Anti-arrhythmic drugs Flashcards
What is an Arrhythmia?
What does it lead to?
What are some of the symptoms?
What conditions can cause them?
What are their 2 places of origin?
- An abnormal heart rhythm
- Incorrect filling and ejection; poor CO
- Palpitations, Dizziness, Fainting/Syncope, Fatigue, Coagulation, Cardiac arrest
- Cardiac ischemia (MI/angina), heart failure, hypertension, heart block, excess sympathetic stimulation.
- Supra-ventricular - SAN, AVN, atria
- Ventricular - cause tachycardia or bradycardia
- Supra-ventricular - SAN, AVN, atria
Outline:
1. Atrial Fibrillation (AF)
- Supra-ventricular Tachycardia (SVT)
- Heart Block
- Ventricular Tachycardia (VT)
- Ventricular Fibrillation (VF)
LOOK AT ECG’s!
- Quivering atria, so there’s no discrete P wave. Irregular ventricular contraction and can produce clots - ↑risk of stroke
- P wave is shadowed by T wave - fast ventricular contractions
- Failure of conduction system (can be in SAN, AVN, bundle of His) - will make uncoordinated atrial and ventricular contractions; poor ejection and CO/SV
- Fast, Regular ventricular contractions - serious
- Fast, Irregular ventricular contractions - serious
What is Arrhythmogenesis?
What are the 2 mechanisms that cause Arrhythmia’s? What are they due to?
- Generation of an arrhythmia
- Abnormal Impulse Generation - due to:
• Automatic rhythms - ↑SAN and ectopic activity
• Triggered rhythms - EADs and DADs:
EAD (Early-after-depolarisation)
DAD (Delayed-after-depolarisation)
- Abnormal Impulse Generation - due to:
- Abnormal Impulse Conduction due to:
• Re-entry electrical circuits in heart
• Conduction blocks (heart blocks)
How does ectopic pacemaker activity lead to abnormal impulse generation?
How do EADs and DADs lead to abnormal impulse generation?
LOOK AT DIAGRAMS!
- Pacemaker activity is initiated in SAN but other parts of the heart can have pacemaker activity in case of SAN damage. These other areas are greatly enhanced by sympathetic activity by an ↑HR, AVN conduction, and ↑Excitability of ventricular tissue.
Therefore, continuous sympathetic stimulation can lead to arrhythmias e.g. during stress or heart failure.
- EADs:
Altered ion channel activity e.g. ↑Na and Ca channels - will remove refractory period and depolarisation can occur
DADs:
Abnormal levels of Ca2+ in SR causes some to leak out into cytosol - this will stimulate Na/Ca exchanger activity = Na+ influx = Depolarisation
How does Re-entry lead to abnormal impulse conduction?
What causes a heart block?
How do the 3 degrees of Heart block lead to abnormal impulse conduction?
LOOK AT DIAGRAMS and ECG’s!
- Normally, refractory periods stop AP conduction. But, Myocardial damage makes parts of heart more conductive than others - will produce re-entry pathways.
- Fibrosis/Ischaemic damage of conduction pathways, common in AVN.
- 1st degree: P-R interval is slower
2nd degree: >1 atrial impulses fail to stimulate ventricles
3rd degree: complete block so atria and ventricles beat independently. Ectopic pacemaker activity will then control ventricular contractions. Slow V rate → Syncope.
What are the goals of anti-arrhythmic drugs and how do they achieve them?
What is the system used to classify these drugs?
- To restore sinus (normal) rhythm and conduction and prevent more serious arrhythmias from occurring.
To do this, they ↓Conduction velocity, alter the refractory period, and ↓Automaticity - ↓EADs/DADs/ectopic activity.
- Vaughan Williams classification system
How do Class I drugs regulate arrhythmias?
What are these used for?
LOOK AT DIAGRAMS!
Na+ channel blockers e.g. Lidocaine
- Block Na channels in NON-NODAL TISSUE when in their in-activated state. - only block channels when there’s high frequency firing; called PROPERTY OF USE-DEPENDENCE.
Is a FAST-DISSOCIATING drug so it can unbind in time for the next impulse - no effect on normal firing during low frequency firing.
During high frequency firing, the drug will still be bound to the inactivate site when the next impulse arrives - high frequencies inhibited.
- Very fast arrhythmias, like VT/VF
How do Class II drugs regulate arrhythmias?
What are these used for?
β-blockers e.g. Atenolol
- Act on NODAL AND NON-NODAL TISSUE. They prevent sympathetic stimulation of heart to avoid sympathetic-associated arrhythmias.
- To reduce VT after an MI, and to slow down contraction through the AVN to reduce ventricular firing rate in SVT.
How do Class III drugs regulate arrhythmias?
What are these used for?
LOOK AT DIAGRAM!
K+ channels blockers e.g. Amiodarone
- Act on NON-NODAL TISSUE to make Plateau phase (refractory period/Phase 2) longer, so another AP can’t be fired.
Inhibit K+ channels responsible for atrial/ventricular repolarisation - maintains depolarisation. Since Na channels are inactivated, no more AP’s can be fired = prevent arrhythmias
- SVT and VT
How do Class IV drugs regulate arrhythmias?
What are these used for?
LOOK AT DIAGRAM!
Ca2+ channel antagonists e.g. Verapamil
- Block the L-type VGCCs on NODAL AND NON-NODAL TISSUE to affect firing of SAN and AVN. The L-type VGCCs are also found on VSM cells involved in vasoconstriction - blockers will cause vasodilation = ↓BP (via Starling’s)
- Control ventricular response rate in SVT
What are 3 Non-classified drugs that regulate arrhythmias? What are each used for?
- Adenosine - ↓SAN and AVN activity - used for SVT
- Atropine - muscarinic antagonist to ↓Parasympathetic activity - used for sinus bradycardia after MI
- Digoxin - ↑Vagus activity to ↓HR and conduction - used for AF
How can anti-arrhythmic drugs be pro-arrhythmic?
Class III drugs ↑Q-T interval (Plateau phase), which can cause an arrhythmia due to EAD and DAD generation.
Classes I, II, and IV may ↑Refractory period and ↓conduction time - potentially causing arrhythmia.
Class IV can also ↓Contractility.
