FUROSEMIDE

FUROSEMIDE (Lasix)

Furosemide (Lasix) is a potent loop diuretic commonly prescribed for the management of fluid retention (edema) and hypertension. It acts by inhibiting the Na+/K+/2Cl− symporter in the thick ascending limb of the loop of Henle, promoting sodium, chloride, potassium, and water excretion.


Uses

  • Edema: Management of edema associated with heart failure, hepatic cirrhosis, renal disease, and nephrotic syndrome.
  • Hypertension: Treatment of hypertension, particularly in patients with renal impairment or heart failure.
  • Acute Pulmonary Edema: Reduces fluid overload in cases of acute pulmonary edema.
  • Hypercalcemia: Used in conjunction with hydration to manage hypercalcemia by promoting calcium excretion.
  • Hyperkalemia: Promotes potassium excretion in the acute management of hyperkalemia.
  • Ascites: Management of ascites associated with liver cirrhosis.
  • Acute Kidney Injury (AKI): Used to manage fluid overload, though not recommended to prevent or treat AKI.


Dosage and Administration

  • Edema and Heart Failure:

    • Adults: 20-80 mg/day PO or IV. Increase by 20-40 mg every 6-8 hours until the desired effect.
    • Pediatrics: 1 mg/kg/dose (max 6 mg/kg/day).
  • Hypertension:

    • Adults: 40 mg twice daily.
  • Acute Pulmonary Edema:

    • Adults: 40 mg IV. If no response, 80 mg IV after 1 hour.
  • Hypercalcemia:

    • Adults: 80-100 mg IV every 1-2 hours with saline infusion.
  • Hyperkalemia:

    • Adults: 40-80 mg IV as a single dose, in combination with other treatments to promote potassium excretion.
  • Infusion Dose (IV):

    • Adults: 0.1 mg/kg/hour, titrate as needed. Max rate: 4 mg/min to avoid ototoxicity.
    • Pediatrics: Initial continuous infusion rate of 0.05-0.2 mg/kg/hour, titrate as needed based on response.
  • Renal Dosing:

    • In severe renal impairment (GFR < 30 mL/min), higher doses may be needed (up to 1000 mg/day) due to decreased tubular secretion.


Dose Adjustment in Different Diseases

  • Hepatic Impairment: Start with lower doses; monitor fluid and electrolyte balance closely.
  • Renal Impairment: Higher doses may be required due to impaired drug excretion.
  • Heart Failure: Gradual dose titration to avoid hypotension and electrolyte imbalances.


Drug Combinations in Use

  • With ACE Inhibitors: Monitor for hypotension and renal function.
  • With Potassium-Sparing Diuretics: Helps maintain potassium levels.
  • With Digoxin: Monitor potassium levels to avoid digoxin toxicity.
  • With NSAIDs: Reduced efficacy due to renal prostaglandin inhibition.


Presentation or Form

  • Tablets: 20 mg, 40 mg, 80 mg.
  • Injection: 10 mg/mL in 2 mL or 10 mL vials.
  • Oral Solution: 10 mg/mL.


Pharmacokinetics

  • Absorption: Rapidly absorbed after oral administration (bioavailability 50-70%).
  • Distribution: Plasma protein binding ~95%.
  • Metabolism: Minimal hepatic metabolism.
  • Excretion: Primarily excreted unchanged in urine.
  • Half-Life: 0.5-2 hours (increased in renal impairment).


Pharmacodynamics

  • Mechanism of Action: Inhibits the Na+/K+/2Cl− symporter in the thick ascending limb of the loop of Henle, increasing sodium, chloride, potassium, and water excretion.
  • Onset and Duration:
    • Onset: 30-60 minutes (oral); 5 minutes (IV).
    • Duration: 6-8 hours (oral); 2 hours (IV).


Drug Interactions

  • Aminoglycosides: Increased risk of ototoxicity.
  • NSAIDs: May reduce diuretic efficacy.
  • ACE Inhibitors: Can increase the risk of hypotension.
  • Lithium: Increased risk of lithium toxicity due to decreased renal clearance.
  • Antidiabetic Agents: Reduced efficacy of antidiabetic medications.


Comparison with Other Drugs in the Same Category

Drug

Potency

Duration

Key Feature

Common Use

Furosemide

Moderate

6-8 hours

Rapid onset

Edema, hypertension

Bumetanide

High

4-6 hours

More potent than furosemide

Severe edema

Torsemide

High

12-16 hours

Longer duration

Hypertension, heart failure

Ethacrynic Acid

Moderate

6-8 hours

No sulfonamide allergy risk

Edema

Precautions and Special Considerations

  • Elderly: Increased sensitivity to hypotension and electrolyte disturbances; monitor closely.
  • Renal Impairment: Higher doses may be required, but monitor renal function closely.
  • Hepatic Impairment: Monitor for fluid and electrolyte imbalance.
  • Pregnancy: Category C; use only if benefits outweigh risks.
  • Lactation: Excreted in breast milk; use with caution.


Side Effects

  • Common: Hypokalemia, hypotension, dehydration, hyperglycemia, dizziness.
  • Serious: Ototoxicity (especially with rapid IV administration), nephrotoxicity, metabolic alkalosis, hypomagnesemia, hyponatremia.


Recent Updates and Guidelines

  • 2023 ACC/AHA Guidelines: Emphasize the importance of monitoring renal function and electrolytes during therapy.
  • New Formulations: Development of sustained-release formulations for improved compliance.


Facts to Remember

  • Monitor electrolytes (especially potassium, sodium, and magnesium) during therapy.
  • Avoid rapid IV administration to prevent ototoxicity.
  • Adjust doses based on renal function.
  • Be cautious of drug interactions, especially with NSAIDs and aminoglycosides.


References

  • NCBI StatPearls - Furosemide: https://www.ncbi.nlm.nih.gov/books/NBK499921/
  • Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edition.
  • Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition.
  • 2023 ACC/AHA Guidelines on Heart Failure Management.

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