SACCM 151: Diuretics Flashcards
Name 2 substances that suppress ADH
- ethanol
- atrial natriuretic hormone
List 6 groups of diuretics
- osmotic diuretics
- carbonic anhydrase inhibitors
- loop diuretics
- thiazide diuretics
- aldosterone antagonists
- water and salt intake
List potential benefits of mannitol for acute kidney injury
- 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
How do high doses of mannitol cause renal damange?
renal vasoconstriction
tubular vacuolization
Explain the mechanism of action of carbonic anhydrase inhibitors for diuresis
inhibit primarily CA type II (cytoplasmic) and CA type IV (membrane) in the proximal tubules
CA II faciliates H2O + CO2»_space; H2CO3
CA IV facilitates H2CO3»_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.
Why is diuresis by carbonic anhydrase inhibitors self-limiting?
will cause metabolic acidosis –> progressively less HCO3- filtered
proximal tubules become less responsive to CA inhibitors
distal Na reabsorption increases to compensate
Name 3 other organs carbonic anhydrase inhibitors will affect
ocular –> decreases production of aqueous humor
brain –> decreased CSF production
RBCs –> decreases ability to transport CO2
What is the most common indication for carbonic anhydrase inhibitors on clinics?
glaucoma - to reduce intraocular pressure
Why does furosemide diuresis not induce a counter-regulatory response via the tubuloglomerular feedback?
inhibition of Cl flux in the macula densa
How does furosemide cause hypokalemia?
directly through NaK2Cl cotransporter inhibition
indirectly –> high Na reaches distal nephron –> promotes kaliuresis through Na-K exchange
How do loop diuretics improve renal parenchymal oxygenation?
- lower energy expenditure via the secondary active Na-K-2Cl transporter
- decreasing renal vascular resistance –> improving renal perfusion
What is the elimination half-life of furosemide?
1-1.5 hours
- risk of intermittent rebound sodium retention
What is the half-life and bioavailability of torsemide?
8 hours
80-100%
What is the mechanism of action of Thiazide diuretics?
NaCl cotransporter on the apical membrane in the distal tubules
What is the most common indication for thiazide diuretics in veterinary medicine?
- for their anti-calciuretic properties –> to reduce urinary Ca cc to reduce Calcium-containing urolith formation
- in diuretic combination protocols
What is the MOA of spironolactone?
aldosterone antagonist
competetively binds aldosterone receptors in the distal tubules and collecting duct –> reduces Na, water, Ca reabsorption, reduces K excretion
K sparing
Name 2 aldosterone antagonistic diuretics
Spironolactone
Eplerenone
Besides diuresis, what positive effect has Spironolactone shown to have on the heart?
- positive effect on myocardial remodelling
- reduces cardiac fibrosis
Name a class of K-sparing diuretics that’s not aldosterone antagonists
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
What are vaptans (examples, MOA, indications)
- 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
What is the “renal dose” of dopamin and what are its current recommendations for the administration in AKI?
0.5-3 mcg/kg/min
not recommended
* no survival benefit
* risk of adverse effects (arrhythmias, vasoconstriction/hypertension)
Explain the indications of diuretics in nephrotic syndrome
in nephrotic syndrome with edema and hypoalbuminema exacerbated by sodium retention
may require natriuretic drug
CAREFUL use - often overhydrated but actually hypovolemic
How does increased salt and water intake alleviate lower urinary tract disease?
- FLUTD - lowers the concentration of inflammatory mediators in the urinary tract (dilution)
- lowers the concentration of calculogenic urinary components
Why may dogs with sterile hemorrhagic cystitis benefit from furosemide administration?
sterile hemorrhagic cystitis from cyclophosphamide treatment
furosemide administration lowers the urinary concentration of cyclophosphamide metabolites
Name an example of a thiazide diuretic
Acetazolamide
Name an example of a Thiazide diuretic
Hydrochlorothiazide
What electrolyte disturbance may enhance the toxic potential of digoxin?
hypokalemia
Name 3 causes for ascites and edema in patients with liver failure
- hypoalbuminemia
- portal hypertension
- RAAS system activation
What is the first choice diuretic for patients with liver failure and why
aldosterone antagonist - spironolactone
hyperaldosteronemia and RAAS activation in liver failure
