Torasemide

Mechanism

Pharmacological Group

Loop diuretic from the sulfonylurea group.

Mechanism of Action

In addition to binding and blocking the NKCC2 cotransporter in the Thick Ascending Branch of Henle, torasemide exerts a unique pleiotropic effect: competitively blocking aldosterone receptors at the renal and myocardial level. This reduces local collagen expression, attenuating myocardial fibrosis in decompensated heart failure, and moderates distal potassium secretion, producing less urinary potassium loss compared to equivalent doses of furosemide.

Pharmacokinetics

Key Pharmacokinetics

• Bioavailability: Excellent, greater than 80-90%, with very low inter-individual and intra-individual variability.
• Protein binding: Extremely high (>99%), bound mainly to plasma albumin.
• Metabolism: 80% metabolized in the liver by the cytochrome P450 system (mainly CYP2C9) to three major metabolites (one of which retains partial diuretic activity).
• Excretion: Only 20% is excreted unchanged through the urine.
• Half-life: 3 to 4 hours. Noticeably longer in patients with congestive heart failure.

Indicators and dose

Clinical Indications

• Chronic heart failure (NYHA Classes II-IV): Demonstrated superiority in reducing rehospitalizations versus furosemide in large-scale observational studies.
• Essential arterial hypertension: At low doses, it acts as an arterial vasodilator as well as a mild diuretic.
• Edema secondary to chronic kidney disease (CKD).

Dosage and Settings

• Heart Failure: Start with 10 mg or 20 mg orally once a day; It can be titrated by doubling the dose up to a maximum of 200 mg/day.
• Hypertension: 2.5 mg to 5 mg per day. At these low doses the net diuretic effect is minimal but it retains its antihypertensive action.
• Renal Failure: No dose adjustment is required since the hepatic elimination half-life remains unchanged in uremia.

Security

Contraindications

Severe anuria; hepatic coma; hypersensitivity to sulfonylureas or sulfonamides.

Adverse Effects (ADR)

• Common: Headache, dizziness, transient elevation of liver enzymes, hypocalcemia, mild-moderate hypokalemia (attenuated by its intrinsic antialdosteronic effect), fatigue.
• Rare: Dry mouth of osmotic origin, late-onset hyperglycemia, transient thrombocytopenia.

Interactions

• CYP2C9 inducers and inhibitors (such as Fluconazole, Amiodarone, Rifampicin): They can drastically alter the plasma clearance rate of torasemide.
• Other diuretics: Massive and potentially lethal diuretic synergy.

Pregnancy and Breastfeeding

FDA Category B. Lower apparent toxicity in animal models compared to furosemide. However, it is preferred to avoid its use unless it is strictly necessary and there are no viable therapeutic alternatives.