2. Complex and progressive disorder
Heart is unable to pump sufficient blood to meet body needs
Impaired ability to adequately FILL with (Diastolic HF) &/or EJECT blood
(Systolic HF)
3. Etiology:
Very high workloads placed on the heart
Atherosclerotic heart disease
Myocyte loss or decreased myocyte contractility
Ischemic heart disease (myocardial infarction)
Congenital heart disease
Preload & Afterload
Weak heart
=
ↆ CO
4. Increase of venous return causes
increase of stretch of myocardium
=
Increased force to pump blood
out.
5. Ejection Fraction:
Definition: It is the ratio of SV compared to EDV.
SV 70
=
EDV 135
Importance:
It is used as indicator for myocardial contractility.
Normal value: about 50 – 60 %.
X 100 X 100
=
6. Heart is unable to pump sufficient blood to meet body needs = Impaired
ability to EJECT blood
CONGESTION or OEDEMA (Increase in ExtraCellular Fluid Volume=Blood
& Interstitial fluid)
In Right HF: Peripheral Oedema occurs
In Left HF: Pulmonary Congestion occurs (leads to Dyspnea)
11. Patients complain of:
Dyspnoea (sensation of breathlessness) on exertion
Orthopnoea (breathlessness when lying down)
Nocturnal Dyspnoea
Tachycardia, sweating,cold extremities
Peripheral edema
cardiomegaly
Fatigue and exercise intolerance
12.
13. • Carry blood toward the heart.
• Muscles surround the veins so that when the muscles
contract, the veins squeeze and the blood is pushed
along the vessels against gravity. just as squeezing a
toothpaste tube ejects toothpaste.
• Have valves to prevent backflow of blood
• Venous blood flow is under low pressure (Venous
return / Preload)
(Afferent vessels)
16. Goals of Pharmacological
Interventions
Acute Heart Failure:
1. ↑↑↑ CO by ↑↑ Contractility → +ve Inotropics.
2. Relief of edema and congestion → Diuretics.
Chronic Heart Failure:
1. ↆↆ Workload of the heart by: ↆↆ Afterload (arteriodialtors) &
ↆↆ Preload (venodilators)
2. Relief of edema and congestion by: Diuretics.
3. To reverse cardiac remodeling: ACE inhibitors, β-blockers
17. Goals of Pharmacological
Interventions
In order to achieve this, one or more of 6 classes are used:
Diuretics
Direct
Vasodilators
Inotropic
Agents
ARBs
β-
Blockers
ACEIs
19. Inotropic Agents
• Positive inotropic agents enhance cardiac contractility
and,thus, increase Cardiac Output (C.O.)
• Although these drugs act by different mechanisms, the inotropic action is
the result of an increased cytoplasmic CALCIUM concentration that
enhances the contractility of cardiac muscle.
22. Mechanism of action:
binds to the K+ binding site in the Na+/K+ ATPase pump
partial inhibition of the pump ↆↆ Na+ efflux
↑↑ intracellular Na+ ↆↆ Na+/ Ca2 exchange ↆↆ
Ca2+ efflux ↑↑ intracellular Ca2+ +ve inotropic
↑↑CO
1. Mechanical effect ( force of contraction)
Digoxin
23. K+ relation to therapeutic efficacy of cardiac glycosides:
K+ competes with Digitalis for its binding site to Na+/K+ ATPase pump.
If K+ levels are low digoxin will work unopposed therapeutic
effect of digoxin and may reach toxicity so hypokalemia digitalis toxicity.
If k+ levels are high k+ will displace digoxin from its binding site
therapeutic effect of digoxin so hyperkalemia digitalis activity.
So it is essential to keep k+ level in normal physiologic level
Hypokalemia may be induced by K-depleting diuretics (e.g. Loop, Thiazide) which are
used to treat edema.
For prevention of hypokalemia either k+-supplement or k+-sparing diuretics.
24. • Vagal tone is also enhanced, so both heart rate and
myocardial oxygen demand decrease.
• Digoxin slows conduction velocity through the AV node
• Low-dose of digoxin → ↆↆↆ sympathetic activation with minimal
effects on contractility.
i.e. ↆↆ effect of A & NA on heart → ↆↆ HR (Bradycardia)
2. Electrical effect
25. • Kidney: It has weak diuretic effect why?
Digitalis → ↑↑ C.O. → ↑↑ Renal perfusion → ↆↆ Renin → ↆↆ
Aldosterone → ↑↑ Na+/H2O loss in urine (diuresis) →
Partial improvement of congestion & edema.
• CNS: overdose → hallucinations, blurred vision
• Hormones: gynecomastia due to estrogenic activity
26. Management of Digoxin toxicity
Stop administration of digitalis & K-depleting diuretics.
Monitoring of K+, and give KCl (K-competes with digioxin on Na/K –
ATPase).
Antiarrhythmic drugs to control ventricular arrhythmia.
Atropine to control the bradycardia and AV block.
Specific digoxin antidote (Digibind).
28. • Dobutamine and dopamine, improve cardiac performance by causing
positive inotropic effects.
Both drugs must be given by intravenous infusion and are primarily
used in the short-term treatment of acute HF in the hospital
setting.
β - agonist
Dopamine, Dobutamine
29. Dopamine Dobutamine
β1 in heart
contractility & HR.
D1 in kidney dilate renal
blood vessel RBF urine
output.
CO & relief edema
Selectively Stimulate β1 in heart
contractility.
advantage:
contractility with minimal
increase in HR.
IV infusion for short term control of severe acute HF patients in
hospitals
Why do β-Adrenergic agonists possess inotropic effects?
Gs protein coupled receptor :
Adenylcyclase
cAMP Ca2+ inc.
ATP
31. ATP Adenylcyclase cAMP Phosphodiesterase-3 Inactive
Ca2+ inc.
• Milrinone is a phosphodiesterase-3 inhibitor that increases the
intracellular concentration of cAMP.
• Like β-adrenergic agonists, this results in an increase of
intracellular calcium and, therefore, cardiac contractility.
cAMP : Myocardial contractility C.O.
IV infusion for short control of acute HF in hospitalized patients
PDEIs
Milrinone
33. 1. Block the enzyme that converts angiotensin I to angiotensin II.
2.Diminish the inactivation of bradykinin.
3.Vasodilation occurs as a result of decreased levels of the vasoconstrictor
angiotensin II and increased levels of bradykinin (a potent vasodilator).
4. ↆ Aldosterone secretion Na/H2O retention relief edema
5. Reversal of cardiac and vascular smooth muscle remodeling.
Actions on the heart:
Vascular resistance (afterload)
Venous tone (preload)
Cardiac output
2- ACEIs
- pril
35. Cardiac Remodeling
(Hypertrophy)
ACEIs
AT1
ACE inhibitors are known to
increase tissue bradykinin
accumulation. Bradykinin has
antigrowth effects and reduces
vasomotor tone. Increased kinin
activation resulting from ACE
inhibition may attenuate structural
remodeling in the cardica muscles.
37. Depending on the severity of HF,ACE inhibitors may be used in
combination with:
Diuretics, β-blockers, Digoxin, Aldosterone antagonists,
Hydralazine / Isosorbide
40. Valsartan & Losartan
• Competitive antagonists of the angiotensin II type 1 receptor (AT1R).
• DO NOT affect bradykinin levels.
• Substitute for ACE inhibitors in those patients who cannot tolerate the
latter (severe cough or angioedema, which are thought to be mediated by
elevated bradykinin levels)
• Have the same action of ACE inhibitors on preload and afterload.
3- ARBs
- sartan
41. Adverse effects:
Similar to that of ACE inhibitors.
However, ARBs have a lower incidence of
cough and angioedema.
Like ACE inhibitors, ARBs are in pregnancy.
43. Vasodilators
• Dilation of venous blood vessels decrease in cardiac preload by
increasing venous capacitance (Isosorbide dinitrate)
• Dilation of arterial blood vessels reduce systemic arteriolar
resistance and decrease afterload (Hydralazine)
• If the patient is intolerant to ACE inhibitors, or if additional
vasodilator response is required, a combination of vasodilator
may be used.
47. • Diuretics relieve pulmonary congestion and peripheral edema.
• Naturesis & diuresis blood volume venous return Preload
• Blood volume venous pressure venous congestion Edema
• This decreases cardiac workload and oxygen demand.
• Diuretics may also decrease afterload by reducing plasma volume, thereby
decreasing blood pressure.
• Loop diuretics are the most commonly used diuretics in HF.
Thiazides, Loop diureteics, K+ sparing diuretics
5- Diuretics
48. Hydrochlorothiazide
Used for long term therapy of HF when edema is not too great.
Efficiency of Thiazide diuretics is dependent on kidney function i.e. ineffective
when glomerular filteration rate (GFR) is low.
Furosemide
They produce profound diuresis even if GFR is low (used in renal failure patients)
Drugs of choice for patients with severe heart failure.
Spironolactone
Very weak diuretics
In CHF adjuvant therapy to counteract hypokalemia
Diuretics
Thiazides
Loop diuretics
K+ sparing
49. Aldosterone antagonists
Adverse effects:
Non selective aldosterone
antagonist i.e. binds to
androgen and progesterone
receptors
• Gynecomastia (due to blocking of testosterone
receptors)
• Hyperkalemia (K+ level should be monitored in case
• of combination with ACE inihibitors & AgII
antagonists).
52. • β-blockade is recommended for all patients with chronic, stable HF.
• SHOULD NOT be used to initiate therapy of acute heart failure
(C.I. in acute heart failure) as they may worsen case by –ve inotropic effect.
• Precautions:
Excessive beta-blockade contractility so doses must be very low
initially and then gradually increased.
