Anti-arrhythmic Drugs and Cardiac Arrhythmias

Anti-arrhythmic Drugs

• Anti-arrhythmic drugs aim to restore normal sinus rhythm
• They achieve this by preventing depolarisation outside the normal sinus rhythm
• They also prevent transmission of non-sinus depolarisations
• Generally, they reduce electrical excitability of the heart

Cardiac Arrhythmias

• Arrhythmias are classified according to the origin of the problem. Examples are atrial fibrillation and ventricular ectopic beats
• They are also classified by the direction of rate change. Examples are tachycardia (increased heart rate) and bradycardia (decreased heart rate)
• Fibrillation is a lack of discernible rhythm. This is a severe concern as it can be survivable (atrial) or fatal (ventricular)
• A defibrillator is used in cases of ventricular fibrillation to resynchronise the heart

Cardiac Contraction Cycle

• Coordinated contractions are essential for efficient blood ejection
• Atrial contraction pushes blood into the ventricles
• Ventricular contraction pumps blood past the aortic valve into circulation
• Relaxation allows chambers to refill for the next contraction
• Any uncoordinated contraction reduces blood transfer efficiency

ECG and Cardiac Activity

• An ECG records changes in the cardiac membrane current
• '0' on an ECG signifies no depolarization or repolarization which indicates fibrillation (the average electrical activity is zero)
• The ECG shows the relationship between cardiac contraction and electrical activity:
  • P wave corresponds to atrial systole
  • QRS complex shows ventricular systole
  • T wave shows ventricular repolarisation
  • The intervals between the waves also have meaning and are measured in milliseconds

Action Potentials

• Cardiomyocyte action potentials are characterized by phases: (0, 1, 2, 3, 4) each with specific ion currents involved (e.g. Na+, K+, Ca2+).

• Various phases of the action potential reflect different ion channels opening/closing leading to electrical changes.

• These ion currents and channels play crucial roles for normal heart function.

• Refractory period: this is a crucial aspect of cardiac function. It is the period where the heart cannot be stimulated to contract again, naturally protecting from arrhythmias

• The refractory period has two parts:

• Effective refractory period

• Relative refractory period

Ion Currents in Cardiomyocytes

• Na+ current: Positive membrane charge activates Na+ channels; Na+ enters the cell making the membrane more positive
• K+ current: Positive membrane charge activates K+ channels; K+ exits the cell making the membrane more negative
• Ca2+ current: Positive membrane charge activates Ca2+ channels; Ca2+ enters the cell making the membrane more negative
• I current: Negative membrane charge activates I channels;cations enter the cell, making the membrane more positive

Voltage-sensitive Na+ channels

• Na+ channels rapidly switch between open and inactivated states
• The channel needs to go through a closed state before being able to reopen after reaching the inactivated state by being exposed to a negative voltage

Anti-arrhythmic Drug Classification

• Class I: Sodium channel blockers (e.g., lidocaine)

• Class II: Beta-adrenergic antagonists (e.g., propranolol) which reduce the effect of sympathetic activation

• Class III: Potassium channel blockers (e.g., amiodarone) which prolong repolarization

• Class IV: Calcium channel blockers (e.g., verapamil)

• The diagram show the effect of the drugs on the cardiac action potential

No Transmission= No Dysrhythmia

• Dysfunction with no transmission = sinus rhythm
• Dysfunction leading to transmission = arrhythmia
• This is due to failure of repolarization failing out of or within the refractory period
• Repolarisation has to be complete before an action potential can happen again

Fibrillation

• Uncoordinated contraction = no ejection
• Electrical cardioversion required to resynchronize cells
• AED (Automated External Defibrillator) and ICD (Implantable Cardioverter Defibrillator) are used to resynchronise the heart

Summary

• Ventricular fibrillation is incompatible with life
• Cardiac arrhythmias reduce heart efficiency and can lead to fibrillation
• Anti-arrhythmic drugs reduce electrical excitability to regulate cardiac activity
• Different classes of anti-arrhythmic drugs target different ion channels or receptors, affecting various aspects of the cardiac action potential.