Diuretics and RAAS Antagonists Use in HF Flashcards
what is Baroreceptor response
incr sympathetic discharge
short term
what is the RAAS response
incr renin release
Goals of heart failure management with pharmacotherapy (3)
1) reduce congestion with diuretics
2) modulate neurohormonal activation (RAAS antag + Beta blocker)
3) improve flow with vasodilations
regardless of HF Type, ___
ALWAYS CONTROL VOLUME FIRST WITH DIURESIS
Chronic HFrEF
1) beta blocker
2) ACE inhibitor/ARB
3) aldosterone antagonist
4) Hydralazine/ISDN
5) +/- digoxin
6) ICD/CRT
Chronic HFpEF
1) control risk factor (DM, HTN, obesity)
2) control volume
Acute HFrEF
1) IV diuresis
2) nitrate (if BP allow)
3) CPAP/BiPAP (if SOB)
4) Pressors (VERY LOW CO, SHOCK)
Acute HFpEF
1) IV diuresis
2) nitrates (if BP allows)
3) CPAP/BiPAP
first thing with chronic HFpEF, acute HFrEF or HFpEF
IV diuresis/volume control
purpose of diuretics
1) Na/H2O excretion
2) decr intravascu fluid volume
3) decr venous congestion
4) decr dyspnea/edema
effect of diuretics of LVEDP vs. SV curve
shift a given point to the left but staying on the same curve line
Diuretics use
USE FIRST AS NEEDED TO REDUCE congestion
Purpose of diuretics
lower preload, decr Na/H2O retention
which type of diuretics preferred?
loop because of efficacy
can augment with thiazide diuretic
diuretics can be used ___ and ___
chronically and acutely
When do you use ACEI’s
during or after optimization of diuretic therapy
effect of ACEI’s?
1) vasodilation
2) decr aldosterone activation
3) antiremodeling effects
when do you use aldosterone antagonists?
ADDED for LVEF <30% with ACEI/ARB and B-blocker therapy
K+ effect of aldosterone antagonist
1) monitor serum K+ 30 mL/min (K+ sparing)
function of aldosterone antagonist
1) antiremodeling action 2) additional Na+ loss at kidney
2 names of aldosterone antagonists
1) spironolactone - gynecomastia
2) eplernone
where do most diuretics exert their effects?
at luminal (urine surface) of renal cells
What is mechanism of thiazide and furosemide?
interact with membrane transport proteins
which diuretics interact with membrane transport proteins?
thiazide
furosemide
what is mechanism of spironolactone
interact with hormone receptor
which diuretic interacts with hormone receptors
spironolactone
how is Na+ level controlled?
active transport via Na+/K+ ATPase at interstitial (BLOOD) surface
in kidney, Na+ reabsoprtion
how do diureitcs affect Na+ levels
1) decr Na+ reabsoprtion
2) Na+ and H2O into urine
mechanism of loop diuretics
1) inhib NaCl transport in thick ascending limb across lumen-urine
2) decr gradient to pump K+ out
3) incr Mg2+/Ca2+ excretion
what is unique about when you can use loop diuretics?
YOU CAN USE ON RENAL FAILURE PATIENTS
pharmacokinetics of loop diuretics
variable bioavaiability with furosemide
fast IV
how are loop diuretics excreted?
glomerular filtration
renal secretion
negative of filtration of loop diuretics?
same transporter as uric acid –> hyperuricemia
which loop diuretic has shortest half life and which has longest?
furosemide = shortest
bumetanide = longest
when do you use loop diuretics
HF patients with volume overload
how are loop diuretics enhanced?
with salt restriction
what happens if furosemie cannot be used?
1) incr dose
2) switch to bumetanide/torsemide (more reliable + longer duration)
3) IV administration
4) ethacrynic acid for non-sulfa form
what are the mechanisms in HF patients with decr diuretic response
1) decr drug delivery to kidney via decr renal blood flow
2) low perfusion ACTIVATES RAAS AND SYMP NS
when do you get refractory edema side effect of loop diuretics?
when you pair with thiazide
how does loop + thiazide cause refractory edema?
1) block distal tubule Na+ reabs
2) counter loop induced incr in Na+ delivery
what can you do to treat patients with refractory edema
1) give them aldosterone antagonist to incr diuresis and incr K+ sparing
side effects of loop diuretics
1) hypokalemic metabolic alkalosis (b/c incr K+ and H+ excretion)
2) hyperuricemia - gout
mechanism of thiazide diuretics
1) inhib Na+/Cl- cotransporter, incr urine excr of NaCl
how effective are thiazides?
less than loops because only 5-10% of filtered Na+ is NORMALLY reabsorbed here
difference btwn thaizides and loops in level of Ca2+
Thiazides - incr reabs of Ca2+
Loop - decr Ca2+
compare use of thiazide and loops for CHF
higher dose for thiazide in HTN
usu need loops for CHF
side effects of thiazides
1) hypokalemia –> ectopic pacemaker
2) hyperglycemia
3) hyperuricemia –> gout
amount of diuresis for K+ sparing diuretics?
mild diuresis alone
difference btwn mechanism of K+ sparing vs. K+ wasting?
K+ sparing –> block collecting tubule Na+ reabs receptor –> decr K+ excretion
K+ wasting –> block proximal Na+ reabs, incr K+ excretion
mechanism of spironolactone
competitive antagonist at aldosterone receptor
mechanism of triamterene/amiloride
direct block Na+ in collecting duct lumen, decr Na+ reabs
NO UTILITY IN HF
what is a key criteria before giving patient K+ sparing diuretic?
make sure kidney works well (or else hyperkalemia)
why are aldosterone antag (K+ sparing) used in HF?
block aldo receptors on heart –> RAAS antagonist
anti-remodeling
incr K+
side effects of aldosterone antag
1) hyperkalemia
2) gynecomastia (block androgen receptor)
factors that incr risk of hyperkalemia with aldosterone antag
1) incr age
2) renal failure
3) higher dose
4) combined ACEI + ARB
5) NSAID
what in common amongst use of ACEI/ARB, B blocker, Aldosterone receptor blocker
anti-remodeling, decr fibrosis/apoptosis
mechanism of ACE inhibitor
decr myocardial hypertrophy and remodeling
pharmacokinetics of ACE inhibitor
1) absorb orally
2) prodrug convert to active metabolity in liver
3) elim by kidney
4) once-daily
side effects of ACE inhibitor
cough
renal dysfunction
hypotension
hyperkalemia
teratogenic
advantage of ARB over ACEI
more complete inhib of Ang II
no cough
disadvantage of ARB over ACEI
loss of bradykinin vasodilation
side effects of ARB
ACEI without cough
contraindicate in pregnancy
