indication

For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.

pharmacology

Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.

mechanism of action

The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.

toxicity

Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.

biotransformation

Not substantially metabolized. 70-95% is excreted unchanged in urine via glomerular filtration and active tubular secretion. Undergoes enterohepatic recycling.

absorption

Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.

half life

Approximately 14 hours.

route of elimination

Most of the drug is excreted in the unconverted form in the urine.

drug interactions

Deslanoside: Possible electrolyte variations and arrhythmias

Digitoxin: Possible electrolyte variations and arrhythmias

Digoxin: Possible electrolyte variations and arrhythmias

Dofetilide: Increased risk of cardiotoxicity and arrhythmias

Lithium: The thiazide diuretic, metolazone, may increase serum levels of lithium.

Tenoxicam: Tenoxicam may antagonize the blood pressure lowering effect of Metolazone. Monitor for changes in the therapeutic effect of Metolazone if Tenoxicam is initiated, discontinued or dose changed.

Trandolapril: The thiazide diuretic, Metolazone, may increase the hypotensive effect of Trandolapril. Metolazone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.