Hyperuricemia with diuretics

Most diuretics cause hyperuricemia. Increased reabsorption of uric acid (along with other solutes) in the proximal tubule as a consequence of volume depletion is one reason however, diuretics also compete with uric acid for excretory transport mechanisms. There is a small increased risk of acute gout in susceptible subjects (73). In the large outcome trials, about 3-5% of subjects treated with diuretics for hypertension developed clinical gout... 

The most important side effects of the thiazide diuretics, chlorthalidone, furosemide, ethacrynic acid and metolazone are potassium losses with resultant hypokalemia, and hyperuricemia. Hyperuricemia may result in acute attacks of gouty arthritis in individuals with a gouty diathesis. 

Adverse reactions associated with loop diuretics include nausea vomiting diarrhea gastric irritation headache fatigue dizziness thrombocytopenia rash orthostatic hypotension hyperuricemia hyperglycemia electrolyte imbalance (decreased chloride, potassium and sodium) dehydration. 

The issues of whether hyperuricemia is an independent risk factor for cardiovascular disease and the clinical relevance of the rise in serum uric acid caused by diuretic treatment are controversial (SED-14, 660 351). In the Systolic Hypertension in the Elderly Program (SHEP), diuretic-based treatment in 4327 men and women, aged 60 years or more, with isolated systolic hypertension was associated with significant reduction in cardiovascular events (SED-14, 657). Serum uric acid independently... 

The thiazide diuretics are primarily used for most patients with mild or moderate hypertension. Used alone they can lower blood pressure by 10-15 mmHg. In more severe hypertension diuretics are used in combination with other agents. Adverse effects include hypokalemia (lowered serum potassium), impotence, impaired glucose tolerance, hyperlipidemia, and hyperuricemia (elevated uric acid in the blood). 

Adverse effects Thiazide diuretics induce hypokalemia and hyperuricemia in 70% of patients, and hyperglycemia in 10% of patients. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular hypertrophy, ischemic heart disease, or chronic congestive heart failure) and who are concurrently being treated with both thiazide diuretics and digitalis glycosides (see p. 160). Diuretics should be avoided in the treatment of hypertensive diabetics or patients with hyperlipidemia. 

Correct answer = D. Among black patients, diuretic and calcium channel blockers are more effective than ACE inhibitors or p-blockers. Diuretics are effective among the elderly. Thiazide diuretics cause hyperuricemia and can precipitate a gout attack in susceptible individuals. Thiazide diuretics increase LDL cholesterol and may increase the risk of atherosclerosis in patients with hyperlipidemia. Patients with evidence of elevated catecholamines are best treated with p-blockers. Thiazides cannot promote sodium excretion when renal function is severely impaired. The loop diuretics, such as furosemide, are used in patients with impaired renal function. 

Unwanted effects of sulfonamide-type diuretics (a) hypokalemia is a consequence of an increased secretion of K1 in the connecting tubule and the collecting duct because more Na+ becomes available for exchange against K1 (b) hyperglycemia (c) increase in serum urate levels (hyperuricemia), which may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system. 

Diuretic drugs often cause a mild reduction of the plasma potassium concentration hyponatremia may be observed. Hypercalcemia may occur with hemoconcentration, but occasionally the free-ionized and the protein-bound fraction is increased. Thiazides cause hyperglycemia and reduce glucose tolerance, especially in diabetics. Thiazides may cause prerenal azotemia with hyperuricemia as a result of decreased renal blood flow and GFR as a result of reduced blood volume. Thiazides, like other diuretics, by causing hemoconcentration increase the plasma concentration of lipids. Many thiazides induce microsomal enzymes and thus affect lipoprotein concentrations. 

Secondary gout is a result of hyperuricemia attributable to several identifiable causes. Renal retention of uric acid may occur in acute or chronic kidney disease of any type or as a consequence of administration of drugs diuretics, in particular, are implicated in the latter instance. Organic acidemia caused by increased acetoacetic acid in diabetic ketoacidosis or by lactic acidosis may interfere with tubular secretion of urate. Increased nucleic acid turnover and a consequent increase in catabolism of purines may be encountered in rapid proliferation of tumor cells and in massive destruction of tumor cells on therapy with certain chemotherapeutic agents. 

Answer E. In approaching the answer to this question, try to sort out the incorrect statements. Spironolactone does not cause hypokalemia, but hyperkalemia. Although loop diuretics may cause hyperuricemia, there is no connection between elevations of uric add and fainting episodes. When used with ACEIs in the treatment of heart failure, spironolactone is reported to increase survival, but there is no evidence of similar efficacy in patients with HTN. Obviously, statement B is erroneous (never choose never ). Although postural hypotension from the combination of antihypertensive drugs is most likely responsible for the fainting episode in this patient, there could also be alternative explanations ... 

In hypercalcemia, excessive volume depletion, hyponatremia, and hypotension are major risks associated with the use of loop diuretics, and the side effects of hypokalemia, hyperuricemia, and hyperglycemia are always present. Loop diuretics should not be used concurrently with ototoxic aminoglycoside antibiotics (i.e., streptomycin, gentamicin, kanamycin, tobramycin). 

Furosemide metabolic alkalosis hyperuricemia blood dyscrasias rashes lipid changes as with thiazide-type diuretics... 

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). 

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