ARRHYTHMIA Dr. Ahmed A. Elberry, MBBCH, MSc, MD Assistant Professor of Clinical Pharmacy Faculty of pharmacy, KAU 1 SINUS RHYTHM SA node is cardiac pacemaker Normal sinus rhythm 60-100 beats/min Depolarisation triggers depolarisation of atrial myocardium Conducts more slowly through AV node Conducts rapidly through His bundles & Purkinje fibres to ventricles SA node is controlled by autonomic nervous system Parasympathetic system predominates (M2 receptors) Sympathetic system (ß1 receptors) 2 1
ECG Recording of electrical activity of the heart Net sum of depolarisation & repolarisation potentials of all myocardial cells P-QRS-T pattern P - atrial depolarisation QRS - ventricular depolarisation T - ventricular repolarisation R P T qs 3 ARRHYTHMIA It is an electrophysiological abnormality leading to loss of cardiac rhythm Pathophysiology of arrhythmia Causes of arrhythmia: Disturbance of impulse formation: Disturbance of impulse conduction Classification of arrhythmia: According to their site of origin Supraventricular & ventricular According to heart rate tachycardia & bradycardia 4 2
Normal Re-entry AV re-entry tachycardia (Wolf-Parkinson-White syndrome) 5 CLINICAL CLASSIFICATION OF ARRHYTHMIAS 1. Bradyarrhytmias sinus block, sick-sinus syndrome, AV block 2. Tachyarrhytmias a) Supraventricular (SV) Atrial fibrillation (AF) or atrial flutter paroxysmal supraventricular tachycardia (PSVT) Wolf-Prkinson-White Syndrome (WPW). b) Ventricular premature ventricular complexes ventricular tachycardia Torsade de pointes is a polymorphic VT ventricular fibrillation 6 3
Atrial fibrillation (AF) or atrial flutter They have similar precipitating factors, consequences, and drug therapy. The mechanism of AF & atrial flutter is reentry, which is usually associated with organic heart disease that causes atrial distention (e.g., ischemia or infarction, hypertensive heart disease, valvular disorders). AF More common extremely rapid (400 to 600 atrial beats/min) & irregular atrial activation. There is loss of atrial contraction, resulting in irregular ventricular activation and irregularly irregular pulse (120 to 180 beats/min). Atrial flutter Less common rapid (270 to 330 atrial beats/min) but regular atrial activation. The ventricular response usually has a regular pattern and a pulse of 300 beats/min. 7 Atrial Fibrillation Atrial Flutter AF is caused by numerous wavelets of depolarization spreading throughout the atria simultaneously absence of coordinated atrial contraction. ECG Characteristics: Absent P waves Presence of fibrillatory waves which vary in amplitude & morphology Irregularly irregular ventricular response Most cases of atrial flutter are caused by a large reentrant circuit in the wall of the right atrium ECG Characteristics: Biphasic sawtooth flutter waves at a rate of ~ 300 bpm Flutter waves have constant amplitude, duration, & morphology There is usually either a 2:1 or 4:1 block at the AV node, resulting in ventricular rates of either 150 or 75 bpm 8 4
1st Degree AV Block Prolongation of the PR interval, which is constant All P waves are conducted 2nd Degree AV Block Progressive prolongation of the PR interval until a P wave is not conducted. As the PR interval prolongs, the RR interval actually shortens 3rd Degree (Complete) AV Block No relationship between P waves and QRS complexes Relatively constant PP intervals and RR intervals Greater number of P waves than QRS complexes 9 CLINICAL MANEFISTATION Asymptomatic Symptomatic: Palpitation dizziness or acute syncopal episodes symptoms of HF; angina; embolic stroke with AF irregular pulse Diagnosis: with ECG 10 5
TREATMENT OF ARRHYTHMIA The use of antiarrhythmic drugs in USA is declining because: many trials showed increased mortality with their use Pro arrhythmia is a significant side effect advancing technology of nondrug therapies as ablation implantable cardioverter-defibrillator (ICD). 11 12 6
Phases of the action potential: Phase 0: activation of Na+ channels rapid Na+ influx. (excitability & conductivity). Phase 1: Inactivation of Na+ channels & K+ efflux. Phase 2: activation of slow Ca++ channels slow Ca++ influx & K+ efflux. Phase 3: Activation of K+ channels rapid K+ efflux. Phase 4: a) b) normal cardiac muscle fiber resting potential Activation of A.T.P ase Na+ / K+ pump restore the electrolyte balance. S.A.N., conductive tissue & ectopic focus slow Na+ & Ca++ influx Slow diastolic depolarization (automaticity) S.A node Atrium & Ventr. 13 Drugs blocking ion channels Activated Na+ channels phase 0 excitability & conductivity. Inactivated Na+ channels phase 4 automaticity. Slow Ca++ channels phase 4 automaticity Short phase 2 K+ channel long phase 3 long (A.P.D) & long (E.R.P) 14 7
Vaughan Williams Classification of Antiarrhythmic Drugs: (1) Class 1: Na+ channel blockers (see below) (2) Class II: beta-blockers : Propranolol, acebutalol & esmolol. (3) Class III: Block mainly K+ channel delay repolarization long phase 3 long APD & ERP Examples: Amiodarone - Bretylium - Sotalol - Ibutilide Dofetilide (4) Class IV: CCB: Verapamil & Diltiazem (5) Unclassified: e.g: Adenosine - Atropine - Digitalis - Magnesium 15 A) Group A: Block both Na+ & K+ B) Group B: C) Group C: 1. Moderate block of activated 1. Minimal block of activated - Marked block of Na+ channel moderate Na+ channel minimal of activated Na+ channel of phase 0 moderate phase 0 minimal effect of marked of phase conductivity & conductivity & excitability. 0 marked of excitability. 2. Block mainly inactivated conductivity & 2. Block inactivated Na+ Na+ channel phase 4 excitability. channel phase 4 automaticity. depress automaticity. 3. Block K+ channel delay 1. May activate K+ channel repolarization long phase rapid repolarization 3 long A.P.D. &E.R.P. short phase 3 short APD & ERP. * Examples: * Example: * Examples: Quinidine, Procainamide & Lidocaine, Mexiletine, Flecainide - Encainide Disopyramide Tocainide & Phenytoin Lorcainide - Propafenone 16 8
Class IA: QUINIDINE Indications: Maintain normal sinus rhythm in supraventricular arrhythmia Adverse effects (common & serious) GIT: diarrhoea, nausea, vomiting (in up to 30% of treated patients) CNS cinchonisms : headache, vertigo, tinnitus, visual disturbances haematological: thrombocytopenia, haemolytic anaemia Skin: urticaria (rash), photosensitisation Myalgia, arthralgia, SLE like, fever, hepatitis Cardiovascular system Ventricular tachycardia (Torsades de pointes) HF, Bradycardia, heart arrest Interactions: strong inhibitor of CYP 2D6 Class IA: PROCAINAMIDE It is the drug of choice in WPW syndrome Adverse effects Hypotension, esp. after rapid i.v. infusion. Long QT syndrome & TdP Lupus-like syndrome: after long treatment (> 6 months): Syndrome disappear spontaneously after drug withdrawal Other: GIT (vomiting, diarrhoea), allergy, CNS (depressions, hallucinations), haematological disturbances DISOPYRAMIDE Adverse reactions: 1. Antimuscarinic (dry mouth, visual disturbances, urinary retention, glaucoma worsening) 2. -ve inotropic: can precipitate HF 9
Class IB: Lidocaine, Mexiletine, Tocainide, Phenytoin Indications: Acute ventricular arrhythmias esp. after M.I. & with digoxin overdose (Phenytoin) Adverse reactions: CNS paresthesia, tremor, nausea, hearing and speaking disturbances In high doses - agitation and convulsions may appear (treatment diazepam), apnoea, negative inotropic action and hypotension Phenytoin: megaloblastic anaemia, Hirsutism & gum hypertrophy Class IC: Flecainide - Encainide Lorcainide - Propafenone Indication: Supraventricular arrhythmia Adverse effects 1. Cardiac: AV block, ventricular tachyarrhythmias 2. GIT : Nausea, vomiting, constipation & metallic taste with propafenone 3. CNS : tremor, restlessness, headache, sleeping disturbances 10
Class III: AMIODARONE It is a broad spectrum antiarrhythmic Adverse effects Cardiac bradycardia, AV blockade long QT syndrome & TdP risk Extracardiac 1. Lungh fibrosis (in a serious form in up to 1% of patients) 2. Hepatotoxicity 3. Skin deposits fotodermatitis and coloured sun-exposed skin (blue-grey) 4. Corneal microdeposits detectable already after few weeks of treatment, it's mostly asymptomatic, but may cause blurred vision in some patients 5. Optic neuropathy/neuritis (rare) may result in blindness 6. Thyreoid dysfunction: hypofunction or hyperfunction Class III SOTALOL Adverse reaction: generally relatively tolerable drug (mostly transient) Long QT & TdP Bradycardia, HF, hypotension, bronchoconstriction, sleep disturbances Dofetilide Proarrhythmogenic TdP, the QT monitoring is essential Ibutilide indicated mainly for rapid pharmacological cardioversion of AF & Flutter to sinus rhythm 11
CLASS II & CLASS IV Class II (BB): indicated in supraventricular & ventricular arrhythmia Class IV (CCB): Indicated in supraventricular arrhythmia (not ventricular) Not combined with BB 23 Unclassified Atropine: Indicated in sinus bradycardia Adenosine: Used in Acute supraventricular arrhythmia (successful in 90-95%) Adverse reactions: flush, headache, dyspnea (bronchoconstriction), palpitations, very rare is induction of ventricular fibrillation Digoxin: Used in supraventricular arrhythmia (CI in ventricular) Mg: Indicated in digoxin-induced tachyarrhythmias & TdP 12
ATRIAL FIBRILLATION OR ATRIAL FLUTTER Goal of treatment: Ventricular rate control: Prevention of embolic stroke: by anticoagulants 25 Ventricular rate control in AF If symptoms are severe direct current cardioversion (DCC) to restore sinus rhythm immediately. If patients are hemodynamically stable In patients with normal LV function (EF >40%) In patients with EF 40% - IV βb (propranolol, metoprolol, esmolol), OR - IV CCB (Diltiazem or verapamil) IV digoxin or amiodarone should be the 1st line therapy 26 13
Anticoagulants in AF Anticoagulation should be initiated prior to cardioversion because return of atrial contraction risk of thromboembolism. Patients with AF for 48 Patients with AF 48 h h or unknown duration: in duration: should receive warfarin do not require warfarin, (target INR 2 to 3) for at least 3 weeks prior to cardioversion & continuing for at least 4 weeks after effective cardioversion. but it is recommended to give IV UFH or LMWH (SC) at presentation prior to cardioversion. 27 Maintenance therapy 1. Quinidine maintained sinus rhythm; however, 1. 2. 50% of patients had recurrent AF within 1 year, more importantly, quinidine increased mortality, presumably due in part to proarrhythmia. 2. Type Ic (e.g., flecainide, propafenone) & type III (eg. amiodarone, sotalol, dofetilide) antiarrhythmics may be alternatives; however, 1. they are also associated with proarrhythmia. Consequently, chronic antiarrhythmic drugs should be reserved for patients with recurrent paroxysmal AF. 28 14
Paroxysmal Supraventricular Tachycardia Acute therapy: Severe symptoms: (e.g., syncope, anginal pain, severe HF) DCC is the treatment of choice Mild to moderate symptoms: Nondrug measures that vagal tone to the AV node (e.g., unilateral carotid sinus massage, Valsalva maneuver). Adenosine is the drug of 1st choice Maintainanace therapy those that vagal tone to the AV node (e.g., digoxin) (2) those that conduction through slow, Ca++-dependent tissue (e.g., adenosine, βb, CCB) (3) those that conduction through fast, Na+-dependent tissue (e.g., quinidine, procainamide, disopyramide, flecainide). (1) 29 Ventricular Tachycardia Acute or severe Ventricular Tachycardia Most patients require & respond to DCC. However, TdP tends to be paroxysmal & often recurs rapidly after DCC. IV magnesium sulfate is considered the drug of choice for preventing recurrences of TdP. Mild or no symptoms IV amiodarone is recommended as first-line therapy. Procainamide or lidocaine given IV is a suitable alternative. 30 15
Ventricular Fibrillation Epinephrine is a drug of first choice for treating VF Vasopressin is a potent VC that Bl Pr & systemic vascular resistance. Amiodarone is the preferred antiarrhythmic during cardiac arrest Lidocaine is recommended as an alternative to amiodarone 31 BRADYARRHYTHMIAS Asymptomatic sinus bradyarrhythmias usually do not require therapeutic intervention. Long-term therapy of choice for patients with significant symptoms is a permanent ventricular pacemaker. AV Block Atropine (0.5 mg IV given every 3-5 min, up to 3 mg total dose) should be given as the pacing leads are being placed. Infusions of epinephrine (2-10 mcg/min) or dopamine (2 10 mcg/kg/min) can be used if atropine failed. 32 16
berry_ahmed@yahoo.com 33 17