Thiazide diuretics hypokalemia with

Early evidence linking thiazide-induced hypokalemia with dysrhythmias and sudden death was indirect and tenuous at best (50,51). One study suggested that diuretics are not responsible for the relation between hjrpokalemia and ventricular fibrillation in acute myocardial infarction (50). Chronic preoperative hypokalemia due to diuretics was not a risk factor for intraoperative dysrhjdhmias (52). Two large studies using 24-hour electrocardiographic monitoring failed to show a relation between diuretic-induced hypokalemia and ventricular dysrhythmias (53,54). 

Usually neither hyperkalemia nor hypokalemia pose a problem for the management of lithium treated patients. However, in lithium-treated subjects given thiazide diuretic, hypokalemia often develops [97]. This is due to the diuretic-induced increase in sodium delivery to the collecting tubule combined with the lithium-induced increase in urine flow. 

Older adults are particularly prone to fluid volume deficit and electrolyte imbalances (see Display 46-1) while taking a diuretic. The older adult is carefully monitored for hypokalemia (when taking the loop or thiazide diuretic and hyperkalemia (with the potassium-sparing diuretics... 

Many drugs can cause hypokalemia (Table 78-5) and it is most commonly seen with use of loop and thiazide diuretics. Other causes of hypokalemia include diarrhea, vomiting, and hypomagnesemia. 

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. 

Captopril, as well as other ACE inhibitors, is indicated in the treatment of hypertension, congestive heart failure, left ventricular dysfunction after a myocardial infarction, and diabetic nephropathy. In the treatment of essential hypertension, captopril is considered first-choice therapy, either alone or in combination with a thiazide diuretic. Decreases in blood pressure are primarily attributed to decreased total peripheral resistance or afterload. An advantage of combining captopril therapy with a conventional thiazide diuretic is that the thiazide-induced hypokalemia is minimized in the presence of ACE inhibition, since there is a marked decrease in angiotensin Il-induced aldosterone release. 

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. 

Sodium removal is the next important step—by dietary salt restriction or a diuretic—especially if edema is present. In mild failure, it is reasonable to start with a thiazide diuretic, switching to more powerful agents as required. Sodium loss causes secondary loss of potassium, which is particularly hazardous if the patient is to be given digitalis. Hypokalemia can be treated with potassium supplementation or through the addition of a potassium-sparing diuretic such as spironolactone. As noted above, spironolactone should probably be considered in all patients with moderate or severe heart failure since it appears to reduce both morbidity and mortality. 

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. 

More recently, it has been shown that hypokalemia and other dose-related adverse metabolic effects of thiazide diuretics increase the risk of sudden death and negate the cardiovascular benefit of blood pressure lowering when high doses these drugs are prescribed (21). Hence, another explanation for the apparent inability of antihypertensive therapy to lower mortality in patients with coronary heart disease is that high thiazide doses were used in many of the trials that were analyzed. As pointed out by Temple (2), this explanation is supported by the results of a trial of antihypertensive therapy in elderly patients with isolated systolic hypertension (22). In this study, only low doses of a thiazide diuretic were prescribed and a 4-mm Hg average decrease in diastolic blood pressure was associated with a 36% reduction in the... 

It has been argued that drug combinations that contain a beta-adrenoceptor antagonist in combination with a thiazide diuretic minimize the hypokalemic effect of the latter however, marked hypokalemia in the absence of primary hyperaldosteronism has been reported in a patient taking Sotazide (a combination of hydrochlorothiazide and the non-selective drug sotalol) (204). The use of a combination formulation of chlortaUdone and atenolol has also produced hypokalemia (205), in one case complicated by ventricular fibrillation after myocardial infarction (206). 

Nifedipine can increase urinary potassium loss in patients treated with thiazide diuretics (17), but it has no effect on adrenaline-induced hypokalemia (18). In the Treatment of Mild Hypertension Study, 4 years of monotherapy with amlodipine maleate caused no change compared with placebo in the serum potassium, uric acid, aspartate transaminase, or creatinine of 114 hypertensive patients (19). 

The use of thiazide diuretics in hepatic cirrhosis is associated with a high incidence of severe hypokalemia, asterixis, and precipitation of encephalopathy (9). 

In cases where sufficient tubulointerstitial damage causing impaired concentrating ability has occurred, amiloride is less effective still, it can be used in combination with a thiazide diuretic to reduce polyuria [2]. Moreover, hypokalemia, a common side effect of thiazides, is not observed with amiloride [26]. Amiloride obviates the need for potassium supplementation, which is required when thiazide diuretics are used to treat polyuria and, in addition, is less likely to cause lithium intoxication. Although both lithium and amiloride interfere with distal urinary acidification. 

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... 

With long-term use hypokalemia due to intestinal potassium loss could occur (Blumenthal, 1998). Thiazide diuretics, corticosteroids, and licorice could exacerbate hypokalemia. The effects of digoxin can be potentiated by hypokalemia. 

There are three diuretics available that impede the outflow of K+ rather than promote it as do the thiazide and loop diuretics. Even though hypokalemia with the potent saluretics can usually be prevented with oral potassium supplements, they can present problems of palatability and are sometimes not reliable in maintaining desirable K+ levels. It may therefore be preferable with certain patients to achieve diuresis without potassium depletion (Fig. 10-17). 

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