to support this is hard to find (SEDA-11, 198) (SEDA-13,188). 

Allergic interstitial nephritis Penicillins, rifampin, sulfonamides, thiazides, cimetidine.phenytoin, allopurinol, furosemide, NSAIDS, ciprofloxacin, pantoprazole, omeprazole, atazanavir, bevacizumab Rash, fever, eosinophilia, eosinophiluria, pyuria... 

Drug interactions May decrease antihypertensive effects of ACE inhibitors, angiotensin II antagonists. May decrease antihypertensive and diuretic effects of thiazide and loop diuretics May decrease absorption of vitamin B,2 Effects decreased by barbiturates, phenytoin, and rifampin decreases effect of salicylates and vaccines Decreases clearance of beta-lactams Risk for hypersensitivity increased in patients who are on thiazides or ACE inhibitors and allopurinol... 

NSAIDs, glafenin, ASA, fenoprofen, naproxen, phenylbutazone, piroxacam, tolemetin, zomepirac, contrast media, sulfonamides, thiazides, phenytoin, furosemide, allopurinol, cimetidine, omeprazole, phenindione. 

It remains to be established whether the increased incidence of rash in patients receiving concurrent allopurinol and ampicillin should be ascribed to allopurinol or to hyperuricemia. Hypersensitivity reactions have been reported in patients with compromised renal function, especially those who are receiving a combination of allopurinol and a thiazide diuretic. The concomitant administration of allopurinol and theophylline leads to increased accumulation of an active metabolite of theophylline, l-methybcanthine the concentration of theophylline in plasma also may be increased (see Chapter 27). 

Severe allergic reactions to allopurinol have been seen in a few patients with renal impairment who were also taking thiazide diuretics. 

Young JL, Boswell RB, Nies AS. Severe allopurinol h3fpersensitivity. Association with thiazides and prior renal compromise. Arch IntemMed (1974) 134, 553. ... 

Some of the patients were receiving diuretic drugs of the thiazide class, which are known to cause hyperuricemia and hypokalemia. Either or both of these may influence renal function. Therefore in all cases receiving thiazides, special attention was paid to correcting possible hypokalemia and to keeping serum uric acid levels below 5 the dose of Allopurinol. 

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