Anti-Arrhythmic Drugs PDF

Cardiac Conduction System Starts w/ the S.A. node ○ We have a group of cells that get depolarized and these nerve cells are activated by the autonomic nervous system ○ If there are activated by the autonomic nervous system, we have the beta-1 receptors...

Cardiac Conduction System Starts w/ the S.A. node ○ We have a group of cells that get depolarized and these nerve cells are activated by the autonomic nervous system ○ If there are activated by the autonomic nervous system, we have the beta-1 receptors (cause acceleration of the heart), muscarinic receptors Inter-nodal pathways A.V. node ○ The one that sends the message from the atrium to the ventricle ○ Also has beta-1 and muscarinic ○ Corresponding muscle: ventricular myocardium; mainly has beta-1 receptors and very little muscarinic bc if there was more muscarinic, we would not have a proper ejection fraction system Bundle of His and branches Purkinje fibers  ○ P wave: depolarization of atria in response to SA node triggering ○ PR segment: delayed passage from sinus node to AV node to allow filling of ventricles ○ QRS complex: involves the depolarization of ventricular muscle that causes contractility, triggers main pumping contractions ○ ST segment: beginning of ventricular repolarization, should be flat ○ T: when the ventricular is repolarized ○ U wave: Residual polarization but in some patients, not all 3 types of supraventricular tachycardia: (Atro-tachycardia) - most common ones ○ Paroximal tachycardia (related to ectopic activation from atrium) ○ Atrial flutter ○ A-fib Is tachycardia and arrhythmia the same thing? ○ Tachycardia is increased heart rate and if it is out of rhythm, it may be pathological Sinus tachycardia is tachycardia w/o arrhythmia ○ But it can lead to arrhythmia if it is too high Ventricular tachycardia Pacemaker Cells Action Potential (this allows to have contractility) Slope of action potential determines HR SA node cells, normal depolarization rate 60-100 PM AV node cells, normal depolarization rate 40-60 PM SA node is the primary pacemaker since it has a higher depolarization rate 3 phases ○ Phase 4 (orange) SA node cells and AV nodes cells Gradient depolarization (prepotential) Slow influx of Na+ ions through Membrane potential changes from -60 mV to reach the threshold potential of -40 mV ○ Phase 0 (red) Phase of depolarization (action potential) Starts when the membrane potential reaches -40 mV Opening of voltage-gated Ca2+ channels causing the influx of Ca2+ ion Results in an upstroke in membrane potential from -40 mV +10 mV ○ Phase 3 (light blue) Phase of depolarization Involves the closing of Ca2+ channels, blocking the inflow of Ca2+ ions Voltage-gated K+ channels open, allowing for efflux of K+ ions Contributes to a rapid decrease of membrane potential from +10 mV to -60 mV because of the outflux of K+ repolarization ○ Phases 1 & 2 are not present in pacemaker cells***  ○ Myocytes Action Potential (this involves 5 phases ○ Phase 0 is the phase of depolarization ○ Phase 1-3, phases during which depolarization occurs ○ Phase 4 is the resting phase w/ no spontaneous depolarization Phase 0 ○ Rapid depolarization ○ Voltage-gated Na+ channels open, resulting in a rapid influx of Na+ ions ○ Membrane potential changes from -85 mV to +20 mV w/ steep upstroke Phase 1 ○ Inactivation of opened voltage-gated Na+ channels ○ Activation of transient outward potassium current ○ Slight drop in the membrane electrochemical potential which results in the initiation of phase 2 Phase 2 (Plateau Phase) ○ Ca2+ influx occurs through an opening of voltage-gated L-type Ca2+ channel ○ Calcium influx balances the K+ efflux, creating a plateau Phase 3 ○ Repolarization ○ L-type Ca2+ channel close, K+ channels remain open ○ This allows more types of K+ channels (rapid delayed rectifier channels) to open and the membrane to depolarize to its resting membrane potential (phase 4)  Arrhythmia: An abnormality in: ○ Heart rhythm - extrasystoles (PAC, PVC) Ectopic pacemakers or disturbance in conduction ○ Heart rate High rate = tachycardia Low rate = bradycardia Sinus tachycardia and sinus bradycardia They regular rhythm: this is NOT arrhythmia Very high or low regular rhythm could predispose arrhythmia Origin of Tachycardia Arrhythmia Altered automaticity Altered conduction ○ Ectopic atrial conduction ○ AVNRT (Atrioventricular nodal re-entry tachycardia) ○ AVRT (Atrioventricular re-entry tachycardia) SVT Cardiac conduction Ectopic atrial conduction  Group of nerve cells that are not supposed to be activated AV node which leads to an extra beat and causes an acceleration in heartbeat See these in paraxosomal tachycardia: suggestive of all of sudden; causing arrhythmic tachycardia AVNRT: When our sinus nodes sends a message to AV nodes, some nerve fibers that send signals to ventricles and others that go back to AV nodes which leads to acceleration/arrhythmia AVRT: Orthodromic (will stimulate normally coming from SA node to AV node but once it gets back to the ventricle, it will send a signal back to AV node which is not supposed to happen) Antidromic (both normal path and also takes an altered different path going directly to the ventricles and from those, the stimulation from the ventricle goes right up to the AV node) AVRT-Wolff-Párkinson White (WPW)**************** Has a specific abnormal path that is called Bundle of Can’t Does not go to AV; goes to ventricles and then goes back AV node and goes to bundle of Can’t (local re-entry)  Goal of treatment for anti-arrhythmic drugs Restore normal rhythm, conduction and rate Effect: ○ Accelerate or reduce velocity of conduction ○ Alter the excitability of cardiac cells ○ Suppress abnormal automaticity ○ They act on the action potential of cardiac myocytes* this is the reason we use the classified drugs Antiarrhythmic Drugs Classification Class I ○ Na+ channel blockers (membrane stabilizing drugs) ○ Drugs that block the rapid inflow of Na+ ions ○ Alters the slope amplitude of depolarization ○ Variable effect on ERP and AP depending on the subclass ○ ○ Class 1A: Quinidine Isomer of quinine Effects on myocytes: ○ Membrane stabilizing effect ○ Block potassium channels leading to prolongation of action potential duration > prolongation of atrial and ventricular refractory period ○ Depress cardiac contractility ECG changes: ○ Prolongation of P-R and Q-T interval can be an issue in some patients like patients w/ … syndrome ○ Widens QRS complex ○ Used for almost all types of arrhythmias Common uses: atrial flutter and fibrillation Can be used for ventricular tachycardia Maintaining sinus rhythm after direct current cardio version Adverse effects:  ○ GIT: anorexia, nausea, vomiting, diarrhea ○ Cardiac: Episodes of fainting May terminate spontaneously or lead to fatal ventricular fibrillation ○ Anticholinergic adverse effects ○ Cinchonism: visual disturbances, tinnitus, HA and dizziness ○ Hypotension Drug interactions: ○ Increase concentration of digoxin: displacement from plasma proteins and inhibitiono of digoxin renal clearance GIVEN ORALLY- rarely given IV because of toxicity and hypotension due to alpha-blocking effect Procainamide Less toxic on the heart, can be given IV More effective in ventricular than in atrial arrhythmias Less depression of contractility No anticholinergic or alpha-blocking actions Effective against most atrial and ventricular arrhythmias Second choice after lidocaine in ventricular arrhythmias after acute myocardial infarction Adverse effect: ○ in long term tx: causes reversible lupus erythematosus-like syndrome in 5-15% of patients ○ Hypotension ○ Torsades de pointes ○ Hallucination and psychosis ○ Class IB Lidocaine Treatment of ventricular arrhythmias in emergency (e.g., cardiac surgery, acute myocardial infarction) ○ Given IV bolus or slow infusion NOT effective in atrial arrhythmias (only ventricular) NOT effective orally (3% bioavailability) Adverse effects ○ Hypotension ○ Like other anesthetic, neurological adverse effects: Paraesthesia Tremor Dysarthria (slurred speech) Hearing disturbances Confusion Convulsions  Mexiletine Effective orally Adverse effects ○ Nausea, vomiting ○ Tremor, drowsiness, diplopia ○ Arrhythmias and hypotension ○ Class IC Flecainide Used in supraventricular arrhythmias in patients w/ normal hearts Wolff-Párkinson-White Syndrome Very effective in ventricular arrhythmias, but very high risk of pro-arrhythmia Should be reserved for resistant arrhythmias Adverse effects: ○ CNS: dizziness, tremor, blurred vision, abnormal taste sensations, paraesthesia ○ Arrhythmias ○ Heart failure due to decreased ventricular(e) inotropic effect Propafenone Used bid Chemical structure similar to propranolol Has weak beta-blocking action Causes metallic taste and constipation Class II ○ Beta-adrenoceptor blocker ○ Pharmacological actions: Block beta-1 receptors in the heart -> reduce the sympathetic effect on the heart causing: Decrease automaticity of SA node and ectopic pacemakers Prolong refractory period (slow conduction) of the AV node, this helps prevent re-entry arrhythmias ○ Clinical uses: Atrial arrhythmias w/ emotion, exercise, and thyrotoxicosis WPW Digitalis-induced arrhythmias (Propranolol or atenolol reduce the incidence of sudden arrhythmic death after myocardial infarction, because of its ability to prevent ventricular arrhythmias ) Class III ○ Drugs that prolong action potential duration & refractory period ○ Prolong phase 3 ○ Amiodarone  Main effect is to prolong action Al potential duration and therefore prolong refractory period (useful in re-entry arrhythmias) Additional Class 1A, 2, and 4 effects Vasodilating effects (due to its alpha adrenoreceptor blocking effects and its calcium channel blocking effects) Use: serious resistant ventricular arrhytmias, very effective in many types of arrhythmias Maintenance of sinus rhythm after D.C. cardio version of atrial flutter and fibrillation Resistant supraventricular arrhythmias (e.g. WPW) Adverse effects Bradycardia, heart block, heart failure Pulmonary fibrosis Hyper- or hypothyroidism Photodermatitis (in 25%) and skin deposits May cause bluish discoloration of the skin Tremor, HA, ataxia, paraesthesia Constipation Corneal micro deposits (swirl) Hepatocellular necrosis Peripheral neuropathy ○ Ibutilide Pure class III and are given by a rapid IV infusion Used for the acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm Causes qt interval prolongation, so it may precipitate torsades de pointes Class IV ○ Calcium channel blockers ○ Main site of action* is SA and AV nodes (slow conduction and prolong effective refractory period) ○ Uses Atrial arrhythmias Re-entry supraventricular arrhythmias (WPW) Not effective in ventricular arrhythmias