Metolazone hypertension

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

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. 

Hypertension therapy suggests wide use of diuretics, including thiazide diuretics, drugs related to them, such as metolazone (21.3.20) and indapamide (21.3.26), furosemide (21.4.11), loop diuretics, as well as potassium sparing diuretics—spironolactone (21.5.8), triamterene (21.5.13), and amyloride (21.5.18). 

Diuretics, specifically the loop diuretics furose-mide or bumetanide, combined with the thiazide like diuretic metolazone are needed in hypertensive urgencies both to lower blood pressure by removing excess volume and to prevent loss of potency from tendency to cause fluid retention. Volume depletion should be watched in patients on diuretics. 

Fluid overload occurs commonly in patients with renal failure, often in the absence of associated heart disease. If salt and water intake is not controlled in the patient who is oliguric or anaemic, plasma volume and symptoms of congestive heart failure ensue. Hypertension and coronary heart disease with increasing age contributes to the congestive heart failure. Diuretics like loop-diuretics or metolazone may be of value. Digitalis should be used with caution in patients on dialysis as cardiac arrhythmias may ensue in patients receiving dialysis in the presence of hypokalemia. 

A 78-year-old man became short of breath. He had been taking rosiglitazone 8 mg/day for 6 months. He had renal insufficiency, atrial fibrillation, hypertension, and congestive heart failure, with pitting edema and bilateral pleural effusions. He was refractory to intravenous furosemide and metolazone. Withdrawal of rosiglitazone and administration of bumetanide gave a net fluid output of 9.5 litres and the edema resolved. 

Uses of indapamide inciude the treatment of essentiai hypertension and edema resulting from congestive heart failure. Like metolazone. indapamide is an effective diuretic drug when GFR faiis beiow 40 mL/min. The duration of action is approximately 24 hours, with the normal oral adult dosage starting at 2.5 mg given each morning. The dose may be increased to 5.0 mg/day, but doses beyond this ievei do not appear to provide additional results. Effects on urine content and side effects are similar to effects induced by thiazide diuretics. 

A 39-year-old man taking ciclosporin, whose second kidney transplant functioned subnormally, and who required treatment for hypertension with atenolol and minoxidil, developed ankle oedema, which was resistant to furosemide, despite doses of up to 750 mg daily. When metolazone 2.5 mg daily was added for 2 weeks his serum creatinine levels more than doubled, from 193 to 449 micromol/L. When metolazone was stopped the creatinine levels fell again. Ciclosporin serum levels were unchanged and neither graft rejection nor hypovolaemia occurred. ... 

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