Print Friendly, PDF & Email


Mechanism of Action

  • Furosemide directly Inhibits the Na+/K+/2Cl- cotransporter within the thick ascending limb of the Loop of Henle (responsible for sodium permeability)
  • Approximately 20-25% of filtered NaCl is reabsorbed by Loop of Henle
  • The ascending limb of Loop of Henle is water impermeable and sodium permeable and is key to creating a hypertonic medullary interstitium required for water reabsorption
  • Furosemide disrupts the creation of the counter-current mechanism as sodium is retained within the lumen → therefore, an excessive amount of water is retained in the lumen with sodium and subsequently excreted
  • Potassium loss is accentuated due to increased volume flow through distal tubule and collecting duct
  • Loop diuretics also enhance production of prostaglandins → renal and venous dilation

Dosing and Monitoring

  • Oral dose = 40-1000mg/day
  • IV Dose = 40-200mg / day


Bioavailability (PO): 10-100%, average of 50%

Onset of action: 1-1.5 hours (PO), 5 minutes (IV)

Peak response: 2 hours (PO), 30 minutes (IV)

Duration of action: 4-6 hours (PO), 2 hours (IV)

Plasma half-life: 0.5-1 hours (normal renal function), 9 hours (ESRD)



  • Oral absorption is variable, the average bioavailability is 50% but ranges from 10-100%
  • Furosemide is highly albumin bound (>95%) so only trivial amounts are filtered
  • Enters lumen via active secretion by proximal tubule
  • 50% of furosemide is metabolised by the kidney and 50% of furosemide is excreted unchanged
  • 85% eliminated by kidney


  • The relationship of drug dose and response follows a sigmoid shape; there is a threshold dose for drug response to occur
  • In the case of furosemide, this relationship is patient specific given the variable bioavailability
  • Individuals achieve a ceiling dose at roughly IV 40mg corresponding to a excretion of 20-25% of filtered sodium (200-250mmol) in 3-4 litres of urine.

Clinical Pearls

  • Variable bioavailability of furosemide means that dosing is individual
  • Action of furosemide is between 4-6 hours in total and therefore dosing is sensible during the morning and afternoon to maximise diuresis + reduces likelihood of increased sodium excretion in the evening for patient comfort
  • The plateau of the dose response curve means that there is a little use of above 400mg intravenous dosing per 24 hours
  • Furosemide is primarily eliminated by kidney
  • Roughly 50% of furosemide is absorbed orally; when converting from IV to oral therapy, roughly double IV dosing to achieve same effect


  • Hypertension
    • Initially, increased urinary sodium excretion and reduced plasma volume, extracellular fluid volume and cardiac output → drop in BP
    • Long term: decline in peripheral resistance
      • Furosemide enhances prostaglandin production which has a vasodilatory effect → reduces cardiac preload
  • Oedema
    • Cardiac (HF)
      • Absorption of furosemide slower than normal in those with decompensated heart failure
        • Oedema of gut wall does not result in malabsorption of diuretics but does take longer to absorb
        • Frequent smaller doses may work effectively
      • Any improvement in cardiac function may reduce this delay in absorption
      • Patient may benefit from combination therapy with more distally acting agents
    • Pulmonary oedema
      • IV furosemide → rapid diuresis due to venodilatory effects seen within 15-30 minutes
  • Use in Renal failure
    • In severe renal impairment maximum amount of sodium filtered is 25mmol
    • Therefore, unless severe sodium restriction is instituted fluid balance is hard to achieve
    • Amount of furosemide delivered produces same sigmoid shape response graph but lower ceiling dose

Diuretic Resistance

Acute tolerance

  • After dosing, volume depletion invokes sodium retention to conserve volume
  • As soon as furosemide dissipates from the site of action, the nephron avidly conserves sodium
    • Between doses, this can nullify natriuresis caused by the diuretic → it is therefore important to enforce dietary restrictions +/- administer multiple doses to main net negative sodium balance
    • Acute tolerance can happen particularly when
      • Diuretic response is low
      • Time of negligible drug effect is long
      • Patient ingests sodium during this interval

Chronic tolerance

  • Enhanced resorption in other segments
    • Mechanisms
      • Increased Na+ receptor expression in other segments
      • Hypertrophy of tubular segments
    • Can be combatted with diuretic synergism e.g. thiazides may be used to block compensatory sodium resorption in distal tubule with chronic furosemide therapy
  • Activation of RAAS, SNS, depletion of ECF and exposure to high sodium at distal nephron induces distal nephron hypertrophy
    • Nephron remodelling can be combatted with thiazide diuretics

Adverse Reactions

  • 3 major types
    • Hypovolaemia and electrolyte imbalance
      • Excessive diuresis –> extracellular fluid volume contraction –> contraction alkalosis
    • Hypersensitivity
    • Ototoxicity
      • Reversible

Drug Interactions

  • NSAIDs
    • Increase risk of nephrotoxicity
  • ACEi and ARB
    • Increased risk of nephrotoxicity and antihypertensive effect
  • Antibiotics:
    • Gentamicin – increased risk of ototoxicity
    • Trimethoprim – increased risk of hyponatraemia
  • Digoxin
    • Furosemide induced hypokalaemia increases risk of arrhythmias with digoxin use
  • Warfarin
    • Furosemide can displace warfarin from binding sites on blood proteins
    • Therefore, lower dose of warfarin may be needed with concomitant furosemide therapy


Author: Dr Sai Arathi Parepalli 

Senior Editor: Dr David Williams 


Links to References