SACCM 151: Diuretics

Question 1

Name 2 substances that suppress ADH

Answer 1

• ethanol
• atrial natriuretic hormone

Question 2

List 6 groups of diuretics

Answer 2

• osmotic diuretics
• carbonic anhydrase inhibitors
• loop diuretics
• thiazide diuretics
• aldosterone antagonists
• water and salt intake

Question 3

List potential benefits of mannitol for acute kidney injury

Answer 3

• prostaglandin-induced renal vasodilation
• decreased tendency of erythrocyte aggregation
• decreased renal vascular congestion
• decreased hypoxic cellular edema
• protection of mitochondrial function
• decreased oxidative damage
• renoprotection

Question 4

How do high doses of mannitol cause renal damange?

Answer 4

renal vasoconstriction
tubular vacuolization

Question 5

Explain the mechanism of action of carbonic anhydrase inhibitors for diuresis

Answer 5

inhibit primarily CA type II (cytoplasmic) and CA type IV (membrane) in the proximal tubules

CA II faciliates H2O + CO2&raquo_space; H2CO3
CA IV facilitates H2CO3&raquo_space; H2O + CO2

main driver of Na and water reabsorption in proximal tubules: NaH3-antiporter –> excreted H+ needs to bind with HCO3 –> H2CO3 –> needs to form CO2 and H2O to be reabsorbed

CO2 and H2O needs to form H+ and HCO3 for more Na to be reabsorbed etc.

Question 6

Why is diuresis by carbonic anhydrase inhibitors self-limiting?

Answer 6

will cause metabolic acidosis –> progressively less HCO3- filtered

proximal tubules become less responsive to CA inhibitors

distal Na reabsorption increases to compensate

Question 7

Name 3 other organs carbonic anhydrase inhibitors will affect

Answer 7

ocular –> decreases production of aqueous humor
brain –> decreased CSF production
RBCs –> decreases ability to transport CO2

Question 8

What is the most common indication for carbonic anhydrase inhibitors on clinics?

Answer 8

glaucoma - to reduce intraocular pressure

Question 9

Why does furosemide diuresis not induce a counter-regulatory response via the tubuloglomerular feedback?

Answer 9

inhibition of Cl flux in the macula densa

Question 10

How does furosemide cause hypokalemia?

Answer 10

directly through NaK2Cl cotransporter inhibition

indirectly –> high Na reaches distal nephron –> promotes kaliuresis through Na-K exchange

Question 11

How do loop diuretics improve renal parenchymal oxygenation?

Answer 11

• lower energy expenditure via the secondary active Na-K-2Cl transporter
• decreasing renal vascular resistance –> improving renal perfusion

Question 12

What is the elimination half-life of furosemide?

Answer 12

1-1.5 hours

• risk of intermittent rebound sodium retention

Question 13

What is the half-life and bioavailability of torsemide?

Answer 13

8 hours

80-100%

Question 14

What is the mechanism of action of Thiazide diuretics?

Answer 14

NaCl cotransporter on the apical membrane in the distal tubules

Question 15

What is the most common indication for thiazide diuretics in veterinary medicine?

Answer 15

• for their anti-calciuretic properties –> to reduce urinary Ca cc to reduce Calcium-containing urolith formation
• in diuretic combination protocols

Question 16

What is the MOA of spironolactone?

Answer 16

aldosterone antagonist
competetively binds aldosterone receptors in the distal tubules and collecting duct –> reduces Na, water, Ca reabsorption, reduces K excretion

K sparing

Question 17

Name 2 aldosterone antagonistic diuretics

Answer 17

Spironolactone
Eplerenone

Question 18

Besides diuresis, what positive effect has Spironolactone shown to have on the heart?

Answer 18

• positive effect on myocardial remodelling
• reduces cardiac fibrosis

Question 19

Name a class of K-sparing diuretics that’s not aldosterone antagonists

Answer 19

electrogenic Na channel inhibitors –> act on the laste distal tubules

the Na absorption here is the driving force for K excretion

not very effective because so distal in the nephron

e.g., Amiloride, triamterene

Question 20

What are vaptans (examples, MOA, indications)

Answer 20

• aquaretics –> inhibit V1 and V2 receptors
• e.g. conivaptan, tolvaptan, mozavaptan
• used to treat hypervolemic (heart or liver failure) or normovolemic hyponatremia (SIADH) in people –> use has not been reported in SA veterinary patient

Question 21

What is the “renal dose” of dopamin and what are its current recommendations for the administration in AKI?

Answer 21

0.5-3 mcg/kg/min

not recommended
* no survival benefit
* risk of adverse effects (arrhythmias, vasoconstriction/hypertension)

Question 22

Explain the indications of diuretics in nephrotic syndrome

Answer 22

in nephrotic syndrome with edema and hypoalbuminema exacerbated by sodium retention

may require natriuretic drug

CAREFUL use - often overhydrated but actually hypovolemic

Question 23

How does increased salt and water intake alleviate lower urinary tract disease?

Answer 23

• FLUTD - lowers the concentration of inflammatory mediators in the urinary tract (dilution)
• lowers the concentration of calculogenic urinary components

Question 24

Why may dogs with sterile hemorrhagic cystitis benefit from furosemide administration?

Answer 24

sterile hemorrhagic cystitis from cyclophosphamide treatment

furosemide administration lowers the urinary concentration of cyclophosphamide metabolites

Question 25

Name an example of a thiazide diuretic

Answer 25

Acetazolamide

Question 26

Name an example of a Thiazide diuretic

Answer 26

Hydrochlorothiazide

Question 27

What electrolyte disturbance may enhance the toxic potential of digoxin?

Answer 27

hypokalemia

Question 28

Name 3 causes for ascites and edema in patients with liver failure

Answer 28

• hypoalbuminemia
• portal hypertension
• RAAS system activation

Question 29

What is the first choice diuretic for patients with liver failure and why

Answer 29

aldosterone antagonist - spironolactone

hyperaldosteronemia and RAAS activation in liver failure