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Drugs for Congestive Heart Failure
1. Drugs for Congestive
Heart Failure
Dr Lokendra Sharma
Sr. Professor, Pharmacology
SMS Medical College, Jaipur
2. Basic Definition
Heart failure is a
medical term that
describes an
inability of the
heart to keep up
its work load of
pumping blood to
the lungs and to the
rest of the body.
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3. Classification
I) Drugs with positive inotropic effects-
a) Cardiac glycosides- Digoxin, Digitoxin,
Ouabain
b) Phosphodiesterase inhibitors- Inamrinone,
Milrinone, Levosimendan
c) Beta adrenergic agonist- Dopamine,
Dobutamine, Dobuxamine
4. II) Drugs without positive inotropic effects-
a) Diuretics- Bumetanide, Furosemide,
Hydrochlorothiazide, Spironolactone
b) ACEIs- Enalapril, Lisinopril, Ramipril
c) Beta-1 adrenoceptor antagonist-
Bisoprolol, Carvedilol, Metoprolol
5. A, B, C, D, Es of Heart Failure Therapy
A Angiotensin converting enzyme inhibitors
anticoagulants, amiodarone, AICD, assist
devices
B Beta blocking drugs
C Calcium channel blocking drugs, coronary
revascularization, cardiac transplant,
cardiomyoplasty, cardiac reduction surgery
D Diet, diuretics, digitalis, dobutamine
E Exercise
6. CHF ClassificationNew York Heart Association
Class I - Asymptomatic
Class II - Symptomatic with moderate
exertion
Class III - Symptomatic with mild exertion
Class IV - Symptomatic with no exertion/or
at rest
7. CHF: Clinical Assessment
Left or right sided
History
– Left sided
• Orthopnea
• Dyspnea
– Right sided
• Anorexia
• Abdominal distension
• Ankle edema
Exam
– Left sided
• Rales
• Narrow pulse pressure
• Increasing S3
– Right sided
• Elevated JVP
• Hepato-jugular reflex
• Loud P2
8. CHF: Pharmacotherapy
Relief of symptoms
Diuretics
Digoxin
Reduction in mortality/hospitalizations
ACE Inhibitors
Beta blockers
Spironolactone
Rescue in advanced failure
Inotropic infusions (dobutamine)
Vasodilators
10. Compensatory Mechanisms in
Heart Failure
Mechanisms
designed for
acute loss in
cardiac output
Chronic
activation of
these
mechanisms
worsens heart
failure
23. Therapeutic Uses of Digitalis
Congestive Heart Failure
Atrial fibrillation
24. Overall Benefit of Digitalis to
Myocardial Function
cardiac output
cardiac efficiency
heart rate
cardiac size
NO survival benefit
25. Other Beneficial Effects
Restoration of baroreceptor
sensitivity
Reduction in sympathetic activity
Increased renal perfusion, with
edema formation
26. Administration
Digoxin has a long enough half life (24-36
hr.) and high enough bioavailability to allow
once daily dosing
Digoxin has a large volume of distribution
and dose must be based on lean body mass
Increased cardiac performance can increase
renal function and clearance of digoxin
Eubacterium lentum
30. Phosphodiesterase
Inhibitors
Amrinone
Milrinone
levosimendan
Mechanism of Action
Inhibition of type III phosphodiesterase
intracellular cAMP
activation of protein kinase A
Ca2+ entry through L type Ca2+ channels
inhibition of Ca2+ sequestration by SR
cardiac output
peripheral vascular resistance
31. Mechanism of action of beta agonists and
PDE isozyme-3 inhibitors in heart failure
40. Mechanism of Action
Afterload reduction
Preload reduction
Reduction of facilitation of
sympathetic nervous system
Reduction of cardiac
hypertrophy
41. ACE Inhibitors: Therapeutic
Uses
Drugs of choice in heart failure
(with diuretics)
Current investigational use:
Acute myocardial infarction
AT II antagonists
42. Diuretics: Mechanism of Action
in Heart Failure
Preload reduction: reduction of excess
plasma volume and edema fluid
Afterload reduction: lowered blood
pressure
Reduction of facilitation of
sympathetic nervous system
43. Vasodilators
Mechanism of action: reduce
preload and afterload
Drugs used
Sodium nitroprusside
Hydralazine
Ca2+ channel blockers
Prazosin
44. b-Blockers in Heart Failure:
Mechanism of Action
Standard b-blockers:
Reduction in damaging sympathetic
influences in the heart (tachycardia,
arrhythmias, remodeling)
inhibition of renin release
Carvedilol:
Beta blockade effects
peripheral vasodilatation via a1-
adrenoceptor blockade (carvedilol)
45. Spironolactone
Aldosterone antagonist, K-sparing diuretic
Prevention of aldosterone effects on:
Kidney
Heart?
Aldosterone inappropriately elevated in CHF
Mobilizes edema fluid in heart failure
Prevention of hypokalemia induced by loop
diuretics (protection against digitalis toxicity?)
Prolongs life in CHF patients
46. Take Home Message
Diuretics of choice in acute CHF- Loop
diuretic
Short term management of acute CHF- Inotropic
drugs
Cardiac glycosides act by inhibiting Na+ K+
ATPase
Digoxin is only inotropic drug, can be given orally
Thrombocytopenia side effect of Inamrinone
CCBs should not used in CHF – may increase
mortality
47. Aldosterone antagonist and beta
blocker- reduce the mortality
Widely used beta blocker- Carvedilol
Beta blockers contraindicated in
acute CHF.