Diuretics Pharmacology Free Course

To understand diuretics first we need to learn the ion and water exchange in the nephron

Diuretics are drugs that make kidney lose water and to make it lose water, we need to make lose sodium first because salt and water moves together. We have five diuretics groups: loop diuretics, Thiazides, Potassium sparing diuretics, Carbonic anhydrase inhibitors, osmotic diuretics…

To understand how diuretics works, first we need to learn the ion and water exchange in the nephron (functional unit of kidney), so the upcoming paragraphs are going to explain the exchange that happen in each segment of the nephron and which diuretic would affect that…

Normally, blood enters the nephron from the afferent arteriole to the glomerular tuft into the efferent arteriole, the blood will undergo filtration process by the glomerular basement membrane into the bowman’s capsule and it’s powered by the hydrostatic pressure exerted by the blood vessels walls. The filtrate contain water, different organic compounds, ions except for the proteins. The speed of filtration is about 120 ml/min and that would convert into 173 L per day (by multiplying it by 60 min and 24 hours) and 99% of this is reabsorbed again and that’s why our urine volume don’t exceed 1.5 L/day…

Nephron Segments and Diuretic Actions

Nephron Segment Normal Function Diuretic Group Mechanism/Effect
Proximal convoluted tubule (PCT)
  • 65% of filtered sodium is actively reabsorbed by the PCT cells and the water moves with the sodium (because salt and water moves together) so we get the same amount of water (65%) reabsorbed through the PCT.
  • Also in the PCT potassium, bicarbonate, hydrogen, amino acids, organic compounds and some of the calcium and magnesium are reabsorbed.
  • Also secretion process occur in the PCT of some compounds like uric acid which is reabsorbed again.
 Carbonic anhydrase inhibitors
  • Works on the PCT by preventing the bicarbonate from getting absorbed there, but that effect would only last from 3- 4 days because the PCT cells are resistant to drugs and adapt really quickly…
Loop of Henle
  • The tubular fluid moves in the descending part of the loop (loop of Henle) and into the ascending part where 25% of sodium is reabsorbed by the NaKCl tranporter, this is also the part where the majority of calcium and magnesium are reabsorbed.
  • The ascending part of the loop is impermeable to water and the descending part is going to reabsorb 25% of water as compensation to the sodium reabsorbed by the ascending part (in total loop will absorb 25% sodium and water).
 Loop Diuretics
  • Block the NaKCl transporter and lead to losing of the 25% of the sodium and water and also losing of calcium, magnesium, hydrogen, Potassium and chloride.
Distal Convoluted Tubule (DCT)
  • Now the filtrate will move into the proximal part of the DCT where 5-7 % of water and soiudm are reabsorbed by NaCl transporter and the rest of calcium and magnesium are resabosrbed by the help of the parathyroid hormone.
  • after that the filtrate moves to the distal part of the DCT where 2-5 % of sodium and water are reabsorbed by the help of aldosterone in expense of potassium and hydrogen (sodium and water reabsorbed, potassium and hydrogen lost).
  • Thiazides diuretics (proximal DCT)
  • Potassium sparing diuretics (distal DCT)
  • Thiazides diuretics works on the proximal part of the DCT and they block NaCl transporter and lead to losing 5-7 % of sodium and water and also chloride is lost.
  • Potassium sparing diuretics works on the distal part of the DCT and they antagonize the aldosteorne which lead to losing of the 2-5 % of sodium and water and conserving the potassium and hydrogen.

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