Pharm 101: Furosemide

Class

Diuretic

Pharmacodynamics
  • Two mechanisms
  • Inhibits Na/K/2Cl pump in thick ascending limb of Loop of Henle
    • Decreases NaCl reabsorption
    • Decreases lumen positive potential from potassium recycling, which increases Magnesium and Calcium excretion
  • Increases COX-2 and therefore prostaglandins
    • Increases renal blood flow
    • Subsequent increased urine output decreases pulmonary congestion and decreases left ventricular filling pressure in congestive cardiac failure
Pharmacokinetics
  • Absorption:
    • Rapid absorption
    • Bioavailability 50%
  • Distribution:
    • Peak effect at 30 mins IV or 1 hour PO
    • 95% protein bound
  • Metabolism/elimination:
    • Urinary excretion of mostly unchanged drug
    • Half-life normally 1.5-2 hours, depends on renal function
    • Duration of action 2-3 hours
Clinical uses
  • Acute pulmonary oedema and other oedematous conditions
  • Hypertension
  • Hypercalcaemia
  • Hyperkalaemia (response enhanced by simultaneous NaCl and water administration)
  • Acute kidney injury*
  • Anion overdose
Adverse effects
  • Hypokalaemic metabolic alkalosis
    • Increased Na delivery to collecting duct due to inhibited salt reabsorption in TAL
    • This causes increased K+ and H+ secretion by the duct (note that K+ secretion in collecting duct is counter-exchange system with Na+, and H+ secretion is ATP-dependent driven by aldosterone in response to high Na+ concentration)
  • Ototoxicity
    • Dose-related hearing loss, usually reversible
    • Increased risk if poor renal function, or concomitant use of other ototoxic agents such as aminoglycoside antibiotics
  • Hypomagnesaemia
  • Hyperuricaemia
  • Allergic reactions
    • Loop diuretics are sulphonamides and therefore skin rash, eosinophilia, and occasionally interstitial nephritis are potential adverse effects
Precautions/contraindications
  • Sulphonamide allergy (rare)
  • Concomitant NSAID and probenecid administration may reduce loop diuretic secretion, as these drugs compete for weak acid secretion in the proximal tubule
Further Reading
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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