Torsemide is a potent loop diuretic used primarily to treat conditions associated with fluid overload and hypertension. It is commonly prescribed in the management of congestive heart failure, chronic kidney disease, and liver cirrhosis, where excess fluid retention (edema) is a key concern. Torsemide works by promoting the excretion of sodium, chloride, and water from the body through its action on the loop of Henle in the kidneys.
BRAND NAMES
It is available both as the brand-name medication Demadex and in generic form.
Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.
MECHANISM OF ACTION:
Torsemide promotes the excretion of sodium, chloride, and water by preventing their reabsorption in the ascending loop of Henle and the distal portion of the collecting tubule. This action occurs through inhibition of the Na⁺/K⁺/2Cl⁻ cotransporter, specifically by blocking its chloride-binding site.
PHARMACOKINETICS
Absorption:
Torsemide is efficiently absorbed through the gastrointestinal tract, with peak blood levels typically reached within one hour after oral administration. It is primarily metabolized in the liver by the cytochrome P450 enzyme CYP2C9, which exhibits genetic variability among individuals. The drug is broken down into inactive metabolites, which are then eliminated via the urine.
Distribution:
In healthy adults and in those with mild to moderate renal impairment or congestive heart failure, the volume of distribution of torsemide ranges from 12 to 15 liters. However, in patients with hepatic cirrhosis, this volume is approximately twice as high, indicating increased distribution of the drug in the body.
Metabolism:
Torsemide undergoes extensive metabolism in the liver, with only about 20% of the administered dose excreted unchanged in the urine. Its metabolism is primarily mediated by the hepatic enzymes CYP2C8 and CYP2C9, through processes such as hydroxylation, oxidation, and reduction, resulting in the formation of five metabolites.
Excretion:
Approximately 80% of an administered dose is excreted in the urine, and the remaining portion is eliminated through feces.
About 20% of the dose is excreted unchanged in the urine, while the rest is excreted as inactive metabolites formed in the liver.
The renal clearance of torsemide reflects both glomerular filtration and tubular secretion.
PHARMACODYNAMICS:
Torsemide has demonstrated effectiveness in reducing extracellular fluid volume and lowering blood pressure in hypertensive patients with chronic kidney disease. Additionally, some studies suggest that torasemide may help reduce myocardial fibrosis by decreasing collagen buildup in the heart. This antifibrotic effect is thought to be linked to a reduction in aldosterone levels, which in turn leads to decreased production of procollagen type I carboxy-terminal proteinase—an enzyme that is typically overexpressed in patients with heart failure.
ADMINISTRATION
Torsemide can be administered orally (as a tablet) or intravenously (IV). It is a loop diuretic that helps treat fluid retention (edema) from conditions such as heart failure, kidney disease, and liver cirrhosis, as well as high blood pressure.
DOSAGE AND STRENGTH
Torsemide is a loop diuretic available in oral tablet and intravenous (IV) injection forms. Dosages vary significantly depending on the medical condition being treated, such as high blood pressure or edema caused by heart, kidney, or liver disease.
DRUG INTERACTIONS
Torsemide, a loop diuretic, has several significant drug interactions, primarily affecting blood pressure, electrolyte levels, and renal function. Combining torsemide with certain medications can increase the risk of toxicity or reduce the effectiveness of one or both drugs.
FOOD INTERACTIONS
While torsemide can be taken with or without food, certain dietary changes and substances can impact its effects.
CONTRAINDICATIONS
Absolute contraindications
Hypersensitivity reactions/sulfa allergy
Relative contraindications
Elderly patients, especially if hypotensive
Patients with hepatic coma
Anuric acute renal failure
Electrolyte abnormalities or arrhythmias at baseline
Patients with diabetes, as torsemide can cause hyperglycemia in high-risk individuals.
OVER DOSE
Normal saline may be used for volume replacement.
Dopamine or norepinephrine may be used to treat hypotension.
If a dysrhythmia is suspected to be caused by low potassium or magnesium levels, promptly initiate aggressive electrolyte replacement.
Discontinue treatment if no symptoms are apparent after 6 hours.
TOXICITY
Toxicity typically arises when torsemide is taken with medications that can elevate its serum levels, such as methotrexate and similar drugs. No antidote is available for the treatment of toxicity. In instances of toxicity, close monitoring of kidney function and electrolytes is essential to promptly identify and treat acute kidney injury and severe electrolyte abnormalities.
