Thiazide diuretics hypertensive renal disease

Thiazide diuretics such as chlorothiazide act on the distal tubule, a portion of the tubule that is permeable to sodium. The mechanism of action of these diuretics involves inhibition of NaCl reabsorption by blocking the Na+, CL symporter in the luminal membrane. The thiazide diuretics are only moderately effective due to the location of their site of action. Approximately 90% of the filtered Na+ ions have already been reabsorbed when the filtrate reaches the distal tubule. These drugs may be used for treatment of edema associated with heart, liver, and renal disease. Thiazide diuretics are also widely used for the treatment of hypertension. 

The abihty of metolazone, chlorothalidone, and indapamide to remove edematous liquid from the body is practically identical to that of thiazide diuretics. These drugs are used for relieving edema associated with hepatic, renal, and cardiac diseases, as well as for treating general hypertension either independently, or in combination with other drugs. 

Therapeutic uses Thiazide diuretics decrease blood pressure in both the supine and standing positions postural hypotension is rarely observed, except in elderly, volume-depleted patients. These agents counteract the sodium and water retention observed with other agents used in the treatment of hypertension (for example, hydralazine). Thiazides are therefore useful in combination therapy with a variety of other antihypertensive agents including (3-blockers and ACE inhibitors. Thiazide diuretics are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function (creatinine clearance less than 50 mls/min). Loop diuretics may be required in these patients. 

Diuretics are highly efficient drugs for the treatment of edema associated with congestive heart failure. They are also used to increase the volume of urine excreted by the kidneys [9]. For example, duranide, 81, a dichlorinated benzene disulfonamide, is an oral carbonic anhydrase inhibitor. Duranide reduces intraocular pressure by partially suppressing the secretion of aqueous humor [11]. Diuril, 82, has an antihypertensive activity and is issued to control blood pressure [9]. Edecrin, 83, is an unsaturated ketone derivative of an aryloxyacetic acid. Edecrin is used in the treatment of the edema associated with congestive heart failure, renal disease, and cirrhosis of the liver [11]. Amiloride, 84, is also used as an adjunctive treatment with thiazide diuretics in congestive heart failure hypertension. 

It is a quinazoline-derived nonthiazide diuretic. It is found to be more effective in comparison to the thiazide-like diuretics in the treatment of edema in such patients who have a histoiy of compromised renal function. It is extensively indicated for hypertension, edema accompanying congestive heart failure, renal disease including the nephrotic syndrome and other conditions of retarded renal function. 

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. ... 

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... 

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