ANTIARRHYTHMIC DRUGS

Every hour 2000 patients around the world die from sudden arrhythmia attack

CARDIAC ARRHYTHMIAS, LOCAL CAUSES

CARDIAC ARRHYTHMIAS SYSTEMIC CAUSES

Extrasystolia, scintillating arrhythmia, paroxysmal tachycardia, fibrillation CausesMechanisms Surplus of catecholamines (thyreotoxicosis) Increasing of frequency of spontaneous diastolic depolarization (calcium type) in Р-cells of sinus node Disturbance of ion balance (hypopotassiumemia, hypomagnesiumemia), ischemia, hypoxia of myocardium, intoxication (cardiac glycosides) Development of sodium ("fast") type of spontaneous depolarization in elements of conductive system of the heart which don’t have automatism in normal conditions Insufficient power of potential which exits from sinus node Manifestation of activity of heterotopous source of impulse development Disturbance of conductivityLocal circulation of impulses (re-entry mechanism)

Scheme of mechanism of repeated entry norm Nervous impulse Wall of the ventricles Impulse goes in reverse direction and enters the starting point (circulation of the impulse), which leads to out of order and non regular contraction of the heart 12 One-side blockade

Arrhythmia riskier in athletes Cardiac problems like an abnormal heartbeat are exacerbated by rigorous exercise in a way that can be fatal in athletes, and regular testing for the problem could save lives

Drugs can provoke arrhythmias (arrhythmogenic action) All antiarrhythmics except beta- adrenoblockers AntidepressantsAdrenomimetics Some antiallergics (terfenadine=telfast)

Supra ventricular tachyarrhythmias

VENTRICULAR ARRHYTHMIAS

Classification of antiarrhythmic drugs accordingly to Williams and Harrison (1970, 1981) ClassMechanism of actionDrugs IMembrane stabilizing, sodium canals blockers I А Slow down Na + ions entry into cells moderately (0-phase of action potential), considerably prolong (during phase 3) action potential and repolarization duration Chinidine, novocainamid, disopyramid, aimalin, imipramin, primalin etc. I B Weakly influence on Na + ions entry, shorten repolarization duration and action potential Lidocain, trimecain, mexyletin, tokainid, difenin I С Considerably depress Na + ions entry but almost don’t influence on repolarization period and action potential duration Flecainid, encainid, ethmosin, ethacisin, alapinin, propaphenon IIBeta-adrenergic receptors blockersAnaprilin, nadolol, esmolol, atenolol, methoprolol, bisoprolol IIIProlong repolarization and action potential (potassium canals blockers) Amiodaron, brethylium, d-sotalol, nibentan etc. IVCalcium canals blockersVerapamil, galopamil, dilthiazem, bepridil 5 th Bradycardiaс agentsAlinidin 6 th Purinergic receptors stimulantsAdenosine, ATP

Chinidine sulfate Indications for using Chinidine sulfate (I-А class) Stabile form of scintillating arrhythmia Stopping of scintillating arrhythmia paroxysms Ventricular extrasystolia and tachycardia (rarely) Supporting of normal rhythm after cardio version (electro-impulse therapy)

Complications chinidine sulfate оf chinidine sulfate 1. Sinus bradycardia 2. Cardiac insufficiency 3. Pirouette tachycardia (“ torsade de points” - polymorphic ventricular tachycardia) 4. Thromboembolia 5.Hypotension 6.Nausea, vomiting 7. Ringing in ears, hearing disorders 8. Eyesight (vision) disorders 9. Skin rash 10. Agranulocytosis (bone marrow suppression) 11. Hepatitis etc.

Indications for administration of Novocain amid Novocain amid (I-А class) 1.Paroxysms of scintillating arrhythmia (in a case when verapamilum and ATP are ineffective) 2. Fibrillation of atria 3. Prophylaxis and treatment of paroxysmal ventricular tachycardia, extrasystolia

Allergic reactions (cross-allergic reactions with other drugs of PABA structure) Nausea, vomiting Nausea, vomiting Insomnia, headache Insomnia, headache Seizures Seizures Arterial hypotensionArterial hypotension Disorders of conductivity and contractility of myocardium Disorders of conductivity and contractility of myocardium Arrhythmogenic action Arrhythmogenic action Leukopenia, agranulocytosis Leukopenia, agranulocytosis Symptoms of system lupus Symptoms of system lupus Complications of novocainamid

Pulsnorma (aimalin) (I-А class)

Indications for administration Lidocain (I В class) It is a drug of choice in case of heavy ventricular arrhythmias (extrasystolia, paroxysmal tachycardia, fibrillation) of different origin, including acute myocardial infarction (0,2 % sol. i. v. very slowly) Difenin (I В class) To treat tachyarrhythmias caused by intoxication with cardiac glycosides

Antiarrhythmic drugs of І С class ethmosin ethacysin Atrial and ventricular paroxysmal tachycardia, extrasystolia Ventricular tachyarrhythmias Nowadays it is recommended to limit administration of 1 C class drugs using only for the most life threatening ventricular arrhythmias with considerable clinical symptoms

IС class

 -adrenoblockers (II class ) (anaprilin, atenolol, methoprolol) Administration: sinus tachycardia (for thyrotoxicosis), supraventricular extrasystolia, paroxysmal tachycardia, including acute myocardial infarction Contraindications: Contraindications: bronchial asthma, diabetes mellitus, diseases of peripheral vessels, atrioventricular blockade

Anaprilin

Atenolol Methoprolol tartrate Vasocardin ( Methoprolol tartrate )

Potassium canals blockers (III class) (amiodaron, brethylium, sotalol) Usage: atrial and ventricular tachyarrhythmias Amiodaron drug of choice in case of paroxysmal scintillating arrhythmia and malignant ventricular disorders of rhythm drug of choice in case of paroxysmal scintillating arrhythmia and malignant ventricular disorders of rhythm

Amiodaron

Scheme of amiodaron administration І - Saturation period (1,5-2 weeks): 200 mg 2-3 times daily ІІ – Supporting therapy: 200 mg daily 5 days, 2-days brake, after - a certain period of time accordingly to this scheme

Arrhythmil (amiodaron)

Amiodaron

Amiodaron induced skin discoloration

Amiodaron induced pulmonary infiltrates

Calcium canals blockers (IV class) (verapamil, dilthiazem) Administration supraventricular tachyarrhythmias (paroxysmal tachycardia, extrasystolia, scintillating arrhythmia)

Finoptin (verapamil)

Verapamilum Combination of verapamilum and digoxinum can cause acute digoxine intoxication (they compete for binding with plasma proteins) I.v. verapamile introduction on the basis of β-adrenoblockers administration can provoke severe bradycardia, heart blockade and acute hypotension

ADENOSINTRIPHOSPHATE (ATP) Administration – supraventricular arrhythmias (i. v. by bolus) Complications ATP introduction after β-adrenoblockers can provoke syno-atrial node depression and even cardiac arrest ATP introduction after β-adrenoblockers can provoke syno-atrial node depression and even cardiac arrest When vasospastic type of IHD – ATP introduction can lead to severe angina attack When vasospastic type of IHD – ATP introduction can lead to severe angina attack Specific antagonist of ATP - theophylline Specific antagonist of ATP - theophylline

Choice of antiarrhythmic agent depending on kind of tachyarrhythmia supraventricular tachyarrhythmiassupraventricular tachyarrhythmias – verapamil, beta-adrenoblockers, cardiac glycosides ventricular tachyarrhythmiasventricular tachyarrhythmias – lidocain, trimecain, mexyletin, phenitoin (diphenin), ornide, flecainid, rhythmilen effective in both caseseffective in both cases - for supraventricular and ventricular tachyarrhythmias – chinidine, novocainamid, ethmosyn, ethacysyn, amiodaron, sothalol, potassium preparates

Administration of antiarrhythmic drugs due to life-threatening indications 1.frequent and polytopic extrasystoles – manifestations of possible fibrillation 2. constant and paroxysmal ventricular tachycardia 3. fibrillation of ventricles 4. atrial rhythm disorders, if accompanied by considerable haemodynamic disorders

Administration of antiarrhythmic drugs Class I Type of arrhythmia Atrium arrhythmia Fibrillation of atria chinidine amiodaron anaprilinverapamildigoxin anticoagulant therapy The most widely used drug The alternative drug Class IIClass IIIClass IVothers !This arrhythmia is accompanied by multiple ectopic seats of impulses in atria, which leads to increasing of frequency of ventricular contractions ( beats per minute), which becomes irregular Antiarrhythmic drugs Scintillation of atria Beta-blockers – are the drugs of choice in case of atria fibrillation. Long lasting administration of anticoagulants in small doses decreases risk of stroke associated with fibrillation of atria lidocain anaprilin Supraventricular tachycardias Mechanism of reentry Acute supraventricular tachycardia anaprilin verapamildigoxin verapamiladenosine CONDUCTION OF IMPULSE THROUGH ATRIO-VENTRICULAR NODE CAN BE SLOWED DOWN BY: ANAPRILIN, VERAPAMIL, DIGOXIN Ventricular tachycardias Acute ventricular tachycardia Fibrillation of ventricles (the previous defibrillation is not effective) lidocain Sotalol, amiodaron brethylium, amiodaron adrenalin This arrhythmia is an often cause of death of patinets with myocardium infarction. It can be quickly transformed into fibrillation of ventricles. It needs an immediate treatment. chinidine

Influence of prolonged administration of antiarrhythmic drugs on mortality (results of placebo-controlled multicenter randomized trials) increasing mortality increasing decreasing mortality decreasing Can possibly decrease mortality (modern data is not convincing) encainid flecainid moracisin beta-adrenoblockers amiodaron dysopyramid mexylethyn novocainamid propaphenon chinidine sotalol ?

MANAGEMENT of ATRIOVENTRICULAR BLOCKADE M-cholinoblockers (atropine) β-adrenomimetics (isadrine) Glucagon Calcium preparations

diphenylhydantoin