Arrhythmias Flashcards
What are the causes of arrhythmia?
AMI, heart failure, hyperthyroidism, hypokalaemia (anorexia), autonomic dysfunction, therapeutic and abuse of drugs, inherited mutations of cardiac ion channels, fever.
What are the type types of ventricular arrhythmia?
Mildest- ventricular premature beat which is not normally treated; most severe- ventricular fibrillation which is rapidly lethal.
What is the initiation of arrhythmias?
The normal heart beat starts in SA node, if a heart beat originates somewhere else this is the result of abnormal pacemaking or the failure of conduction to stop at the end of the heart beat (re-entry).
What can abnormal automaticity initiate?
May initiate ventricular tachycardia in infarction; there is a focus of enhanced automaticity in Purkinje fibres, the direction of propagation move away from focus.
What is the mechanism of re-entry?
It is caused by localised slow conduction due to depolarisation which makes the wave-front meander and become ragged. The wave front splits into two which then may circle around and re-enter its original pathway.
How are arrhythmias maintained?
They are all maintained by re-entry, once it starts it can become stable and persistent.
What are the different classes of anti-arrhythmic drugs?
Class I: Na+ blockers such as lidocaine
Class II: B1-adrenoceptor antagonists
Class III: drugs delaying repolarisation
Class IV: Ca2+ anatagonists such as verapamil
What is the mechanism of re-entry suppression (direct)?
Direct block of conduction in damaged region is achieved by localised blocking of ion channels responsible for depolarisation in damaged area. Channel block makes damaged cells inexcitable- Na+ channels are potential drug targets in AVN and atria and ventricles. Class I drugs target Na+ channels.
What is the issue with direct targeting of re-entry?
Class I drugs must target channels selectively in the damaged region, blocking local conduction. Most are not selective enough therefore may cause conduction slowing in surrounding healthy tissue. Thus, the drug may mimic in healthy tissue the effects of ischaemia, causing re-entry.
How do you achieve benefit by direct targeting of re-entry?
Increasing amounts of sodium channel block in damaged region- most channels are blocked thus conduction is blocked and re-entry stops.
What is the problem with direct targeting of re-entry?
May have an undesired effect of drug in healthy tissue; increasing amounts of sodium ion channel block in healthy regions may cause some channels to be blocked which slows conduction causing re-entry. Adding more drug will cause most channels to be blocked which blocks conduction and causes asystole.
How can the problem of direct targeting of re-entry be overcome?
Make a drug that acts only on ischaemic heart tissue, lidocaine is ischaemia selective but has other issues. Re-entry could also be blocked if drug had selectivity during the fast arrhythmia. Re-entry causes causes tachycardia and fibrillation however, no class I drug has sufficient rate-dependence of action to make it tachycardia selective.
What is lidocaine and how is it used to treat arrhythmias?
It is a prototype 1b drug and is highly selective for Na+ channels. It is used after MI and is effective against VPBs in hospital but no reduction in death caused by VF in the long term. It has to be given intravenously which restricts its use and effectiveness. It is highly ischaemic selective meaning it has no effect in healthy heart regions so does not increase the risk of re-entry (pro-arrhythmia). However, has a off target effects on nerves which can cause paraethestia and convulsions therefore, its use is declining.
What is the mechanism of re-entry suppression (indirect)?
It is achieved by delaying repolarisation anywhere in re-entrant pathway including healthy tissue. This is because cells are inexcitable during AP (prolonging the refractory period). K+ channels mediate repolarisation and so are the drugs targets for indirect conduction block. Class III drugs block re-entry by blocking K+ channels, delaying repolarisation so split wave front encounters fewer excitable cells: re-entry wave is blocked.
How are class III drugs indirect re-entry blockers?
Prolonging refractory period means indirect block of Na+ channels and conduction as channels are in a state where they cannot open for a longer period. However, effect needs to be selective for abnormal rhythms to block re-entry during the tachyarrhythmia.
