Introduction

Loop diuretics play a vital role in the management of various conditions associated with fluid retention and volume overload. Their powerful diuretic action, achieved through inhibition of the Na⁺/K⁺/2Cl⁻ cotransporter in the loop of Henle, makes them highly effective in reducing excess fluid. However, due to their strong effects, careful monitoring is essential to prevent complications such as electrolyte disturbances and dehydration. When used appropriately, loop diuretics are valuable tools in both acute and chronic clinical settings.

History

1957: The first loop diuretic, ethacrynic acid, was discovered. It does not contain a sulfa group.

1962: Furosemide (Lasix) was introduced and became the most widely used loop diuretic due to its high potency.

Later, bumetanide and torsemide were developed — both more potent and with longer duration of action.

Loop diuretics became essential in treating heart failure, liver disease, and kidney disorders.

Today, they are also used in combination with other diuretics for diuretic resistance.

Mechanism of action

Examples of Medication

Piretanide

Bumetanide

Torsemide

Furosemide

Ethacrynic Acid

Indications

Loop diuretics are primarily indicated for treating conditions involving fluid overload and edema, including:

Edema due to congestive heart failure, chronic kidney disease, nephrotic syndrome, or liver cirrhosis

Pulmonary edema

Hypertension, especially in patients with impaired kidney function

Hyperkalemia (high potassium levels)

Cerebral edema (in combination with other agents)

They work by inhibiting sodium and water reabsorption in the thick ascending limb of the loop of Henle, promoting diuresis and reducing fluid retention.

Side effects

1. Hypokalemia – low potassium levels.

2. Hyponatremia – low sodium levels.

3. Dehydration – due to excessive fluid loss.

4. Hypotension – low blood pressure.

5. Metabolic alkalosis – due to increased excretion of hydrogen ions.

6. Hyperuricemia – can lead to gout.

7. Ototoxicity – hearing loss or tinnitus, especially with high doses or rapid IV administration.

8. Hypomagnesemia – low magnesium levels.

9. Hyperglycemia – can impair glucose tolerance.

10. Increased LDL and triglycerides – may affect lipid profile.

precautions and contraindications

Precautions:

Careful dosing is essential to avoid excessive diuresis, which can cause dehydration and serious electrolyte imbalances such as hyponatremia, hypokalemia, hypochloremia, hypomagnesemia, and metabolic alkalosis, potentially leading to cardiac arrhythmias.

Regular monitoring of kidney function, electrolytes, and fluid status is necessary during treatment.

Ototoxicity risk increases with high doses, renal impairment, or concurrent use of aminoglycosides; ethacrynic acid has a higher ototoxic potential than others.

Use caution in patients with sulfonamide allergy; ethacrynic acid may be safer in these cases.

Patients with liver disease or hepatic coma require caution as electrolyte disturbances may precipitate hepatic encephalopathy.

Diabetic patients should be monitored for hyperglycemia.

Avoid excessive salt intake, and do not use potassium-containing salt substitutes without medical advice.

Digoxin co-administration increases risk of toxicity due to electrolyte disturbances.

Contraindications:

Anuria (inability to urinate).

Known hypersensitivity to loop diuretics (furosemide, bumetanide, torsemide) or sulfonamides (except ethacrynic acid).

Hepatic coma or severe electrolyte depletion.

Monographs

Mohamed Mostafa Elmessiry.pdf