2. INTRODUCTION
• Inability of the heart to pump an
adequate amount of blood to the
body’s needs
• CO is inadequate to provide oxygen
needed by peripheral tissues
3. AFTERLOAD AND PRELAOD
• Afterload is the tension or stress
developed in the wall of the left ventricle
during ejection
• Preload is the stretch exerted on the
muscle in the resting state. (diastolic
phase.)
7. CAUSES OF HEART
FAILURE
• Hypertension
• Prolonged Alcohol or Drug Addiction
• Previous Heart Attack
• Chronic Rapid Heart Beats
8. SYMPTOMS OF HEART FAILURE
• Edema of the
bronchial mucosa
• Pulmonary edema
• Cardiomegaly
• Edema in other body
parts
• Tachycardia
• Coughing
• Dyspnea
• Fatigue
10. SYSTOLIC DYSFUNCTION (FORWARD
FAILURE)
• Inadequate force is generated to eject blood
normally
• Reduce cardiac output, ejection fraction (< 45%)
Typical of acute heart failure
• Responsive to inotropics
11. DIASTOLIC DYSFUNCTION (BACKWARD
FAILURE)
• Inadequate relaxation to permit normal filling
• Hypertrophy and stiffening of myocardium
• Cardiac output may be reduced
• Ejection fraction is normal
• Do not respond optimally to inotropic agents
12.
13. HIGH OUTPUT FAILURE
• Increase demand of the body with insufficient
cardiac output
• Hyperthyroidism, beri-beri, anemia, AV shunts
• Treatment is correction of underlying cause
14. ACUTE HEART FAILURE
• Sudden development of a large myocardial
infarction or rupture of a cardiac valve in a patient
who previously was entirely well, usually
predominant systolic dysfunction
15. CHRONIC HEART FAILURE
• Typically observed in patients with dilated
cardiomyopathy or multivalvular heart diseases
that develops or progresses slowly
16. COMPENSATORY MECHANISMS OF
BODY DURING HEART FAILURE
• Three types of compensatory mechanisms
2. Neuronal Responses
3. Neuro-endocrinal system
4. Autoregulatory systems
17. Neuronal Responses
• Baroreceptors in the vascular system detect decrease in
BP
• Enhanced sympathetic outflow to the heart and to
peripheral vasculature
• Individual feeling status will also increase sympathetic
system
• Results in release of nor adrenaline and catecholamines
which increase heart rate and redistribution of blood to
vital organs
• Kidney will also help by retention of water and
electrolytes
•
18. Neuro-endocrinal system
• Reduced blood pressure will Stimulate the renin
angiotensin system
• Reduced blood supply to kidney lead to secretion of
renin
• Production of angiotensin II
• Retention of water and electrolyte
• Less oxygen supply to kidney enhances production of
erythropoetin which increases RBC’s production
20. Autoregulatory systems
• Neuronal structures of heart capable of secreting
catecholamines due to anoximia
• Self stimulation of heart muscle called as catecholamine
heart drive
• Do not work during congestive heart failure
22. AUTOREGULATORY MECHANISMS
Atrial pressure
Oxygen supply
Tachycardia
Self Stimulation of heart
muscle
Atrio-peptide
releases
Release of catecholamine
Relaxation of
blood vessels Heart rate
Compensatory
mechanism
23. STRATEGIES FOR CHF
• Increase cardiac contractility
• Decrease preload ( left ventricular pressure)
• Decrease after load (systemic vascular resistance)
• Normalize heart rate and rhythm
24. REDUCE WORK LOAD OF HEART
1.Adjustment of heart rate(AV and SA nodal blocking agents)
2. Restrict sodium (low salt diet)
3. Give diuretics (removal of retained salt and water)
4. Give angiotensin-converting enzyme inhibitors
(decreases afterload and retained salt and water)
5. Give digitalis (positive inotropic effect on depressed heart)
6. Give vasodilators (decreases preload & afterload)
25. STRATEGIES TO TREAT CHF
Factor Mechanism Therapeutic Strategy
1. Preload (work or stress increased blood volume -salt restriction
the heart faces at the end of and increased venous -diuretic therapy
diastole) tone--->atrial filling -venodilator drugs
2. After load (resistance pressure sympathetic
increased - arteriolar vasodilators
against which the heart stimulation & activation of -decreased angiotensin II
must pump) renin-angiotensin system (ACE inhibitors)
---> vascular resistance --->
increased BP
3. Contractility decreased myocardial -inotropic drugs (cardiac
contractility ---> decreased glycosides)
CO
4. Heart Rate decreased contractility and
decreased stroke volume ---
> increased HR (via
activation of b
adrenoceptors)
26. CLASSIFICATION OF DRUGS USE TO
TRAET CONGESTIVE HEART FAILURE
• Drugs improving force of cardiac contractility(postive
ionotropic)
• Drugs improving compensatory stresses upon the
cardiac performance
27. Drugs improving force of cardiac
contractility(positive ionotropic)
• Cardiac glycosides (digoxin,digitoxin)
• Phospho-di-estrase inhibitors (Inamrinone)
• Beta I agonists(dobutamine)
28. Drugs improving compensatory stresses
upon the cardiac performance
• Diuretics(Thaizides)
• Vasodilators(diazoxide,minoxidil)
• ACE Inhibitors(captopril,inapril)
• Angiotensin II receptor inhibitor(losartan,candisartan)
• Beta-blockers (atinolol,propranol)
29. CARDIAC GLYCOSIDES
• Stimulates myocardial contractility(+ inotropic)
• Improves ventricular emptying
• Increase cardiac output
• Augments ejection fraction
• Promotes diuresis so lowers blood volume.
• Reduce cardiac size
• Used in acute congestive HF
• Not used with diuretics
• Reduces pace maker conduction by stimulating vegal
nerve
30. PHOSPHO-DI-ESTRASE ENZYME
INHIBITORS(INAMRINONE,MILRENONE)
• Increase CAMP and CGMP levels that activates IP3
• These enzymes inhibitors increase cytosolic ca level
• Alter intracellular SR calcium
• Increase cardiac contractility(positive ionotropic effect)
• Cause vasodilatation
• Reduce preload
• Used in acute or refractory HF
31. Beta I agonists
• Stimulate cardiac muscles for rapid contractility
• Increase cardiac output with decrease ventricular filling
pressure
• Used in last stages when patients is in ICU in proper
monitoring
• Used to keep alive the patients at last stages
32. DIURETICS(THIZIDES)
• Increase water secretion from kidney
• Decrease blood volume
• Redude oedema
• Decrease venous return(reduce oxygen demand)
• Reduce cardiac size
• Decrease ventricular pre load
• Improve cardiac efficiency
• E.g Spironolactone
• Aldosterone receptors inhibitors
• Aldosterone cause myocardial and vascular fibrosis and baro-
receptors dysfunctioning
• Beneficial in patients receiving ACE inhibitors
34. ACE INHIBITORS
• Inhibits ACE
• Reduce TPR
• Reduce blood volume
• Reduce sodium water retention by inhibiting aldosterone
• Reduce after load and some how preload
• Reduction in sympathetic outflow
• Excellent drug for long term remodeling of heart and
blood vessels
36. BETA-
BLOCKER(atinolol,propranalol)
• Blocks beta I receptors on heart
• Relax cardiac muscle by reducing cardiac work
• Save from extra heart muscle exercise
• Used in long term therapy
37. CARDIAC GLYCOSIDES
• Also called as cardinolides.
• In 1875 William Withering wrote a treatise on Digitalis.
• It was considered essential in the treatment of CHF.
• It is used in chronic CHF. with chronic atrial fabriliation.
• It is still extremely favoured drug.
39. ADVANTAGES:
• It has two main advantages
2. It is an inotropic agent ( increases myocardial
contractility)
3. It can be administered orally.
40. DISADVANTAGES:
• Its therapeutic index is low.
• Its correct dose, correct therapeutic blood level ranges
are uncertain.
• It has many interactions.
41. CHEMISTRY:
• Molecule consisting of
2. A CPP ring
3. Sugar
4. Lactone
• CCP ring + Lactone together is called Aglycon
46. ABSORPTION
• Digoxin is less lipid soluble than Digitoxin
• Digitoxin completely absorbed after oral administration
• Digoxin can be converted to ineffective agent by bacteria
of gut flora
• Half life of digoxin is 1.5 days
• Half life if digitoxin is 5 days
47. METABOLISM
• Therapeutic window of digoxin is narrow
• Metabolized by liver microsomal enzymes
• Digitoxin is converted to inactive products
• Digitoxin is converted into digoxin after hydroxylation of
digitoxin
• Digoxin level should be measured in patients receiving
this drug
51. FACTORS FACILLATING TOXICITY
• Depletion of serum potassium level
• Concomitant use of drugs
• Presence of renal failure
• Hypothyroidism
• Old age
54. CARDIAC GLYCOSIDES
• MODE OF ACTION:
• Direct Effect on Myocardial contractility, and
electrophysiological properties and also has
vagomimetic effect
• Force of contraction:
• Dose dependent increase in force of contraction in
failing heart – positive ionotropic effect
• Systole is shortened and prolonged diastole
• Contracts more forcefully when subjected to
increased resistance
• Increase in cardiac output – complete emptying of
failed and dilated heart
• Tone:
• Decrease end diastolic size of failing ventricle
• Reduction in oxygen consumption
55. Contd. ---
• Rate and Conduction:
1. Bradycardia
2. Slowing of impulse generation (SAN)
3. Delay of conductivity of AVN
• Direct depressant action on SA and AV nodes
(extravagal)
• Increase in vagal tone:
• Is due to improvement in circulation
• Also due to direct stimulation in vagal center,
sensitization of baroreceptors and sensitization of SA
node to Ach
58. EFFECTS ON HEART
• Increases force of myocardial contraction
• Heart size
• Ejection fraction
• Refractory period in AV node and bundle of hiss
• Number and irregularity of ventricular contraction
59. VAGAL EFFECTS
• Vagal effects at early stages when there is minimum
therapeutic value
• Slowed down the activity of pace maker
• Relaxation phase
• Ejection fraction
60. PHOSPHODIESTRASE INHIBITORS
• Mechanism of Action
• inhibition of type III phosphodiesterase
↑ intracellular cAMP
↑ activation of protein kinase A
o Ca2+ entry through L type Ca channels
• ↑ cardiac output
• ↓ peripheral vascular resistance
61. BETA I AGONIST
Mechanism of Action:
Stimulation of cardiac β1−adrenoceptors: ↑
inotropy > ↑ chromotropy
peripheral vasodilatation
62. ACE INHIBITORS
• Mechanism of Action:
• Afterload reduction
• Preload reduction
• Reduction of facilitation of sympathetic nervous system
• Reduction of cardiac hypertrophy
63. BETA BLOCKERS
• Mechanism of Action:
• influences in the heart (tachycardia, arrhythmias,
remodeling)
• Reduction in damaging sympathetic inhibition of renin
release
64. DIURETICS
• Mechanism of Action:
• Preload reduction: reduction of excess plasma volume
and edema fluid
• After load reduction: lowered blood pressure
• Reduction of facilitation of sympathetic nervous system
65. VASODILATORS
• MODE OF ACTION:
• Reduction in preload through venodilatation or
reduction in afterload through arteriolar dilation or
both
