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

• Nickson C. Sulfa Drug Discombobulation. LITFL
• Nickson C. Frusemide CCC. LITFL