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Pharmacology > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What was the first clinically developed diuretic?

A

acetazolamide

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2
Q

Kidneys control ECF volume by adjusting ____ and ____ exretion

A

NaCl and water

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3
Q

Diuretics are used mainly to reduce ECV by ____________________

A

decreasing NaCl content

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4
Q

What part of the loop of henle can reabsorb water?

A

thin descending limb

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5
Q

Where does acetazolamide work?

A

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

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6
Q

What does Mannitol do?

A

osmotic diuretic

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

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7
Q

Where does Furosemide work?

A

thick ascending limb of Henle

inhibits Na/K/2Cl transport

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8
Q

Where doe the thiazide diuretics work?

A

DCT

inhibit NaCl cotransport in DCT

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9
Q

Where do the K+ sparing diuretics act?

A

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

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10
Q

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

A

spironolactone

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11
Q

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

A

mannitol

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

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12
Q

What is responsible for driving sodium reabsorption?

A

Na/K ATPase at the basolateral membrane

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13
Q

What is the MOA of acetazolamide?

A

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

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14
Q

How does acetazolamide get into the tubule?

A

secreted via organic acid transporter

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15
Q

What are adverse effects of acetazolamide?

A

metabolic acidosis
hypokalemia
calcium phosphate stones
drowsiness

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16
Q

What is contraindication for acetazolamide?

A

cirrhosis (reduced NH3 secretion so increased serum NH3)

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17
Q

Ammonia exretion is _____________ related to urine pH

A

inversely

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18
Q

Which CA inhibitor is 30x more potent than acetazolamide?

A

dichlorphenamide

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19
Q

Which CA inhibitor is 5m more potent than acetazolamide?

A

methazolamide

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20
Q

Which CA inhibitor is used topically for eye stuff?

A

dorzolamide

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21
Q

What is the effect of mannitol?

A

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

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22
Q

How does mannitol get into the tubular fluid?

A

glomerular secretion

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23
Q

What is a big toxicity of mannitol?

A

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

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24
Q

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

A

FALSE - cannot be used in chronic failure patients

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25
Q

What are 3 indications of mannitol?

A
  • increase urine volume

- reduce ICP and IOP

26
Q

What is the MOA for loop diuretics?

A

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

27
Q

What is the most efficacious class of diuretics?

A

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

28
Q

What effect do loop diuretics have on the vasculature?

A

vasodilation

29
Q

What is the one unique toxicity of furosamide?

A

ototoxicity

30
Q

What loop diuretic is used as a last resort only?

A

ethacrynic acid (nephro and ototoxic)

31
Q

What is the important transporter on the DCT?

A

Na/Cl cotransporter and the Ca++ channel

Ca is pumped out of cell via Na/Ca countertransport

32
Q

What is hydrochlorothiazide?

A

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

33
Q

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

A

metolazone

10x more potent than hydrochlorothiazide

34
Q

What do the principal cells of the collecting duct do?

A

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

aldosterone works here

35
Q

What do intercalated cells do?

A

proton pumps transport H into lumen

HCOs/Cl countertransported

36
Q

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

A

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

HYPOkalemia

37
Q

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

A

increases it leading to hypokalemia

why all of these diuretics can lead to hypokalemia

38
Q

How do diuretics lead to metabolic alkalosis?

A

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

39
Q

What should potassium sparing diuretics NEVER be given with?

A

potassium supplements

ACE inhibitors

40
Q

What is spironolactone?

A

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

41
Q

How rapid is the onset of spironolactone?

A

slow - takes days

42
Q

What is eplerenone?

A

competitive antagonist of aldosterone binding to mineralocorticoid receptor

more expensive, does not inhibit testosterone

43
Q

What are the effects of spironolactone?

A

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

44
Q

What does amiloride do?

A

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

45
Q

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

A

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

46
Q

What were the 2 original, unintended ADH antagonists?

A

demeclocycline

lithium

47
Q

What is the currently used ADH antagonist?

A

Tolvaptan (selectively inhibits vasopressin V2 receptor)

48
Q

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

A 
NaCl = loop
NaHCO3 = CA inhibitors
49
Q

Diuretics __________ capillary hydrostatic pressure and ___________ plasma oncotic pressure

A

DECREASE hydrostatic
INCREASE oncotic

favors absorption over filtration

50
Q

How does hepatic cirrhosis lead to edema?

A

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

51
Q

What is the most common electrolyte disorder in hospitalized patients?

A

hyponatremia

52
Q

What are the symptoms of hyponatremia?

A

CNS related (headache, etc)

53
Q

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

A

true

54
Q

What are the best diuretics to use for hyponatremic patients?

A

AVP receptor agonists

55
Q

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

A

thiazide diuretic

56
Q

What are the 5 symptoms of metabolic syndrome?

A 
fasting hyperglycemia
high blood pressure
central obesity
decreased HDL
elevated triglycerides
57
Q

What is a unique, counterintuitive application of thiazide?

A

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

58
Q

What are conditions conducive to kidney stone formation?

A

hypercalcemia

59
Q

What diuretic would you give to treat kidney stones?

A

thiazide (decrease calcium conc in urine by reabsorbing)

60
Q

True or false: you would give thiazides to treat hypercalcemia

A

FALSE (they increase calcium reabsorption)

Pharmacology (21 decks)

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