Furosemide

Usage

Furosemide is prescribed for conditions involving fluid retention (edema) due to heart failure, liver cirrhosis, or kidney disease. It’s also used to treat hypertension. Its pharmacological classification is a loop diuretic. Furosemide inhibits sodium and chloride reabsorption in the ascending loop of Henle, leading to increased water excretion.

Alternate Names

Furosemide is also known as Frusemide internationally. Brand names include Lasix, Furoscix, and Diurin.

How It Works

Pharmacodynamics: Furosemide acts primarily on the ascending loop of Henle in the kidney, inhibiting the sodium-potassium-chloride cotransporter (NKCC2). This action blocks reabsorption of these ions, leading to increased excretion of water, sodium, chloride, potassium, magnesium, and calcium. The resulting diuresis reduces blood volume, decreasing venous return and preload to the heart, thus lowering blood pressure.

Pharmacokinetics:

• Absorption: Furosemide is well-absorbed orally. Intravenous administration results in rapid onset of action.
• Metabolism: Primarily metabolized in the liver, with some renal excretion of unchanged drug.
• Elimination: Excreted predominantly through the kidneys, with a smaller portion eliminated through bile and feces.

Mode of Action: Furosemide directly inhibits NKCC2, a symporter that transports sodium, potassium, and chloride ions across the apical membrane of epithelial cells in the thick ascending limb of the loop of Henle. This inhibition disrupts electrolyte balance and reduces the osmotic gradient necessary for water reabsorption, causing increased urine production.

Elimination Pathways: Renal excretion is the primary elimination pathway. A portion of furosemide is metabolized by the liver, with metabolites also excreted in urine and feces.

Dosage

Standard Dosage

Adults:

• Oral: Initial: 20-80 mg once daily. May be increased by 20-40 mg every 6-8 hours until desired effect is achieved. Maximum: 600 mg/day. Maintenance: Administer the effective dose once or twice daily.
• IV/IM: Initial: 20-40 mg slowly over 1-2 minutes. May repeat with the same dose or increase by 20 mg no sooner than 2 hours after the previous dose, until desired effect is achieved. Maximum: 200mg/dose
• Continuous Infusion: Initial: 0.1mg/kg IV bolus followed by 0.1mg/kg/hour. Double every 2 hours prn. Maximum 0.4mg/kg/hr.

Children:

• Oral: Initial: 2 mg/kg once daily. May increase by 1-2 mg/kg every 6-8 hours if needed. Maximum: 6 mg/kg/day.
• IV/IM: 0.5-2 mg/kg every 4-24 hours. Maximum single dose 6 mg/kg. Most often unnecessary to exceed 4mg/kg/dose.
• Continuous Infusion: 0.05-0.4mg/kg/hr, titrate to clinical effect.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously.
• Patients with Renal Impairment: Lower doses may be required, especially in severe renal failure. In cases where GFR < 20ml/min, start with 250mg IV and can increase in increments of 250mg every 4-6 hours up to maximum daily dose of 2000mg.
• Patients with Hepatic Dysfunction: Close monitoring is recommended, especially with high doses.
• Patients with Comorbid Conditions: Careful consideration is required for patients with diabetes, cardiovascular diseases, and other conditions, adjusting the dose based on individual needs and monitoring closely for adverse effects.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Initial IV bolus of 40-80 mg (or double the patient’s usual daily oral dose if applicable) followed by continuous infusion titrated according to patient response.
• Emergency Situations (e.g., Acute Pulmonary Edema/Hypertensive crisis/Increased Intracranial Pressure): 40 mg IV over 1-2 minutes; may increase to 80 mg if no adequate response within 1 hour (maximum: 160-200 mg/dose). Hyperkalemia in ACLS: 40-80 mg IV. Hypermagnesemia in ACLS: 20-40 mg IV every 3-4 hours PRN.

Dosage Adjustments:

Adjustments are made based on patient response, renal function, hepatic function, and other comorbid conditions.

Side Effects

Common Side Effects:

Dizziness, lightheadedness, headache, blurred vision, orthostatic hypotension, dehydration, electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia, hypomagnesemia, hypocalcemia), hyperuricemia, hyperglycemia, gastrointestinal upset (nausea, vomiting, diarrhea, constipation).

Rare but Serious Side Effects:

Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis, hepatic encephalopathy, aplastic anemia, thrombocytopenia, jaundice, hearing loss, kidney failure.

Long-Term Effects:

Chronic electrolyte disturbances, ototoxicity (hearing loss), kidney damage.

Adverse Drug Reactions (ADR):

Severe hypotension, anaphylaxis, agranulocytosis, arrhythmias

Contraindications

• Anuria
• Hypersensitivity to furosemide or sulfonamides
• Severe electrolyte depletion (hypokalemia, hyponatremia, hypovolemia).

Drug Interactions

Aminoglycosides (increased risk of ototoxicity), digoxin (increased risk of digoxin toxicity due to hypokalemia), lithium (increased lithium levels), NSAIDs (reduced diuretic effect), corticosteroids (increased potassium loss), antihypertensives (additive hypotensive effect), sucralfate (reduced furosemide absorption).

Pregnancy and Breastfeeding

Furosemide is generally avoided during pregnancy and breastfeeding due to potential risks to the fetus/infant. If deemed absolutely necessary, its use should be under close medical supervision and only if benefits clearly outweigh the risks.

Drug Profile Summary

• Mechanism of Action: Inhibits NKCC2 in the thick ascending limb of the loop of Henle, promoting increased water and electrolyte excretion.
• Side Effects: Dizziness, electrolyte imbalances, gastrointestinal upset, hypotension; rarely, severe skin reactions, ototoxicity, kidney damage.
• Contraindications: Anuria, hypersensitivity to sulfonamides, severe electrolyte depletion.
• Drug Interactions: Aminoglycosides, digoxin, lithium, NSAIDs, corticosteroids, antihypertensives.
• Pregnancy & Breastfeeding: Generally avoided.
• Dosage: See detailed section above.
• Monitoring Parameters: Blood pressure, electrolytes (sodium, potassium, chloride, magnesium, calcium), renal function (BUN, creatinine), uric acid, blood glucose.

Popular Combinations

Furosemide is often combined with potassium-sparing diuretics (e.g., spironolactone, amiloride) to prevent hypokalemia and enhance the diuretic effect. In cases of ascites due to liver cirrhosis, the combination of furosemide and spironolactone is commonly used.

Precautions

• Monitor electrolytes, renal function, and blood glucose during therapy.
• Correct hypokalemia before initiating furosemide.
• Use cautiously in patients with diabetes, gout, and cardiovascular disease.
• Avoid rapid intravenous administration to prevent ototoxicity.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Furosemide?

A: See detailed dosage section above, as dosing varies significantly by patient age, condition, and administration route.

Q2: How does furosemide differ from thiazide diuretics?

A: Furosemide is a loop diuretic, acting on the loop of Henle, while thiazides act on the distal convoluted tubule. Furosemide is more potent and effective even in patients with impaired renal function.

Q3: What are the most serious side effects of furosemide?

A: Severe hypotension, electrolyte disturbances (particularly hypokalemia), ototoxicity (hearing loss, tinnitus), kidney damage, and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Q4: Can furosemide be used in pregnant women?

A: Furosemide should generally be avoided during pregnancy and breastfeeding due to potential risks to the developing fetus/infant. Use only if clearly necessary and under strict medical supervision.

Q5: How should furosemide be administered intravenously?

A: Intravenous furosemide should be administered slowly over 1-2 minutes for bolus doses. Rapid administration can cause ototoxicity. For continuous infusions, use appropriate dilution and infusion pumps.

Q6: What are the key drug interactions to consider with furosemide?

A: Significant interactions occur with aminoglycosides (increased ototoxicity risk), digoxin (hypokalemia-induced digoxin toxicity), lithium (increased lithium levels), NSAIDs (reduced diuretic effect), and antihypertensives (additive hypotensive effects).

Q7: What are the monitoring parameters for patients on furosemide?

A: Monitor blood pressure, electrolytes (sodium, potassium, chloride, magnesium, calcium), renal function (BUN, creatinine), uric acid levels, and blood glucose regularly.

Q8: How does furosemide affect electrolyte levels?

A: Furosemide can cause hypokalemia, hyponatremia, hypochloremia, hypomagnesemia, and hypocalcemia. It can also cause hyperuricemia and hyperglycemia.

Q9: Can furosemide be used in patients with renal impairment?

A: Yes, but the dosage may need to be adjusted based on the degree of renal impairment. Close monitoring of renal function is essential. Furosemide remains effective even in patients with reduced GFR, unlike thiazide diuretics.