16 – Diuretics

Question 1

What are the 4 types of diuretic classes?

Answer 1

1. Loop diuretics
2. Thiazides
3. Potassium-sparing diuretics
4. Osmotic diuretics (BEST)

Question 2

What are the sites of Na reabsorption

Answer 2

• Proximal tubule: 60%
• Thick ascending tubule: 25%
• Distal tubule: 7%
• Late distal tubule/collecting duct: 3%

Question 3

What is the major force for filtration in the nephron?

Answer 3

• Blood pressure

Question 4

Where is the nephron impermeable to water?

Answer 4

• Thick ascending loop: hypotonic in filtrate
• Distal tubule and collecting duct: permeability is controlled by ADH

Question 5

What is the main osmotic diuretic?

Answer 5

• Mannitol

Question 6

Where is the site of action for osmotic diuretics?

Answer 6

• Proximal tubule
• *and entire nephron
  o in FILTRATE and exerting osmotic action
• VERY LARGE DIURETIC EFFECT
• Use in an emergency

Question 7

What is the main loop diuretic?

Answer 7

• Furosemide

Question 8

Where is the site of action for loop diuretics?

Answer 8

• Thick ascending loop of Henle
• 2nd best (used in vet med quite a bit)
• More gradual effects

Question 9

What is the mechanism of loop diuretics?

Answer 9

• ‘High-ceiling’ diuretics (=large therapeutic effect)
• Inhibit Na/K/2Cl symporter in ASCENDING loop of Henle
• *initially get a mix of natriuretic/kaliuretic effect in ascending limb
• Secondarily: causes Ca and Mg loss in urine

Question 10

Loop diuretics: initially get a mix of natriuretic/kaliuretic effect in ascending limb leading to…

Answer 10

• Increased volume of NaCl (and K)-enriched fluid to late distal tubule and collecting duct
• Stimulates Na exchange for K in distal tubule and collecting duct
• *end result=strong kaliuretic effect

Question 11

Kaliuretic definition

Answer 11

• Extra K in urinary filtrate

Question 12

What is the main thiazide diuretic?

Answer 12

• Hydrochlorothiazide

Question 13

Where is the site of action for Thiazide diuretics?

Answer 13

• Early portion of distal tubule
• Safer, but less diuresis

Question 14

What is the mechanism of thiazides?

Answer 14

• Primarily early portion of distal tubule to INHIBIT Na/Cl symporter (natriuresis and diuresis)
  o Na exchanged for K in distal tubule and collecting duct
  o *less kaliuresis than with furosemide (loop diuretic)
• *natriuretic effect TO kaliuretic effect

Question 15

What is the main potassium-sparing diuretic?

Answer 15

• Spironolactone

Question 16

Where is the site of action for K-sparing diuretics?

Answer 16

• Late distal tubule and collecting duct
  o Usually Na is exchanged for K (body wants to conserve Na and K is excreted)
• *prevent Na from being exchanged for K=Na will be lost

Question 17

What is the mechanism of K-sparing diuretics?

Answer 17

• NOT a transport inhibitor
• Mineralocorticoid (aldosterone) receptor ANTAGONIST
• Minor diuretic effect
• Prevents transcription of Na channel and Na pump genes of late distal tubule and collecting duct=pee out Na instead of K
• *PREVENTS HYPOKALEMIA
• Anti-steroid hormone side effects (limits it’s use)

Question 18

Since K-sparing diuretics prevent hypokalemia they may be used in combination with

Answer 18

• Other diuretics

Question 19

Clinical trial of co-treatment of Pimobendan in Doberman DCM

Answer 19

• Seems effective in canine mitral valve failure

Question 20

Anti-steroid hormone side effects of K-sparing diuretics in males

Answer 20

• Breast growth in males