pharmacology of diuretics

• Diuretics

  Drugs that increase the amount of fluid and salts excreted by the kidneys

  
• Diuretics

  • Main uses are to help reduce oedema and reduce hypertension
• How diuretics work with oedema

  1. Diuretics increase urine production

  2. This draws more fluid from swollen areas in the tissue and reduces swelling

  3. Area returns to normal
• How diuretics help with hypertension

  1. Increase volume of urine produced

  2. Decrease blood volume

  3. Decrease pressure on blood vessels

  4. Decrease blood pressure
• Salts

  Transported via active transport (pumps, transporters, co-transporters) and passive transport (channels)
• Water

  Moves via osmosis - wherever salts go, water goes too
• Classes of diuretics

  • Loop diuretics
  • Thiazides and related diuretics
  • Potassium-sparing diuretics
  • Carbonic anhydrase inhibitors
  • Osmotic diuretics
• Loop diuretics

  • Site of action is the thick ascending limb of the Loop of Henle
  • Used for oedema in severe heart failure and acute ventricular failure
  • Not normally used for hypertension but still have an effect on blood volume
• Mechanism of action of loop diuretics

  • Blocks Na+/K+/2Cl- ATPase (or co-transporter) on the apical membrane
  • Increases excretion of sodium, chloride, potassium
  • Increases urine output

  
• Efficacy of loop diuretics

  • Very powerful diuretics
  • Up to 20% of filtered sodium can be excreted
  • Urine flow rate increases from 1ml/min to 8ml/min
  • High ceiling concentration - increased dose increases diuresis up to a point
  • Act within an hour and for up to 6hrs
  • Braking effect after 6hrs due to distal compensation
• Side effects of loop diuretics

  • Hypokalaemia (low potassium)
  • Metabolic alkalosis
  • Hyponatraemia, hypocalcaemia, hypomagnesaemia
  • Deafness (very high doses)
• Thiazides and related diuretics

  • Site of action is the distal convoluted tubule
  • Have a direct vasodilatory effect
  • Used for oedema and long-term treatment of hypertension
• Mechanism of action for thiazides

  • Blocks Na+/Cl- ATPase (transporter) in the distal tubule
  • Increases excretion of sodium, chloride, potassium
• Efficacy of thiazides

  • Relatively potent diuretics, but less so than loop diuretics
  • Up to 8% of filtered sodium can be excreted
  • Urine flow rate increases from 1ml/min to 3ml/min
  • Low ceiling concentration
  • Act within 1-2hrs and for up to 24hrs
• Side effects of thiazides

  • Hypokalaemia and metabolic alkalosis
  • Hypocalcaemia and hypomagnesaemia
  • Hyperuricaemia (gout)
  • Hyperglycaemia (diabetes)
• Thiazides are relatively ineffective in patients with severe chronic kidney disease (stages 4 & 5) unless co-prescribed with a loop diuretic
• Potassium-sparing diuretics

  • Can be sodium channel blockers or aldosterone antagonists
  • Site of action is the late distal tubule and collecting duct
  • Used for oedema and hypertension
  • Can be co-prescribed with loop diuretics and thiazides to adjust potassium loss
• Mechanism of action of potassium-sparing diuretics

  • Increase sodium and water excretion
  • Decrease excretion of potassium and H+
• Efficacy of potassium-sparing diuretics

  • Fairly weak diuretics compared to thiazides and loop diuretics
  • Up to 2-3% of filtered sodium can be excreted
• Side effects of potassium-sparing diuretics

  • Hyperkalaemia and metabolic acidosis
• Antidiuretics

  • Site of action is mainly the collecting duct
  • Used for central diabetes insipidus
  • Examples are vasopressin and desmopressin
• Mechanism of action of antidiuretics

  Increases number of aquaporins which increases passive reabsorption of water
• Diuretics are classed according to their site of action and generally inhibit electrolyte reabsorption from the lumen of the nephron, increasing osmolarity and enhancing water excretion

  
• The efficacy and side effects of diuretics are linked to their mechanism and site of action
• The most common side effect of diuretics is mild hypovolaemia which can lead to transient dehydration and increased thirst
• Diuresis is necessary for oedematous and non-oedematous conditions