CV Pharmacology: Arrhythmias

CV Pharmacology: Arrhythmias

• Lecture objectives include the electrophysiology behind cardiac action potentials, mechanisms of how antiarrhythmic drugs alter ion flux and electrical properties of heart cells, and descriptions of the therapeutic uses and adverse effects of anti-arrhythmic drugs.
• Classes of anti-arrhythmic drugs include sodium channel blockers, beta-blockers, potassium channel blockers, calcium channel blockers, and others.
• The heart's electrical activity involves the sino-atrial node, atrio-ventricular node, and Purkinje fibers.
• Cardiac syncytium is a network of cells connected by gap junctions. Electrical signals, or action potentials, pass directly through these junctions allowing coordinated heart contractions.
• Cardiac myocytes exhibit action potentials with defined phases including rapid depolarization, partial repolarization, plateau, repolarization, and rest. Specific ion channels (VG Na+, VG K+, L-type VG Ca2+) are associated with each phase.
• Cardiac nodal action potentials differ from myocardial potentials, exhibiting a unique pacemaker depolarization phase. The autonomic nervous system (sympathetic and parasympathetic) influences these potentials.
• The electrocardiogram (ECG) demonstrates electrical activity events within the heart, including atrial depolarization (P wave), ventricular depolarization (QRS complex), and ventricular repolarization (T wave).
• Arrhythmias are classified by location (superventricular, atrial, junctional, ventricular) and rate (tachycardia, bradycardia, fibrillation, flutter, heart block, arrest).
• Terminology used in this context includes chronotropic (rate affecting), inotropic (contraction strength affecting) properties, automaticity (spontaneous action potential generation), and ectopic beats (abnormal action potential origin).
• Common causes of tachycardia include after-polarization (high Ca2+ triggering AP trains), re-entry (impulse re-excitation of previously active tissue), and ectopic pacemaker activity (overactive nodes or ectopic activity outside nodes).
• Triggered activity involves early and delayed afterdepolarizations, associated with abnormal Ca2+ levels.
• Re-entry occurs when an action potential re-excitees a previously active tissue area, leading to repetitive firing in a circuit.
• Wolfe-Parkinson-White syndrome involves an accessory electrical pathway bypassing the AV node, potentially causing atrial tachycardias that are transmitted to the ventricles.
• Abnormal automaticity describes pacemaker activity being excessively active. This is often caused by increased phase 4 depolarization and decreased AP thresholds.
• Vaughan-Williams classification categorizes antiarrhythmic drugs based on their electrophysiological effects; classes include I (Na+ channel blockers), II (beta-blockers), III (K+ channel blockers), IV (Ca2+ channel blockers), and others.
• Class I drugs (sodium channel blockers) are also used as local anesthetics and anticonvulsants; slows AP generation; adverse effects include edema and dizziness.
• Class 1a drugs such as quinidine and disopyramide have intermediate dissociation and are used for atrial and ventricular tachycardias.
• Class Ib, exemplified by lidocaine, exhibit rapid dissociation and are primarily used for ventricular tachycardias.
• Class Ic drugs such as flecainide and propafenone can cause dangerous complications following a heart attack. They are generally less effective on atrial arrhythmias.
• Class II comprises beta-blockers, which antagonize sympathetic beta receptors and reduce heart rate, reducing excess sympathetic activity.
• Class III drugs, like amiodarone and sotalol, block potassium channels increasing the refractory period. Amiodarone has a very long half-life.
• Class IV drugs (calcium channel blockers such as verapamil and diltiazem) reduce the amplitude and increase the length of action potentials, mainly in nodal cells, for atrial fibrillations.
• Digoxin is an Na+/K+ pump inhibitor with positive inotropic effects, but also has negative chronotropic actions.
• Adenosine is a short-acting, emergency medication mainly for superventricular tachycardias; it directly affects potassium channels, causing hyperpolarization.
• Atropine is used for acute bradycardia decreasing vagal influence on heart rate. Other drugs for bradycardia including adrenaline, dopamine, and dobutamine increase beta-adrenoceptor activity increasing heart rate.
• Atrial tachycardias necessitate careful management to ensure orderly ventricle activation, preventing atrial fibrillation and flutter transmission to the ventricles, through rate and rhythm control.
• Rate control strategies for atrial fibrillation often involve beta-blockers or calcium channel blockers.
• Rhythm control may include cardioversion or drugs to restore sinus rhythm.
• Ventricular tachycardias, especially those compromising blood flow to the body are critical emergencies.
• Summary of anti-arrhythmic classes includes their particular effects on each phase of cardiac action potentials and their general chronotropic, or rate-modifying, mechanisms.
• Pictorial summary displays how various anti-arrhythmic classes affect different stages of the cardiac action potential in individual cells and tissues.
• Additional antiarrhythmic drugs are reviewed and their effects on channels, receptors, and heart function are included, showing some classification strategies currently in practice.
• Learning outcomes include outlining the mechanisms of action and therapies for drugs that affect the heart and vascular system.

This quiz explores the electrophysiology behind cardiac action potentials and the mechanisms by which antiarrhythmic drugs operate. It covers the different classes of anti-arrhythmic drugs and their therapeutic uses and adverse effects. Test your knowledge on the heart's electrical activity and the characteristics of cardiac myocytes.