This PPT covers Drug therapy for Congestive heart failure. In this PPT only Pharmacotherapy of Digoxin is explained in detail.

1. DRUG THERAPY FOR
CONGESTIVE HEART FAILURE
PREPARED BY: JEGAN.S.NADAR

2. HEART FAILURE
Results from any structural or functional abnormality that impairs the ability of the
ventricle to eject blood (Systolic Heart Failure) or to fill with blood (Diastolic Heart
Failure).

4. The Vicious
Cycle of
Congestive
Heart
Failure
Decreased Blood Pressure and
Decreased Renal perfusion
Stimulates the Release
of renin, Which allows
conversion of
Angiotensin
to Angiotensin II.
Angiotensin II stimulates
Aldosterone secretion which
causes retention of
Na+ and Water,
increasing filling pressure
LV Dysfunction causes
Decreased cardiac output

5. As the heart's pumping becomes less effective, blood may back up in other areas of the body. Fluid
may build up in the lungs, liver, gastrointestinal tract, and the arms and legs. This is called congestive
heart failure.

6. Risk Factors
• CAD
• Age
• HTN
• Obesity
• Cigarette smoking
• Diabetes mellitus
• High cholesterol

9. CLINICAL PRESENTATION OF HEART FAILURE
 Due to excess fluid accumulation:
 Dyspnea (most sensitive symptom)
 Edema
 Hepatic congestion
 Ascites
 Orthopnea.
 Due to reduction in cardiac ouput:
 Fatigue (especially with exertion)
 Weakness

10. DRUG THERAPY
1. LOOP DIURETICS
2.ACE INHIBITORS
3.ARB
4.BETA BLOCKERS
5.ALDOSTERONE ANTAGONIST
6.VASODILATORS
7.INOTROPIC AGENTS

12. INOTROPIC AGENTS
CARDIAC GLYCOSIDES
 These are glycosidic drugs having cardiac inotropic property
 They increase myocardial contractility and output in a hypodynamic heart without
a proportionate increase in O2 consumption
 Digitalis lanata is the source of Digoxin, the only glycoside that is currently in use
 Digoxin increases force of contraction of failing heart
 It decreases HR

13. MECHANISM OF ACTION
Digitalis increases force of cardiac contraction
It selectively binds to extracellular face of the membrane associated of myocardial fibres
Inhibits Na+K+ ATPase pump
Inhibition of this cation pump results in progressive accumulation of Na+ intracellularly
This indirectly results in intracellular Ca2+ accumulation
During depolarization Ca2+ ions enter the cell driven by the steep Ca2+ gradient (>1 mM
extracellular to < 100 nM cytosolic during diastole)

14. This triggers release of larger amount of Ca2+ stored in sarcoplasmic reticulum (SR)
through Ryanodine calcium channel 2 (RYR2)
Cytosolic Ca2+ increases transiently to about 500 nM
Triggers contraction by activating troponin C on myofibrils.
Force of contraction increases
The Sarcoplasmic-endoplasmic reticular Cal. ATPase 2 pump (SERCA2) is then
activated which pumps Ca2+ back into the SR.

15. A fraction (equal to that which entered from outside during depolarization) is
extruded mainly by 3Na+/1Ca2+ exchange transporter (NCX-antiporter) and to a
lesser extent by sarcolemmal Ca2+ pump (Ca2+ ATPase).
There is more complete emptying of failing and dilated ventricles
Cardiac output is increased and end-diastolic volume is reduced

16. A fraction (equal to that which entered from outside
during depolarization) is extruded mainly by
3Na+/1Ca2+ exchange transporter (NCX-antiporter)
and to a lesser extent by sarcolemmal Ca2+ pump
(Ca2+ ATPase).
A fraction (equal to that which entered from outside
during depolarization) is extruded mainly by
3Na+/1Ca2+ exchange transporter (NCX-antiporter)
and to a lesser extent by sarcolemmal Ca2+ pump
(Ca2+ ATPase).

18. ADVERSE EFFECTS
Toxicity of digitalis is high, margin of safety is low
(Therapeutic index 1.5–3).
About 25% patients develop one or other toxic symptom. The manifestations are:
Extracardiac
 Anorexia, nausea, vomiting, abdominal pain, Fatigue, malaise, headache, mental confusion,
restlessness, disorientation, psychosis and visual disturbances
Cardiac
 Almost every type of arrhythmia can be produced by digitalis
 Partial to complete A-V block
 Severe bradycardia

19. CONTRAINDICATIONS
 Hypokalemia: enhances digitalis toxicity
 Elderly, renal or severe hepatic disease
 Myocardial ischaemia
 Ventricular tachycardia
 Partial A-V block: may be converted to complete A-V block by digoxin

20. INTERACTIONS
Should not be taken with
Diuretics
Quidindine
Adrenergic drugs
Verapamil ,diltiazem
Non selective beta blockers