Positive inotropic drugs: Catecholamines and PDE3 inhibitors
Positive inotropic agents increase myocardial contractility by increasing the level of calcium in the cytoplasm of the muscle cells or by increasing the sensitivity of the heart to calcium. Positive inotropes are indicated in acute conditions where there is low cardiac output (CO), such as cardiogenic shock following myocardial infarction, acute decompensated heart failure, low CO states after cardiac surgery, cardiogenic shock, septic shock, and cardiomyopathy. In contrast, negative inotropes weaken the force of contraction of the heart
There is limited evidence to suggest that one particular positive inotrope is better than another. The choice of which drug to prescribe will depend on factors such as the patient’s underlying disease state and the clinician’s preference.
Drugs that act as positive inotropes include the catecholamines (dobutamine and isoprenaline [synthetic catecholamines] and adrenaline and noradrenaline [endogenous catecholamines]) and phosphodiesterase type-3 (PDE3) inhibitors.
Cardiac effects of catecholamines are attributed to their action as agonists of alpha and beta adrenoceptors, in particular activation of the ß1-adrenoceptor increases heart contractility and heart rate. Dobutamine is predominantly a ß1 agonist, but its action at ß2 receptors causes vasodilation (and decreases afterload) which can be compensated by administering a vasopressor such as noradrenaline. Isoprenaline has a similar profile to dobutamine but tends to cause more tachycardia. Noradrenaline, acting mainly via α1-adrenoceptors, is primarily used as a vasopressor (increasing afterload to maintain mean arterial pressure) rather than an inotrope. It is often used with other inotropes, such as dobutamine, to maintain adequate perfusion (supra). As adrenaline has activity at all adrenoceptors other more specific inotropes are often preferred over adrenaline. The main use of adrenaline is as the bolus administered during resuscitation after cardiac arrest.
Inhibition of PDE3 increases intracellular calcium causing vasodilation and increased myocardial contractility and is the causative mechanism of action of the PDE3 inhibitors enoximone, milrinone and the non-selective phosphodiesterase inhibitor theophylline.
Role of inotropic drugs in treating congestive cardiac failure
This video is approximately 37 minutes long and discusses the role of inotropic drugs in treating congestive heart failure with the help of concept maps/diagrams and animations.This presentation starts with an overview of pathophysiological basis of treating congestive cardiac failure (CCF). Various drugs commonly used to treat CCF are listed to show how inotropic drugs fit in the larger picture. Then, a description of the mode of action, uses and side effects of inotropic agents and their role in CCF is given in greater detail. Finally, a summary is given.
This 24-slide slide set provides an introduction at new learner to intermediate level to some of the most common drugs that are used clinically to modulate the rate and force of contraction of the heart. The specific drug classes presented include: agonists and antagonists of beta-adrenoceptors, an antagonist of muscarinic acetylcholine receptors (i.e. atropine), cardiotonic agents including cardiac glycosides (i.e. digoxin) and miscellaneous other agents.