Products
Loop diuretics are commercially available as tablets, sustained-release capsules, and injection and infusion preparations. Torasemide and furosemide are the most commonly used in many countries today.
Structure and properties
Available loop diuretics are usually sulfonamide or sulfonylurea derivatives. Representatives without a sulfonamide structure also exist, for example, the phenoxyacetic acid derivative etacrynic acid.
Effects
Loop diuretics (ATC C03CA) have diuretic, antioedematous, and antihypertensive properties. The effects are due to inhibition of Na+/K+/2Cl–-cotransporter (NKCC2) at the ascending thick branch of the loop of Henle in the nephron of the kidney. This results in increased excretion of sodium, potassium, chloride, and water in the urine. The Na+/K+-ATPase at the basolateral membrane provides the concentration gradient required for reabsorption of sodium. In addition, because inhibition of loop diuretics alters the membrane potential, paracellular reabsorption of calcium and magnesium ions is reduced, and these also enter the urine.
Indications
- High blood pressure (hypertension)
- Edema (water retention), for example, as a result of heart failure, kidney disease or as a result of burns.
- Abdominal dropsy (ascites)
Dosage
According to the prescribing information. Loop diuretics are usually taken in the morning because of the diuretic effects, so that patients can empty the bladder during the day. During treatment, laboratory values should be checked regularly because the diuretics have an influence on blood parameters and can, for example, lead to hypokalemia or increase blood glucose levels. In the case of renal insufficiency, unlike other agents, the dose must be greatly increased and not reduced. This is because the site of action of loop diuretics is in the nephron.
Active Agents
- Furosemide (Lasix, generic).
- Torasemide (Torem, generic)
- Piretanide (Trialix + ramipril)
Other active ingredients, not commercially available in many countries:
- Azosemide
- Bumetanide
- Etacrynic acid
Abuse
Loop diuretics can be abused in sports as masking agents, with the aim of disguising the use of doping by increasing excretion. They are included in the doping list and are banned both during and outside of athletic competition.
Contraindications
Contraindications include (selection):
- Hypersensitivity
- Hypotension
- Pregnancy, lactation
- Hypovolemia
- Hyponatremia, hypokalemia
Full precautions can be found in the drug label.
Interactions
Loop diuretics potentiate the effects of other antihypertensive agents. Because of the excretion of electrolytes, they may increase the adverse effects of cardiac glycosides. Other drug interactions occur with antidiabetics, NSAIDs, glucocorticoids, and lithium, among others.
Adverse effects
The most common possible adverse effects include:
- Gastrointestinal discomfort
- Low blood pressure
- Headache, dizziness, fatigue
- Metabolic disorders such as hyperuricemia, hyperglycemia and hyperlipidemia.
- Disturbances of water and electrolyte balance, including low levels of potassium, sodium, chloride, magnesium and calcium.
Loop diuretics have ototoxic effects and can cause hearing impairment and tinnitus.