Cardioinhibitory+Drugs

__Therapeutic Use and Rationale__ Cardioinhibitory drugs depress cardiac function by decreasing heart rate (chronotropy) and myocardial contractility (inotropy), which decreases [|cardiac output] and [|arterial pressure]. These cardiac changes reduce the work of the heart and [|myocardial oxygen consumption]. The mechanisms of action of these drugs also lead to depressed [|electrical conduction] (dromotropy) within the heart. Some of these drugs may also impair relaxation (lusitropy). The mechanical and metabolic effects of these drugs make them very suitable for treating hypertension, angina caused by coronary artery disease, and myocardial infarction. Furthermore, their effects on electrical activity make them good candidates for the treatment of cardiac arrhythmias. Finally, some cardioinhibitors, notably certain [|beta-blockers], are used in the treatment of heart failure. __Drug Classes and General Mechanisms of A____ction__ Cardioinhibitors used in clinical practice can be divided into three mechanistic classes: beta-adrenoceptor antagonists (beta-blockers), calcium-channel blockers, and centrally-acting sympatholytics. Click below on a drug class for more details: Note that all these drugs have actions besides cardiac inhibition, and therefore are also classified under other drug mechanism classes.
 * Cardioinhibitory Drugs**
 * //Hypertension://** [|Hypertension] is defined as an arterial systolic pressure greater than 140 mmHg and/or a diastolic pressure greater than 90 mmHg. Hypertension can be caused by either an increase in [|cardiac output] or by an increase in [|systemic vascular resistance]. It is not uncommon for hypertension to be caused by elevations in both. Since cardiac output is the product of heart rate and stroke volume, cardioinhibitory drugs that reduce either or both will decrease cardiac output and thereby decrease arterial pressure.
 * //Angina and myocardial infarction://** Cardioinhibitors, by reducing heart rate, contractility, and arterial pressure, reduce the work of the heart and the oxygen demand of the heart. By reducing oxygen demand, the [|oxygen supply/demand ratio] is improved, which can relieve a patient of [|anginal pain] that is caused by a reduction in the oxygen supply/demand ratio due to coronary artery disease. Furthermore, cardioinhibitors that block beta-adrenoceptors have been found to be very important in the treatment of myocardial infarction. Their benefit is derived not only from improving the oxygen supply/demand ratio, but also from their ability to inhibit subsequent cardiac remodeling.
 * //Arrhythmias://** Because cardioinhibitors alter pacemaker activity and electrical conduction within the heart, they are useful for treating [|arrhythmias] caused by both [|abnormal automaticity] and [|abnormal conduction].
 * //Heart failure://** Although it seems counterintuitive that cardioinhibitors would be used in [|heart failure] that occurs because of a functionally depressed myocardium, clinical studies have shown very conclusively that some cardioinhibitors (i.e., specific beta-blockers) significantly improve cardiac function in certain types of heart failure. Furthermore, they have been shown to reduce deleterious cardiac remodeling that occurs in chronic heart failure. Their benefit may be derived from their blockade of excessive sympathetic influences on the heart, which are known to be harmful to the failing heart.
 * [|Beta-blockers]** 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 primarily bind [|norepinephrine] that is released from sympathetic adrenergic nerves. Additionally, they bind norepinephrine and epinephrine that circulates in the blood. Beta-blockers prevent the normal ligand (norepinephrine or epinephrine) from binding to the beta-adrenoceptor by competing for the binding site. Because there is generally some level of sympathetic tone on the heart, beta-blockers are able to reduce sympathetic influences that normally stimulate chronotropy, inotropy, dromotropy and lusitropy. These drugs have an even greater effect when there is elevated sympathetic activity. Beta-blockers that are used clinically are either non-selective (b1/b2) blockers, or relatively selective b1 blockers. Some beta-blockers have additional mechanisms of action besides beta-blockade. Beta-blockers are used for treating hypertension, angina, myocardial infarction and arrhythmias.
 * [|Calcium-channel blockers]** (CCBs) bind to L-type calcium channels located on cardiac myocytes and cardiac nodal tissue ([|sinoatrial and atrioventricular nodes]). These channels are responsible for regulating the influx of calcium into cardiomyocytes, which in turn stimulates cardiac myocyte contraction. In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents and in phase 0 of the action potentials. Therefore, by blocking calcium entry into the cell, CCBs decrease myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decrease conduction velocity within the heart (negative dromotropy particularly at the atrioventricular node). CCBs are used in treating hypertension, angina and arrhythmias.
 * [|Centrally acting sympatholytics]** block sympathetic activity by binding to and activating alpha2 (α2)-adrenoceptors located on cardioregulatory cells within the medulla of the brain. This reduces sympathetic outflow to the heart, thereby decreasing cardiac output by decreasing heart rate and contractility. These drugs are only used for treating hypertension.
 * **Beta-adrenoceptor antagonists (beta-blockers)**
 * **Calcium-channel blockers (CCBs)**
 * **Centrally acting sympatholytics**