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History of diuretic use:

  • 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.

Potential indications for diuretics:

General Pharmacology of Diuretics:

  • 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;

Classes of diuretics

potassium losing diuterics

potassium-sparing diuretics

  • these share the risk of causing hyperkalaemia
  • 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:
      • triamterene: N/V/leg cramps/dizziness/mod. azotaemia;
      • high dose triamterene → 1 in 1500 → nephrolithiasis (metabolites in stone);
      • amiloride: N/V/D/headache;
diuretics.txt · Last modified: 2009/01/21 02:35 by

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