Diuretics and RAAS Antagonists Use in HF

Question 1

what is Baroreceptor response

Answer 1

incr sympathetic discharge

short term

Question 2

what is the RAAS response

Answer 2

incr renin release

Question 3

Goals of heart failure management with pharmacotherapy (3)

Answer 3

1) reduce congestion with diuretics
2) modulate neurohormonal activation (RAAS antag + Beta blocker)
3) improve flow with vasodilations

Question 4

regardless of HF Type, ___

Answer 4

ALWAYS CONTROL VOLUME FIRST WITH DIURESIS

Question 5

Chronic HFrEF

Answer 5

1) beta blocker
2) ACE inhibitor/ARB
3) aldosterone antagonist
4) Hydralazine/ISDN
5) +/- digoxin
6) ICD/CRT

Question 6

Chronic HFpEF

Answer 6

1) control risk factor (DM, HTN, obesity)

2) control volume

Question 7

Acute HFrEF

Answer 7

1) IV diuresis
2) nitrate (if BP allow)
3) CPAP/BiPAP (if SOB)
4) Pressors (VERY LOW CO, SHOCK)

Question 8

Acute HFpEF

Answer 8

1) IV diuresis
2) nitrates (if BP allows)
3) CPAP/BiPAP

Question 9

first thing with chronic HFpEF, acute HFrEF or HFpEF

Answer 9

IV diuresis/volume control

Question 10

purpose of diuretics

Answer 10

1) Na/H2O excretion
2) decr intravascu fluid volume
3) decr venous congestion
4) decr dyspnea/edema

Question 11

effect of diuretics of LVEDP vs. SV curve

Answer 11

shift a given point to the left but staying on the same curve line

Question 12

Diuretics use

Answer 12

USE FIRST AS NEEDED TO REDUCE congestion

Question 13

Purpose of diuretics

Answer 13

lower preload, decr Na/H2O retention

Question 14

which type of diuretics preferred?

Answer 14

loop because of efficacy

can augment with thiazide diuretic

Question 15

diuretics can be used ___ and ___

Answer 15

chronically and acutely

Question 16

When do you use ACEI’s

Answer 16

during or after optimization of diuretic therapy

Question 17

effect of ACEI’s?

Answer 17

1) vasodilation
2) decr aldosterone activation
3) antiremodeling effects

Question 18

when do you use aldosterone antagonists?

Answer 18

ADDED for LVEF <30% with ACEI/ARB and B-blocker therapy

Question 19

K+ effect of aldosterone antagonist

Answer 19

1) monitor serum K+ 30 mL/min (K+ sparing)

Question 20

function of aldosterone antagonist

Answer 20

1) antiremodeling action 2) additional Na+ loss at kidney

Question 21

2 names of aldosterone antagonists

Answer 21

1) spironolactone - gynecomastia

2) eplernone

Question 22

where do most diuretics exert their effects?

Answer 22

at luminal (urine surface) of renal cells

Question 23

What is mechanism of thiazide and furosemide?

Answer 23

interact with membrane transport proteins

Question 24

which diuretics interact with membrane transport proteins?

Answer 24

thiazide

furosemide

Question 25

what is mechanism of spironolactone

Answer 25

interact with hormone receptor

Question 26

which diuretic interacts with hormone receptors

Answer 26

spironolactone

Question 27

how is Na+ level controlled?

Answer 27

active transport via Na+/K+ ATPase at interstitial (BLOOD) surface in kidney, Na+ reabsoprtion

Question 28

how do diureitcs affect Na+ levels

Answer 28

1) decr Na+ reabsoprtion | 2) Na+ and H2O into urine

Question 29

mechanism of loop diuretics

Answer 29

1) inhib NaCl transport in thick ascending limb across lumen-urine 2) decr gradient to pump K+ out 3) incr Mg2+/Ca2+ excretion

Question 30

what is unique about when you can use loop diuretics?

Answer 30

YOU CAN USE ON RENAL FAILURE PATIENTS

Question 31

pharmacokinetics of loop diuretics

Answer 31

variable bioavaiability with furosemide fast IV

Question 32

how are loop diuretics excreted?

Answer 32

glomerular filtration renal secretion

Question 33

negative of filtration of loop diuretics?

Answer 33

same transporter as uric acid --> hyperuricemia

Question 34

which loop diuretic has shortest half life and which has longest?

Answer 34

furosemide = shortest bumetanide = longest

Question 35

when do you use loop diuretics

Answer 35

HF patients with volume overload

Question 36

how are loop diuretics enhanced?

Answer 36

with salt restriction

Question 37

what happens if furosemie cannot be used?

Answer 37

1) incr dose 2) switch to bumetanide/torsemide (more reliable + longer duration) 3) IV administration 4) ethacrynic acid for non-sulfa form

Question 38

what are the mechanisms in HF patients with decr diuretic response

Answer 38

1) decr drug delivery to kidney via decr renal blood flow | 2) low perfusion ACTIVATES RAAS AND SYMP NS

Question 39

when do you get refractory edema side effect of loop diuretics?

Answer 39

when you pair with thiazide

Question 40

how does loop + thiazide cause refractory edema?

Answer 40

1) block distal tubule Na+ reabs | 2) counter loop induced incr in Na+ delivery

Question 41

what can you do to treat patients with refractory edema

Answer 41

1) give them aldosterone antagonist to incr diuresis and incr K+ sparing

Question 42

side effects of loop diuretics

Answer 42

1) hypokalemic metabolic alkalosis (b/c incr K+ and H+ excretion) 2) hyperuricemia - gout

Question 43

mechanism of thiazide diuretics

Answer 43

1) inhib Na+/Cl- cotransporter, incr urine excr of NaCl

Question 44

how effective are thiazides?

Answer 44

less than loops because only 5-10% of filtered Na+ is NORMALLY reabsorbed here

Question 45

difference btwn thaizides and loops in level of Ca2+

Answer 45

Thiazides - incr reabs of Ca2+ Loop - decr Ca2+

Question 46

compare use of thiazide and loops for CHF

Answer 46

higher dose for thiazide in HTN usu need loops for CHF

Question 47

side effects of thiazides

Answer 47

1) hypokalemia --> ectopic pacemaker 2) hyperglycemia 3) hyperuricemia --> gout

Question 48

amount of diuresis for K+ sparing diuretics?

Answer 48

mild diuresis alone

Question 49

difference btwn mechanism of K+ sparing vs. K+ wasting?

Answer 49

K+ sparing --> block collecting tubule Na+ reabs receptor --> decr K+ excretion K+ wasting --> block proximal Na+ reabs, incr K+ excretion

Question 50

mechanism of spironolactone

Answer 50

competitive antagonist at aldosterone receptor

Question 51

mechanism of triamterene/amiloride

Answer 51

direct block Na+ in collecting duct lumen, decr Na+ reabs NO UTILITY IN HF

Question 52

what is a key criteria before giving patient K+ sparing diuretic?

Answer 52

make sure kidney works well (or else hyperkalemia)

Question 53

why are aldosterone antag (K+ sparing) used in HF?

Answer 53

block aldo receptors on heart --> RAAS antagonist anti-remodeling incr K+

Question 54

side effects of aldosterone antag

Answer 54

1) hyperkalemia | 2) gynecomastia (block androgen receptor)

Question 55

factors that incr risk of hyperkalemia with aldosterone antag

Answer 55

1) incr age 2) renal failure 3) higher dose 4) combined ACEI + ARB 5) NSAID

Question 56

what in common amongst use of ACEI/ARB, B blocker, Aldosterone receptor blocker

Answer 56

anti-remodeling, decr fibrosis/apoptosis

Question 57

mechanism of ACE inhibitor

Answer 57

decr myocardial hypertrophy and remodeling

Question 58

pharmacokinetics of ACE inhibitor

Answer 58

1) absorb orally 2) prodrug convert to active metabolity in liver 3) elim by kidney 4) once-daily

Question 59

side effects of ACE inhibitor

Answer 59

cough renal dysfunction hypotension hyperkalemia teratogenic

Question 60

advantage of ARB over ACEI

Answer 60

more complete inhib of Ang II no cough

Question 61

disadvantage of ARB over ACEI

Answer 61

loss of bradykinin vasodilation

Question 62

side effects of ARB

Answer 62

ACEI without cough contraindicate in pregnancy