Diuretics

Question 1

What was the first clinically developed diuretic?

Answer 1

acetazolamide

Question 2

Kidneys control ECF volume by adjusting ____ and ____ exretion

Answer 2

NaCl and water

Question 3

Diuretics are used mainly to reduce ECV by ____________________

Answer 3

decreasing NaCl content

Question 4

What part of the loop of henle can reabsorb water?

Answer 4

thin descending limb

Question 5

Where does acetazolamide work?

Answer 5

in the PCT as a CA inhibitor (inhibits 85% sodium bicarb reabsorption)

Question 6

What does Mannitol do?

Answer 6

osmotic diuretic

limits water reabsorption in water permeable segments of nephron (PCT, thin desc limb, CT)

Question 7

Where does Furosemide work?

Answer 7

thick ascending limb of Henle

inhibits Na/K/2Cl transport

Question 8

Where doe the thiazide diuretics work?

Answer 8

DCT

inhibit NaCl cotransport in DCT

Question 9

Where do the K+ sparing diuretics act?

Answer 9

on the CT by inhibiting aldosterone or by blocking Na+ channels directly

Question 10

except for ___________ and some ADH antagonists, diuretics generally exert their effects from the luminal side of the nephron

Answer 10

spironolactone

Question 11

What is the one diuretic that can easily get into the tubular fluid by filtration at the glomerulus?

Answer 11

mannitol

the others are highly protein bound and undergo little filtration - they are secreted

Question 12

What is responsible for driving sodium reabsorption?

Answer 12

Na/K ATPase at the basolateral membrane

Question 13

What is the MOA of acetazolamide?

Answer 13

reversible inhibition of carbonic anhydrase (inhibits reabsorption of bicarb in PCT)

Question 14

How does acetazolamide get into the tubule?

Answer 14

secreted via organic acid transporter

Question 15

What are adverse effects of acetazolamide?

Answer 15

metabolic acidosis
hypokalemia
calcium phosphate stones
drowsiness

Question 16

What is contraindication for acetazolamide?

Answer 16

cirrhosis (reduced NH3 secretion so increased serum NH3)

Question 17

Ammonia exretion is _____________ related to urine pH

Answer 17

inversely

Question 18

Which CA inhibitor is 30x more potent than acetazolamide?

Answer 18

dichlorphenamide

Question 19

Which CA inhibitor is 5m more potent than acetazolamide?

Answer 19

methazolamide

Question 20

Which CA inhibitor is used topically for eye stuff?

Answer 20

dorzolamide

Question 21

What is the effect of mannitol?

Answer 21

increase urine volume (impairs water reabsorption in the PCT and descending loop)

Question 22

How does mannitol get into the tubular fluid?

Answer 22

glomerular secretion

Question 23

What is a big toxicity of mannitol?

Answer 23

hypertonic cells (fluid leaves to go to the plasma which now has increased osmolality)

Question 24

True or false: mannitol can be used in both chronic and acute renal failure patients

Answer 24

FALSE - cannot be used in chronic failure patients

Question 25

What are 3 indications of mannitol?

Answer 25

- increase urine volume | - reduce ICP and IOP

Question 26

What is the MOA for loop diuretics?

Answer 26

block Na/K/2Cl cotransporter in apical membrane of thick ascending limb (reducing ability to concentrate ECF and dilute luminal fluid)

Question 27

What is the most efficacious class of diuretics?

Answer 27

loop diuretics (can excrete up to 20% of filtered sodium)

Question 28

What effect do loop diuretics have on the vasculature?

Answer 28

vasodilation

Question 29

What is the one unique toxicity of furosamide?

Answer 29

ototoxicity

Question 30

What loop diuretic is used as a last resort only?

Answer 30

ethacrynic acid (nephro and ototoxic)

Question 31

What is the important transporter on the DCT?

Answer 31

Na/Cl cotransporter and the Ca++ channel | Ca is pumped out of cell via Na/Ca countertransport

Question 32

What is hydrochlorothiazide?

Answer 32

prototypical thiazide diuretics (blocks Na/Cl channel in DCT)

Question 33

What is the only thiazide diuretic that can be used in cases of renal insufficiency?

Answer 33

metolazone | 10x more potent than hydrochlorothiazide

Question 34

What do the principal cells of the collecting duct do?

Answer 34

Na/K channel (Na in, K out with net more Na in making tubular fluid negative) aldosterone works here

Question 35

What do intercalated cells do?

Answer 35

proton pumps transport H into lumen HCOs/Cl countertransported

Question 36

How does increased delivery of bicarb to the distal nephron affect K balance?

Answer 36

increased bicarb leads to increased lumen negative potential which ENHANCES K efflux HYPOkalemia

Question 37

How does a negatively charged tubular fluid affect K+ efflux?

Answer 37

increases it leading to hypokalemia why all of these diuretics can lead to hypokalemia

Question 38

How do diuretics lead to metabolic alkalosis?

Answer 38

increased lumen negative charges lead to increased H+ efflux (just like K+ behavior) from intercalated cells

Question 39

What should potassium sparing diuretics NEVER be given with?

Answer 39

potassium supplements | ACE inhibitors

Question 40

What is spironolactone?

Answer 40

competitive inhibitor of aldosterone receptor (decreases Na+ reabsorption and spares K+)

Question 41

How rapid is the onset of spironolactone?

Answer 41

slow - takes days

Question 42

What is eplerenone?

Answer 42

competitive antagonist of aldosterone binding to mineralocorticoid receptor more expensive, does not inhibit testosterone

Question 43

What are the effects of spironolactone?

Answer 43

deceased lumen neg potential, reduced driving force for H+ --> metabolic acidosis

Question 44

What does amiloride do?

Answer 44

block Na channels in the principal cells (decreasing driving force on K+ thus sparing it)

Question 45

What is a second drug that blocks Na channels in the principal cells like amiloride?

Answer 45

triamterene (but it is 10x LESS potent than amiloride)

Question 46

What were the 2 original, unintended ADH antagonists?

Answer 46

demeclocycline | lithium

Question 47

What is the currently used ADH antagonist?

Answer 47

Tolvaptan (selectively inhibits vasopressin V2 receptor)

Question 48

What is the most efficient diuretic for shedding NaCl? NaHCO3?

Answer 48

``` NaCl = loop NaHCO3 = CA inhibitors ```

Question 49

Diuretics __________ capillary hydrostatic pressure and ___________ plasma oncotic pressure

Answer 49

DECREASE hydrostatic INCREASE oncotic favors absorption over filtration

Question 50

How does hepatic cirrhosis lead to edema?

Answer 50

hypoalbuminemia --> reduced plasma volume --> activation of RAA --> hyperaldosteronism results in increased Na+ retention

Question 51

What is the most common electrolyte disorder in hospitalized patients?

Answer 51

hyponatremia

Question 52

What are the symptoms of hyponatremia?

Answer 52

CNS related (headache, etc)

Question 53

True or false: you can have hyponatremia in all volemic states?

Answer 53

true

Question 54

What are the best diuretics to use for hyponatremic patients?

Answer 54

AVP receptor agonists

Question 55

For uncomplicated hypertensio, _____________________ should be used in drug treatment (either alone or combined with drugs of another class)

Answer 55

thiazide diuretic

Question 56

What are the 5 symptoms of metabolic syndrome?

Answer 56

``` fasting hyperglycemia high blood pressure central obesity decreased HDL elevated triglycerides ```

Question 57

What is a unique, counterintuitive application of thiazide?

Answer 57

treats nephrogenic diabetes insipidus (which loses its sensitivity to ADH)

Question 58

What are conditions conducive to kidney stone formation?

Answer 58

hypercalcemia

Question 59

What diuretic would you give to treat kidney stones?

Answer 59

thiazide (decrease calcium conc in urine by reabsorbing)

Question 60

True or false: you would give thiazides to treat hypercalcemia

Answer 60

FALSE (they increase calcium reabsorption)