Thiazide diuretics with triamterene

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

The thiazide diuretics (and triamterene) can cause calcium retention by reducing its urinary excretion. This, added to the increased intake of calcium, resulted in excessive calcium levels. Alkalosis (the milk-alkali syndrome, associated with hypercalcaemia, alkalosis, and renal impairment) may also occur in some individuals because the thiazide limits the excretion of bicarbonate. 

Amiloride (Midamor) is used in the treatment of CHF and hypertension and is often used with a thiazide diuretic. Spironolactone and triamterene are also used in tiie treatment of hypertension and edema caused by CHF, cirrhosis, and the nephrotic syndrome Amiloride, spironolactone, and triamterene are also available with hydrochlorothiazide, a thiazide diuretic that enhances tiie antihypertensive and diuretic effects of the drug combination while still conserving potassium. 

C. Although still highly controversial, the initial use of a thiazide diuretic for monotherapy has been recommended by the Joint National Committee on Detection, Evaluation and treatment of High Blood Pressure. Triamterene and Aldactone are rarely used alone and exhibit no antihypertensive activity. A recent study found that the loop diuretics bumetanide and furosemide effectively reduced blood pressure. Serum lipid levels were less affected than with thiazide diuretics or chlorthalidone. However, thiazide diuretics are a more conservative and approved approach for the initial treatment of hypertension that avoid the more dramatic fluid and electrolyte shifts that occur with loop diuretics. 

Drugs that can precipitate lactic acidosis in patients taking metformin include ACE inhibitors, thiazide diuretics, NSAIDs, and drugs such as furosemide, nifedipine, cimetidine, amiloride, triamterene, trimethoprim, and digoxin, which are all secreted in the renal tubules, compete with metformin, and can contribute to increased plasma metformin concentrations (76). 

Potassium-sparing diuretics include amiloride (Midamor) and triamterene (Dyrenium). They are used in the treatment of cirrhosis and congestive heart failure. They may be used in conjunction with thiazide diuretics to offset the potassium loss associated with those medications. 

Many diuretic agents (loop diuretics, thiazides, amiloride, and triamterene) exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (spironolactone). 

Among the diuretics, thiazides are particularly recommended for treatment of hypertension. To avoid undue loss of K combination with triamterene or amiloride is often advantageous. 

Patients with congenital nephrogenic diabetes insipidus are often treated with a combination of a thiazide and a potassium-sparing diuretic, without consensus on the preferred potassium-sparing diuretic. A Japanese adult was systematically studied to determine the renal effects of hydrochlorothiazide plus amiloride and hydrochlorothiazide plus triamterene (1). The combination with amiloride was superior to that with triamterene in preventing excessive urinary potassium loss, hjrpokalemia, and metabolic alkalosis. These results suggest that amiloride is the preferred add-on therapy to hydrochlorothiazide in nephrogenic diabetes insipidus. 

Thiazide diuretics do not stimulate or require prostaglandins to produce their desired effect and they do not directly interact with NSAIDs. The magnitude of increased risk of NSAID-induced AKI with concomitant triamterene cannot be estimated based on sporadic case reports [44]. 

The risk of ACE inhibitor-induced renal impairment in patients with or without renovascular disease can be potentiated by diuretics. " In an analysis of 74 patients who had been treated with captopril or lisinopril, reversible acute renal failure was more coimnon in those who were also treated with a diuretic (furosemide and/or hydrochlorothiazide) than those who were not (11 of 33 patients compared with 1 of 41 patients). Similarly, in a prescription-event monitoring study, enalapril was associated with raised creatinine or urea in 75 patients and it was thought to have contributed to the deterioration in renal function and subsequent deaths in 10 of these patients. However, 9 of these 10 were also receiving loop or thiazide diuretics, sometimes in high doses. Retrospective analysis of a controlled study in patients with hypertensive nephrosclerosis identified 8 of 34 patients who developed reversible renal impairment when treated with enalapril and various other antihypertensives including a diuretic (furosemide or hydrochlorothiazide). In contrast, 23 patients treated with placebo and various other antihypertensives did not develop renal impairment. Subsequently, enalapril was tolerated by 7 of the 8 patients without deterioration in renal function and 6 of these patients later received diuretics. One patient was again treated with enalapril with recurrence of renal impairment, but discontinuation of the diuretics (furosemide, hydrochlorothiazide, and triamterene) led to an improvement in renal function despite the continuation of enalapril. ... 

Retrospective analysis of clinical study data found no evidence that the safety or efficacy of lovastatin was altered by the use of potassium-sparing diuretics (hydrochlorothiazide with triamterene or amiloride), or thiazide diuretics (mostly hydrochlorothiazide). Another retrospective study of 19 patients found that the addition of lovastatin to diuretic treat-... 

Diuretics (Figure 4.8) are an important class of drugs which act on the kidney to increase urine output and thereby reduce the fluid load in the body. They are valuable in the treatment of hypertension and congestive heart failure. There are several modes of action possible which result in different effects on the amount of sodium and potassium ions excreted. The thiazide diuretics are exemplified by furosemide (Hoechst, 1964) which is among the world s top 25 products by sales value, and cyclopenthiazide (Ciba, 1961) which is currently among the top 20 products by prescription number in the UK. Because agents of this type lead to loss of potassium they are commonly prescribed with potassium chloride. Triamterene (Smith Kline and French, 1962) and amiloride (MSD, 1971) are diuretics which do not produce potassium loss. Amiloride and triamterene are commonly used as combinations with hydrochlorthiazide (Ciba, 1959). Spironolactone (Searle, 1962)... 

The answer is c. (Hardman, pp 704-706J Triamterene produces retention of the K ion by inhibiting in the collecting duct the reabsorption of Na, which is accompanied by the excretion of K ions. The loop diuretics furosemide and bumetanide cause as a possible adverse action the development of hypokalemia. In addition, thiazides (e g, hydrochlorothiazide) and the thiazide-related agents (e.g., metolazone) can cause the loss of K ions with the consequences of hypokalemia. Triamterene can be given with a loop diuretic or thiazide to prevent or correct the condition of hypokalemia. 

Strategies are available to overcome diuretic resistance (Table 75-5), a common problem in patients with ARF. Agents from different pharmacologic classes, such as diuretics that work at the distal convoluted tubule (thiazides) or the collecting duct (amiloride, triamterene, spironolactone), may be synergistic when combined with loop diuretics. Metolazone is commonly used because, unlike other thiazides, it produces effective diuresis at GFR less than 20 mL/min. 

In order to correct potassium losses and the consequent diuretic-induced hypokalemia, spironolactone or triamterene can be successfully combined with the thiazide, metolazone, chlorthalidone, furosemide or ethacrynic acid. 

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