Diuretic Pharmacology

Loop Diuretics

• Frusemide, Bumetanide, Torsemide (sulfa-containing)
• Ethacrynic acid (nil sulfa group)
• MOA:
  • Inhibit Na+/K+/2Cl- cotransporter in ascending limb
  • Decreased reabsorption of Na+ and H2O
  • Decreased reabsorption Ca2+ and Mg2+ secondary to K+ recycling
  • Increase prostaglandins
    • Vasodilate renal vascular bed
    • Decrease total peripheral vascular tone->  reduce LV filling pressure
• Indications:
  • Oedematous states = APO, peripheral oedema, ascites in setting of CCF, cirrhosis, nephrotic syndrome
  • HTN
  • Elimination of ions = hypercalcaemia, hyperkalaemia, Lithium overdose, hypermyoglobinaemia in rhabdomyolysis
• AE:
  • Hypovolaemia, dehydration
  • Hyponatraemia
  • Hypochloraemic hypokalaemic metabolic alkalosis
  • Hypomagnesaemia
  • Ototoxicity
  • Hyperuricaemia
  • Hyperglycaemia
  • Sulfa related = AIN: rash, arthralgia, AKI

Thiazides

• Hydrochlorothiazide
  • MOA: Inhibit NaCl transporter in distal convoluted tubule
  • Inhibit reabsorption Na+
  • Enhance Ca2+ reabsorption
• Indications:
  • HTN
  • CCF
  • Nephrolithiasis due to hypercalciuria
  • Nephrogenic diabetes insipidus
• AE:
  • Hypokalaemia metabolic alkalosis
  • Hyperuricaemia
  • Hyperglycaemia (hypokalaemia causing impaired pancreatic release of insulin)
  • Hyperlipidaemia
  • Hyponatraemia
  • Sulfa allergic reaction
  • Haemolytic anaemia, acute necrotizing pancreatitis, thrombocytopenia

Potassium sparing diuretics: Collecting ducts

• Spironolactone, eplerenone = inhibit aldosterone R and antagonise action
• Amiloride = inhibit ENaC and inhibit Na+ entry into cell (K+ secretion coupled with Na+ reabsorption)
• Triameterine
• Indication:
  • Hyperaldosteronism (primary = Conn’s or secondary = CCF, cirrhosis, nephrotic syndrome)
  • Liddle Syndrome (autosomal dominant disorder, activation of Na+ channels in collecting ducts->  sodium reabsorption and potassium secretion)
• AE:
  • Hyperkalaemia
  • Hyperchloraemic metabolic acidosis (inhibit H+ secretion with K+)
  • Gynaecomastia
• Contraindicated in CKD patients due to hyperkalaemia

Osmotic agents: PCT and descending loop

• Mannitol
• MOA: osmotically active agent causes water diuresis
  • Decreases contact time between fluid and tubular epithelium->  reduced Na+ reabsorption
• Poorly absorbed GI, thus given IV
• Indications:
  • Reduction of ICP and IOP
• AE:
  • Expansion of extracellular volume prior to diuresis = worsen CCF, APO
  • Dehydration->  hyperkalaemia, hypernatraemia
  • If used in renal impairment, mannitol cannot be extracted and is retained in blood->  water extraction from cells and hyponatraemia

Last Updated on September 24, 2021 by Andrew Crofton