Download Free Medical Antiarrhythmic drugs PowerPoint Presentation

Antiarrhythmic drugs PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Antiarrhythmic drugs

Tags : Antiarrhythmic drugs

Published on : Oct 07, 2020 | Views : 5541 | Downloads : 97

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Anti-arrhythmic Drugs Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science MD of Clinical Pharmacology
Slide 2-

Learning outcomes Pathogenesis & Types Action potential and ions permeability ECG Types & Etiology Mechanism of arrhythmias Classification of anti-arrhythmic drugs Pharmacological action Mechanism of action Adverse effects and Clinical uses 2
Slide 3-

Important Abbreviations Action potential (AP) Action Potential Duration (APD) Effective Refractory Period (ERP) Sino atrial Node (SA) Atrio ventricular Node (AV) Myocardial infarction (MI) Atrio ventricular(AV) Block 3
Slide 4-

Introduction 4
Slide 5-

Cardiac Rhythm & Arrhythmias 5
Slide 6-

The ECG The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, And the T wave by ventricular repolarization. Thus, the PR interval is a measure of conduction time from atrium to ventricle, and the QRS duration indicates the time required for all of the ventricular cells to be activated (i.e., the intraventricular conduction time). The QT interval reflects the duration of the ventricular AP 6
Slide 7-

The ECG 7 3 2, 5 1 4 6
Slide 8-

Normal cardiac contraction 8
Slide 9-

Ionic Basis of Membrane Electrical Activity The trans membrane potential of cardiac cells is determined by the concentrations of several ions. sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl–) on either side of the membrane and the permeability of the membrane to each ion. These ions move across cell membranes in response to their gradients only at specific times during the cardiac cycle when these ion channels are open. 9
Slide 10-

Na+ Channels Cycling During The Cardiac Action Potential (AP) 10 Activation (m) gates of sodium channel Inactivation (h) gates of sodium channel
Slide 11-

Cardiac Arrhythmias Normal cardiac contraction at a frequency of 60–100 bpm Arrhythmias consist of cardiac depolarization that deviate from normal conducting system in one or more aspects: there is an abnormality in the site of origin of the impulse or there is an abnormality in its rate/regularity, or there is an abnormality in its conduction. Rhythms are too rapid, too slow, or asynchronous can reduce cardiac output Precipitate serious or even lethal rhythm disturbances; 11
Slide 12-

Two forms of abnormal rhythmic activity 12 Early after depolarization (EAD) Delayed after depolarization (DAD) In both for, abnormal depolarization arise during or after a normally evoked action potential.
Slide 13-

Etiology and Types of Arrhythmias 13
Slide 14-

Etiology - Cardiac Arrhythmias 1. Congenital & 2. Acquired Congenital cardiac arrhythmias: Mutations in the ion channels Example: ventricular tachycardia of torsade de pointes prolongation of the QT interval, syncope, and sudden death congenital long QT (LQT) syndrome 14
Slide 15-

Etiology - Cardiac Arrhythmias Acquired cardiac arrhythmias: 25% of patients treated with digitalis. 50% of anesthetized. Patients, and over 80% of patients with acute MI Overstretching of cardiac fibers; presence of scarred or otherwise diseased tissue. Ischemia, hypoxia, acidosis or alkalosis Electrolyte abnormalities Excessive catecholamine exposure & autonomic influences. 15
Slide 16-

Types of Arrhythmias 16 SVT, supraventricular tachycardia AFL, atrial flutter AFib, atrial fibrillation VT,ventricular tachycardia VT-TdP, ventricular tachycardia of the torsade de pointes type.
Slide 17-

Mechanisms of arrhythmias 17
Slide 18-

Mechanisms of arrhythmias 1. Disturbances of Impulse Formation Shortening of duration of AP results in an increase in pacemaker rate. Hypokalemia, β-adrenoceptor stimulation, positive chronotropic drugs, fiber stretch, acidosis, and partial depolarization by currents of injury EADs are exacerbated at slow heart rates – Due to long QT-related arrhythmias DADs are exacerbated by fast heart rates - Due to digitalis excess, to catecholamines, and to myocardial ischemia 18
Slide 19-

Mechanisms of arrhythmias… 2. Disturbances of Impulse Conduction Severely depressed conduction may result in simple block Another common abnormality of conduction is reentry (also known as "circus movement"), in which one impulse reenters and excites areas of the heart more than once 19
Slide 20-

Classification of Anti-arrhythmic agents 20
Slide 21-

Specific antiarrhythmic agents Four classes: Class 1 action is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade Drugs with class 1A action prolong the APD and dissociate from the channel with intermediate kinetics; PROCAINAMIDE, QUINIDINE drugs with class 1B action shorten the APD in some tissues of the heart and dissociate from the channel with rapid kinetics; LIDOCAINE, MEXILETINE drugs with class 1C action have minimal effects on the APD and dissociate from the channel with slow kinetics. FLECAINIDE, PROPAFENONE 21
Slide 22-

Specific antiarrhythmic agents Class 2 action is sympatholytic. Drugs with this action reduce -adrenergic β2 activity in the heart. PROPRANOLOL Class 3 action manifests as prolongation of the APD. Most drugs with this action block the rapid component of the delayed rectifier potassium current, IKr. AMIODARONE, SOTALOL Class 4 action is blockade of the cardiac calcium current. This action slows conduction in regions where the action potential upstroke is calcium dependent, eg, the Sinoatrial and atrioventricular nodes. VERAPAMIL, DILTIAZEM 22
Slide 23-

Non-specific antiarrhythmic agents 1. Adenosine 2.Magnesium 3.Potassium 23
Slide 24-

Class 1 10/10/2020 24
Slide 25-

Specific Anti-arrhythmic Agents Drugs with local anesthetic action block sodium channels and reduce the sodium current, INa 25 Class 1 Sodium Channel-Blocking Drugs Class 1A Class 1B Class 1C
Slide 26-

Class 1A Procainamide More effective in blocking sodium channels in depolarized cells. Direct depressant actions on SA and AV nodes Slows the upstroke of the AP, slows conduction, Prolongs the QRS duration of the ECG. Ganglion-blocking properties results hypotension Prolongs the APD: by nonspecific blockade of K+ channels. 26
Slide 27-

Toxicity: Long-term therapy Lupus erythematosus syndrome (arthralgia and arthritis) Increased antinuclear antibody titer Excessive action potential prolongation & risk of new arrhythmias hypotension 27 Class 1A Procainamide
Slide 28-

Actions similar to those of procainamide Prolongs the APD by blockade of several K+ channels Toxicity: Cinchonism (at toxic concentration) headache, dizziness, and tinnitus Excessive QT interval prolongation and induction of torsade de pointes arrhythmia Idiosyncratic or immunologic reactions Thrombocytopenia, hepatitis, angioneurotic edema, and fever 28 Class 1A Quinidine
Slide 29-

Effects very similar to those of procainamide and quinidine It has Antimuscarininc effects Toxicity - negative inotropic effect- may precipitate heart failure de novo or in patients with preexisting depression of left ventricular function. - It should not be used in patients with heart failure. - Antimuscarininc effects Urinary retention , dry mouth, blurred vision, constipation, and worsening of preexisting glaucoma. 29 Class 1A Disopyramide
Slide 30-

Class 1B Lidocaine It is used only by the IV route. Undergoes extensive first-pass hepatic metabolism (only 3% in plasma) high degree of effectiveness in arrhythmias associated with acute MI blocks activated and inactivated sodium channels with rapid kinetics one of the least cardio toxic of the currently used Na+ channel blockers No pro-arrhythmic effects Need loading and maintenance doses 30
Slide 31-

Toxicity: It may cause hypotension—partly by depressing myocardial contractility Common neurologic: paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions Therapeutic Use: Lidocaine is the agent of choice for termination of ventricular tachycardia and prevention of ventricular fibrillation after cardioversion in the setting of acute ischemia. 31 Class 1B Lidocaine
Slide 32-

An orally active congener of Lidocaine Long elimination half-life is 8–20 hours and permits administration two or three times per day. Toxicity: Neurologic: tremor, blurred vision, and lethargy. Nausea is also a common effect. Effective in relieving chronic pain ( pain due to diabetic neuropathy and nerve injury This application is off label 32 Class 1B Mexiletine
Slide 33-

Class 1C Flecainide A potent blocker of Na+ and K+ channels with slow unblocking kinetics. It does not prolong the action potential or the QT interval. It is currently used for patients with normal hearts who have supra-ventricular arrhythmias. Toxicity: Cause arrhythmia (normal doses) in: Patients with preexisting ventricular tachyarrhythmias Patients with a previous MI and ventricular ectopy. 33
Slide 34-

Its spectrum of action is very similar to that of quinidine. The drug is used primarily for supraventricular arrhythmias. The most common ADRs: Metallic taste and Constipation Moricizine: Has been withdrawn from the US market. 34 Class 1C Propafenone & Moricizine
Slide 35-

Class 2 Beta-Adrenoceptor Blocking Drugs 35 Specific Anti-arrhythmic Agents
Slide 36-

Beta-Blockers Propranolol, Sotalol and Esmolol These drugs have selectivity for cardiac β1 receptors, Some have intrinsic sympathomimetic activity, some have marked direct membrane effects, and some prolong the cardiac AP. Efficiency lower than Class 1 sodium channel blockers However, there is good evidence that these agents can prevent recurrent infarction and sudden death in patients recovering from acute MI Esmolol is a short-acting blocker used primarily as an antiarrhythmic drug for intra-operative arrhythmias. Sotalol is a nonselective -blocking drug that prolongs the AP (also has class 3 action). 36
Slide 37-

Class 3 Drugs that Prolong Effective Refractory Period by Prolonging the Action Potential 37 These drugs prolong action potentials, usually by blocking K+ channels in cardiac muscle Specific Anti-arrhythmic Agents
Slide 38-

Class 3 Amiodarone Has iodine molecule It is used to treat serious supraventricular ventricular arrhythmias atrial fibrillation (very effective) Dronedarone, an analog that lacks iodine atoms, is under investigation. 38
Slide 39-

Cardiac Effects: Prolongs the APD and the QT interval on the ECG by blockade of IKr. During chronic administration, IKs is also blocked. It also significantly blocks inactivated sodium channels. It also has weak adrenergic and calcium channel blocking actions. The broad spectrum of actions may account for its relatively high efficacy and low incidence of torsade de pointes despite significant QT-interval prolongation. It causes peripheral vasodilation 39 Class 3 Amiodarone
Slide 40-

Toxicity: Produce bradycardia and heart block in patients with preexisting SA or AV node disease. The drug accumulates in many tissues Dose-related pulmonary toxicity - fatal pulmonary fibrosis Abnormal liver function tests and hepatitis The skin deposits result - photodermatitis and a gray-blue skin discoloration in sun-exposed areas, eg, the malar regions. It causes corneal microdeposits (Halos develop in the peripheral visual fields) 40 Class 3 Amiodarone
Slide 41-

Rarely, an optic neuritis may progress to blindness. It blocks the peripheral conversion of thyroxine (T4 ) to T3. It is also a potential source of large amounts of inorganic iodine. It may cause hypothyroidism or hyperthyroidism. Thyroid function should be evaluated before drug and periodically 41 Class 3 Amiodarone
Slide 42-

Pharmacokinetics: unusual pharmacokinetics After discontinuation of the drug, effects are maintained for 1–3 months. Measurable tissue levels may be observed up to 1yr after discontinuation. It has many important drug-drug interactions: It is a substrate for liver cytochrome CYP3A4 Its levels are increased by Enzyme inhibitors : eg, Cimetidine. Its levels are decreased Enzyme inducers : eg, Rifampin It has drug interactions with digoxin and warfarin. 42 Class 3 Amiodarone
Slide 43-

Therapeutic Use: Low doses are effective in maintaining normal sinus rhythm in patients with atrial fibrillation. It is not associated with an increase in mortality in patients with coronary artery disease or heart failure. It is used to decrease the frequency of the implanted cardioverter-defibrillator (ICD) The drug increases the pacing and defibrillation threshold and these devices require retesting after a maintenance dose has been achieved. 43 Class 3 Amiodarone
Slide 44-

Dronedarone Has No thyroid or pulmonary toxicity It is the first antiarrhythmic drug to demonstrate a reduction in mortality or hospitalization in patients with atrial fibrillation Dronedarone has multiple actions like Amiodarone, blocking IKr, IKs, ICa, INa, and adrenoceptor
Slide 45-

It has both β receptor blocking (Class2) + AP prolonging (Class3) actions. It Is formulated as a racemic mixture of D- and L-Sotalol. All the β-blocking activity resides in the L-isomer; the D- and L-isomers share AP prolonging actions. It is well absorbed orally with bioavailability of ~100%. Patients with overt heart failure may experience further depression of left ventricular function during treatment with Sotalol. It is approved for the treatment of life-threatening ventricular arrhythmias and the maintenance of sinus rhythm in patients with atrial fibrillation. It used for treatment of arrhythmias in the pediatric age group. It decreases the threshold for cardiac defibrillation. 45 Class 3 Sotalol
Slide 46-

It blocks K+ current (Ikr), and the blockade of IKr increases in hypokalemia. It is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow Cimetidine, prolong the half-life of dofetilide by inhibition of the renal cation secretion mechanism of dofetilide 46 Class 3 Dofetilide
Slide 47-

It slows cardiac repolarization by blockade delayed rectifier K+ current. Activation of slow inward sodium current has also been suggested as an additional mechanism of AP prolongation. The drug is more effective in atrial flutter than atrial fibrillation 47 Class 3 Ibutilide
Slide 48-

Class 4 Calcium Channel-Blocking Drugs Drugs: Verapamil & Diltiazem 48 Specific Anti-arrhythmic Agents
Slide 49-

Class 4 Verapamil Cardiac Effects: It blocks both activated and inactivated L-type calcium channels. AV nodal conduction time and effective refractory period (ERP) are invariably prolonged Verapamil usually slows the SA node by its direct action, but its hypotensive action result in a small reflex increase of SA nodal rate. Verapamil can suppress both EAD and DAD and may antagonize slow responses arising in severely depolarized tissue. Extra cardiac Effects: Peripheral vasodilatation 49
Slide 50-

Toxicity Hypotension Negative inotropic effects may limit its clinical usefulness in diseased hearts AV block (At large doses or in patients with AV nodal disease) This block can be treated with atropine and β-receptor stimulants. It must be administered with caution in patients with hepatic disease. 50 Class 4 Verapamil
Slide 51-

Therapeutic Use: Used for supraventricular tachycardia (Major indication). Either adenosine or verapamil are preferred It reduces the ventricular rate in atrial fibrillation and flutter. 51 Class 4 Verapamil
Slide 52-

Miscellaneous Anti-arrhythmic Agents (Non-specific) 52 ADENOSINE, MAGNESIUM, POTASSIUM
Slide 53-

Adenosine It is a nucleoside that occurs naturally throughout the body. Its half-life in the blood is less than 10 seconds. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization and suppression of calcium-dependent action potentials. It directly inhibits AV nodal conduction and increases the AV nodal refractory 53
Slide 54-

Adenosine A drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90–95% ) It is usually given in a bolus dose of 6 mg followed, if necessary, by a dose of 12 mg. It is less effective in the presence of adenosine receptor blockers such as theophylline or caffeine, and its effects are potentiated by adenosine uptake inhibitors such as dipyridamole. 54
Slide 55-

Adenosine Toxicity It causes flushing in about 20% of patients and shortness of breath or chest burning (perhaps related to bronchospasm) in over 10%. Induction of high-grade AV block may occur but is very short-lived. 55
Slide 56-

Magnesium Originally used for patients with digitalis-induced arrhythmias who were hypomagnesaemia magnesium infusion has been found to have antiarrhythmic effects in some patients with normal serum magnesium levels. It influences Na+,K+ ATPase, Na+, K+ and Ca+ channels. It is indicated in patients with digitalis-induced arrhythmias if hypomagnesaemia is present. It is also indicated in some patients with torsade de pointes even if serum magnesium is normal. The usual dosage is 1 g (as sulfate) given intravenously over 20 minutes and repeated once if necessary. 56
Slide 57-

Potassium The effects of increasing serum K+ can be summarized as (1) a resting potential depolarizing action and (2) a membrane potential stabilizing action (caused by increased K+ permeability) Hypokalemia results in an increased risk of EAD, DAD and ectopic pacemaker activity, especially in the presence of digitalis. Hyperkalemia depresses ectopic pacemakers and slows conduction. Because both insufficient and excess K+ is potentially arrhythmogenic It is indicated for K+ gradients and pools in the body. 57
Slide 58-

Summary 58
Slide 59-

THANK YOU FOR YOUR ATTENTION