Furosemide (Lasix) Injection: Indications and Mechanism of Action
Primary Indications
Injectable furosemide is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, renal disease (including nephrotic syndrome), and as adjunctive therapy in acute pulmonary edema, particularly when rapid onset of diuresis is required or when oral administration is impractical. 1
Specific Clinical Scenarios for IV Administration
- Acute pulmonary edema requiring rapid diuresis 1
- Emergency situations where immediate fluid removal is critical 1
- Impaired gastrointestinal absorption or inability to take oral medications 1
- Severe fluid overload in heart failure, cirrhosis, or renal disease when greater diuretic potential is needed 1
Pediatric Indications
- Treatment of edema in pediatric patients associated with the same conditions as adults (heart failure, cirrhosis, renal disease including nephrotic syndrome) 1
Mechanism of Action
Furosemide acts at the luminal surface of the thick ascending limb of the loop of Henle by inhibiting the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2), blocking active reabsorption of chloride and sodium. 2, 3
Detailed Pharmacodynamic Mechanism
- Site of action: Furosemide is delivered to its site of action via active secretion through the nonspecific organic acid pump in the proximal tubule 2
- Luminal activity: The drug must reach the tubular lumen to exert its effect, acting from the urinary side of the epithelium 2
- Concentration-response relationship: Diuretic response correlates with urinary drug concentration and excretion rate, NOT plasma concentration 2
Secondary Physiological Effects
- Renal hemodynamics: May affect renal blood flow and glomerular filtration rate through tubuloglomerular feedback activation and renin release 3
- Systemic vascular effects: Can cause vasodilation through nonspecific NKCC inhibition and changes in venous compliance 3
- Electrolyte handling: Increases excretion of sodium, chloride, potassium, calcium, and magnesium 2
Important Clinical Considerations
Pharmacokinetic Factors Affecting Response
- Bioavailability variability: Oral absorption is highly variable (37-82% in cirrhotic patients), making IV route more reliable in acute settings 4
- Protein binding: Furosemide is highly bound to plasma proteins (almost exclusively albumin), which restricts volume of distribution 2
- Peak effect timing: Peak diuretic effect occurs within 1-1.5 hours after oral administration, faster with IV dosing 5, 2
Common Pitfalls
- Tolerance development: Acute and chronic tolerance occurs due to homeostatic mechanisms, with subsequent doses showing up to 25% less effect than the first dose at the same concentration 5, 2
- Absorption delays: In cirrhosis and heart failure, absorption is significantly slowed independent of edema presence, following a "flip-flop" pharmacokinetic model 4
- Renal function compromise: Furosemide can worsen renal function through tubuloglomerular feedback activation, particularly in patients with pre-existing renal impairment 6, 3
- Electrolyte disturbances: Most common adverse effects are extensions of therapeutic action—volume depletion (4.6%), hypokalemia (3.6%), and other electrolyte disturbances (1.5%) 7
Safety Profile
- Furosemide is relatively safe across a wide range of clinical situations, with serious adverse reactions being uncommon and occurring primarily in seriously ill patients 7
- Life-threatening adverse effects occurred in only 0.6% (14/2,367) of hospitalized patients receiving furosemide 7
- Adverse reaction frequency increases progressively with higher daily doses but does not correlate with total cumulative dose 7