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C H A P T E R 4 5 Antiarrhythmic agents

A s discussed in earlier chapters, disruptions in impulse formation and in the conduction of impulses through the myocardium are called arrhythmias. (They also are called dysrhythmias by some healthcare providers.) Arrhythmias occur in the heart because all of the cells of the heart possess the property of automaticity (discussed later in this chapter) and therefore can generate an excit- atory impulse. Disruptions in the normal rhythm of the heart can interfere with myocardial contractions and affect the cardiac output , the amount of blood pumped with each beat. Arrhythmias that seriously disrupt cardiac output can be fatal. Drugs used to treat arrhyth- mias, called antiarrhythmics, suppress automaticity or alter the conductivity of the heart. ARRHYTHMIAS Arrhythmias involve changes to the automaticity or conductivity of the heart cells. These changes can result from several factors, including electrolyte imbalances that alter the action potential, decreased oxygen delivery to cells that changes their action potential, struc- tural damage that changes the conduction pathway, or acidosis or waste product accumulation that alters the action potential. In some cases, changes to the heart’s automaticity or conductivity may result from drugs that alter the action potential or cardiac conduction. Conductivity With normal heart function, each cycle of cardiac con- traction and relaxation is controlled by impulses arising spontaneously in the sinoatrial (SA) node and transmit- ted via a specialised conducting system to activate all parts of the heart muscle almost simultaneously (see Chapter 42) (Figure 45.1). These continuous, rhythmic

contractions are controlled by the heart itself. This property allows the heart to beat as long as it has enough nutrients and oxygen to survive, regardless of the status of the rest of the body. Automaticity All cardiac cells possess some degree of automaticity (see Chapter 42) in which the cells undergo a spontane- ous depolarisation during diastole or rest because they decrease the flow of potassium ions out of the cell and probably leak sodium into the cell, causing an action potential. The action potential of the cardiac muscle cell consists of five phases: • Phase 0 occurs when the cell reaches a point of stimulation. The sodium gates open along the cell membrane and sodium rushes into the cell; this positive flow of electrons into the cell results in an electrical potential. This is called depolarisation. • Phase 1 is a very short period during which the sodium ion concentration equalises inside and outside the cell. • Phase 2 , or the plateau stage, occurs as the cell membrane becomes less permeable to sodium, calcium slowly enters the cell and potassium begins to leave the cell. The cell membrane is trying to return to its resting state, a process called repolarisation. • Phase 3 is a time of rapid repolarisation as the sodium gates are closed and potassium flows out of the cell. • Phase 4 occurs when the cell comes to rest; the sodium–potassium pump returns the membrane to its resting membrane potential and spontaneous depolarisation begins again. Each area of the heart has a slightly different- appearing action potential that reflects the complexity of the cells in that area. Because of these differences in the action potential, each area of the heart has a slightly different rate of rhythmicity. The SA node generates an impulse about 60 to 100 times per minute, the atrio- ventricular (AV) node about 40 to 50 times per minute and the complex ventricular muscle cells about 10 to 20 times per minute. Haemodynamics The study of the forces that move blood throughout the cardiovascular system is called haemodynamics . The ability of the heart to effectively pump blood depends on the coordinated contraction of the atrial and ventricular muscles, which are stimulated to contract via the con- duction system. The conduction system is designed so that atrial stimulation is followed by total atrial con- traction and ventricular stimulation is followed by total ventricular contraction.

SA node

Left atrium

AV node

Bundle of His

Right atrium

Left ventricle

Right ventricle

Left bundle branch Purkinje fibres

Right bundle branch

FIGURE 45.1  The conducting system of the heart. Impulses originating in the sinoatrial (SA) node are transmitted through the atrial bundles to the atrioventricular (AV) node and down the bundle of His and the bundle branches by way of the Purkinje fibres through the ventricles.