Cardiostimulatory+Drugs

__Therapeutic Use and Rationale__ Cardiostimulatory drugs (also called "cardiotonic drugs") enhance cardiac function by increasing heart rate (chronotropy) and myocardial [|contractility (inotropy)], which increases cardiac output and arterial pressure. Many of these drugs also increase electrical conduction (dromotropy) within the heart and augment relaxation (lusitropy). Some of the drugs produce systemic vasodilation, whereas others produce vasoconstriction by mechanisms that are different from their cardiac mechanisms. The cardiac effects of these drugs make them suitable for heart failure, cardiogenic shock and hypotension. __Drug Classes and General Mechanisms of A____ction__ Cardiostimulatory drugs used in clinical practice can be divided into four mechanistic classes: beta-adrenoceptor agonists (b-agonists), digitalis compounds, phosphodiesterase inhibitors, and calcium sensitizers. Click below on a drug class for more details: //Revised 08/29/06//
 * Cardiostimulatory Drugs**
 * //[|Heart failure] and cardiogenic shock://** The primary defect in heart failure and hypotension due to acute heart failure (cardiogenic shock) is a loss of cardiac contractile function. This leads to reduced organ perfusion and hypotension. Because the primary problem is cardiac in origin, therapeutic interventions that improve cardiac function should be of benefit to the patient because improving cardiac output should lead to improved organ perfusion and normalization of arterial pressure. Cardiac function can be improved by reducing [|afterload], increasing [|preload] by increasing fluid volume (seldom appropriate except for hypovolemic and circulatory shock), and enhancing [|contractility] of the heart. Cardiostimulatory drugs work by this latter mechanism (some cardiostimulatory drugs also are capable of reducing afterload by separate mechanisms). Cardiostimulatory drugs that are [|sympathomimetics] or [|phosphodiesterase inhibitors] are only useful, however, for short-term therapy because of long-term deleterious effects. [|Digitalis] compounds, in contrast, are safe and effective for long-term therapy of heart failure.
 * //[|Circulatory shock]://** This form of hypotensive shock can be caused by an inadequate blood volume (e.g., hypovolemia caused by hemorrhage) or due to a loss of vascular tone caused by infection and inflammation (e.g., septic shock). Cardiostimulatory drugs (especially sympathomimetics such as [|beta-agonists]) are frequently used for these conditions to improve arterial pressure. They are often used in conjunction with fluid loading and [|vasoconstrictor drugs].
 * [|Beta-agonists]** are [|sympathomimetic drugs] that bind to beta-adrenoceptors located in cardiac [|nodal tissue], the conducting system, and contracting myocytes. The heart has both [|beta1 (b1) and beta2 (b2) adrenoceptors], although the predominant receptor type in number and function is b1. These receptors normally bind [|norepinephrine] that is released from sympathetic adrenergic nerves. Additionally, they bind norepinephrine and [|epinephrine] that circulate in the blood. b1 and b2 adrenoceptor activation increases heart rate and contractility, which increases cardiac output. Activation of these receptors also increases conduction velocity within the heart as well as the rate of mechanical relaxation (lusitropy). These drugs are used to treat acute and refractory heart failure, as well as circulatory shock.
 * [|Digitalis compounds]** have been used for more than two hundred years to treat heart failure. These drugs inhibit the cardiac sarcolemmal [|Na+/K+-ATPase], which leads to an increase in intracellular calcium through the [|Na+-Ca++-exchanger]. Increased intracellular calcium stimulates increased release of calcium by the sarcoplasmic reticulum and thereby makes more calcium available to bind to [|troponin-C], which increases contractility.
 * [|Phosphodiesterase inhibitors]** are drugs that inhibit the enzyme (cAMP-dependent phosphodiesterase) responsible for breaking down cAMP. This leads to an increase in cAMP. In the heart, this produces positive inotropic and chronotropic responses similar to beta-agonists. These drugs are used to treat acute and refractory heart failure, not chronic heart failure.
 * Calcium sensitizing drugs** represent the newest class of cardiostimulatory drugs. These drugs increase the sensitivity of troponin-C for calcium so that more calcium becomes bound to troponin-C, which enhances contractility. At present, these drugs are under clinical investigation for heart failure, and therefore not yet approved.
 * **[|Beta-adrenoceptor agonists]**
 * **[|Digitalis]**
 * **[|Phosphodiesterase inhibitors]**
 * **Calcium sensitizers**