Thiazide diuretics toxicity

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. 

The answer is b. (Hardman, pp 703-704J Low K stores due to the effects of thiazide diuretics such as hydrochlorothiazide increase susceptibility to cardiac glycoside toxicity... 

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. 

The toxic effects of digitalis are frequent and may be fatal. Toxicity may result from overdosage, decreased metabolism and excretion, and hypokalemia stemming from the use of thiazide diuretics, diarrhea, and vomiting. Digitalis toxicity has several manifestations ... 

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... 

In an 80-year-old woman a 2-month history of diarrhea, nausea, and abdominal distress attributed to irritable bowel syndrome was ultimately determined to be due to early lithium intoxication (356). Her lithium concentration when she was hospitalized was 1.2 mmol/1, although she had taken no lithium for the previous 10 days. Treatment with a thiazide diuretic contributed to the toxicity. 

Thiazide diuretics predictably reduce renal lithium clearance and increase the risk of toxicity (652). The same may be true of potassium-sparing diuretics, although this is less well established. 

Alkalosis and hypokalaemia (possibly caused by secondary hyperaldosteronism or use of diuretics) shift the dissociation constant towards free, toxic NH3. By contrast, ammonia is considered - in a process resembling a vicious circle - to be a secondary stimulus for aldosterone production. Thiazide diuretics in particular put an overload on the detoxification capacity of the scavenger cells. This is because of an insufficient supply of bicarbonate for carbamoyl phosphate synthetase reaction due to diuretic-induced inhibition of the mitochondrial carboanhydrase. 

A close watch is also being kept on the thiazide diuretics, where through molecular modification vastly more potent diuretics have been created. So far, in my experience, and from what has appeared in the literature, there seems to be a lessening incidence of serious adverse, allergic, and other toxic effects other than those inherent in the drug s action, as the potency is increased and the dose decreased. Since allergy and other toxic effects, except those inherent in the molecule s pharmacological action, are so small in the case of the steroid hormones, no definite trend can be seen in that series of compounds as yet. 

Quinidine and thiazide diuretics can both enhance the toxicity of digitalis. The action of quini-dine is attributed to phtirmacokinetic mechanisms, especially inhibition of its clearance. The plasma concentration of digoxin predictably increases when quinidine is added. The enhancement of digitalis toxicity by thiazides is due to a pharmacodynamic mechanism, namely, the action of these diuretics to reduce extracellular potassium. Sulfasalazine decreases plasma levels of digitalis by interfering with gut absorption of the drug. The answer is (D). 

Concomitant use of diuretic herbs with prescription loop diuretics, thiazide diuretics, osmotic diuretics, and potassium-sparing diuretics may cause excessive fluid loss. Reductions in potassium levels caused by diuretics may increase the toxicity of cardiac glycosides, such as digoxin, and their combination should be avoided (Anon 2010). 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

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