ACEi, angiotensin antagonists, diuretics Flashcards

1
Q

RAAS pathway

A
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2
Q

where is renin produced

A

in the juxtaglomerular cells in kidney

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3
Q

what causes renin release

A

drop in BP in pre-glomerular arteries (systolic <90 mmHg)
low NaCl in kidney’s distal tubule
increased SNS activity (beta1)

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4
Q

where is angiotensinogen produced

A

liver

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5
Q

where is angiotensin converting enzyme (ACE) produced

A

kidney

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6
Q

what does angiotensin II cause

A

aldosterone secretion
vasoconstriction

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7
Q

what does angiotensin II mediated vasoconstriction cause

A

increased peripheral vascular resistance
–> increased BP

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8
Q

what does angiotensin II mediated aldosterone secretion cause

A

increased retention of Na and water –> increased BP

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9
Q

where does renin cleave angiotensinogen

A

between Leu-Val aa

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10
Q

where does ACE cleave angiotensin I

A

between Phe-His aa

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11
Q

where does aminopeptidase cleave angiotensin II

A

between Asp-Arg

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12
Q

what is the name of renin inhibitor drug

A

Aliskiren

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13
Q

aliskiren moa

A

direct inhibitor renin
decreases formation of angiotensin I from angiotensinogen

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14
Q

aliskiren clinical use

A

not 1st line tx for htn

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15
Q

aliskiren effect

A

drops BP bc it inhibits renin

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16
Q

aliskiren problems

A

do not use in pregnant and nursing mothers

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17
Q

what is common identifying factor of ACEi

A

all ACEi ends in -pril

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18
Q

what are the sulfahydryl-containing ACEi structurally related to Captopril

A

fentiapril, pivalopril, zofenopril, alacepril

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19
Q

what are the dicarboxyl-containing ACEi structurally related to Enalapril

A

lisinopril, benazepril, quinapril, moexipril, ramipril, trandolapril, perindopril, spirapril, pentopril, cilazapril

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20
Q

what are the phosphorous-containing ACEi

A

Fosinopril

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21
Q

ACEi action

A

inhibits angiotensin converting enzyme

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22
Q

ACEi effects

A

reduces vasoconstriction caused by angiotensin II
reduce Na and Cl retention caused by aldosterone
reduce total peripheral resistance
reduces myocardial mitogenic activity

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23
Q

ACEi clinical use

A

1st line tx for htn, hf

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24
Q

ACEi and ARBs in different races

A

particular useful in whites but not african americans as monotherapy for htn but appropriate for hf

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25
Q

ACEi in pts with diff. diseases

A

better for pts with diabetes than thiazides
better for pts with ischemic heart disease than direct vasodilators

26
Q

ACEis AEs

A

cough, angioedema, hyperkalemia

27
Q

why should ACEi not be used in pregnancy

A

can cause fetal hypotension, renal failure, mortality

28
Q

what may reduce ACEi effectiveness

A

NSAIDs

29
Q

what can ACEi/ARBs also be used in

A

renal artery stenosis, but not if GFR drops by more than 30%

30
Q

bradykinin effects

A

causes vasodilation, in part mediated by PGI2

31
Q

why can ACEi cause hyperkalemia

A

decreased production of aldosterone

32
Q

why can ACEi cause angioedema of lips and tongue

A

accumulation of bradykinin

33
Q

which race has bigger risk of angioedema from ACEi

A

black pts have a 4-5x higher risk than white pts

34
Q

what is common identifying factor of ARBs

A

all ARBs end in -sartan

35
Q

ARBs affinity

A

blocks angiotensin II receptors with higher affinity for AT1 than AT2 receptor

36
Q

ARBs potency ranking

A

candesartan = omesartan > irbesartan = eprosartan > telmisartan = valsartan > EXP 3174 (active metabolite of losartan) > losartan

37
Q

lisinopril info

A

t1/2 = 12h
not a prodrug

38
Q

enalapril info

A

prodrug, hydrolyzed to active diacid enalaprilat

39
Q

captopril info

A

thiol-containing
not a prodrug
t1/2 <3h

40
Q

what design is ARBs based off

A

carboxy terminus of angiotensin II

41
Q

ARBs structure activity relationship

A

acidic group: o-phenylcarboxylic acid (or the tetrazole isostere) or carboxylic acid
substituted imidazole or isosteric equivalent
in some cases, a second carboxylic acid group

42
Q

ARBs effects

A

decreased myocardial and vascular remodeling
decreased cardiomyocyte apoptosis
reduce total peripheral resistance

43
Q

ARBs clinical use

A

1st line monotherapy for htn IN pts who cannot tolerate ACEi

44
Q

ARBs AEs

A

hypotension, hyperkalemia, lower rate of angioedema, fetal pathologies, reduction in GFR

45
Q

why do ARBs not cause persistent cough

A

ARBs do not inhibit breakdown of bradykinin

46
Q

ARBs are particularly useful in pts with:

A

diabetes
ischemic heart disease
pts with CKD

47
Q

what are the aldosterone (mineralocorticoid) receptor antagonists (aka potassium sparing diuretics)

A

spironolactone, eplerenone

48
Q

K sparing diuretic moa

A

blocks reabsorption of sodium

49
Q

what causes K sparing diuretic’s effectiveness in hf

A

not primarily due to diuretic effect.
increases production of aldosterone which promotes development of cardiac hypertrophy, remodeling, fibrosis.
maintenance of normal K levels –> reduces risk of arrhythmias.

50
Q

K sparing diuretic clinical use

A

chronic hf.
aldosteronism.
not monotherapy for htn but used to reduce hypokalemia.

51
Q

K sparing diuretic AEs

A

hyperkalemia.
spironolactone can cause gynecomastia and impotence due to interaction with other steroid receptors.

52
Q

what is the thiazide diuretic drug

A

chlorthalidone

53
Q

thiazides moa

A

diuretic blocking sodium-chloride symporter (NCC) on distal convoluted tubule

54
Q

what does thiazide lower when used long term

A

peripheral vascular resistance –> lower BP

55
Q

thiazide clinical use

A

1st line monotherapy for mild-moderate htn

56
Q

what race is thiazides useful in

A

african americans

57
Q

what pts do you not use thiazides for

A

pts with diabetes, hyperlipidemia, gout

58
Q

thiazide AEs

A

hypokalemia, metabolic alkalosis, hyperuricemia, hypercalcemia, hyperglycemia, hyperlipidemia

59
Q

what does thiazides do initially

A

reduce blood volume and cardiac output
–> decrease BP

60
Q

which diuretic is not recommended as 1st line monotherapy for htn

A

loop diuretics

61
Q

why are K sparing diuretics not recommended as 1st line monotherapy for htn

A

weak acting.
associated with hyperkalemia

62
Q

what htn meds can you use for pregnancy

A

methyldopa
beta blockers (e.g. labetalol, metoprolol)