Nowadays Cardiac Failure is the most common disease faced by many people so awareness on this one is very important.In my presentation i included types of cardiac failure, classification of cardiac failure,cardiac drugs,mechanism of action of cardiac drugs,drug therapy.

1. Presented by
K.Harshitha
1

2. Definition
Etiology
Clinical classification of cardiac failure
Pathophysiology
Stages of cardiac failure
Causes of cardiac failure
Multi system effects of cardiac failure
Classification of cardiac drugs
Mechanism of action of cardiac drugs
Drug therapy and Treatment
References 2

3. 3

4. Cardiac failure is a physiological state in
which the heart cannot pump enough blood to
meet the metobolic needs of the body.
• Cardiac failure occurs when the cardiac out put is
inadequate to provide the oxygen needed by the
body.
•The most common cause of cardiac failure is in
Ejection fraction.
4

5. Ejection fraction:
5

6. Etiology
Cardiac performance is depends on
four essential components:
Preload
After load
Contractility of the muscle
Heart rate

7. Preload:
Volume of blood in ventricles at the end of diastole
 Due to CO Blood volume remains after systole
Stretch of myocardial fibers.
 But in failed heart Did not response
 As heart failure worsens
Preload contributes to
symptoms
Dyspnoea
Hepatic enlargement
7

8. Afterload: The pressure against which the left
ventricle ejects.
Systemic resistance CO
• Afterload is the tension or stress
developed in the wall of the left
Ventricle during ejection.
8

9. Contractility of the muscle:
It is the force of contraction generated by the
myocardium under loading conditions.
Heart Rate:
it is the major determinant of the cardiac failure
As the function of the heart in failure, an in heart
rate is the first compensatory mechanism.
9

10. Clinical classification of Cardiac Failure:
According to the position
• Backward failure
• Forward failure
According to the location of heart failure
• Left ventricular failure
• right ventricular failure
• Biventricular failure(Total Heart failure)
According to the cardiac out put
• High output failure
• low output failure
According to the function impaired
• Systolic failure
• Diastolic failure 10

11. Backward failure : It is the condition of venous
congestion arising from the damming of blood
behind the failing chamber.
Forward Failure : it is the condition of inadequate
perfusion. It results when reduced contractility
produces stroke volume and cardiac output.
11

12. 12

13. Left ventricular failure(Left sided Heart failure)
The failure of the left ventricle to maintain adequate
cardiac output.
In LVF basic fault lies in the heart muscles itself .
Practically always result from damage to the ventricular
myocardium.
 Precipitating factors:
• MI
• Hypertension
• Dysrhythmias
13

14. Right ventricular failure(Right sided Heart failure)
• Occurs when the right pump fails.
• It develop as a result of the stress placed upon the right
ventricle it attempts to pumps blood against resistance
into the patient’s congested lungs.
• Causes of right ventricular failure
Pulmonary diseases
Constrictive pericarditis
Tricuspid and pulmonic valve disorders
Infarction of the right ventricle(rare)
Biventricular failure: LV Failure + RV failure
14

15. High out put failure: It occurs when the body need
excess oxygen. The heart increases out put but is still unable
to meet body’s needs.
Low out put failure: It is the condition when the heart
is unable to pump an adequate supply of blood to the body.
• Low output failure results in Hypoperfused tissue cells.
• It occurs when the myocardium is so damaged that it cannot
maintain adequate cardiac output.
• Right and left sided cardiac failure are sometimes referred to
as low output failure.
15

16. Systolic failure:
Systolic dysfunction or ejection failure is the inability of
the ventricles to pump and empty adequately.
The ventricles are dilated and therefore need to develop
higher tension in its walls to eject the blood efficiently.
Diastolic failure:
Stiffening and loss of
adequate relaxation
of the myocardium
during diastole.
Cardiac out put is reduced
but ejection fraction may be
normal.
16

17. Systolic Ventricles cannot pump
Dysfunction effectively
Diastolic ventricles cannot relax
Dysfunction and fill during diastole
17

18. Systolic and diastolic heart compare with normal heart
18

19. Pathophysiology of cardiac failure:
• Neurohumoral or extrinsic compensation involves
two major mechanisms:
The sympathetic nervous system
Renin-angiotensin aldosterone
 The most important intrinsic compensatory
mechanism is Myocardial Hypertrophy or
Ventricular Remodeling.
19

20. Cardiac failure
Reduced CO Ses
cardiac filling
Renin Sympathetic pressure
NS activation
Angiotension I
vasoconstriction Na & Water
Angiotension II retention
Aldosterone
Cardiac remodeling
20

21. Salt and water retention
Due to CO & RBF RAA activation(renin
angiotensin aldosterone activation)
Angiotensin Sympathetic activation
Aldosterone Causes salt and water retention
via renal tubules
Both tries to compensate the low CO & low BP
But it can worsen the venous pressure(preload)
More fluid accumulation in the interstitium
Worsens the signs of heart failure
21

22. Ventricular remodeling:
It is the most important intrinsic compensatory
mechanism referred as cardiac remodeling
It is the process of progressive of ventricular size,
shape and function owing to the influence of
Mechanical, Neurohumoral and possibly genetic
factors in clinical conditions including
• Myocardial infraction
• Cardiomyopathy
• Hypertension
• Valvular heart disease
Hall marks are: Hypertrophy, loss of myocytes and
interstitial fibrosis.
22

23. 23
Ventricular remodeling in diastole &systole

24. Stages of Cardiac Failure:
Stage A: A symptomatic with no heart damage but have risk
factors for heart failure.
 These could include persons with hypertension diabetes,
alcohol abuse, family history of cardiomayopathy.
Stage B: Asymptomatic but have signs of structural heart
damage
 Patients in this category may have left ventricular
hypertrophy, valvular heart disease.
Stage C: Have symptoms and heart damage.
 Patients exhibit fatigue and dyspnoea as a result of
ventricular dysfunction
Stage D: End stage cardiac failure
24

25. New York Heart Association (NYHA)
Classification of cardiac failure
Class-1 No limitation. Normal physical exercise does
not cause fatigue,dyspnoea or palpitations
Class-2 Mild limitation. Comfortable at rest but
normal physical activity produces fatigue,dyspnoea
or palpitations
Class-3 Marked limitation. comfortable at rest but
gentle physical activity produces marked symptoms
of cardiac failure
Class-4 Symptoms of heart failure occur at rest and are
exacerbated by any physical activity.
25

26. Causes of Cardiac Failure
 Dysfunction of myocardium
Myocardial damage
 Myocardial infraction
 Cardiomyopthay
 Myocarditis
 Metabolic disturbance
Ischemia and Hypoxia
Beriberi
26

27. Causes of cardiac failure cont’d…………….
• Overload of myocardium
• Infection like lung infection
• Arrhythmia
• Tachycardia
• Bradycardia
• Excessive physical activity
• Pregnancy and delivery
• Anemia
• Alcohol consumption, obesity
• Dyslipidemia / Hypercholesterolemia
27

28. Multisystem effects of cardiac failure:
Respiratory system
Dyspnea on exertion
Shortness of breath
Tachypnea
Orthopnea
Dry cough
Gastro intestinal
Anorexia , nausea
Abdominal distention
Liver enlargement
Right upper quadrant pain
28

29. Multisystem effects of cardiac failure cont’d…….
Musculoskeletal
 Fatigue
 Weakness
Neurologic
 Confusion
 Impaired memory
 Anxiety , restlessness
 Insomnia
Cardiovascular system
 Tachycardia
 Palpitations
 Hepatojugular reflux 29

30. Classification of the drugs:
 Cardiac Glycosides Digoxin
 Other positive inotropic drugs
 Bipyridines Milrinone
 Beta adrenergic agonists Dobutamine , Dopamine
 Drugs without positive inotropic effects
 Angiotension converting enzyme inhibitor(ACEI)
Captopril , Enalapril , Lisinopril
 Diuretics Furosemide,Thiazide
 Angiotension II receptor blockers (ARB)
Losartan , Valsartan
 Vasodilators Hydralazine
 Beta Blockers Carvedilol , Bisoprolol , Metoprolol
30

31. Drug Therapy:
To increase force of contraction
Digoxin
 β agonists (dobutamine , dopamine)
Bipyridines ( Milrinone)
To reduce cardiac workload
To decrease preload(Diuretics , nitrates)
To decrease afterload (arterial vasodilators)
To decrease preload and afterload (ACEI,ARB)
(Nitrates , sodium, nitroprusside)
To prolong the survival
β adrenoreceptor blockers
31

32. Cardiac glycosides
Digoxin is the derivative of digitalis in current use
All of the cardiac glycosides of which digoxin is the
prototype combine asteroid nucleus
 Cardiac glycosides are the extract of many common
plants
 Digitalis purpurea(red foxglove)
 Digitalis lutea
32

33. Mechanism of action:
Cardiac glycosides
Inhibit Na+ pump in cardiac cells
Accumulation of intracellular Na+
Prevents extrusion of Ca+ entry of Ca++ into the cell
Intracellular Ca+ + Stored in sarcoplasmic reticulum
Ca++ released during each contraction
force and velocity of contraction
33

34. Mechanism of action of digoxin
It is the result of 2 step process
SERCA-sarcoplasmic endoplasmic reticulum calcium ATPase
RyR- Ryanodine receptor calcium channel, TnC- Troponin C
34

35. Pharmacological action of digoxin
Cardiac effect
• At therapeutic dose
 Direct FOC of heart
 Indirect HR may leads to AV block
• At higher concentration
 Direct Increase automaticity of heart
 Indirect Sympathetic activation
 Both may lead to ventricular arrhythmias
35

36. Therapeutic uses of digoxin
Heart failure with atrial fibrillation (use only when
diuretics and ACEI have failed to control the
symptoms
Mild symptoms Slow loading dose
Acute heart failure Rapid Digitalization
Treatment of atrial arrhythmia( atrial fibrillation &
flutter)
36

37. How digoxin corrects Cardiac Failure
Due to FOC CO RBF (relieve oliguria)
Due to better tissue perfusion relieve Cyanosis
Due to blockage of AV node , conducting tissues
Slow ventricular rate relieve tachycardia
Due to Co Better emptying of the ventricles
increase venous return better drainage from the
tissues with relief of congestion in the lungs and liver
and reduction of oedema ,relief of dyspnea
Better results are obtained in patients with atrial
fibrillation than with normal rhythm
Narrow therapeutic index (safety margin)
37

38. Why digoxin is used in atrial fibrillation, flutter
In atrial flutter and fibrillation
Digitalis controls the excessive ventricular rate
Improvement is due to direct effect of digitalis as well
as the effect of vagus on the SA node and conducting
tissue
In atrial fibrillation , Reduction of ventricular rate is
the best measure of glycoside effect.
38

39. Adverse effects of digoxin
CNS : Digitalis has little apparent CNS effect in therapeutic
dose
 Higher doses cause CTZ activation
nausea and vomiting
 Higher doses produces
 Hyperpnoea
 Visual disturbances
Disorientation
Mental confusion
39

40. Adverse effects of digoxin Cont’d…………..
 CVS Ventricular arrhythmia
 Interaction with electrolytes
Hypokalaemia
Hypercalcaemia
 d/t steroid structure gynaecomastia(rare)
GIT : Gastrointestinal tract is most common site of
digitalis toxicity outside the heart
ANVD Anorexia , nausea , vomiting , diarrhea
40

41. Digitalis Toxicity
Toxic effects may occur before the therapeutic end
point is detected
Serum digitalis , k+ levels and ECG should be
monitored during therapy of digitalis toxicity
In severe intoxication , serum k+ is already elevated ,
automaticity is depressed and antiarrhythmic agents
may lead to cardiac arrest.
Digitalis antibodies(digoxin immune Fab)
41

42. Positive inotropic drugs
 They increase the heart’s ability to pump more
effectively by improving the contractile force of the
muscle.
 It include selective beta agonists and Bipyridines
Dobutamine
 Mechanism of action: selective agonist on cardiac activity
 Pharmacological action: Increase Cardiac output(CO)
Most commonly used inotropic agent other than
digitalis
Mainly inotropic rather than chronotropic action
 Route of administration : Given by I.V infusion
 Adverse effects : cardiac arrhythmia
 Therapeutic use : used in acute decomposed heart failure
42

43. Dopamine
Mechanism of action : Dose related action D1,β1,α1
Pharmacological action:
Low dose activate D1
in RBF
Intermediate dose activate β1
FOC,HR,CO
Route of administration: Given by IV infusion
Adverse effects: cardiac arrhythmia
Therapeutic use : used in acute decompensated cardiac
failure
43

44. Bipyridines(Milrinone)
Mechanism of action
• Inhibits phosphodiesterase type 3 enzyme
• Decrease cAMP breakdown cAMP FOC of heart
Pharmacological action : cause increase FOC
Route of administration
Parentral
Adverse effects
Cardiac arrhythmia
Therapeutic use
Acute heart failure
or severe exacerbation of
chronic heart failure
44

45. Angiotension converting enzyme inhibitors
(ACEI)
Plays a vital role in the management of cardiac failure
due to systolic dysfunction . ACEI given in combine with
diuretics.
ACE inhibitors promotes vasodilation and diuresis by
decreasing afterload and preload
Decrease the secretion of aldosterone a hormone that
causes the kidneys to retain sodium and water
Stimulate the kidneys to excrete sodium and fluid
thereby reducing left ventricular filling pressure &
decreasing pulmonary congestion
Patients receiving ACE inhibitors should be monitored
for Hypotension , Hyperkalemia , alteration in renal
function
45

46. ACE Inhibitors : Captoprill,Enalapril,Lisinopril
Mechanism of action:
• Inhibits angiotensin converting enzyme (which converts
angiotensin I to angiotensin II)
• Reduce formation of angiotensin II
• Angiotension II is the potent vasoconstrictor in body & it
causes production to aldosterone , which causes salt and
water retention from kidney.
Pharmacological Action:
• ACEI decrease the formation of Ang II and aldosterone
• Atrial fibrillation Afterload
• Venous dilation preload
• Aldosterone action Salt & water retention
Vascular volume
• Sympathetic activation
46

47. Diuretics
• Eliminate excess body water and decrease ventricular
pressure.
• A low sodium diet and fluid restriction complement
this therapy.
• Some diuretics may have slight venodilator
properties.
• Diuretics are used in chronic heart failure usually in
combination with others.
47

48. Diuretics (Thiazide)
Mechanism of action
• Hydrochlorothiazide , chlorthalidone(milder diuretics)
inhibits Na +- Cl
_
symport in PCT (primary convoluted
tubule) of nephrons
Pharmacological action
• Mild diuresis action + venodilation action Can cause
salt and water excretion & reduction of preload
Route of administration : given orally
Adverse effects : electrolyte imbalance ( especially
Hypokalaemia which can worsen digitalis toxicity)
48

49. Diuretics (Furosemide)
Mechanism of action:
• Highly potent loop diuretics inhibits Na+-k+-Cl- symport in
loop of Henley of nephrons.
Pharmacological action:
• Diuresis action + venodilation action + decreases in L.V
filling pressure
• Can cause salt and water excretion & reduction of preload
Route of administration: available as oral as well as IV
Therapeutic use: first choice in acute CHF to relieve morbidity
Quick onset , short duration
Adverse effects: Hypotension,dehydration,temporary deafness
(with large doses),Hypokalaemia(offset by k sparing diuretics
49

50. Angiotension II receptor blockers(ARB)
Blocks the effects of Angiotension II at the Ang II receptor
ACE inhibitors and ARBs have similar
Hemodynamic effects: BP , systemic vascular resistance,
improved cardiac output
ARBs are Used in patients who cannot tolerate ACEI
due to cough.
50

51. Beta blockers:
Epinephrine & nor epinephrine exert their effects by
binding to beta adrenergic in the heart and walls of the
blood vessels.
β blockers bind to beta receptors thus obstructing the
binding of catecholamines.
Hence β blockers reduce sympathetic of the heart and
blood vessels.
Therefore ,beta blockers heart rate, contractility
and reduce blood pressure.
51

52. Mechanism of Action of Beta blockers
52

53. Vasodilators
 Ses the workload of the heart by dilating peripheral
vessels.
By relaxing capacitance vessels(veins ,venules) ,
vasodilators decrease preload and volumes.
Hydralazine predominantly affects arterioles ; reduces
arteriolar tone.
Prazosin Balanced effect on both arterial and venous
circulation.
Morphine venous return pain & anxiety.
Sodium nitroprusside predominantly affects arterioles.
53

54. Nitrates
 Nitrates such as NTG , Isosorbate , NTG ointment
predominantly dilate systemic veins.
 Nitrates are useful for patients with pulmonary
congestion ,dyspnoea symptoms
54

55. 55

56. References:
Review articles from published journals.
Principles of pharmacology by Sharma & Sharma.
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