Robert Widdop; Week 12 MED1022; Pharmacology
Calcium current is important in nodal tissue. Classification is based on site of abnormality and
tachycardia/bradycardia. Atrial fibrillation is persistent/irregular; SVT is rapid/regular, paroxysmal SVT is intermittent. AF is most common, associated with high incidence of heart failure and stroke. Ventricular ectopics are premature contractions, ventricular tachycardia is rapid/regular, ventricular fibrillation is irregular. Common after MI, CAD can cause sudden death due to VF. General mechanisms of arrhythmias are abnormal impulse generation (altering normal automaticity, ectopic automaticity), abnormal impulse conduction/repolarisation such as in heart block (1st is prolonged PR interval; 2nd is no impulses conducted so P wave but no QRS, 3rd is no conduction through AV node). Reentry circuits and after-depolarisations also occur. Early after-depolarisation causes decreased K , there is QT prolongation. Delayed after-depolarisation has Ca overload.
Arrhythmias can be caused or exacerbated by ischaemia, MI, cardiac surgery, electrolyte disturbances, hypoxia, valvular disease, catecholamines, some drugs. Drug induced arrhythmias can be from alcohol, sympathomimetics, tricyclic antidepressants, antiarrythmics such as digoxin (almost any), b blockers/Ca antagonists (bradyarrythmias), diuretics (electrolyte disturbances with arrhythmias). Some antihistamines can also cause arrhythmias along with volatile solvents and general anaesthetics.
In bradyarrythmias drugs are only used acutely, in tachyarrythmias are only used if life threatening or if there are moderate/severe symptoms. Classes of antiarrythmic drugs are I: Na channel blockers; II beta blockers; III block cardiac K channels and other actions; IV are Ca channel blockers. Class I are local anaesthetic or membrane stabilising, blocks fast sodium current, slows cardiac conduction, depresses normal and abnormal automaticity. Class Ia is AP prolonged (quinidine, procainamide, disopyramide); Ib AP shortened (lignocaine), Ic is AP duration unchanged (flecainide). Has use dependant Na channel block. Class II reduce pro-arrythmic effects of adrenaline, NA and sympathetic tone, decreases sinus node automaticity. Used in AF, flutter, post MI. III (sotalol, amiodarone) prolongs action potential by blocking K channels, prolongs refractory period (increases QT interval), sotalol is b blocker with class III activity, amiodarone has serious adverse effects. IV eg verapamil, dilitazem blocks slow calcium entry responsible for conduction in nodal tissues, suppresses all automaticity. Verapamil is used orally for AF and to prevent SVT recurrence. Do not combine with b blockers.
Digoxin blocks AV conduction, slows ventricular rate in AF. Adenosine IV converts SVT to sinus rhythm, stimulates pathway similar to ACh- hyperpolarises by increasing K outflow. Digoxin inhibits Na/K ATPase and increases myocardial intracellular calcium, leads to increased contractility and reduced oxygen use in failing heart and increases CO. More effective in cardiomyopathies, less effective secondary to hypertension. Vagal stimulation causes bradycardia, reduced AV contraction with increased PR interval on ECG. High doses cause membrane depolarisations with increased abnormal automaticity, various ventricular arrythmias. Digoxin stimulates the vagus nerve to slow ventricular rate by slowing AV conduction.
In AF there should be control of ventricular rate (digoxin, b blockers, Ca blocker), can attempt reversion to normal rhythm, anti-coagulants should be used. Paroxysmal SVT can be treated non-pharmacologically (Valsalva maneuver, carotid sinus massage unilaterally) or with adenosine/verapamil. VF can be treated with lignocaine post MI, or class II/III drugs to prevent, as well as defib. Bradycardia can be treated with atropine, adrenaline, isoprenaline (IV); or chronically by stopping bradycardic medication or with a pacemaker.
Many of these drugs are potentially toxic and can have pro-arrythmic effects, beta blockers reduce exercise ability and calcium blockers can cause hypotension and fainteness.