Anti-arrhythmic drugs Flashcards
What is the anti-arrythmic drug classification
Class 1: Na channel blockers
lidocaine, quinidine, flecainide
Class 2: beta blockers
atenolol, metoprolol
Class 3: drugs delaying repolarisation/ blocks K+ channels
amiodarone, sotalol
Class 4: Ca2+ channel antagonists
verapamil, diltiazem
8 possible causes of arrythmias
- fever
- heart failure
- acute myocardial infarction
- therapetuic e.g. digitalis and abuse drugs (cocaine is pro-arrythmic)
- acute myocardial infarction
- hypokalaemia (esp in anorexia nervosa)
- autonomic dysfunction- nervous system acting too sympathetically than parasympathetically
- inherited mutations of ion channels- channel neuropathy
- hyperthyroidism
What is an ectopic beat?
Disturbance of the cardiac rhythm in which beats arise from fibres outside of the region in the heart muscle ordinarily responsible for impulse formation
What are the drug targets in arrhythmias?
initiation and maintenance of arrhythmias
What may be the cause of a heartbeat originating elsewhere other than the SA node?
- abnormal pacemaking- automaticity
- failure of conduction to stop at the end of the heart beat causing re-entry
drugs blocking re-entry are more important than drugs blocking abnormal automaticity
what may abnormal automaticity cause?
May initiate ventricular tachycardia in infarction
What is a wave front?
Is a surface containing points affected in the same way by a wave at a given time.
Mechanism of re-entry
- caused by localised slow conduction
- wave front may become ragged and meander
- wave front may split into two
- may circle around and re-enter its original pathway
- slow conduction causes a ragged wave front
- followed by a spiral wave front
How can re-entry cause an arrythmia?
If an injury such as ischaemia causes localised unidirectional conduction block and retrograde conduction
What is retrograde conduction
it is a conduction backward phenomena in the heart where conduction comes from the ventricles or from the AV node into and through the atria
How to suppress arrhythmias caused by abnormal automaticity?
As abnormal automaticity may be due to high beta adrenergic drive
treat with class II beta blockers
How to suppress arrhythmias caused by re-entry?
By blocking the conduction of the re-entry wave either directly or indirectly
Mechanism of direct re-entry suppression?
Direct conduction block in damaged region/ retrograde conduction region
- localised block of ion channels responsible for depolarisation in the damage area
- blocking Na+ channels in the AV node, atria and ventricles
- blocking Ca2+ channels in the AV node
- makes cells inexcitable
Mechanism of indirect re-entry suppression?
- target K+ channels
- block the conduction/ delay repolarisation anywhere in the re-entrant pathway
- to prolong refractory period
Action of class IV drugs
Directly block re-entry in the AV node by blocking Ca2+ channel
Action of class I drugs
Directly block re-entry in AV node, atria and sometimes ventricles by blocking Na+ channels
Action of class III drugs
- indirectly block re-entry in atria, by blocking K+ channels
- are indirect re-entry blockers because prolonging the refractory period indirectly blocks Na channels and conduction
- delays repolarisation/ prolongs refractory period
- ragged or split wave fronts encounter fewer excitable cells
- re-entry wave is therefore blocked
Why are class III drugs no longer used for ventricular fibrillation?
- originally developed for treating VF causing ventricular repolarisation
- in ECG, seen as QT prolongation
- ALL CLASS III DRUGS PROLONG QT
- but is dangerous and can cause torsades de pointes syndrome
so now used in lose dose for atrial arrhythmias
Problems with drugs targeting re-entry
- class I and class IV drugs must selectively target Na and Ca channels in the damaged region
- however most are not selective enough so cause conduction block in normal tissue
- can use a lower dose drug but this causes slow conduction block allowing for re-entry of wave front again
- proarrhythmias
How are class IV drugs administered?
Verapamil, diltiazem are class IV Ca2+ antagonists
- bolus i.v. converts re-entry in the AV node to sinus rhythm
- allows a high concentration to arrive at the AV node to block conduction in the damaged section
- BUT are vascular selective/ not AV selective
- this is overcome by iv bolus administration
- drug hits the AV node in high concentration
- drug is then diluted in ventricular blood
- low concentration is pumped out to the rest of the body to produce side effects (vasodilation)
Can nifedipine be used to treat arrhythmias?
No, it is completely vascular selective
No action on AV node even after iv bolus
How is a drug classified as class I or class III?
depends on its relative selectivity of action
- a QT widening drug with no appreciable effects on conduction velocity at therapeutically relevant concentrations is defined as class III
How were older antiarrhythmics classified?
Class 1a: quinidine
Class 1b: lidocaine
Class 1c: flecainide
Class 1a quinidine
- effective against supraventricular arrhythmias
- lethal ventricular arrhythmias not suppressed
- substantial class III effects such as QT widening at therapeutic concentrations
- torsades de pointes is a major side effect
- sinus tachycardia due to muscarinic antagonism
