S2: Heart: Anti-Arrhythmic Drugs Flashcards
What are the two types of AP present in the heart?
- in nodal (SA, AV)
2. non-nodal (contractile)
Define Arrhythmias
Abnormalities in heart rhythm
Symptoms of Arrhythmias
Palpitations Dizziness Fainting Fatigue Loss of Conscious Cardiac Address Blood Coagulation (e.g. Stroke, MI)
Causes of Arrhythmias
- Cardiac Ischemia (MI, angina)
- Heart Failure
- Hypertension
- Coronary Vasospasm
- Heart Block
- Excess Sympathetic Stimulation
Origin of Arrhythmias
- Supraventricular (above the ventricles - SA node, atria, AV node)
- Ventricular
Effect of Arrhythmias
- Tachycardia (>100bpm)
- Bradycardia (<60 bpm)
Arrhythmias lead to incorrect filling and ejection - incorrect cardiac output
Describe ECG irregularities in Atrial Fibrillation (AF)
- Quivering atria activity (no discrete P waves)
- Irregular ventricular contraction
- ‘Clot-producing’ - risk of stroke
Describe ECG irregularities in Supraventricular tachycardia (SVT)
- P wave buried in T wave
- Extra electrical activity
- Fast ventricular contractions
Describe ECG irregularities in Heart Block
- P waves and QRS complex independent of each other
- P and R waves regular
- Failure of the conduction system (e.g. SA, AV, or bundle of His)
- Uncoordinated atria/ventricular contractions
Describe ECG irregularities in Ventricular Tachycardia (VT)
Fast, regular
Describe ECG irregularities in Ventricular Fibrillation (VF)
- Fast, irregular
- Both (VF and VT) serious as ventricles can’t fill with blood properly so proper ejection cannot occur
What are the 2 mechanisms of arrhythmogenesis?
- Abnormal impulse generation due to automatic rhythms (increased SAN or ectopic activity) or triggered rhythms (early after depolarisations EAD or delayed after depolarisations DADs)
- Abnormal conduction due to re-entry circuits in heart conduction block
Describe ectopic pacemaker activity in abnormal impulse generation
Pacemaker activity is initiated in SAN but other areas of the heart can have pacemaker activity to safeguard against SAN damage.
These other ‘pacemaker’ areas are enhanced by sympathetic activity which:
- Increases heart rate
- Increases AVN conduction
- Increases excitability of ventricular tissue
Hence continuous/enhanced stimulation of sympathetic nervous system (stress, heart failure) can lead arrhythmias.
Describe EADs and DADs in abnormal impulse generation
EAD causes peaks during the plateau phase (2) in non nodal AP
DAD causes peaks in resting phase after non nodal AP (4)
This is because:
- Abnormal levels of Ca2+ in SR
- Ca2+ leaks out of cytosol
- Stimulate Na/Ca exchanger (NCX)
Describe EADs and DADs in abnormal impulse generation
EAD causes peaks during the plateau phase (2) in non nodal AP
DAD causes peaks in resting phase after non nodal AP (4)
This is because:
- Abnormal levels of Ca2+ in SR
- Ca2+ leaks out of cytosol
- Stimulate Na/Ca exchanger (NCX) which causes Na+ influx causing inappropriate depolarisation (not via VGNa+ channels)
- Refractory period is inactivated
- This leads to arrhythmias
Compare normal and re-entry pathways for abnormal impulse conduction
The basis for the SAN to ventricles ‘wave’ conduction pathway of the heart:
- Action potentials stop conducting because surrounding tissue is refractory and cannot conduct any more APs
- However, damage to the myocardium means that there are some areas of the heart that are more conductive than other producing re-entry pathways.
In a normal pathway, impulses cancel each other out as there is a consistent wave front followed by refractory tissue.
In an re-entry pathay, one branch has impaired conduction while the other is normal. This slows orthograde impulses which allows retrograde impulses to be conducted. This causes premature impulses down all branch
Describe 3 phases of heart block (including ecg) in abnormal impulse conduction
Heart block is caused by fibrosis/ischaemic damage of conducting pathway. This often occurs in AVN tissue.
First degree - P-R interval >0.2s
Second degree - >1 sec as atria impulses fail to stimulate ventricles
Third degree (complete block) - Atria and ventricles beat independently of one another. Ventricles contract at a slow rate depending on what ectopic pacemaker sets the rate (e.g. Bundle of His, Ventricular Tissue). This can cause loss of consciousness e.g. Adams-Stokes attacks - syncope
What is the goal and rationale in the treatment of arrhythmias?
GOAL
- Restores sinus rhythm and normal conduction
- Prevent more serious and possibly fatal arrhythmia occurring
RATIONALE
- Reduce conduction velocity
- Alter refractory period of cardiac action potentials
- Reduce automaticity (decrease EAD, DAD, ectopics)
What system are anti-arrhythmic drugs classified to?
Based upon the Vaughan Williams classification system
What are the 4 classes of anti-arrhythmic drug?
Class I: Na+ channel blockers (non-nodal tissue)
Class II: B blockers (nodal and non nodal tissue). They act at SAN, AVN, atria and ventricles as b1 receptors are found in all these areas.
Class III: K+ channel blockers (non-nodal tissue)
Class IV: Ca2+ channel blockers (non-nodal and nodal tissue)
Describe mechanism of Class I drugs - Na+ channel blockers
Block Na+ channels in:
- Non-nodal tissue e.g. atria/ventricles
- Na+ channels in their in-activated state. They have a property of use-dependence as they only block Na+ channels in high frequency firing tissue.
Low activity causes Na+ channels to return to closed state
High activity causes lots of Na+ channels to be in in-activated state. Inactivated state causes absolute and relative refractive periods.
- The drug binding to channel in in-activated state inhibits high frequencies of impulses
Give an example of a Class I -Na+ channel blocker drug
Lidocaine which is used for very fast arrhythmia e.g. VT and VF. It helps fast frequency firing become much slower.
Describe mechanism of Class II drugs - B blockers
Increased sympathetic activity is associated with arrhythmias.
Stimulation of sympathetic nerves leads to activation of B1 receptors in the heart causing increase in SAN and AVN firing rate and increase in ventricular excitability by raising Ca2+. Both these effects are arrhythmic.
B blockers therefore reduce these effects by blocking the receptors
Give an example of a class II drug - B blocker
B1 Blockers eg. Atenolol
They reduce VT after myocardial infarctions caused by increase in sympathetic nerve activity. This slows conduction through AVN reduce ventricular firing rate in SVT.
Describe mechanism of Class III drugs - K+ channel blockers
Increasing the length of the action potential increases refractory period of heart (cannot fire another AP)
Class III drugs inhibit K+ channels responsible for repolarisation in atria/ventricles) not K+ in AVN/SAN) increasing the plateau phase 2 (refractory period)
Rationale: Block channels that are involved in repolarisation –> Maintain depolarisation –> Na+ channels are in-activated –> Cannot fire any more AP –> prevent arrhythmias
Give an example of a class III drug - K+ channel blockers
Amiodarone, sotalol
These are used for SVT and VT
Describe mechanism of Class IV drugs - Ca2+ channel antagonists
Block L-type voltage gates Ca2+ channels mainly affects firing of SAN and AVN (but also phase 2 of atria/ventricles)
L-type Ca2+ channels also found on vascular smooth muscle and are involved in vasoconstriction - so blockers can produce relaxation of blood vessels and decrease in blood pressure.
Give examples of class IV drugs - Ca2+ channel antagonists
Class IV e.g. Verapamil (more cardiac specific), diltiazem (cardiac and vascular smooth muscle)
However, these drugs can be dangerous as they reduce Ca2+ influx which reduces contraction so can be dangerous in heart failure patients.
Class IV drugs are used to control ventricular response rate in SVT
What classes of drugs act on non-nodal tissue only?
Class I : Na+ channel blockers
Class III: K+ channel blockers
What classes of drugs act on non-nodal tissue and nodal tissue?
Class II: B blockers
Class IV: Ca2+ channel blockers
List 3 non classified drugs in the treatment of arrhythmias
Adenosine= Decreases activity in SAN and Avn. It is used for SVT.
Atropine= Muscarinic antagonist and reduces parasympathetic activity, May be used to treat sinus bradycardia (very low HR) after MI.
Digoxin= Central effects, increases vagus nerve activity (para), decrease heart rate and conduction. It is used for AF.
Describe how anti-arrhythmic drugs can be pro-arrhythmic
Class III drugs increases QT duration. Long QT syndrome (arrhythmia) is due to EADs and DADs generation.
- Extending plateau phase to an inappropriate level, too much Ca2+, Na/Ca exchanger activated leading to inappropriate depolarisation
Classes I, II, IV may increase refractory period (less SA, AV, atria/ventricular firing) and reduce conduction time. It is potentially pro-arrhythmic.
Class IV may also reduce contractility.
Name the goal of treatment and what drug for sinus tachycardia
Goal: Slow down SAN
Drug: Class II, III
Name the goal of treatment and what drug for atrial fibrillation (AF)
Goal: Reduce atria activity, return of atria output, prevent clot formation
Drug: Class II, III, IV, digoxin + anticoagulants
Name the goal of treatment and what drug for supraventricular tachycardia (SVT)
Goal: Reduce ventricular response rate
Drug: Class II, III, IV
Name the goal of treatment and what drug for heart block
Goal: Coordinate atria/ventricular contractions
Treatment: Pacemaker
Name the goal of treatment and what drug for ventricular tachycardia(VT)/fibrillation (VF)
Goal: Reduce ventricular activity, return ventricular output
Drug: Class I, II, III
