Thiazide diuretics hypercalcemia with

Calcium is contraindicated in patients with hypercalcemia or ventricular fibrillation and in patients taking digitalis. Calcium is used cautiously in patients with cardiac disease. Hypercalcemia may occur when calcium is administered with the thiazide diuretics. When calcium is administered with atenolol there is a decrease in Hie effect of atenolol, possibly resulting in decreased beta blockade. There is an increased risk of digitalis toxicity when digitalis preparations are administered with calcium. The clinical effect of verapamil may be decreased when the drug is administered with calcium. Concurrent ingestion of spinach or cereal may decrease file absorption of calcium supplements. 

Might antagonize verapamil Might induce hypercalcemia with thiazide diuretics Fiber laxatives (variable), oxalates, phytates, and sulfates can decrease calcium absorption if given concomitantiy Phenytoin, barbiturates, carbamazepine, rifampin increase vitamin D metabolism... 

Cholestyramine, colestipol, orlistat, or mineral oil decrease vitamin D absorption Might induce hypercalcemia with thiazide diuretics in hypoparathyroid patients... 

Therapy with hydrochlorothiazide, up to 50 mg twice daily, or chlorthalidone, 50-100 mg daily, is recommended. Loop diuretics such as furosemide and ethacrynic acid should not be used because they increase urinary calcium excretion. The major toxicity of thiazide diuretics, besides hypokalemia, hypomagnesemia, and hyperglycemia, is hypercalcemia. This is seldom more than a biochemical observation unless the patient has a disease such as hyperparathyroidism in which bone turnover is accelerated. Accordingly, one should screen patients for such disorders before starting thiazide therapy and monitor serum and urine calcium when therapy has begun. 

Kawaguchi M, Mitsuhashi Y, Kondo S. Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24 OH2D3) combined with thiazide diuretics in a case of psoriasis. J Dermatol 2(X)3 30 801 —4. 

Symptomatic reversible hypercalcemia was seen in two elderly patients taking apparently safe amounts of vitamin D and thiazide diuretics. Their unusual susceptibility to this effect resulted from an interaction with calcium carbonate which had been taken simultaneously. In the presence of other predisposing factors, hypercalcemia can develop in patients taking calcium carbonate 5-10 g/day (72,73). 

Since unresolved nephrocalcinosis may lead to residual abnormalities in the kidney including microscopic hematuria, hypercalcemia, and impaired tubular function [100,104,105], renal ultrasonography within a few months of initiating loop diuretics may be warranted [100 104]. If long-term diuretic therapy is needed, a thiazide diuretic alone or in combination with furosemide may reduce the risk of renal calcifications by decreasing urinary calcium and oxalate excretion [100,102,104,107,108]. However, two studies of premature infants failed to show a reduction in either urinary oxalate or calcium excretion when thiazides were added to furosemide therapy [107,109]. 

Loop diuretics may be used fur (he treatment of certain nnncdemalous disorders. Symplomatie hypercalcemia may be (tcalcd with a loop diuretic, provided no reduction in pksma volume occurs and the fluid used for replacemcnl of ihc urinary losses is calcium free. In addition, furosemide has been used for (he treatment nf hypertensinn. Some inve.s-ligators believe, however, (hat because of its relatively short dunUion of action. i( may be le.ss effective than (he thiazide or thiazide-like diuretics. It has been suggested (hat furo.se-mide be reserved for hypertensive patients with fluid retention refractory (n thiazides or patients with impaired renal function. ... 

Hypercalcemia and hypokalemia should be corrected and medications that may contribute to the pathogenesis should be discontinued. One key goal in treating nephrogenic DI is to induce a mild ECFVd (1 to 1.5 L) with a thiazide diuretic and dietary sodium restriction (85 mEq Na+ or 2,000 mg sodium chloride per day), which... 

Diuretics are used widely for the treatment of hypertension see Chapter 32), and loop diuretics appear to lower blood pressure as effectively as Na+-CL symporter inhibitors e.g., thiazides and thiazide-hke diuretics) while causing smaller perturbations in the Upid profile. However, the short elimination half-lives of loop diuretics render them less useful for hypertension than thiazide-type diuretics. The edema of nephrotic syndrome often is refractory to other classes of diuretics, and loop diuretics often are the only drugs capable of reducing the massive edema associated with this disease. Loop diuretics also are employed in the treatment of edema and ascites of hepatic cirrhosis however, care must be taken not to induce encephalopathy or hepatorenal syndrome. In patients with a drug overdose, loop diuretics can be used to induce a forced diuresis to facilitate more rapid renal elimination of the offending drug. Loop diuretics, combined with isotonic saline administration to prevent volume depletion, are used to treat hypercalcemia. Loop diuretics interfere with the kidney s capacity to produce a concentrated urine. Consequently, loop diuretics combined with hypertonic saline are useful for the treatment of hfe-threatening hyponatremia. Loop diuretics also are used to treat edema associated with chronic renal insufficiency. Most patients with ARE receive... 

ADVERSE EFFECTS AND PRECAUTIONS Adverse effects of diuretics see Chapter 28) determine tolerance and adherence. Erectile dysfunction is a troublesome adverse effect of thiazide diuretics physicians should inquire specifically regarding its occurrence. Albeit uncommon, gout may be a consequence of the hyperuricemia induced by these diuretics. Either of these adverse effects is reason to consider alternative therapies. Hydrochlorothiazide may cause rapidly developing, severe hyponatremia in some patients. Thiazides inhibit renal Ca " excretion, occasionally leading to hypercalcemia although generally mUd, this can be more severe in patients subject to hypercalcemia, such as those with primary hyperparathyroidism. The thiazide-induced decreased Ca excretion may be used therapeutically in patients with osteoporosis or hypercalciuiia. 

There is a strong correlation between hypercalcemia and hypertension (9,10). Black males may have a higher risk for this side effect (H). Caution must be used when treating hypercalcemia-induced hypertension since thiazide diuretics can transiently produce hypercalcemia. With long-standing hypercalcemia, calcium may be deposited on the cardiac valves and coronary arteries (12.). Another cardiovascular side effect of hypercalcemia is lengthening of the ECG OT interval. 

Following initiation of anti hypertensive therapy with thiazide diuretics, transient hypercalcemia has been seen in over one-third of patients (87). Two percent of patients receiving long-term thiazide diuretics administration had persistent hypercalcemia (68). In the elderly (especially women), combined administration of thiazides with vitamin 0 supplements (for osteoporosis) can have synergistic effects on the elevation of serum calcium levels resulting in severe hypercalcemia (69). Similarly, if the patient is predisposed to hypercalcemia (IHPT, 2HPT or immobilization), thiazides can precipitate significant and sustained hypercalcemia (68,70). 

D. Hyperglycemia, hypercalcemia, and hyperuricemia may occur, especially with thiazide diuretics. 

Because Henle s loop is indirectly responsible for water reabsorption by the downstream collecting duct, loop diuretics can cause severe dehydration. Hyponatremia is less common than with the thiazides (see below), but patients who increase water intake in response to hypovolemia-induced thirst can become severely hyponatremic with loop agents. Loop agents are sometimes used for their calciuric effect, but hypercalcemia can occur in volume-depleted patients who have another—previously occult—cause for... 

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. 

In patients with hypercalcemia, treatment with a loop diuretic plus saline promotes calcium excretion and helps lower serum calcium. In patients with intact regulatory function, increases in calcium resorption promoted by thiazides have minor impact on serum calcium due to buffering in bone and gut. However, thiazides can unmask hypercalcemia that occurs in diseases that disrupt normal calcium regulation (eg, hyperparathyroidism, sarcoidosis, carcinoma). 

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