General Instruction for Writing Report for

Continuous
Guru Nanak Institute of Pharmaceutical Science
and
Technology
157/ F, Nilgunj Road, Panihati, Kolkata 700114

Title of Work: Drugs used in congestive heart failure

Paper Code: PT 518

Paper Name: PHARMACOLOGY II

Report Submitted for the Evaluation of Continuous Assessment II

Submitted by

Name: Sovan Sarkar

Roll No: 186012111012

Program: B.Pharm

Semester: 5

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Sl.
Title Pg. No.
No.

1. Abstract 3

2. Introduction 4

3. Discussion 4-11

4. Conclusion 12

5. References 13

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 Abstract

Congestive cardiac failure is a condition in which the heart loses the ability to pump
blood efficiently throughout the body. The disease affects other organs in the body,
resulting in breathing difficulty, reduced kidney function, and fluid accumulation in
body tissues (edoema) from poor circulation.

Congestive cardiac failure develops when the heart muscle becomes weakened and can
no longer circulate blood effectively through the body. Most commonly, people
develop congestive cardiac failure as a result of coronary artery disease (disease of the
arteries that supply blood and oxygen to the heart). Other causes of congestive cardiac
failure are infection, congenital heart disease, heart attack, heart valve disease, and
some types of heart rhythm irregularities (arrhythmias).

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 Introduction

Congestive Heart Failure

In chronic congestive heart failure, cardiac pump performance falls below a level
required by the body’s organs for maintaining function and metabolism. The most
common primary causes of heart failure are coronary disease, hypertension, volume
overload, or cardiomyopathies. Diminished cardiac performance leads to a precordial
congestion
of venous blood. Congestion in front of the left ventricle causes dyspnoea and
pulmonary
edema. Ankle edemas, enlarged liver, and ascites signal congestion in front of the right
ventricle.

Causes

 Coronary artery disease and heart attack. Coronary artery disease is the
most common form of heart disease and the most common cause of heart

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 failure. The disease results from the build-up of fatty deposits in the
arteries, which reduces blood flow and can lead to heart attack.

 High blood pressure. If your blood pressure is high, your heart has to work
harder than it should to circulate blood throughout your body. Over time,
this extra exertion can make your heart muscle too stiff or too weak to
properly pump blood.

 Faulty heart valves. The valves of the heart keep blood flowing in the
proper direction. A damaged valve — due to a heart defect, coronary
artery disease or heart infection — forces the heart to work harder, which
can weaken it over time.

 Damage to the heart muscle. Heart muscle damage can have many causes,
including certain diseases, infection, heavy alcohol use, and the toxic
effect of drugs, such as cocaine or some drugs used for chemotherapy.
Genetic factors also can play a role.

 Inflammation of the heart muscle (myocarditis). Myocarditis is most

commonly caused by a virus, including the COVID-19 virus, and can lead
to left-sided heart failure.

 A heart problem that you're born with (congenital heart defect). If your
heart and its chambers or valves haven't formed correctly, the healthy parts
of your heart have to work harder to pump blood, which may lead to heart
failure.

 Abnormal heart rhythms (arrhythmias). Abnormal heart rhythms may

cause your heart to beat too fast, creating extra work for your heart. A slow
heartbeat also may lead to heart failure.

 Other diseases. Long-term diseases — such as diabetes, HIV, an

overactive or underactive thyroid, or a build up of iron or protein — also
may contribute to chronic heart failure.

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Symptoms

Heart failure can be ongoing (chronic), or it may start suddenly (acute).

 Shortness of breath with activity or when lying down

 Fatigue and weakness

 Swelling in the legs, ankles and feet

 Rapid or irregular heartbeat

 Reduced ability to exercise

 Persistent cough or wheezing with white or pink blood-tinged mucus

 Very rapid weight gain from fluid build-up

 Nausea and lack of appetite

 Chest pain if heart failure is caused by a heart attack

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There are two distinct goals of drug therapy in CHF:

(a) Relief of congestive/low output symptoms

and restoration of cardiac performance. This
can be achieved by:

 Inotropic drugs—Digoxin, dobutamine/

 dopamine, amrinone/milrinone
 Diuretics—Furosemide, thiazides
 RAS inhibitors—ACE inhibitors/ARBs
 Vasodilators—hydralazine, nitrate,
nitroprusside
 Beta blocker—Metoprolol, bisoprolol,
carvedilol, Nebivolol

(b) Arrest/reversal of disease progression and

prolongation of survival, possible with:
o ACE inhibitors/ ARBs,
o Aldosterone antagonist—Spironolactone,

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Diuretics
Almost all cases of symptomatic CHF are treated with a diuretic. High ceiling diuretics
(furosemide, bumetanide) are the diuretics of choice for mobilizing edema fluid; later
they may be continued in low doses. In advanced CHF after chronic use, resistance may
develop to even high ceiling diuretics. Addition of a
thiazide/metolazone/spironolactone to furosemide may overcome the resistance.
Thiazide alone has very limited role in CHF. Diuretics:
(a) Decrease preload and improve ventricular
efficiency by reducing circulating volume.
(b) Remove peripheral edema and pulmonary
congestion.
Intravenous furosemide promptly increases
systemic venous capacitance and produces rapid
symptomatic relief in acute left ventricular failure.
It has, in conjunction with vasodilators, virtually obviated the need for i.v.
digitalization.

Renin-angiotensin system (RAS) inhibitors

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Since RAS activation is pivotal to development of symptoms and disease progression
in CHF, the ACE inhibitors and ARBs are the sheet anchor of drug therapy in CHF.
They afford symptomatic as well as disease modifying benefits in CHF by causing
vasodilatation,
retarding/preventing ventricular hypertrophy, myocardial cell apoptosis, fibrosis
intercellular matrix changes and remodeling. In addition to decreasing Ang II
production, ACE inhibitors raise the level of kinins which stimulate generation of
cardioprotective NO and PGs. Symptomatic and prognostic benefits of ACE
inhibitors/ARBs have been established in mild to severe (NYHA class I to IV) CHF as
well as in subjects with asymptomatic systolic dysfunction.They are thus recommended
for all grades of CHF,
unless contraindicated, or if renal function deteriorates by their use (mainly in those
with
decresed renal blood flow/renal artery stenosis).

Aldosterone antagonist
(Spironolactone, Eplerenone)
Over the past 2 decades it has been realized that 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:
(a) Expansion of e.c.f. volume → increased
cardiac preload.

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(b) Fibroblast proliferation and fibrotic change
in myocardium → worsening systolic dysfunction
and pathological remodeling.
(c) Hypokalemia and hypomagnesemia →
increased risk of ventricular arrhythmias and
sudden cardiac death.
(d) Enhancement of cardiotoxic and remodeling
effect of sympathetic overactivity.

Vasodilators
Vasodilators were first used i.v. to treat acute heart failure that occurs in advanced cases
or following MI, and serve to tide over crisis. Their use by oral route has been extended
to long-term therapy of chronic CHF, but vasodilators other than ACE inhibitors/ARBs
have only limited utility. (i) Preload reduction: Nitrates cause pooling of blood in
systemic capacitance vessels to reduce ventricular end-diastolic pressure and volume.
With reduction in size of ventricles, effectiveness of myocardial fibre shortening in
causing ejection of blood during systole improves.

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Sympathomimetic inotropic drugs
Drugs with β adrenergic and dopaminergic D1 agonistic actions have positive inotropic
and (at low doses) vasodilator properties which may be utilized to combat emergency
pump failure. Dobutamine (2–8 μg/kg/min) a relatively selective β1 agonist with
prominent inotropic action is the preferred drug for i.v. infusion in acute heart failure
accompanying myocardial infarction (MI), cardiac surgery as well as to tide over crisis
in advanced decompensated CHF. Dopamine (3–10 μg/kg/min by i.v. infusion) has
been used in cardiogenic shock due to MI and other causes. While dobutamine does not
raise
(may lower) systemic vascular resistance and is preferred in heart failure, dopamine
tends to
increase afterload, especially at higher rates of infusion (>5 μg/kg/min) and has limited
utility
in patients who are not in shock. Low rates of dopamine infusion (~2 μg/kg/min) cause
selective renal vasodilatation (D1 agonistic action) which improves renal perfusion and
g.f.r. This can restore diuretic response to i.v. furosemide in refractory CHF.

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 Conclusion

A chronic condition in which the heart doesn't pump blood as well as it should.
There are two distinct goals of drug therapy in
CHF:
(a) Relief of congestive/low output symptoms
and restoration of cardiac performance. This
can be achieved by: Inotropic drugs Diuretics RAS inhibitors Vasodilator Beta blocker

(b) Arrest/reversal of disease progression and prolongation of survival, possible with:

ACE inhibitors/ ARBs, Aldosterone antagonist

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 Reference

1. Simpson, Scot H., et al. "Using focus groups to identify barriers to drug use in
patients with congestive heart failure." Pharmacotherapy: The Journal of
Human Pharmacology and Drug Therapy 20.7 (2000): 823-829.
2. Bagchi, Ann D., et al. "Utilization of, and adherence to, drug therapy among
medicaid beneficiaries with congestive heart failure." Clinical
therapeutics 29.8 (2007): 1771-1783.
3. Monane, Mark, et al. "Noncompliance with congestive heart failure therapy in
the elderly." Archives of Internal Medicine 154.4 (1994): 433-437.
4. Heerdink, E. R., Leufkens, H. G., Herings, R. M., Ottervanger, J. P., Stricker,
B. H., & Bakker, A. (1998). NSAIDs associated with increased risk of
congestive heart failure in elderly patients taking diuretics. Archives of Internal
Medicine, 158(10), 1108-1112.
5. Podrid, Philip J., Richard I. Fogel, and Therese Tordjman Fuchs. "Ventricular
arrhythmia in congestive heart failure." The American journal of
cardiology 69.18 (1992): 82-96.
6. Page, John, and David Henry. "Consumption of NSAIDs and the development
of congestive heart failure in elderly patients: an underrecognized public health
problem." Archives of internal medicine 160.6 (2000): 777-784.
7. Chin, Marshall H., and Lee Goldman. "Factors contributing to the
hospitalization of patients with congestive heart failure." American Journal of
Public Health 87.4 (1997): 643-648

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