Loop diuretics 

EXAMPLES 
Furosemide, bumetanide

MECHANISM OF ACTION 

  • Inhibits the reabsorption of Na+ and Cl in the ascending limb of the Loop of Henle by inhibiting the Na+/K+/2Cl co-transporter.
  • This results in increased Naþ excretion and free water clearance, thereby reducing preload.

INDICATIONS 

  • Pulmonary oedema is secondary to LVF.
  • Chronic heart failure

CAUTIONS AND CONTRA-INDICATIONS

  • Severe hypokalaemia/hyponatraemia.
  • Hypovolaemia.
  • Renal failure due to nephrotoxic drugs.
  • Comatose patients with liver cirrhosis.
  • Anuria.

SIDE-EFFECTS 

  • Electrolyte disturbances (hypokalaemia, hyponatraemia, hypocalcaemia). Hypotension.
  • Tinnitus and deafness (associated with large IV boluses).
  • GI disturbance.
  • Dyslipidaemia

METABOLISM AND HALF-LIFE 

  • t½ is variable (furosemide 90 min).
  • The onset of action occurs within 1h and diuresis is complete within 6 h.
  • Excreted largely unchanged in the urine.

MONITORING 

  • Check U&Es prior to initiating and during treatment.

DRUG INTERACTIONS

  • Risk of cardiotoxicity when given with digoxin (secondary to hypokalaemia).
  • Risk of ototoxicity when given with aminoglycosides or vancomycin.
  • Enhanced hypotensive effect with other antihypertensives.
  • Can reduce lithium excretion.
  • NSAIDs can reduce the effectiveness of loop diuretics (due to reduced GFR)

IMPORTANT POINTS

  • Patients with low GFR may require higher doses(diuretic resistance due to poor perfusion to target tissues).
  • IV furosemide has a very early vasodilatory effect