Drugs Used in Heart

Failure
 Heart Failure
• It’s a contractility disorder of the heart and is
defined as a clinical syndrome characterized by
symptoms of breathlessness and fatigue, usually with
signs of fluid overload Fatigue describes a state of tiredness or exhaustion. In
general usage, fatigue often follows prolonged physical
or mental activity.

• Heart failure (HF) is a complex, progressive disorder

in which the heart is unable to pump sufficient blood
to meet the needs of the body
Physiology of Cardiac Contraction
 Heart Failure

Cardinal symptoms are

• Dyspnea Shortness of breath

• Fatigue and

• Fluid retention
 Heart Failure

Typical signs of HF
• Dyspnea on exertion
• Orthopnea Orthopnea or orthopnoea is a shortness of breath that occurs when lying flat

• Paroxysmal nocturnal dyspnea

• Fatigue
• Peripheral edema
 Causes of HF

• Underlying causes of HF include arteriosclerotic

heart disease, myocardial infarction, hypertensive
heart disease, valvular heart disease, dilated
cardiomyopathy and congenital heart disease
 Pathophysiology of heart failure
Heart failure

FOC (Force of contraction)

Renal blood Cardiac output Sympathetic tone
flow
Residual volume
GFR
EDV(End diastolic volume)
Renin release
Vasoconstriction
Formation of Length of muscle fibre to Heart rate
Angiotensin I I follow Frank-Starling law
Release of Peripheral resistance
Residual volume
Aldosterone
Length of muscle fibre beyond
Na+ and water Frank-Starling law
retention (edema) After load
Cardiac hypertrophy and
Intravascular volume hyperplasia (remodeling)

Preload Worsening of heart failure

 Goals of pharmacologic
intervention in HF

• Alleviate symptoms To alleviate symptoms means to make them

less intense or more bearable

• Slow disease progression

• Improve survival
 In heart failure Aim of treatment

Decrease cardiac output Increase cardiac output

Edema Reduce Edema
Increase preload Reduce preload
Increase afterload Reduce afterload
 Role of physiologic compensatory
mechanisms in the progression of HF

• Chronic activation of the sympathetic nervous

system and the renin–angiotensin–aldosterone
system is associated with the remodeling of cardiac

tissue, loss of myocytes, hypertrophy, and fibrosis.

a muscle cell:

This prompts additional neurohormonal activation,

creating a vicious cycle that, if left untreated, leads

to death
fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces
normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and
the formation of permanent scar tissue.
Compensatory mechanism in HF
Compensatory mechanism in HF &
Drug interfering the progression of
HF
At1 receptor - angiotensin II type 1 receptor
Classification of drugs Used in Heart
Failure on the basis of mode of action
1. Relief of congestive/low output symptoms, restoration of
cardiac performance and treatment of acute
decompensation:

• lnotropic drugs- Digoxin, dobutamine/dopamine,

inamrinone/milrinone

• Diurerics-Frusemide, thiazides, metolazone

• RAS inhibitors- ACE inhibitors/ARBs arbs angiotensin receptor blockers

• Vasodilators- Hydralazine, nitrate, nitroprusside

• Synhetic BNP-Nesiritide BNP - brain natriuretic peptide

• β blocker- Metoprolol, bisoprolol, carvedilol, nebivolol

HCN - Hyperpolarization-activated cyclic nucleotide–gated (HCN)
channels are integral membrane proteins that serve as nonselective
• HCN channel blocker-Ivabradine voltage-gated cation channels in the plasma membranes of heart
and brain cells.
Classification of drugs Used in Heart
Failure on the basis of mode of action
2. Arrest/reversal of disease progression and
prolongation of survival
• ACE inhibitors/ ARBs

• β blockers

• Aldosterone antagonist-Spironolactone, eplerenone

• Neprilysin inhihibitor- Sacubitril (Combination of

neprilysin inhibitor with an angiotensin receptor blocker-
sacubitril/valsartan)
Classification of drugs Used in Heart Failure on
the basis of mode of action

• Angiotensin-converting enzyme inhibitors

• Angiotensin-receptor blockers
• Aldosterone antagonists
• β-blockers
• Diuretics
• Hyperpolarization-activated cyclic nucleotide gated channel blockers
• Combination of neprilysin inhibitor with an angiotensin receptor blocker
• Recombinant B-type natriuretic peptide
• Direct vaso- and venodilators and
• Inotropic agents
 Digoxin

• It’s a cardiac glycoside

• Positive inotropic agent that improve cardiac

contractility
 Digoxin

Sources

• Digitalis lanata-Digoxin

• Digilalis purpurea- Digitoxin and

• Strophanthus gratus- Ouabain

 Mechanism of action of digoxin
Direct effect: Digoxin

Inhibit Na+/ K+ - ATPase pump

Decreased Na+ extrusion leads to an increased cytosolic

Na+ concentration

Inhibit Na+/ Ca++ exchanger causes reduction of calcium expulsion from

the cell by the Na+/Ca2+ exchanger caused by the increased in intracellular sodium

The increased cytoplasmic calcium then trigger the release of

calcium from the sarcoplasmic reticulam

Calcium binds with troponoin-tropomycin complex which causes

interaction between actin & myosin & thus causes contraction of myocardium

Increase cardiac output

Indirect effect:
Digoxin

Vagal tone in heart

Decrease firing in SA node

Slowing of AV nodal conduction
Slowing of atrial action potential
Decrease heart rate
By direct ( cardiac output) and indirect ( vagal tone) effect digoxin
improve the syndrome of heart failure in following way :
FOC (Force of contraction)
Renal blood flow Cardiac output Withdrawl of
sympathetic outflow
GFR
Residual volume
Renin release EDV(End diastolic volume)
Heart rate ( also due
to increase vagal tone)
Diuresis Length of heart muscle fibre No vasoconstriction

Preload When length of muscle fibre come

with in limit, follow Frank – Starling law
After load
Relief edema
Myocardial contraction
Complete emptying of heart
Heart size come to normal

Improve heart failure

 Adverse effects of digoxin
EATING DISORDER leads to weight loss

• GI adverse effects are anorexia, nausea, and

vomiting
• Cardiac toxicity in healthy persons presents as
extreme bradycardia, atrial fibrillation, and AV
block
 Stages of HF with management
Stage Description Management
A High risk with no symptoms Risk factor reduction, patient
education
B Structural heart disease, no Treat HTN, diabetes, dyslipidemia;
symptoms ACEIs or ARBs in selective patients
C Structural heart disease, • ACEIs and β-blockers in all
previous or current symptoms patients;
• Aldosterone antagonist and FDC
HYD/ISDN in selective patients
• Replace any ACEI or ARB with
an ARNI in selective patients
• Dietary sodium restriction;
diuretics, digoxin and ivabradine
D Refractory symptoms Transplant, LVAD ventricular assist device (VAD)

ARNI (angiotensin receptor/neprilysin inhibitor) medication is a newer treatment for heart failure. The combination of sacubitril
and valsartan has helped people live longer and have a better quality of life.
ef - ejection
fraction
 Drugs for heart failure
Acute failure
• Diuretics-frusemide

• Vasodilators-nitroglucerine,
nitroprusside

• Beta agonists-Dopamine,
dobutamine

• PDE3/4 inhibitors

• Levosimendan