Cardiac Glycosides Notes / Pharmacology Cardiac Glycosides Notes / CONGESTIVE HEART FAILURE Notes / Pharmacy Notes / Solution Pharmacy Notes

Introduction

When a heart fails to pump blood in a quantity sufficient to fulfil the body

requirements, a condition of Congestive Heart Failure (CHF) occurs, which is

also known as a Heart Failure (HF).

CHF is caused due to:

1) Narrowing of the arteries supplying blood to the heart muscles,
2) Any congenital heart defects,
3) Endocarditis (infection in heart valves) or myocarditis (infection of heart muscles),
4) Cardiomyopathy (disease of the heart muscles),
5) Any long -term heart valve disease (due to past rheumatic fever or other causes) and high blood pressure, and
6) Past history of the patient who has suffered from myocardial infar ction or heart attack and the injured tissue obstructs the normal functioning of heart.

Some common symptoms of CHF are:

1) Fatigue, 2) Swelling or oedema,

3) Shortness of breath, and 4) Increased urination.

1.2.2. Classification

The following drugs are employed in the treatment of CHF:

1) Drugs with Positive Inotropic Effects

i) Cardiac Glycosides: Digoxin, Digitoxin, and Ouabain.
ii) Bipyridines/Phosphodiesterase Inhibitors: Amrinone and Milrinone.
iii) β-Adrenergic Agonists: Dobutamine and Dopamine.

2) Drugs without Positive Inotropic Effects

i) Diuretics: Thiazides, Furosemide, and Spironolactone.
ii) Angiotensin Antagonists: ACE inhibitors and Losartan.
iii) β-Adrenergic Antagonists: Bisoprolol, Carvedilol, and Metoprolol.
iv) Vasodilators: Nitrates and Hydralazine.

1.2.3. Cardiac Glycosides

Cardiac glycosides are derived from plant derivatives and are steroidal in nature .

A glycoside is a sugar-containing compound in which one of the hydroxyl groups

of the sugar molecule is replaced with another compound.

Digoxin, digitoxin, and ouabain are the commonly used cardiac glycosides.

Often, the term digitalis refers to the complete group of cardiac glycosides as all

the drugs in this group exert the same effects on the heart. They differ only in

lipid solubility, rapidity, degree of absorption, protein binding, metabolic

pathway, and excretion.

1.2.3.1. Mechanism of Action

The mechanism of action of digitalis can be explained as follows (figure 1.2):

1) Digitalis exerts a positive inotropic effect due to its ability to potentiate the

excitation-contraction coupling. This is possible since digitalis increases the

concentration of free intracellular Ca2+ ions.

2) It inhibits the membrane bound Na +/K+-ATPase transport system (sodium

pump), resulting in increase of intracellular Na + ions and loss of intracellular

K+ ions.

3) As Na+ ions accumulate inside the cell, it activates a Na +/Ca2+ carrier system

(a non -enzymatic protein carrier) within the membrane. The activation of

Na+/Ca2+carrier system results in an increase in the influx of Ca 2+ ions. Three

Na+ ions are exchanged for each Ca2+ ion, thereby generating an electrogenic

potential by this exchanger.

4) Normally, the concentration of Ca2+ ions around the myofilaments is lowered by

the Ca2+ ion pump in the Sarcoplasmic Reticulum (SR). The energy for driving

this pump is obtained by ATP hydrolysis carried out by Na +/K+-ATPase.

However, digitalis inhibits this enzyme and hence less energy is available for

driving the Ca2+ ion pump. Thus, the supply of Ca2+ ions from SR around the

myofilaments increases, which in turn activates the contractile machine ry.

5) The binding of digitalis to sodiu m pump is inhibited by the K+ ions present in

the serum. Hence, conditions of hypokalaemia facilitate the action of

digitalis. On the other hand, conditions of hyperkalaemia can decrea se

cardiac toxicity. Arrhythmia induced by digitalis, is increased by co nditions

of hypercalcaemia or hypomagnesaemia.