Continuing Education:  Cardiac Drugs – Lecture I
Larry Birnbaum, PhD, FASEP, EPC
Associate Professor
Department of Exercise Physiology
The College of St. Scholastica
Duluth, MN  55811

One of the aspects of professionalism is competency and one means by which professionals maintain competency is continuing education.  Continuing education characteristically involves attending national, regional, and local seminars, reading professional journals, completing post-graduate training, and so forth.  In the interest of continuing education, the next series of articles in JPEPonline will be committed to a review of cardiac drugs.  Granted this will be most useful for exercise physiologists working in cardiac rehabilitation settings, but all exercise physiologists can benefit from this review.

Before discussing cardiac drugs, a review of the autonomic nervous system and cardiovascular physiology will assist the reader in understanding how various cardiac drugs work (i.e., mechanisms of action) as well as some of their potential side effects.  The central nervous system consists of the brain and spinal cord.  The peripheral nervous system includes cranial nerves and spinal nerves which receive sensory input (sensory system) and deliver signals to all parts of the body (motor system).  The motor system includes the voluntary (somatic) system and the involuntary (autonomic) system.  The autonomic nervous system has two divisions, the sympathetic (SNS) and parasympathetic (PsNS) nervous systems.  Thus, the autonomic nervous system is a division of the peripheral nervous system, and it is a pure motor system.  It innervates smooth muscles, glands, and organs (e.g., the SA and AV nodes).  It is under the control of the hypothalamus and cerebrum.

The PsNS is also called the cranial-sacral outflow system because the pre-ganglionic neurons originate from the cranial and sacral areas of the body.  The neurochemical transmitter is acetylcholine, which also allows for the name, the cholinergic system.  Acetylcholine is also the transmitter for peripheral nervous system, and parts of the central nervous system [1].  The majority of PsNS influence (about 85%) is transmitted via the vagus nerve.  The SNS originates anatomically at the thoracic and lumbar areas of the body.  Hence, it is often referred to as the thoracolumbar outflow system.  The post-ganglionic neurons release norepinephrine to innervate the target/effector organs, from which it is also referred to as the adrenergic system.   

The actions of the PsNS and SNS are generally, but not always, antagonistic.  For example, actions of the PsNS on the cardiovascular system include decreased heart rate (HR), constriction of coronary arteries, and increased blood flow to the GI tract.  The SNS increases HR and ventricular contractility, dilates coronary arteries, and decreases blood flow to the GI tract.  The atria are innervated by both PsNS and SNS nerve fibers, whereas innervation of the ventricles is nearly all SNS.  When the PsNS is stimulated by cholinergic drugs (e.g., digitalis), HR and AV conduction decrease, blood vessels in the skin dilate, secretion of digestive enzymes and motility of the GI tract increase, and bronchi constrict.  On the other hand, when the PsNS is blocked by anti-cholinergic drugs (e.g., atropine), HR and AV conduction will increase.

The SNS affects adrenergic receptors of which there are two major types (and several subtypes) [2,3].  Alpha 1 receptors are the predominant form of alpha receptors and are found in the smooth muscle of arterioles and veins and other tissues.  When stimulated, they usually cause contraction of smooth muscle (i.e., vasoconstriction) and are responsible for maintaining vasomotor tone.  If alpha 1 receptors are blocked, vasodilation occurs.  The other major family of adrenergic receptors are beta receptors.  Beta 1 receptors are found in the heart muscle and kidney; beta 2 receptors in arterioles, the lungs, and the GI tract.  Stimulation of beta 1 receptors by a drug such as isoproterenol (Isuprel) increases HR (chronotropic effect), contractility/force of contraction (inotropic effect), and AV conduction (dromotropic effect).  Conversely, blockage of beta 1 receptors by beta blockers (e.g., propanolol/Inderal) produces a decrease in HR, contractility, and AV conduction.  Stimulation of beta 2 receptors causes smooth muscle relaxation, thus vasodilation in skeletal muscle and bronchodilation.  Blockage of beta 2 receptors leads to bronchoconstriction.

Since the primary role of the cardiovascular system is to deliver oxygen to all parts of the body, it is instructive to view the effects of the autonomic nervous system on the cardiovascular system from the perspective of the Fick equation (VO₂ = HR x SV x a-vO₂ diff or oxygen consumption = heart rate x stroke volume x arteriovenous oxygen difference) [4].  Inhibition of the PsNS and/or stimulation of the SNS will increase HR and SV (via greater strength of contraction) which produces an increase in cardiac output (Q = HR x SV).  The greater Q results in an increase in systolic blood pressure (SBP) and an increase in blood flow, particularly to the skeletal muscles where the arterioles dilate and capillary sphincters open.  Thus, more oxygen is delivered to the working muscles.  This is a typical response to exercise, but what about the diseased heart?  A primary concern for the person who suffers from an arrhythmia is to keep the HR constant and at a normal rate (i.e., normal sinus rhythm).  For the diseased heart exhibiting bradyarrhythmia (resting HR <60 bpm), a PsNS blocker (e.g., atropine) or SNS stimulator (e.g., isoproterenol) may be administered.  If tachycardia (resting HR >100 bpm) is the problem, a PsNS stimulator (e.g., digitalis) or SNS beta blocker (propanolol) may be given.

Myocardial workload is an important concept of the cardiovascular system, especially for the diseased heart.  A good indicator of myocardial workload is double product (DP) or rate-pressure product.  It is determined by multiplying HR and SBP.  Obviously, increased HR and/or SBP will increase the work of the heart.  Several cardiac drugs decrease HR or SBP or both, thus decreasing the myocardium’s need for oxygen.  Also, as HR decreases, diastolic filling time of the coronary arteries increases, thus allowing for an increase in myocardial oxygen supply (i.e., increased perfusion).

Some cardiac drugs affect other aspects of the cardiovascular system in addition to the heart.  For example, venous capacitance may be increased due to venodilation, which could lead to reduced Q since preload (amount of tension/stretch on heart muscle before it begins to contract; related to volume of blood entering the heart chambers) is decreased.  However, vasodilation on the arterial side will also reduce afterload (amount of tension the heart muscle must achieve before it can start to contract; the resistance the left ventricle must overcome to eject blood into the arterial system), which reduces systemic vascular resistance and enables the heart to eject more blood into the vasculature.  Nitrates produce vasodilation but affect the venous side more than the arterial side.  Consequently, SV may decrease somewhat leading to a compensatory increase in HR.

With this brief overview of the autonomic nervous system, the cardiovascular system, and how several drugs interact with each, we are ready to discuss specific groups of cardiac drugs.  The next issue will cover drugs used to treat angina.

 References

1.  http://www.elmhurst.edu/~chm/vchembook/662cholinergic.html

 2.  http://plantbiotech.metu.edu.tr/bio417/noradrenalin.pdf

 3.  Robergs, R.A., Roberts, S.O.  (1997).  Exercise Physiology:  Exercise, Performance, and Clinical Applications.  St Louis:  Mosby.

 4.  Wilmore, J.H., Costill, D.L.  (2004).  Physiology of Sport and Exercise, 3^rd Ed.  Champaign, IL:  Human Kinetics.