308 Drugs used in arrhythmias Flashcards
What are the 2 types of cardiac cells?
contractile cells - which make up most of the walls of the atria and ventricles - when stimulated they generate force for contraction of the heart (myocyte)
conducting cells - initiate the electrical impulse which controls those contractions (automaticity). Found in SA node, AV node, His bundles and purkinje fibres
Why is the SA node the natural pacemaker of the heart?
It reaches membrane potential the fastest
Describe normal cardiac conduction
SA node action potential triggers atrial depolarisation
- AV node is the only pathway for AP to enter the ventricles
- The bundle of His and its branches conduct the impulse to the Apex of the heart
What are the areas of fast and slow conduction within the heart?
- Slow conduction: complete atrial systole before ventricular systole starts (SA/AV node)
- Fast conduction: His bundles and Purkinje fibres (ventricular depolarisation and contraction)
What causes arrhythmias?
-Changes in automaticity of the natural pacemaker
- Etopic foci causing abnormal APs
-excitable groups of cells that cause premature heart beats
-hypoxic/ischaemic tissue can undergo spontaneous depolarisation and can become an ectopic pacemaker
-the normal conduction pathway is interrupted
-abnormal conduction pathways
-electrolyte disturbances and drugs
What are the mechanisms of tachycardias?
Abnormal automaticity
- when membrane becomes abnormally permeable to sodium
- this can cause other cells to accelerate
automaticity thus generating impulses faster than the SA node
Triggered activity
- Anormal leakage of positive ions into cardiac cell leading to bump on action
potential called after depolarisation
- if sufficient magnitude can trigger premature AP, can lead to TdP
Re-entry
-Where an extra/accessory pathway exists
between upper and lower chambers of the heart
Eg. Wolf-parkinson-white syndrome
- AVNRT
- cardiac re-entry is responsible for the majority of clinically important arrhythmias
How can drugs cause arrhythmias?
- Suppressing enhanced automaticity
- Decreasing conduction velocity
- Changing the effective refractory period to suppress re-entry
What is the Vaughan Williams Classification?
Classifies antiarrhythmic drugs
agents by their ability to directly or indirectly block flux of one or more of these ions across the membranes of excitable cardiac
muscle cells
What are some class 1A agents in the Vaughan Williams Classification?
Disopyramide, quinidine (not licensed in
the UK), procainamide
Block fast sodium and potassium channels infast APs and depress phase 0, prolong repolarisation. Can prolong QRS duration and QT interval on the ECG: can be pro-arrhythmic
- Useful for supraventricular arrhythmias, and
ventricular arrhythmias
Only in patients with good ventricular function because of their negative inotropic effects
What are some class 1B agents in the Vaughan Williams Classification?
Lidocaine: causes weak blockade of fast sodium channels, shorten repolarisation and
therefore action potential
-Only used to treat ventricular arrhythmias (does not work on atrial tissues
or on normal cardiac tissues)
-Given by intravenous bolus followed by a continuous intravenous
infusion (high first pass metabolism)
Mexiletine: lidocaine’s orally active sister
-Do not prolong QT interval
-The most frequent side effects are CNS:
including tinnitus and seizures, and occasionally hallucinations, drowsiness,
and coma, nausea/vomiting with mexiletine
What are some class 1C agents in the Vaughan Williams Classification?
Propafenone, flecainide
Potent fast Na channel blockade
depress phase 0 depolarisation markedly and inhibits His/purkinje conduction system, with
limited effect on repolarisation period
- No effect on AP duration
- No effect on QRS length
- treatment of refractory ventricular arrhythmias
Flecainide: A potent fast inward sodium channel blocker used to treat symptomatic supraventricular arrhythmias
-Lowers ventricular function in most patients
-It also raises the threshold of pacing and cardiac defibrillators and should be used with caution in patients with
pacemakers or ICDs
What are some class 2 agents in the Vaughan Williams Classification?
Beta blockers
Competitive beta1 receptor blockade preventing action of catecholamines on the heart
-Depress sinus node automaticity, slows conduction in AV node which
causes reduction in heart rate and contractility
-Prolonged repolarisation phase, which helps reduce incidence of re-entry
-Increases diastolic filling time (chronotropy), reduces the force of
contraction (inotropy)
-Improves coronary perfusion
-Prolongs PR interval which may lead to 1st degree AV block
Give examples of class 2 Vaughan Williams Classification edications
-Propranolol
-Labetalol
-Atenolol
-Metoprolol
-Bisoprolol
-Nebivolol
-Carvedilol
-Esmolol
What are some side effects of beta blockers?
Side effects:
o Bronchospasm – Asthma and COPD
o Hypotension
o Bradycardia
o Cardiac failure
o Impotence
o Exacerbation of PVD
Overdose:
o Glucagon
o Temporary pacing
o Inotropic support
No proarrhythmic effects
What are some class 3 agents in the Vaughan Williams Classification?
Potassium channel blockers
Eg. Amiodarone, Dronaderone, Sotalo
Prolong repolarization phase by blocking outward potassium flux in phase 3 causing
prolonged refractory period
- leads to increase in duration of AP and decreases incidence
of re-entry - Anti-fibrillatory agents
- Useful in re-entry tachyarrhythmias (supraventricular)
