CV Pharmacology: Antiarrhythmics Overview

CV Pharmacology: Arrhythmias

• The lecture covers the electrophysiology behind the cardiac action potential.
• It outlines how antiarrhythmic drugs alter ion flux and electrical properties of heart cells.
• Specific targets are sodium channel blockers, beta-blockers, potassium channel blockers, and calcium channel blockers.
• The therapeutic uses and adverse effects of these antiarrhythmic drugs are also addressed.

Cardiac Electrical Activity

• The heart's electrical activity is controlled by the sino-atrial node, atrio-ventricular node, and Purkinje fibres.

Cardiac Syncytium

• The heart's syncytium is a network of cells connected by gap junctions.
• Electrical signals, in the form of action potentials, directly pass through these junctions to synchronise muscle contraction.
• A histological picture of cardiac myocytes with intercalated disks are included. A schematic diagram of cardiac myocytes is also shown.

Cardiac Myocyte Action Potential (AP)

• The cardiac myocyte AP includes rapid depolarisation (VG Na+), partial repolarisation (VG K+), a plateau phase (L-type VG Ca2+ vs. K+), repolarisation (VG K+), and rest (leak K+).
• The effective refractory period (ERP) is a crucial phase in the AP.

Cardiac Nodal AP

• Nodal APs have distinct phases: depolarisation (T/L-type VG Ca2+), repolarisation (VG K+), and pacemaker depolarisation (leak K+ & leak Na+).
• Sympathetic (β1/2) and vagal (parasympathetic; mAChR) innervation play a role.

Electrocardiogram (ECG)

• The ECG displays the electrical activity of the heart over time.
• Key components are P-wave (atrial depolarisation), QRS complex (ventricular depolarisation), and T-wave (ventricular repolarisation).

Dysrhythmia Classifications

• Arrhythmias are categorized by their location (e.g., superventricular, atrial, junctional, ventricular).
• Arrhythmias are also categorized by their rate (tachycardia or bradycardia) and patterns (e.g., fibrillation, flutter).

Terminology

• Chronotropic: altering the heart rate.
• Inotropic: altering the strength of heart contractions.
• Automaticity: the property of heart cells to spontaneously generate action potentials.
• Ectopic beats: action potentials generated in the wrong place or phase compared to the normal electrical conduction pathway.

Common Causes of Tachycardias

• After-polarization: high [Ca2+], triggering trains of APs and causes ectopic beats.
• Re-entry: impulse re-excites previously active tissue, often associated with damaged heart tissue.
• Ectopic pacemaker activity: excessive automaticity in nodes or activity outside normal nodes.

Triggered Activity

• Early afterdepolarisations occur during phase 2/3 of the cardiac action potential, mediated by elevated Ca2+
• Delayed afterdepolarisations occur during phase 4, potentially initiating arrhythmias.

Re-entry

• Action potentials blocked in part of the myocardium (cells in refractory period). Refractory cells may be activated by backpropagation.
• APs pass through myocardium from node to node, leading to synchronised depolarisation in normal conditions. In re-entry, the signal may backpropagate out of phase, causing additional contractions.

Slow-Fast AVN Path

• A discussion of the electrical pathways through the atrioventricular node (AVN). The schematic diagrams show the slow and fast pathways, highlighting the differences in conduction velocity and their clinical relevance.

Wolfe-Parkinson-White Syndrome

• Re-entry occurs in Wolfe-Parkinson-White syndrome with an accessory pathway bypassing the AV node.
• This pathway can transmit atrial tachycardias to ventricles.

Abnormal Automaticity

• Pacemaker cells are excessively active, increasing phase 4 depolarisation and lowering the AP threshold.
• This can lead to tachycardia.

Vaughan-Williams Classification

• This system classifies antiarrhythmic drugs based on their electrophysiological effects. It is clinically outdated, but useful for learning purposes.

Class 1: Sodium Channel Blockers

• Block sodium channels to slow or prevent the generation of action potentials in myocytes.
• Adverse effects include oedema (feet/ankles), dizziness.

Class 1A, 1B, and 1C Drugs

• Detailed information on different types of sodium channel blockers, their mechanisms of action, therapeutic uses, side effects and ECG characteristics.

Class II: Beta-blockers

• Antagonise adrenergic beta receptors. Reducing sympathetic nervous system activity and preventing tachycardia.
• Specific drugs like atenolol, bisoprolol, metoprolol, and propranolol are discussed.

Class III: Potassium Channel Blockers

• Prolong the refractory period in nodal and myocardial tissues through blocking potassium channels. Amiodarone is heavily highlighted as a prominent drug in this Class, as well as its therapeutic and potential toxicities.

Class IV: Calcium Channel Blockers

• Block calcium channels (L-type) to decrease nodal action potential amplitude and increase length of the nodal AP.
• Verapamil and Diltiazem are key drugs in this category.

Digoxin

• Digoxin inhibits the Na+/K+ pump in myocytes.
• This increases intracellular calcium levels, leading to a positive inotropic effect but a negative chronotropic effect, particularly on nodes.

Adenosine

• Emergency medication for superventricular tachycardias.
• Activates A1 receptors in the AV node causing hyperpolarisation and slowing conduction rates.

Drugs for Bradyarrhythmias

• Atropine, and sympathomimetic agents (adrenaline, dopamine, dobutamine) are mentioned as drugs to treat bradyarrhythmias through increasing heart rate.

Atrial Tachycardias

• Focuses on maintaining orderly ventricular activation to prevent the conduction of atrial tachycardia.
• Discussion of rate control and rhythm control strategies in the treatment of atrial tachycardias.

A-fib: Rate and Rhythm Control

• Details about strategies for treating atrial fibrillation (A-fib), including rate and rhythm control interventions. Discussing the relevant drugs and procedures.

Ventricular Tachycardias

• Discusses non-heamodynamically stable ventricular tachycardias and treatment strategies.
• Strategies for management when haemodynamically stable.

Summary

• Antiarrhythmics modify cardiac action potentials.
• General negative chronotropic effects slow AP generation and lengthen the refractory period.
• Various drug classes (1-4) with their mechanisms are summarized.

Pictorial Summary

• A visual representation of the various drug classes and their effects on different aspects of cardiac action potentials.

Sicilian Gambit

• A detailed table outlining a variety of antiarrhythmic drugs, their mechanisms of actions, and various other factors.

MBBS Learning Outcomes

• Indicates the importance of the topic in relation to broader medical education.

This quiz explores the electrophysiology of cardiac action potentials and the role of antiarrhythmic drugs. It covers sodium channel blockers, beta-blockers, potassium channel blockers, and calcium channel blockers, discussing their mechanisms, therapeutic uses, and side effects. Additionally, it touches on cardiac electrical activity and syncytium, enhancing your understanding of cardiac function.