Compensatory Mechanisms of CHF
To enhances the cardiac output, body compensates for the intrinsic cardiac effects in the following manner.
1. Increased sympathetic discharge.
2. To complete the remittent B.P., baroreceptors set within the arch of artery arterial blood vessel sinuses and walls of the center get excited and causes activation of beta-adrenergic receptors resulting in an increase in rate and force of contraction of heart.
3. An increase in blood vessel comes back (preload) is additionally seen because of the activation of alpha adrenergic receptors.
4. Increased rate associated force of contraction at the side of the enhanced preload ends up in an initial increase within the flow.
5. Vasoconstriction of the arteries due to alpha stimulation also causes an increase in after load, leading to fall in ejection fraction. Activation of Renin Angiotensin Aldosterone (RAA)
• Fall within the flow decreases the urinary organ perfusion rate; as a result the RAA system gets activated.
• Angiotensin II may cause atrophic response in vascular smooth muscle (with vasoconstriction) and myocardial hypertrophy, attempting to restore wall stress to normal.
It is most vital mechanism by that body stipendiary for the intrinsic internal organ effects.
• It involves changes within the form of the center (from traditional to spherical) because of cardiac muscle hypertrophy.
• During cardiac remodeling, the connective tissue cells as well as the abnormal myocardial cells undergo proliferation and dilation instead of stretching under the influences of angiotensin-2.
• In the early stages, the remodeled heart maintains the cardiac performances.
• But later on, hypertrophy may exert certain adverse effects like ischaemic changes, decrease in the rate and force of contraction of heart. After certain period of time the antagonistic mechanisms get exhausted and worsen the cardiac performances.
The stress on heart increases and a stage is reached where these mechanisms fails to maintain the adequate cardiac output. Clinical manifestations/signs and symptoms
• Fluid retention
• Pulmonary congestion
• Dyspnoea and orthopnoea
Effect on automaticity, conductivity, contractility, blood pressure, heart rate:
• Automaticity: Digitalis increases the ability of purkinje cells and ventricular muscles
to initiate impulses.
• Conduction velocity: The conduction velocity is slightly increased in the atria and
ventricle by small doses of digitalis.
• Blood pressure: Digitalis increases mean arterial pressure in normal individuals only.
• Heart rate: Digitalis does not affect heart rate in normal individuals, but reduces it in
Extra Cardiac Actions:
• On kidney: Digitalis increases rate of excretion of Na+ and water by kidney and thus
• On Gastro-intestinal Tract: High doses of digitalis produces diarrhea, nausea,
• Anorexia, nausea, vomiting, diarrhoea.
• Headache, fatigue, insomnia.
• Yellow/green vision, blurred vision.
• Cardiac arrhythmia.
• To treat heart failure.
• To treat atrial fibrillation.
• To treat atrial flutter.
• To treat paroxysmal atrial tachycardia.
Digitalis is strictly contraindicated in following clinical conditions:
• Myocardial infraction
• Ventricular tachycardia
Pharmacology – II 2.7 Drugs used in Congestive Heart Failure
• Partial heart block
• Previous digitalis therapy
• Calcium administration.
• Digitalis, Calcium: Calcium ions increase the force of contraction of heart. High plasma calcium levels stimulate the myocardium so much, that it leads to cardiac arrest during systole. Digitalis is also known to increase the force of contraction of heart. Thus digitalis and calcium act synergetically and may prove to be toxic. Hence during digitalis therapy Ca++ ion administration must be avoided.
• Digitalis, Quinidine: Quinidine, when administrated in individuals taking digitalis, increases serum digoxin levels. This may cause adverse effects of digitalis and other clinical complexities. Hence must be avoided.
Treatment of over digitalisation:
• Immediately stop the administration of digitalis.
• Stop if any diuretic administration is in continuation.
• Mild tachycardia can be treated with atropine.
• Mild toxicity can be treated by administration of potassium salts – 5 to 7.5 g of potassium chloride orally daily.
• Ventricular tachycardia can be treated with phenytoin (250 mg well diluted).
Rapidly Acting Inotropic Agents In critically sick infants with CHF, in those with renal dysfunction (e.g., infants or in postoperative cardiac patients with heart failure) quickly acting catecholamines with a short duration of action is preferable to digoxin.
β1-Blockers-bisoprolol, carvedilol, metoprolol.
Mechanism of Action:
• Heart failure is accompanied by an increase activation of sympathetic nervous system.
• This brings about structural and functional modification in the myocardium.
• β Blockers inhibit the sympathetic outflow of nor epinephrine and counteract the changes produced.
• The ventricular remodeling in heart failure is also reversed by β Blockers.
• Increases beta receptor sensitivity.
1. Define cardiotonics. Explain the pharmacology of digitalis.
2. Explain the mechanism of action and toxicity of cardiac glycosides.