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Pharmacotherapy 1 > 2 - Diuretics (Barker) > Flashcards

2 - Diuretics (Barker) Flashcards

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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?

Study These Flashcards
A

inhibit NaCl reabs in DCT

enhance Ca2+ reabs

24
Q

What are the clinical uses of thiazide diuretics?

Study These Flashcards
A

HTN
CHF
nephrolithiasis d/t idiopathic hypercalcuria
nephrogenic diabetes insipidus

25
How are thiazide diuretics useful in nephrogenic diabetes insipidus?
reduce BP and plasma volume reduce UOP not completely understood
26
How do thiazide diuretics promote Ca2+ reabs?
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
What are thiazide diuretic toxicities?
- 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
What are contraindications to thiazide diuretics?
sulfa allergies otherwise very well-tolerated in pts!
29
What types of diuretics act in the collecting duct?
K-sparing diuretics: Na+ channel inhibitors aldosterone antagonists ADH antag
30
What is the moa of diuretics that act in the collecting tubule?
inhibit Na+ channels | --> stop potassium loss
31
What are a few diuretics that inhibit the Na+ channel in the CD?
amiloride (Midamor) | triamterene (Dyrenium)
32
What are the actions of amiloride (Midamor) and triamterene (Dyenium)?
- inhibit Na+ channels in apical membrane of the CD | - -> reduces K+ excretion
33
What are clinical uses of amiloride (Midamor)?
adjunctive Tx w thiazide or loop diuretic in CHF or HTN
34
What are toxicities of amiloride (Midamor) or triamterene (Dyrenium)?
hyperkalemia | hyperchloremic metabolic acidosis
35
What are contraindications for amiloride (Midamor)?
K+ supplements | ACEI
36
What are the clinical uses of triamterene (Dyrenium)?
edema assoc'd w CHF, hepatic cirrhosis, nephrotic syndrome, or hyperaldosteronism
37
What are contraindications for triamterene (Dyrenium?
kidney stones (poor drug solubility) K+ supplements ACEI
38
How do aldosterone antagonists act to promote diuresis in the CD?
AIP-aldosterone-induced proteins AIPs work to incr Na+ reabs aldosterone antag reduce the # of Na+ channels available to move Na+ and K+
39
What type of hormone is aldoesterone?
mineralcorticoid producted in the zona glomerulosa of the adrenal gland
40
What is the structure-activity relationship of aldosterone antag?
resemble aldosterone!
41
What are examples of aldosterone antagonists?
spironolactone (Aldactone) | Eplerenone (Inspra)
42
What are the actions of spironolactone (Aldactone)?
block actions of aldosterone | inhib 5alpha-reductase (responsible for formation of active metabolites of aldosterone)
43
What are the clinical uses of spironolactone (Aldactone)?
HTN or CHF w/ other diuretics mineralocorticoid excess aldosteronism (primary or secondary resulting from CHF, hepatic cirrhosis or nephrotic syndrome)
44
What are toxicities assoc'd w spironolactone (Aldactone)?
``` hyperkalemia hyperchloremia metabolic acidosis gynecomastia impotence benign prostatic hyperplasia ```
45
What are contraindications for spironolactone (Aldactone)?
K+ supplements ACEI chronic renal insuff
46
What are actions of eplerenone (Inspra)?
selective antagonism of mineralocorticoid receptor in kidney, heart, blood vessels, and brain
47
What are clinical uses of eplerenone (Inspra)?
HTN, alone or in combination | full therapeutic effect should be observed w/in 4 wks
48
What are the toxicities and adverse reactions of eplerenone (Inspra)?
hyperkalemia | hypertriglyceridemia
49
What are contraindications for eplerenone (Inspra)?
K+ supp, K+-sparing diuretics, ACEI chronic renal insuff diabetes assoc'd w microalbuminuria CYP3A4 inhib (e.g. ketoconazole)
50
What is an example of osmotic diuretics?
mannitol
51
What are the actions of mannitol?
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
What are indications for mannitol?
increase urine volume | reduction of intracranial or intraocular pressure (esp after head trauma)
53
What are toxicities assoc'd w mannitol?
EC volume expansion | dehydration and hypernatremia
54
What is an example of an ADH antagonist?
demeclocycline (Declomycin)
55
What are the actions of demeclocycline (Declomycin)?
tetracycline derivative inhibit ADH effects at CD reduce water reabs lithium salts have similar effect
56
What are indications for demeclocycline (Declomycin)?
SIADH | elevated ADH
57
What are toxicities assoc'd w demeclocycline (Declomycin)?
nephrogenic diabetes insipidus | renal failure

Pharmacotherapy 1 (26 decks)

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