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Pharmacotherapy 1 > 2 - Diuretics (Barker) > Flashcards

2 - Diuretics (Barker) Flashcards

1
Q

What class of diuretics acts in the proximal tubule?

A

carbonic anhydrase inhibitors

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2
Q

What is the moa of carbonic anhydrase inhibitors?

A

decrease bicarb reabs
sodium and bicarb stay in urine
more fluid stays in the urine
(increased Na in urine in CD–>K wasting)

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3
Q

What is the structure-activity relationship of Cl-, Br-, CF3-, or NO2- substituents on carbonic anhydrase inhibitors?

A

maximize diuretic activity

subsitute with an amine–>
increase natriuretic activity
decrease CA inhibitor activity

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4
Q

What is the structure-activity relationship of an unsubstituted sulfamoyl moiety for CA inhibitors?

A

required for activity

-can be replaced w electrophilic group, which increases diuretic activity but decr CA inhibitory activity

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5
Q

What is an example of a carbonic anhydrase inhibitor?

A

acetazolamide (Diamox)

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6
Q

What are the actions of acetazolamide?

A

decrease sodium and bicarb reabs
decrease H2O reabs
metabolic acidosis

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7
Q

What are the clinical uses of acetazolamide?

A

acute mountain sickness
metabolic alkalosis
glaucoma
urinary alkalinization

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8
Q

Where do loop diuretics act?

A

thick ascending limb of loop of Henle

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9
Q

What are some examples of loop diuretics?

A

furosemide (Lasix)
bumetanide (Bumex)
ethacrynic acid (Edecrin)
torsemide (Demadex)

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10
Q

What is the moa of Loop diuretics?

A

inhibit Na/K/2Cl- symporters
more electrolytes in urine–> more water in urine

more K+ in urine –> K-wasting (also more Na in CD…)
–>electrochemical gradient normally Ca2+ and Mg2+ to be paracellularly reabs’d. this is now decreased.

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11
Q

What is the structure-activity relationship for loop diuretics that are sulfonamide derivatives?

A

-NHR in the 2 (Lasix) or 3 position (Bumex)

slide 7

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12
Q

What is the structure-activity relationship for loop diuretics that are NOT sulfonamide derivatives?

A
  • sulfonylurea (Demadex)

- ethacrynic acid is a prodrug with an electrophilic moiety that reacts with cysteine or glutathione

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13
Q

What are the actions of lop diuretics?

A
  • inhibitor Na+/K+/2Cl- cotransporter n the thick ascending limb
  • reduce NaCl, K+, and divalent cation reabs
  • incr renal blood flow
  • rapid response after IV admin
  • duration of action depen on renal fxn
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14
Q

What are the clinical uses of loop diuretics?

A 
edematous condition
acute pulmonary edema
acute hypercalcemia
hyperkalemia
acute renal failure
anion overdose
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15
Q

What are some toxicities for loop diuretics?

A 
dehydration
hypokalemic metabolic alkalosis (K-wasting)
ototoxicity (dose-dep & reversible)
hyperuricemia (d/t dehydration-->gout)
hypomagnesemia
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16
Q

What are some contraindications for loop diuretics?

A

sulfa allergy (sulfonamides only)

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17
Q

What class of diuretics works in the DCT?

A

thiazides

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18
Q

What is the moa of thiazide diuretics?

A

inhibits NaCl symporter
more fluid in urine
more sodium in urine –> K-wasting

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19
Q

What are the thiazide diuretics?

A

don’t memorize but know that they end in thiazide!

chlorthiazide (Diuril)
HCTZ (HydroDiuril ESidrix)
trichlormethiazide (Naqua, Metahydrin)
methylchlothiazide (Enduron, Aquatensen)
polythiazide (Renese)
cyclothiazide (Anhyron)
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20
Q

What are the thiazide-like diuretics?

A

chlorthalidone (Hygroton)
indapamide (Lozol)
metolazone (Diulo, Zaroxolyn)

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21
Q

What is the sulfamoyl moiety?

A

H2NO2S-

or
-SO2NH2

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22
Q

What structural feature of thiazides is unique among diuretics?

A

bicyclic

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23
Q

What are the actions of thiazide diuretics?

A

inhibit NaCl reabs in DCT

enhance Ca2+ reabs

24
Q

What are the clinical uses of thiazide diuretics?

A

HTN
CHF
nephrolithiasis d/t idiopathic hypercalcuria
nephrogenic diabetes insipidus

25
Q

How are thiazide diuretics useful in nephrogenic diabetes insipidus?

A

reduce BP and plasma volume
reduce UOP
not completely understood

26
Q

How do thiazide diuretics promote Ca2+ reabs?

A

lower IC Na+ levels
Na/Ca exchanger in basement membrane moves Na into cell and Ca2+ into blood.
Creates gradient for moving Ca2+ out of urine and into blood.
(PTH normally stimulates Ca2+ transporters on the luminal membrane (passive))

27
Q

What are thiazide diuretic toxicities?

A
  • hypokalemic metabolic alkalosis and hyperuricemia
  • imp’d carb tolerance (imp’d insulin release and glucose utilization for DM pts)
  • hyperlipidemia (corrects over time)
  • hyponatremia
28
Q

What are contraindications to thiazide diuretics?

A

sulfa allergies

otherwise very well-tolerated in pts!

29
Q

What types of diuretics act in the collecting duct?

A

K-sparing diuretics:
Na+ channel inhibitors
aldosterone antagonists
ADH antag

30
Q

What is the moa of diuretics that act in the collecting tubule?

A

inhibit Na+ channels

–> stop potassium loss

31
Q

What are a few diuretics that inhibit the Na+ channel in the CD?

A

amiloride (Midamor)

triamterene (Dyrenium)

32
Q

What are the actions of amiloride (Midamor) and triamterene (Dyenium)?

A
  • inhibit Na+ channels in apical membrane of the CD

- -> reduces K+ excretion

33
Q

What are clinical uses of amiloride (Midamor)?

A

adjunctive Tx w thiazide or loop diuretic in CHF or HTN

34
Q

What are toxicities of amiloride (Midamor) or triamterene (Dyrenium)?

A

hyperkalemia

hyperchloremic metabolic acidosis

35
Q

What are contraindications for amiloride (Midamor)?

A

K+ supplements

ACEI

36
Q

What are the clinical uses of triamterene (Dyrenium)?

A

edema assoc’d w CHF, hepatic cirrhosis, nephrotic syndrome, or hyperaldosteronism

37
Q

What are contraindications for triamterene (Dyrenium?

A

kidney stones (poor drug solubility)
K+ supplements
ACEI

38
Q

How do aldosterone antagonists act to promote diuresis in the CD?

A

AIP-aldosterone-induced proteins
AIPs work to incr Na+ reabs
aldosterone antag reduce the # of Na+ channels available to move Na+ and K+

39
Q

What type of hormone is aldoesterone?

A

mineralcorticoid producted in the zona glomerulosa of the adrenal gland

40
Q

What is the structure-activity relationship of aldosterone antag?

A

resemble aldosterone!

41
Q

What are examples of aldosterone antagonists?

A

spironolactone (Aldactone)

Eplerenone (Inspra)

42
Q

What are the actions of spironolactone (Aldactone)?

A

block actions of aldosterone

inhib 5alpha-reductase (responsible for formation of active metabolites of aldosterone)

43
Q

What are the clinical uses of spironolactone (Aldactone)?

A

HTN or CHF w/ other diuretics
mineralocorticoid excess
aldosteronism (primary or secondary resulting from CHF, hepatic cirrhosis or nephrotic syndrome)

44
Q

What are toxicities assoc’d w spironolactone (Aldactone)?

A 
hyperkalemia
hyperchloremia metabolic acidosis
gynecomastia
impotence
benign prostatic hyperplasia
45
Q

What are contraindications for spironolactone (Aldactone)?

A

K+ supplements
ACEI
chronic renal insuff

46
Q

What are actions of eplerenone (Inspra)?

A

selective antagonism of mineralocorticoid receptor in kidney, heart, blood vessels, and brain

47
Q

What are clinical uses of eplerenone (Inspra)?

A

HTN, alone or in combination

full therapeutic effect should be observed w/in 4 wks

48
Q

What are the toxicities and adverse reactions of eplerenone (Inspra)?

A

hyperkalemia

hypertriglyceridemia

49
Q

What are contraindications for eplerenone (Inspra)?

A

K+ supp, K+-sparing diuretics, ACEI
chronic renal insuff
diabetes assoc’d w microalbuminuria
CYP3A4 inhib (e.g. ketoconazole)

50
Q

What is an example of osmotic diuretics?

A

mannitol

51
Q

What are the actions of mannitol?

A

excreted, not reabs’d from urine
creates osmotic resistance that limits water reabs in the PCT and descending limb of loop of Henle
natriuresis

52
Q

What are indications for mannitol?

A

increase urine volume

reduction of intracranial or intraocular pressure (esp after head trauma)

53
Q

What are toxicities assoc’d w mannitol?

A

EC volume expansion

dehydration and hypernatremia

54
Q

What is an example of an ADH antagonist?

A

demeclocycline (Declomycin)

55
Q

What are the actions of demeclocycline (Declomycin)?

A

tetracycline derivative
inhibit ADH effects at CD
reduce water reabs

lithium salts have similar effect

56
Q

What are indications for demeclocycline (Declomycin)?

A

SIADH

elevated ADH

57
Q

What are toxicities assoc’d w demeclocycline (Declomycin)?

A

nephrogenic diabetes insipidus

renal failure

Pharmacotherapy 1 (26 decks)

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