Drugs used for CHF

Drugs Used In-CHF
By:- Dr. Manish Pal Singh,
Associate Professor
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

Congestive heart failure (CHF)
❑ CHF is a condition in which the heart can't pump enough blood to the body's
other organs.
❑ In some of the pathological conditions like- ‘Hypovolemic Shock’- decrease
CO- due to reduction of intravascular volume.
❑ Its primary cause is an impairment of the heart ability to fill or empty the left
ventricle properly.
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Source*- Jaypee Digital-ebook reader

Basic Causing Factor’s of CHF:
1. Narrowed arteries that supply blood to the heart muscle -
coronary artery disease.
2. Past heart attack, with scar tissue that interferes with the heart
muscle's normal work.
3. High blood pressure, etc.
3

Clinical Manifestations of CHF:
• Frequent bathroom usage.
• Tired and weak.
• Weight gain from excess fluid.
• Chest pain.
• Swollen feet, legs, and/or ankles.
• Loss of appetite.
• Swollen neck veins.
• Skin is cold and sweaty.
• Pulse is irregular.
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Treatment’s of CHF (cardiac Glycosides):
➢ Drugs having- “Cardiac Inotropic” action.
➢ They increase myocardial cardiac contractility and output in hypodynamic
heart with out a proportionate increase oxygen consumption.
➢ Cardiac glycosides having this property , rather than ‘Cardiac Stimulant’
(Adr, theophylline)- tend to increase oxygen consumption .
➢ ‘Cushney and Mackenizie’ in 20th century discovered its used in CHF.
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Unsaturated Lactone
Steriods

Sources of cardiac Glycosides
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5. Thevetia nerifolia (nut) Proscillaridin-A
6. Bufo Vulagaris (Toad skin) Bufotoxin

MAO- Cardiac Glycosides:
❑ Digitalis increases force of cardiac contraction by a direct action.
❑ It selectively binds to extracellular face of the membrane associated Na+ K+
ATPase of myocardial fibres and inhibits this enzyme. Inhibition of this cation
pump results in progressive accumulation of Na+ intracellularly.
❑ This indirectly results in intracellular Ca2+ accumulation.
❑ Ca2+ ions enter the cell driven by the steep Ca2+ gradient (>1 mM extracellular to
< 100 nM cytosolic during diastole) through voltage sensitive L type Ca2+
channels.
❑ 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 500nM → triggers contraction by activating troponin C on
myofibrils.
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▪ Cytosolic calcium to initiation of
interaction with contractile
protein, the force of contraction of
myofibril of cardiac cell increase.
Mechanism of positive inotropic action
of cardiac glycosides-
oSR-Sarcoplasmic reticulum;
oTnC- Troponin C;
oNCX- Na+-Ca2+ exchanger;
o RyR2- Ryanodine receptor calcium
channel2;
oPL- Phospholamban;
oSERCA2- Sarcoplasmic-endoplasmic
reticulum calcium ATPase 2.

Pharmacological Actions:
1. Heart:-
▪ Digitalis has direct effects on myocardial contractility and electrophysiological
properties.
▪ Digitalis causes a dose dependent increase in force of contraction of heart- a
positive inotropic action.
▪ This is especially seen in the failing heart which is exquisitely sensitive.
▪ There is increased velocity of tension development and higher peak tension can be
generated.
▪ Systole is shortened, diastole is prolonged.
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▪ Digitalis increase cardiac tone------ “Cardio tonic Agents”.
▪ The digitalized failing heart regains some of its capacity to contract more forcefully
when subjected to increased resistance to ejection.
▪ Heart rate is decreased by digitalis.
▪ Digitalis slows the heart by vagal and extravagal actions.
▪ Vagal tone is increased reflexly by sensitization of baroreceptors, as well as by
stimulation of vagal center.
▪ Extravagal direct depressant action on SA and A-V nodes. This component of
bradycardia is not reversed by atropine.
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Relationship between peripheral
resistance and stroke output in normal
and failing heart, and the action of
digitalis on failing heart
Effect of digitalis on Purkinje fiber action
potential

Electrophysiological Properties:-
▪ The Purkinje fibers, automatic and conducting tissues are more sensitive.
▪ The resting membrane potential (RMP) is progressively decreased (to less
negative values) with increasing doses.
▪ The rate of 0 phase depolarization is reduced resulting in slowing of
conduction. This action is most marked in A-V node and bundle of His.
▪ Digoxin increases ERP (Effective refractory Period) & decrease conduction
velocity in AV nodal tissue.
▪ The slope of phase-4 depolarization is increased in the PFs—ectopic
automaticity is enhanced- latent pacemakers become overt at high doses
producing extra-systoles.
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ECG:-
▪ Therapeutic doses of digitalis produce changes in the ECG. These are
accentuated at high doses- may also produce arrhythmias.
▪ Decreased amplitude or inversion of T wave.
▪ Increased P-R interval (due to slowing of A-V conduction), A-V block at toxic
doses.
▪ Shortening of Q-T interval (reflecting shortening of systole).
▪ Depression of ST segment (at high doses—due to interference with
repolarization).
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ADR’S:
❑ Digitalis is a low ‘Therapeutic window’ drug (1.5-3), toxic action occur at
narrow range doses.
❑ Extracardiac – Anoxesia, vomiting, nausea, Vomiting (CTZ-stimulation).
❑ Cardiac- Arrhythmia, partial to complete AV-block & bradycardia.
❑ Tachyarrhythmia- chronic use of digitalis & diuretics ( K+ depletion) .
❑ Note:- DIGOXIN ANTIBODY- treating toxicity of digitalis.
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Drug Interactions:-
▪ Diuretics- Hypokalemia – induced digitalis arrhythmias
▪ Calcium- potentiate action of digitalis- toxicity
▪ Qunidine- decrease binding of digoxin to tissue protein as well as its renal &
biliary clearance- toxicity can occur.
▪ Antacids- reduced absorption of digoxin- reduced effect
▪ Propranolol & Verapamil- block the Ca++ channels- may additively depress
AV conduction- opposite to + inotropic action.
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Other Treatment Approach’s to CHF:
❑ ACE inhibitors/AT1-blockers/beta-blockers- arrest/reversal of disease
❑ Aldosterone antagonist – (Spironolactone, Eplerenone)- Rise in plasma
aldosterone in CHF, in addition to its well known Na+ and water retaining
action, is an important contributor to disease progression by direct and indirect
effects.
❑ Sympathomimetic inotropic drugs- (Dobutamine) (β1- agonist) with
prominent inotropic action is the preferred drug for i.v. infusion in acute heart
failure.
❑ Phosphodiesterase 3 inhibitors- (Amrinone)- increases myocardial cAMP and
transmembrane influx of Ca2+.
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❑ (Nesiritide)- is a recombinant brain natriuretic peptide (BNP) has been
approved for i.v. use to relieve dyspnea and other symptoms in refractory CHF.
❑ (Tolvaptan)- This is an orally active nonpeptide vasopressin V2 receptor
antagonist introduced recently for the correction of water retention and
hyponatremia occurring in ‘syndrome of inappropriate ADH secretion’
(SIADH) as well as in advanced CHF.
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Drugs used for CHF

Drugs used for CHF

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