↓ myocardial

function

↓ CO

sympathetic RAAS
activation ADH
activation

↑ contractility ↑ HR v/c
↑ H2O
retention
arteriolar venous
↑ cardiac
workload ↑ venous
maintain
return
BP
(preload)
hypertrophy (afterload)
& > O2 ventricular
demand dilation
↑ CO
peripheral
edema &
pulmonary
↑ SV congestion
AIM OF HEART FAILURE
MEDICATIONS

↑ contractility ↓ preload

↓ remodeling ↓ afterload
 HF MEDICATIONS

• angiotensin converting enzyme inhibitor (ACEi)

• angiotensin II receptor blocker (ARB)
• beta blocker (receptor antagonist)
• cardiac glycoside
• diuretics (loop and potassium sparing)
 ACE
INHIBITORS
(ACEi)

e.g. captopril (and all –prils)

Block the conversion of

angiotensin I to angiotensin
II by inhibiting angiotensin
converting enzyme.
 ANGIOTENSIN
II RECEPTOR
BLOCKERS
(ARB)

e.g. losartan (and all –

sartans)

Block angiotensin II (AII)

receptors (competitive
antagonist that inhibits the
binding of AII).
 THERAPEUTIC EFFECTS OF
ACEi and ARB
Decreased production or action of AII, causing:
1. vasodilation
2. reduced aldosterone release (decrease
sodium and fluid retention and potassium
excretion)
3. reduced ADH release (decrease fluid
retention)
4. reduced growth effects of AII on the heart
Why use an ACEi or ARB in heart failure?

↑ contractility ↓ preload

↓ remodeling ↓ afterload
 decrease fluid retention
(↓ symptoms of congestion
and filling pressures)

ACEi
ARB

↑ contractility ↓ preload decrease

BV and VR

ACEi ACEi
ARB ARB

↓ remodeling ↓ afterload

vasodilation
(↓ cardiac workload
and O2 demands)
ACE inhibitors can cause a
dry cough or angioedema
that might warrant a switch
to an ARB.

What effect might ACE inhibitors and ARBs have

on blood potassium levels?
 BETA
BLOCKERS

e.g. bisoprolol (all the “-

olols”)

Block 𝛃1 receptors of
pacemaker, myocardial,
and JG cells (competitive
antagonist that inhibits
the binding of epi/NE).
1st e.g. propranolol
generation non-selective
beta-1 and beta-2

2nd e.g. bisoprolol

generation beta-1 selective

e.g. carvedilol
3rd
non-selective
generation
beta-1 and alpha-1
 THERAPEUTIC EFFECTS OF
BETA BLOCKERS
Beta blockers interfere with sympathetic
influences on:

1. the heart
• reduce myocardial contractility, heart rate,
and cardiac workload

2. the kidney
• reduce renin release and the activation of the
RAAS (and thus fluid retention)
Why use beta blockers in heart failure?

↑ contractility ↓ preload

3rd gen
beta beta
blockers blockers

↓ remodeling ↓ afterload

decrease cardiac workload vasodilation

(and hypertrophy)
What is a benefit of decreasing heart rate for
patients with diastolic dysfunction?

BUT… at high doses may cause a severe decrease

in HR.
 CARDIAC GLYCOSIDES

e.g. digoxin

Digoxin inhibits the Na+/K+ pump which causes an

increase in intracellular Na+.
 3#%'
3#%'
456'
7% '
58,'!"#$%$&"'#$
"#$%'
58,'!"#$%$/#$*01*$ "()*+,-.,$+,9:;#1,-'
>#()1#()-'18,' ()1+#*,;;:;#+'!"#$%&'<='
!"#$%&'
*0)*,)1+#20)' ()*+,#-,.' >0?()9'"#$%'0:1@'A8(;,'
9+#.(,)1'C0+'3#%B' #/,+' 3#%'(-'>0?,.'()'.0A)'(1-'
*0)1+#*20)'' *0)*,)1+#20)'9+#.(,)1B'

8(98''
!"#$%&'

What effect does digoxin have on intracellular

[Na+], [Ca2+], and thus contractility?
 THERAPEUTIC EFFECTS OF
DIGOXIN
Digoxin inhibits the Na+/K+ pump resulting in
increased intracellular calcium levels:
1. increases myocardial contractility (more
calcium is available to bind to troponin
allowing cross-bridges to form)
2. slows HR (decreased sympathetic activation
when CO increases)
What effect will digoxin have on ejection fraction?
Why use digoxin in heart failure?

↑ contractility ↓ preload

↓ remodeling ↓ afterload
 increased CO
(decreases back up of blood,
improves renal perfusion,
slows HR)

digoxin

↑ contractility ↓ preload

↓ remodeling ↓ afterload
K+ SPARING
DIURETICS ↓ synthesis
of Na+
channels and
Na+/K+
e.g. spironolactone pumps

aldosterone

Block aldosterone Na+ Na+

K+
receptors (a competitive
K+

antagonist) in renal
tubules causing the loss
of Na+ and water in the
urine and the retention
of K+. also called a
mineralocorticoid
receptor antagonist
(MRA)
What effect will this have on blood potassium
levels?
 THERAPEUTIC EFFECTS OF
DIURETICS
Diuretics increase urine output to decrease blood
volume and blood pressure.
 Why use K+ sparing diuretics in heart failure?
reduce
diuretics fluid
retention

↑ contractility ↓ preload

↓ remodeling ↓ afterload

reduce
aldosterone- K+ Sparing
induced cardiac
remodeling
 digoxin diuretics ACEi
ARB

↑ contractility ↓ preload

ACEi ACEi
beta ARB ARB
blockers

↓ remodeling ↓ afterload

K+ Sparing