Hydrochlorothiazide/spironolactone Disease Interactions

Acidosis alters the ratio of extracellular to intracellular potassium and may commonly lead to rapid increases in serum potassium levels. Conversely, high serum potassium concentrations may potentiate acidosis. Because of their hyperkalemic effects, therapy with potassium-sparing diuretics should be avoided in patients with metabolic or respiratory acidosis. These agents should be used cautiously in patients in whom acidosis may occur, such as patients with cardiopulmonary disease, severe respiratory disease, or poorly controlled diabetes. Acid-base balance and serum potassium levels should be monitored at regular intervals.

Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Patients with diabetes mellitus, with or without nephropathy, may be particularly susceptible to the hyperkalemic effect of these drugs due to a defect in the renin-angiotensin-aldosterone axis. Therapy with potassium-sparing diuretics should be avoided, if possible, in patients with diabetes, especially uncontrolled or insulin-dependent diabetes mellitus. If these drugs are used, serum potassium levels and renal function should be monitored at regular intervals. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

All diuretics may cause or aggravate fluid and electrolyte disturbances. Potassium-sparing diuretics may cause hyperkalemia and, infrequently, hyponatremia. The latter generally occurs when these agents are combined with other diuretics such as thiazides or used in markedly edematous patients with restricted sodium intake. Therapy with potassium-sparing diuretics should be administered cautiously in patients with or predisposed to electrolyte abnormalities. Electrolyte imbalances should be corrected prior to initiating therapy, and serum electrolyte concentrations should be monitored periodically and maintained at normal ranges during therapy. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

The use of potassium-sparing diuretics is contraindicated in the presence of elevated serum potassium concentrations (> 5.5 mEq/L). Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Careful monitoring of serum potassium levels is necessary in all patients treated with potassium-sparing diuretics, especially during initiation of therapy, after dosage adjustment, and during illness that could alter renal function. The diuretic should be withdrawn immediately if hyperkalemia develops, and measures should be initiated to lower serum potassium if it exceeds 6.5 mEq/L. The combined use of a potassium-sparing diuretic with a kaliuretic diuretic (e.g., thiazides) may decrease the risk of hyperkalemia.

Rapid alterations in fluid and electrolyte balance may precipitate hepatic coma in patients with liver disease. Hepatic encephalopathy has been associated with the use of diuretics, most frequently thiazides but also some potassium-sparing diuretics. Therapy with all diuretics should be administered cautiously in patients with severely impaired hepatic function. These patients should be monitored carefully for signs and symptoms of hepatic encephalopathy such as tremors, confusion, increased jaundice, and coma. Since spironolactone and triamterene are primarily metabolized by the liver, reduced dosages of these drugs may also be necessary in severe hepatic impairment.

The use of potassium-sparing diuretics is contraindicated in patients with anuria, acute or progressive renal insufficiency, or diabetic nephropathy. Potassium-sparing diuretics can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Patients with impaired renal function may be particularly susceptible to the hyperkalemic effect of these drugs. Therapy with potassium-sparing diuretics should be administered cautiously in patients with evidence of renal function impairment (BUN > 30 mg/dL or serum creatinine > 1.5 mg/dL). If these drugs are used, serum potassium levels and renal function should be monitored at regular intervals. Determination of serum electrolytes is especially important during initiation of therapy, after a dosage adjustment, and during illness that could alter renal function.

The use of thiazide diuretics is contraindicated in patients with anuria.

The use of thiazide diuretics is commonly associated with loss of electrolytes, most significantly potassium but also sodium, chloride, bicarbonate, and magnesium. The loss of other electrolytes such as phosphate, bromide and iodide is usually slight. Potassium and magnesium depletion may lead to cardiac arrhythmias and cardiac arrest. Other electrolyte-related complications include metabolic alkalosis and hyponatremia, which are rarely life-threatening. Therapy with thiazide diuretics should be administered cautiously in patients with or predisposed to fluid and electrolyte depletion, including patients with primary or secondary aldosteronism (may have low potassium levels); those with severe or prolonged diarrhea or vomiting; and those with poor nutritional status. Fluid and electrolyte abnormalities should be corrected prior to initiating therapy, and blood pressure as well as serum electrolyte concentrations monitored periodically and maintained at normal ranges during therapy. Patients should be advised to immediately report signs and symptoms of fluid or electrolyte imbalance, including dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Digitalized patients and patients with a history of ventricular arrhythmias should be monitored carefully, since development of hypokalemia may be particularly dangerous in these patients. The risk of hypokalemia may be minimized by slow diuresis, a lower thiazide dosage, potassium supplementation, or combined use with a potassium-sparing diuretic.

Patients with severe liver disease or cirrhosis are very susceptible to thiazide-induced hypokalemic hypochloremic alkalosis. Blood ammonia concentrations may be further increased in patients with previously elevated concentrations. Hepatic encephalopathy and death have occurred secondary to the electrolyte alterations accompanying diuretic use. Therapy with thiazide diuretics should be administered cautiously in patients with impaired hepatic function or progressive liver disease, and discontinued promptly if signs of impending hepatic coma appear (e.g., tremors, confusion, and increased jaundice).

The use of thiazide diuretics has been reported to possibly exacerbate or activate systemic lupus erythematosus. Reported cases have generally been associated with chlorothiazide and hydrochlorothiazide. Therapy with thiazide diuretics should be administered cautiously in patients with a history or risk of SLE.

Thiazide diuretics may be ineffective when the glomerular filtration rate is low (GFR < 25 mL/min) because they are not expected to be filtered into the renal tubule, their site of action. In addition, thiazide diuretics decrease the GFR and may precipitate azotemia in renal disease. Cumulative effects may also develop because most of these drugs are excreted unchanged in the urine by glomerular filtration and active tubular secretion. Therapy with thiazide diuretics should be administered cautiously at reduced dosages in patients with renal impairment. If renal function becomes progressively worse, as indicated by rising BUN or serum creatinine levels, an interruption or discontinuation of thiazide therapy should be considered.

Potassium-sparing diuretics have been reported to elevate serum uric acid levels. Therapy with these agents should be administered cautiously in patients with a history of gout.

Thiazide diuretics should be used with caution in patients with history of bronchial asthma as sensitivity reactions may occur.

Thiazide diuretics may cause hyperglycemia and glycosuria in patients with diabetes. They may also precipitate diabetes in prediabetic patients. These effects are usually reversible following discontinuation of the drugs. Therapy with thiazide diuretics should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during thiazide therapy, and their antidiabetic regimen adjusted accordingly.

Thiazide diuretics may increase serum triglyceride and cholesterol levels, primarily LDL and VLDL. Whether these effects are dose-related and sustained during chronic therapy are unknown. Patients with preexisting hyperlipidemia may require closer monitoring during thiazide therapy, and adjustments made accordingly in their lipid-lowering regimen

Urinary calcium excretion is decreased by thiazide diuretics during chronic administration. Pathologic changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been reported during prolonged therapy. However, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Clinicians should be cognizant of these effects when prescribing or administering thiazide therapy to patients with hyperparathyroidism. These drugs should be discontinued before carrying out tests for parathyroid function.

Thiazide diuretics decrease the rate of uric acid excretion. Hyperuricemia occurs frequently but is usually asymptomatic and rarely leads to clinical gout except in patients with a history of gout or chronic renal failure. Therapy with thiazide diuretics should be administered cautiously in such patients.

Thiazide diuretics may decrease serum PBI (protein-bound iodine) levels without associated thyroid disturbance. Clinicians should be cognizant of this effect when prescribing or administering thiazide therapy to patients with thyroid disorders.