Drug Treatments Of Heart Failure Biology Essay

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Heart failure is a clinical condition in which one or both ventricles are damaged leading to the heart not being able to maintain sufficient blood flow through peripheral tissues and organs. As a result, the heart weakens and peripheral tissues face oxygen and nutrients being taken away. The symptoms are tiredness, shortness of breath and congestion of blood because the heart cannot fill or empty blood properly causing perfusion of tissues and retention of fluid. Some of the drugs used in the treatment of heart failure are called Bisoprolol and Enalapril.5,6 Nowadays these drugs are known on the market as Bisoprolol Fumarate and Enalapril Maleate.8 Bisoprolol Fumarate is available as 5 mg tablets and 10 mg tablets. In a heart failure condition the initial dose is 1.25 mg once daily for one week and if well tolerated the dose is gradually increased to 7.5 mg once daily for four weeks and then to 10 mg once daily. It is important do not stop taking this medicine except on your doctor's advice (Label 8). Enalapril Maleate on the other hand is available as 2.5 mg tablets, 5 mg tablets, 10 mg tablets and 20 mg tablets. The initial dose is 2.5 mg once daily under close medical supervision and then gradually increased to 10-20 mg over 2-4 weeks twice daily if well tolerated.9

Bisoprolol is also used for curing of high blood pressure which is a systolic blood pressure of 130-139 mmHg and a diastolic blood pressure of 85-89 mmHg,6 abnormal rate of muscle contractions in the heart known as arrhythmias, coronary heart diseases for example the heart pain known as angina and glaucoma which is raised intraocular pressure in eyes.7) The drug is a competitive β (1)-selective adrenergic receptor blocking agent.

Bisoprolol has less effect on β (2) receptors located in the bronchial smooth muscle cells as well as peripheral vascular smooth muscle cells and a greater effect on β (1) receptors located in both cardiac myocytes and conduction cells in the heart 7)10)and therefore it is called a cardioselective adrenergic antagonist 8) which binds to the receptor but does not activate it and at the same time blocks the effect of agonist (stimulates the receptor) on that receptor.7) This antagonist is not cardiospecific as Bisoprolol can also lead to spasm of the bronchi by competitively inhibit β (2) receptors.8) β (1) receptors are found mainly in the heart. Stimulation of these receptors by adrenaline causes a rise in both heart rate and blood pressure and as a result of this effect the demand of heart for oxygen is very high. Adrenergic antagonist selectively blocks the activation of β (1) receptors found in the heart and also in vascular smooth muscles. This brings the opposite effect. The sympathetic system is inhibited as well. In addition, Bisoprolol prevents the neurotransmitters called noradrenalin and adrenaline to bind to β receptors on nerves near the heart and in blood vessels. Also, β (1)-selective antagonist inhibits the release of renin from the juxtaglomerular cells of kidney. 3)4)7)

D=the juxtaglomerular cells of kidney

(Google images)

All these effects leading to a decrease of the heart rate and force therefore the heart contracts with a smaller force and blood pressure goes down by expansion of blood vessels known as vasodilatation. The cardiac output, systolic and diastolic blood pressures decrease too. By decreasing heart rate and the force of heart muscle contraction, the work of the heart reduces. That means the demand of the heart for oxygen supply reduces too and the heart is not deprived of oxygen as it was during the heart failure 3)4)7). The statistics shows that Bisoprolol have decreased the death rate by 34-5 % 11). So this drug is very beneficial in taking during a heart failure condition.

Enalapril is another a very important drug also used for treatment of high blood pressure as well as kidney problems due to diabetes, for curing of myocardial infarction especially when ventricles of the heart do not work properly, for treatment of ischaemic heart diseases for example angina and for improvement of recovery after a heart attack. Enalapril is an angiotensin-converting enzyme (ACE) inhibitor.1)2)12)

Renin is a proteolytic enzyme. This enzyme is released from a juxtaglomerular apparatus found in the kidney. Renin converts angiotensin to angiotensin I while acting on angiotensinogen which is a plasma globulin synthesised in the liver. The role of ACE in the body located throughout the tissue is the conversion of inactive angiotensin I to vasoactive angiotensin II. In addition, ACE makes bradykinin which is a potent vasodilator not active. Angiotensin II binds to AT1 receptors which are classified as G-protein-coupled receptors. This effect leads to narrowing of blood vessels. It is either a direct vasoconstriction or vasoconstriction happens because of increased release of noradrenalin from the sympathetic nerve terminals; vasoconstriction especially happens in efferent arterioles of the kidney. Also, this effect leads to a rise in heart rate and force of contraction. The drug blocks an angiotensin-converting enzyme and therefore prevents the conversion of angiotensin I to angiotensin II chemicals and inhibits the formation of the angiotensin II chemical.7)10)


↓ →Renin acts on Angiotensinogen

Angiotensin I

↓ → ACE →ACE inhibitor

Angiotensin II (formation of that chemical is inhibited)

AT1 receptors

↓ ↘

Vasoconstriction Rise in heart rate and force of contraction

↓ ↓

Vasodilatation Slowing down in heart rate and force of contraction 7)

That effect results in vasodilatation of blood vessels and lowering of blood pressure, both heart rate and force of contraction decrease too. Also, that results in making longer of half-life of bradykinin meaning that vasodilatation is prolonged 7). Large clinical trials show that ACE inhibitor decreases the death rates significantly by 31 % at one year as well as decrease the chances of getting a heart failure condition 13). So this drug is very useful and necessary to take during a heart failure.

To summarise, a heart failure is identified as the heart not being able to pump enough of blood to maintain normal functions of the body. The drugs that are used for treatment of heart failure and other conditions are called Enalapril and Bisoprolol. Enalapril belongs to a group of drugs collectively known as ACE inhibitors whereas Bisoprolol belongs to a group of drugs collectively known as Beta-blockers. An ACE inhibitor drug (Enalapril Maleate) is recommended for patients who suffer from asymptomatic left ventricular failure. The β-blocker drug (Bisoprolol Fumarate) is advised for people who experience a stable heart failure and left-ventricular systolic dysfunction 9). Each drug has its own mode of action; however both drugs make blood vessels wider by vasodilatation causing a decrease in blood pressure and making a heart to function properly and normally.

References used are:


Eve Redstone ''Enalapril and the Treatment of High Blood Pressure'' Jan 1, 2008



Frederic H. Martini ''Fundamentals of Anatomy and Physiology'', seventh edition, pages 694 and 703

Dr Ian Greenwood '' Master of Pharmacy Degree Course module guide; Systems Pharmacology I; Module Code: PY2050, Semester II, 2011; Handbook one'' Lecture ''Heart Failure'' by Dr Tareck F Antonios and Lecture ''Management of Hypertension'' by Dr Teck Khong

H.P. Rang, M.M. Dale, J.M. Ritter, R.J. Flower ''Rand and Dale's Pharmacology'' Sixth edition, pages 180-181,303-304, 308-313, 153, 9

BNF N57, ''Beta-adrenoceptor blocking drugs'' and '' Angiotensin-converting enzyme inhibitors'' Pages 85, 88, 100, 103

BNF N60 (online ) ''Bisoprolol Fumarate''; ''Enalapril Maleate''; ''Heart Failure''

Dr.John R. Vyselaar, R3; Senior Medical Student Lecture Series ''Cardiac

Pharmacology'' pages 1, 5

Cruickshank JM. ''Beta-blockers and heart failure'' Indian Heart Journal 2010 Mar-Apr;62(2): 101-10


The Concensus Trial Study Group ''Effects of Enalapril on Mortality in Severe Congestive Heart Failure'' N Engl J Med June 4, 1987; 316:1429-1435