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 Emergency Medicine Advanced Trainee based in Melbourne, Australia. Co-author of the LITFL ECG Library. Likes Ultrasound, Echo, ECGs, and anything and everything with caffeine. Part of the 2021 ANZCEN Clinician Educator Incubator Programme | @rob_buttner | ECG Library |

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