Introduction
Furosemide is a powerful loop diuretic widely used to manage fluid overload conditions such as edema associated with congestive heart failure, liver cirrhosis, and renal dysfunction. It is also utilized in the management of hypertension, particularly in patients with renal impairment or in those who require immediate reduction in fluid retention. Furosemide is available in both oral and intravenous formulations, and its diuretic effects are more potent than thiazide diuretics, making it a key medication in critical care settings.
Pharmacokinetics
Furosemide is rapidly absorbed after oral administration, though its bioavailability can vary from 50% to 70%. When given intravenously, it acts more quickly, with an onset of action within 5 minutes, while oral formulations take 30 to 60 minutes to begin working. The drug reaches peak plasma concentrations in about 1-2 hours after oral administration.
Furosemide is highly protein-bound (approximately 95%), with a volume of distribution of around 0.2 L/kg. It is primarily eliminated via the kidneys, with around 50-80% being excreted unchanged in the urine. The half-life of Furosemide is 1.5 to 2 hours in individuals with normal kidney function, but this can be significantly prolonged in patients with renal insufficiency.
Mechanism of Action
Furosemide acts by inhibiting the Na+/K+/2Cl− cotransporter in the thick ascending limb of the loop of Henle in the nephron. This inhibition prevents the reabsorption of sodium, chloride, and potassium, leading to increased urinary excretion of these ions along with water. The loss of water helps to reduce blood volume, leading to a decrease in blood pressure and alleviation of edema.
By reducing sodium reabsorption, Furosemide also leads to increased excretion of calcium and magnesium. The potent diuretic effect of Furosemide makes it suitable for conditions requiring rapid fluid removal, such as acute pulmonary edema.
Pharmacodynamics
Furosemide causes an increase in the excretion of sodium, potassium, and chloride, leading to a pronounced diuresis. Its effects on diuresis generally last for about 6 hours after oral administration, which is why Furosemide is sometimes referred to as “Lasix” (short for “lasts six hours”).
It reduces preload and afterload in the cardiovascular system by decreasing blood volume and lowering blood pressure. Furosemide can also reduce the vascular resistance in patients with congestive heart failure, making it particularly effective for reducing symptoms related to fluid overload.
Adverse Effects
Electrolyte Imbalances: Furosemide can lead to significant electrolyte imbalances, including hypokalemia (low potassium), hyponatremia (low sodium), hypomagnesemia, and hypocalcemia. These imbalances are more common with long-term use or high doses and require close monitoring of serum electrolyte levels.
Dehydration and Hypotension: Excessive diuresis may result in dehydration, hypotension, and orthostatic hypotension, particularly in older patients or those taking antihypertensive medications.
Ototoxicity: Furosemide has the potential to cause ototoxicity (hearing loss), especially when administered at high doses or intravenously at a fast rate. This hearing loss may be reversible or permanent depending on the duration and dosage.
Hyperglycemia: Furosemide may lead to elevated blood sugar levels, particularly in diabetic patients or those with preexisting hyperglycemia.
Hyperuricemia: Furosemide can increase uric acid levels, potentially leading to gout or worsening of existing gout in predisposed individuals.
Drug Interactions
NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the diuretic and antihypertensive effects of Furosemide by decreasing renal blood flow, especially in patients with compromised kidney function.
Aminoglycosides: Concurrent use of Furosemide with aminoglycoside antibiotics (e.g., Gentamicin) increases the risk of ototoxicity, especially when high doses of both drugs are used.
Antihypertensive Medications: Furosemide can enhance the effects of other antihypertensive medications, leading to excessive lowering of blood pressure.
Digoxin: The hypokalemia caused by Furosemide increases the risk of digoxin toxicity, as low potassium levels sensitize the myocardium to the effects of digoxin.
Corticosteroids: Concurrent use of corticosteroids can exacerbate hypokalemia, requiring careful monitoring of potassium levels.
Dosages
Adults (Edema): The usual initial dose is 20-80 mg orally once daily, with doses adjusted based on the clinical response. Doses may be divided into two daily doses if needed. For intravenous use, the dose ranges from 20 to 40 mg injected over 1-2 minutes, and it can be repeated every 1-2 hours based on response. The maximum daily dose is 600 mg.
Adults (Hypertension): For hypertension, the typical dose is 40 mg twice daily.
Pediatrics: For children, the usual dose is 1-2 mg/kg orally once or twice daily, with a maximum dose of 6 mg/kg/day.
Renal Impairment: In patients with renal impairment, higher doses may be required due to decreased drug clearance, but careful monitoring is essential to avoid toxicity.
Hepatic Impairment: Furosemide should be used cautiously in patients with hepatic impairment, with regular monitoring of fluid balance, electrolytes, and liver function tests.
