Diuretics Flashcards

1
Q

the site of action for loop diuretics is the ____

A

thick ascending loop of henle

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2
Q

loop diuretics block what transporter

A

Na+/K+/2Cl- symporter

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3
Q

loop diuretics compete with ____ for binding to the Na+/K+/2Cl sympoter

A

Cl

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4
Q

approximately __% of filtered sodium is reabsorbed at the thick ascending loop of henle

A

25

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5
Q

the most serious side effects of loop diuretics are due to ______

A

fluid and electrolyte imbalance (an extension of the therapeutic effect)

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6
Q

what are the loop diuretics

A

furosemide, bumetanide, torsemide, ethacrynic acid

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7
Q

what is different about ethacrynic acid

A

it has no sulfa moiety

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8
Q

what is the most potent diuretic

A

loop

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9
Q

what are the side effects of loops

A

hypokalemia, hyponatremia, volume depletion, hypotension, hearing loss, hyperuricemia, hyperglycemia, increase cholesterol and triglycerides

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10
Q

clinical uses of loops

A

emergency treatment of acute pulmonary edema, edema associated w/ CHF, cirrhosis, and liver disease. use after less potent diuretics have failed to work, use in combo with other diuretics

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11
Q

what are the thiazides

A

chlorthalidone, indapamide, metolazone, chlorothiazide, hydrochlorothiazide

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12
Q

what site in the renal tubule do thiazides work

A

distal convoluted tubule

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13
Q

what protein do thiazides bind to

A

a carrier protein that symports Na and Cl out of the renal tubule

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14
Q

thiazides must ______ to exert effect

A

enter the renal tubule

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15
Q

thiazides are actively secreted by the ____

A

proximal tubule

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16
Q

thiazides inhibit ____ reabsorption from the luminal side

A

sodium

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17
Q

the diuretic effect of thiazides is max __%

A

5%; because most of the sodium has been reabsorbed before filtrate arrives

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18
Q

why are thiazides safe drugs

A

toxic doses are many times greater than the therapeutic dose

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19
Q

the most serious adverse effects of thiazides are due to ____

A

disturbances of fluid and electrolyte balance

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20
Q

what are the adverse effects of thiazides

A

hyponatremia, volume depletion, hypotension, hyperuricemia, decreased glucose tolerance, increased cholesterol and triglycerides

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21
Q

clinical uses of thiazides

A

hypertension; congestive heart failure (adjunct)

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22
Q

what are the two types of potassium sparing diuretics

A

aldosterone antagonists/mineralocorticoid receptor antagonists, and sodium channel blockers

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23
Q

what are the aldosterone antagonists

A

spironolactone, eplerenone, finerenone

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24
Q

what are the sodium channel blockers

A

triamterene, amiloride

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25
what is the site of action of the potassium sparing diuretics
collecting duct
26
aldosterone antagonists are structurally related to ____
aldosterone
27
aldosterone antagonists bind to _____
cytoplasmic mineralocorticoid receptors
28
how do aldosterone antagonists promote sodium loss and potassium conservation
they prevent aldosterone from stimulating sodium reabsorption, and the capacity of aldosterone to make more sodium channels is blocked so less sodium absorbed= potassium not eliminated
29
what are the side effects specific to spironolactone; and WHY
gynecomastia, impotence, menstrual disorders; because it lacks specificity, also blocks androgen and progesterone
30
what is the most common side effect of potassium sparing diuretics
hyperkalemia
31
the risk of hyperkalemia with K+ sparing diuretics is INCREASED when used with what other drug class
RAAS inhibitors
32
why does eplerenone not share the same side effects as spironolactone
is is a SELECTIVE aldosterone blocker, greater specificity for MR
33
what makes finerenone different from the other aldosterone antagonists
it is nonsteroidal, more potent anti-inflammatory and anti-fibrotic effects
34
what is finerenone approved for
reduce risk of sustained estimated GFR decline, end stage kidney disease, CV death, nonfatal MI, and hospitalization for HF in pts w/ CKD associated w/ T2DM
35
what is the mechanism for the sodium channel blockers
they bind to and inhibit epithelial sodium channels. since less sodium is absorbed, potassium is not eliminated in exchange
36
pearl for K+ sparing diuretics
weak antihypertensive activity, major benefit is when used in conjunction with thiazides or loops to reduce incidence of hypokalemia
37
clinical uses of all K+ sparing diuretics
prevent hypokalemia from thiazides and loops
38
clinical use of spironolactone
heart failure, primary aldosteronism, acne
39
clinical uses of eplerenone
adjunct treatment of HTN & post-MI w/ HF
40
what are the carbonic anhydrase inhibitors
acetazolamide, dorzolamide
41
what is the site of action of the carbonic anhydrase inhibitors
proximal tubule
42
what is the mechanism of the carbonic anhydrase inhibitors
inhibit carbonic anhydrase-- both the membrane bound and cytoplasmic forms, which interferes with normal bicarb reabsorption, so the urine becomes alkaline and urine pH increases to 8. meanwhile, pH of blood decreases and may result in metabolic acidosis. the increased H+ concentration in the tubular fluid diminishes H+ concentration gradient which normally favors sodium reabsorption by the Na/H exchange transport proteins. more sodium is left in the tubular fluid as it travels toward other segments of the tubule
43
why do carbonic anhydrase inhibitors have a mild diuretic action
much of the Na+ whose reabsorption is prevented in the proximal tubule can be reabsorbed thru compensation by the other downstream portions of the tubule
44
pharmacologic uses of carbonic anhydrase inhibitors
glaucoma (dorzolamide), acute mountain sickness, metabolic alkalosis
45
how do carbonic anhydrase inhibitors work for glaucoma
reduce the rate of aqueous humor formation by the ciliary process, and reduce intraocular pressure
46
how do carbonic anhydrase inhibitors work for acute mountain sickness
they increase the breathing rate
47
what are the osmotic diuretics
mannitol, urea (Ure-Na)
48
how do osmotic diuretics work
they increase osmolarity of the tubular fluid and thereby attract water by osmosis in the tubule.
49
osmotic diuretics are freely filtered at the ____
glomerulus
50
osmotic diuretics are pharmacologically ____
inert
51
what are the uses of mannitol
to decrease intracranial pressure in neurological conditions, decrease intraocular pressure before opthalmic procedures
52
what is the use of urea
is is a medical food for hyponatremia
53
why is mannitol used for intracranial pressure
it is trapped in the blood vessels and acts as an osmotically active agent to pull water into the circulation from the interstitial fluid of the brain
54
why is mannitol used before opthalmic procedures
it takes advantage of its high concentration in the blood, causing water to be pulled from the eye into the blood
55
why does urea treat hyponatremia
it helps to normalize serum sodium levels by inducing osmotic excretion of free water
56
why is mannitol IV only
it is a 6 carbon sugar like glucose, but it is not a substrate for sugar transporters so it cannot be absorbed from the intestine. if it was given orally it would cause diarrhea by osmotically pulling water into the intestine
57
what are the vasopressin antagonists
tolvaptan, conivaptan
58
vasopressin antagonists are ____
aquauretics
59
what does aquauretic mean
they promote free water loss but do not affect sodium excretion
60
what are the vasopressin receptor subtypes
V1alpha, V1beta, V2
61
___ vasopressin receptors are in the vascular smooth muscle, and their stimulation results in contraction
V1alpha
62
____ vasopressin receptors are in the anterior pituitary, and their stimulation results in the release of ACTH and beta-endorphin
V1beta
63
__ vasopressin receptors are located in the collecting ducts, and their stimulation results in increased water reabsorption
V2
64
tolvaptan blocks __ causing what
V2, water diuresis
65
conivaptan blocks ___, causing ____
V1 and V2, relaxation of blood vessels and water loss
66
which vasopressin antagonist is IV only
conivaptan
67
what are the clinical uses of vasopressin antagonists
they are used in hyponatremia. they are studied in patients with heart failure. they are not used for hypertension