OzEMedicine - Wiki for Australian Emergency Medicine Doctors

see also pharmacology main index, hypertension, congestive cardiac failure

• Use of mercurials to Rx syphilis & their common diuretic side effect led to the use of mercurial diuretics in 1920's & despite toxicity, these potent loop diuretics dominated Rx of CCF until advent of modern loop diuretics.
• The diuretic side effect of sulphonamide antibiotics resulted in acetazolamide - a carbonic anhydrase inhibitor 1st used in 1930's.
• Further research on sulphonamides led to thiazide diuretics in the 1950's & then, in early 1960's, to frusemide, the protypic sulphonamide diuretic in this group.

• Congestive cardiac failure - ACE inhib. now taking a more dominant role;
• nephrotic syndrome
• Hepatic failure
• Impending acute renal tubular necrosis
• idiopathic cyclic oedema
• renal calculi
• renal tubular acidosis
• benign intracranial hypertension
• diabetes insipidus
• glaucoma
• hypertension

• Diuretics are substances that incr. urine volume & incr. net loss of water/solutes & are used for:
  • maintenance of adequate urine volume;
  • mobilisation of oedema fluid → -ve fluid balance to return ECFV to normal;
• All act either by osmotic effects or on specific renal tubular sites although may have indirect effects at sites distal in nephron:
  • change in tub. function will alter conditions downstream;
  • body reacts to diuretic-induced decr. in ECFV via homeostatic mechanisms;
• All tend to distort normal composition of body fluids:
  • direct effect on altered ion excretion rates;
  • distorted nephron axial flow → abnormal function (eg. incr. flow → incr. K excretion);
  • homeostatic mechanisms may alter fluid composition;

• these share the risk of causing hypokalaemia
• osmotic diuretics
• carbonic anhydrase inhibitors
• thiazides
• loop diuretics

• these share the risk of causing hyperkalaemia
• aldosterone antagonists
• other potassium-sparing diuretics:
  • examples: triamterene, amiloride
  • Organic bases that inhibit electrogenic entry of Na in distal segments nephron, thus reducing the electrical potential across tubular epithelium (one of the normal driving forces for K secretion).
  • In addition,
    • they are not carbonic anhydrase inhib.;
    • may cause slight urine pH as decr. proton secretion distal nephron;
    • prox.tub. Na-H exchange inhib. (amiloride only? but only @ v.high [ ]);
    • decr. Ca excretion (amiloride) additive to thiazide effect;
  • P/K:
    • 50% absorbed orally (no parenteral form), large VD ;
    • Triamterene extensively metab. but amiloride not metabolised;
    • Both secreted in proximal tubule ? via organic anion secretory mechanism;
  • Adverse effects:
    • hyperkalaemia
    • triamterene: N/V/leg cramps/dizziness/mod. azotaemia;
    • high dose triamterene → 1 in 1500 → nephrolithiasis (metabolites in stone);
    • amiloride: N/V/D/headache;