Diuretics

Question 1

Diuretic classes

Answer 1

-loop diuretics (furosemide)

-thiazides (hydrochlorothiazide)

-potasssium-sparing diuretics (spironolactone)

-osmotic diuretics (mannitol)

Question 2

Na reabsorption in Nephron

Answer 2

Water follows Na. So decrease Na reabsorption, increase water loss (diuresis)

Proximal tubule- 60% of Na reabsorbed here

Thick ascending tubule- 25% of Na reabsorbed; water is impermeable here

Distal tubule- 7%

Late distal tubule/collecting tubule: 3% Na reabsorbed; Water permeability controlled by ADH (vasopressin)

Question 3

What is the major force for filtration?

Answer 3

Blood pressure

Question 4

Drugs acting on proximal tubule

Answer 4

Osmotic diuretics
-most effective drug group
-hold the water within and cause large diuresis (and ion loss)
-usually IV; some oral but rare. Usually given in clinic

Question 5

Drugs acting on Thick ascending tubule

Answer 5

Loop diuretics
-2nd most effectiveness
-can send animal home with these drugs

Question 6

Drugs acting on (early) distal tubule

Answer 6

Thiazides
-safe

Question 7

Drugs acting on late distal tubule/collecting duct

Answer 7

K sparing diuretics
**Na exchanged for K typically. Body keeps K and will lose Na (no Na resorption, so more water loss)

Question 8

Loop diuretics mechanism

Answer 8

-high ceiling diuretics

-inhibit Na/K/Cl symporter in ascending limp of loop of henle so more Na and K stays in tubule and water stays in filtrate

Question 9

What does Loop diuretic inhibition result in?

Answer 9

1. Powerful mixed natriuretic/kaliuretic effect in ascending limb
   -increased volume of NaCl and K enriched fluid to late distal tubule and collecting duct
   -Then stimulates Na exchange for K in distal tubule and collecting duct
   -end result is a strong kaliuretic effect (high K loss in urine)
2. Causes calcium and magnesium loss in urine
   *because need K to build up in the tubule epithelium (which does not happen) to drive Ca, Mg transport

Question 10

Thiazides

Answer 10

Act mostly on early portion of distal tubule to inhibit Na/Cl symporter = natriuresis and diuresis

Then results in Na exchange for K in distal tubule and collecting duct= final kaliuretic effect

**Less kaliuresis than with furosemide (loop diuretic)

Question 11

Potassium-sparing diuretics

Answer 11

-Spironolactone
-Mineralocorticoid receptor antagonist (receptor for aldosterone)= resulting in prevention of aldosterone
*aldosterone used to increase blood volume

Question 12

What does Potassium-sparing diuretics result in?

Answer 12

Prevents transcription of Na channel and Na pump genes of late distal tubule and collecting duct
-prevents hypokalemia
-loss of Na, not as large a concern because when these drugs are used its due to higher aldosterone and high fluid levels

**may be used in combination therapy with other diuretics

Question 13

Why is it not as big of a concern to lose Na when using K sparing drugs?

Answer 13

loss of Na, not as large a concern because when these drugs are used its due to higher aldosterone and high fluid levels (access Na)

Question 14

Clinical trials of Potassium-sparing diuretics

Answer 14

Conducted to examine the efficacy of co-treatment with pimobenden in Doberman DCM.
-inconclusive
-may be effective in canine mitral valve failure

Question 15

Anti-steroid effects of K sparing diuretics

Answer 15

Antagonist effecting androgens and estrogen receptors resulting in anti steroid effect
-Used for gender transitions, breast growth in males