Diuretics Flashcards
What was the first clinically developed diuretic?
acetazolamide
Kidneys control ECF volume by adjusting ____ and ____ exretion
NaCl and water
Diuretics are used mainly to reduce ECV by ____________________
decreasing NaCl content
What part of the loop of henle can reabsorb water?
thin descending limb
Where does acetazolamide work?
in the PCT as a CA inhibitor (inhibits 85% sodium bicarb reabsorption)
What does Mannitol do?
osmotic diuretic
limits water reabsorption in water permeable segments of nephron (PCT, thin desc limb, CT)
Where does Furosemide work?
thick ascending limb of Henle
inhibits Na/K/2Cl transport
Where doe the thiazide diuretics work?
DCT
inhibit NaCl cotransport in DCT
Where do the K+ sparing diuretics act?
on the CT by inhibiting aldosterone or by blocking Na+ channels directly
except for ___________ and some ADH antagonists, diuretics generally exert their effects from the luminal side of the nephron
spironolactone
What is the one diuretic that can easily get into the tubular fluid by filtration at the glomerulus?
mannitol
the others are highly protein bound and undergo little filtration - they are secreted
What is responsible for driving sodium reabsorption?
Na/K ATPase at the basolateral membrane
What is the MOA of acetazolamide?
reversible inhibition of carbonic anhydrase (inhibits reabsorption of bicarb in PCT)
How does acetazolamide get into the tubule?
secreted via organic acid transporter
What are adverse effects of acetazolamide?
metabolic acidosis
hypokalemia
calcium phosphate stones
drowsiness
What is contraindication for acetazolamide?
cirrhosis (reduced NH3 secretion so increased serum NH3)
Ammonia exretion is _____________ related to urine pH
inversely
Which CA inhibitor is 30x more potent than acetazolamide?
dichlorphenamide
Which CA inhibitor is 5m more potent than acetazolamide?
methazolamide
Which CA inhibitor is used topically for eye stuff?
dorzolamide
What is the effect of mannitol?
increase urine volume (impairs water reabsorption in the PCT and descending loop)
How does mannitol get into the tubular fluid?
glomerular secretion
What is a big toxicity of mannitol?
hypertonic cells (fluid leaves to go to the plasma which now has increased osmolality)
True or false: mannitol can be used in both chronic and acute renal failure patients
FALSE - cannot be used in chronic failure patients
What are 3 indications of mannitol?
- increase urine volume
- reduce ICP and IOP
What is the MOA for loop diuretics?
block Na/K/2Cl cotransporter in apical membrane of thick ascending limb (reducing ability to concentrate ECF and dilute luminal fluid)
What is the most efficacious class of diuretics?
loop diuretics (can excrete up to 20% of filtered sodium)
What effect do loop diuretics have on the vasculature?
vasodilation
What is the one unique toxicity of furosamide?
ototoxicity
What loop diuretic is used as a last resort only?
ethacrynic acid (nephro and ototoxic)
What is the important transporter on the DCT?
Na/Cl cotransporter and the Ca++ channel
Ca is pumped out of cell via Na/Ca countertransport
What is hydrochlorothiazide?
prototypical thiazide diuretics (blocks Na/Cl channel in DCT)
What is the only thiazide diuretic that can be used in cases of renal insufficiency?
metolazone
10x more potent than hydrochlorothiazide
What do the principal cells of the collecting duct do?
Na/K channel (Na in, K out with net more Na in making tubular fluid negative)
aldosterone works here
What do intercalated cells do?
proton pumps transport H into lumen
HCOs/Cl countertransported
How does increased delivery of bicarb to the distal nephron affect K balance?
increased bicarb leads to increased lumen negative potential which ENHANCES K efflux
HYPOkalemia
How does a negatively charged tubular fluid affect K+ efflux?
increases it leading to hypokalemia
why all of these diuretics can lead to hypokalemia
How do diuretics lead to metabolic alkalosis?
increased lumen negative charges lead to increased H+ efflux (just like K+ behavior) from intercalated cells
What should potassium sparing diuretics NEVER be given with?
potassium supplements
ACE inhibitors
What is spironolactone?
competitive inhibitor of aldosterone receptor (decreases Na+ reabsorption and spares K+)
How rapid is the onset of spironolactone?
slow - takes days
What is eplerenone?
competitive antagonist of aldosterone binding to mineralocorticoid receptor
more expensive, does not inhibit testosterone
What are the effects of spironolactone?
deceased lumen neg potential, reduced driving force for H+ –> metabolic acidosis
What does amiloride do?
block Na channels in the principal cells (decreasing driving force on K+ thus sparing it)
What is a second drug that blocks Na channels in the principal cells like amiloride?
triamterene (but it is 10x LESS potent than amiloride)
What were the 2 original, unintended ADH antagonists?
demeclocycline
lithium
What is the currently used ADH antagonist?
Tolvaptan (selectively inhibits vasopressin V2 receptor)
What is the most efficient diuretic for shedding NaCl? NaHCO3?
NaCl = loop NaHCO3 = CA inhibitors
Diuretics __________ capillary hydrostatic pressure and ___________ plasma oncotic pressure
DECREASE hydrostatic
INCREASE oncotic
favors absorption over filtration
How does hepatic cirrhosis lead to edema?
hypoalbuminemia –> reduced plasma volume –> activation of RAA –> hyperaldosteronism results in increased Na+ retention
What is the most common electrolyte disorder in hospitalized patients?
hyponatremia
What are the symptoms of hyponatremia?
CNS related (headache, etc)
True or false: you can have hyponatremia in all volemic states?
true
What are the best diuretics to use for hyponatremic patients?
AVP receptor agonists
For uncomplicated hypertensio, _____________________ should be used in drug treatment (either alone or combined with drugs of another class)
thiazide diuretic
What are the 5 symptoms of metabolic syndrome?
fasting hyperglycemia high blood pressure central obesity decreased HDL elevated triglycerides
What is a unique, counterintuitive application of thiazide?
treats nephrogenic diabetes insipidus (which loses its sensitivity to ADH)
What are conditions conducive to kidney stone formation?
hypercalcemia
What diuretic would you give to treat kidney stones?
thiazide (decrease calcium conc in urine by reabsorbing)
True or false: you would give thiazides to treat hypercalcemia
FALSE (they increase calcium reabsorption)
