Diuretics

• Diuretics are the most commonly used agents which act on the kidneys
  • Increase urine flow, normally by inhibiting the reabsorption of electrolytes (mainly sodium salts) at various sites in the nephron
  • Are used to enhanced excretion of salt and water in conditions where there is an increase in the volume of ECF (i.e. oedema) causes tissue swelling

Oedema

• Oedema results from an imbalance between the rate of formation and absorption of interstitial fluid

• Disease states that increase Pc or decrease πp and produce oedema include the nephrotic syndrome, congestive heart failure and hepatic cirrhosis with ascites

Nephrotic syndrome

• Involves a disorder of glomerular filtration, allowing large protein (mainly albumin) to appear in the urine (proteinuria)

Congestive heart failure

• Arises from reduced cardiac output and subsequent renal hypoperfusion that activates the RAAS
• Expansion of blood volume contributes to increased venous and capillary pressures that combined with (pi)p causes pulmonary and peripheral oedema

Hepatic cirrhosis with ascites

• Increased pressure in the hepatic portal vein combined with decreased production of albumin, causes loss of fluid into the peritoneal cavity and oedema (ascites)
• Activation of the RAAS occurs in response to decreased circulating volume

Sodium reabsorption and sites of diuretic action in the kidney

• A very large proportion of NaCl and H2O entering the filtrate via the glomerulus is reabsorbed - a modest inhibition of reuptake can cause a marked increase in Na+ excretion
• The site of action of most diuretics (thiazides, loop agents, some potassium-sparing) is the apical membrane of tubular cells hence, if hydrophilic, they must enter the filtrate to act
• Entry to the filtrate occurs by:
  • Glomerular filtration (for drug not bound to large plasma protein)
  • Secretion via two important transport process in the proximal tubule
    • The organic anion transporters (OATs) - transport acidic drugs (e.g. thiazides and loop agents)
    • The organic cation transporters (OCTs) - transport basic drugs (e.g. triamterene and amiloride)