This document provides an overview of the cardiovascular system module presented by Dr. Mohamed Farouk Ahmed. It discusses normal cardiac rhythm, cardiac cell action potentials, definitions and causes of arrhythmias, classification of antiarrhythmic drugs, and specific drugs from each class including their mechanisms of action, uses, and side effects. The goals of antiarrhythmic therapy and classification systems for arrhythmias and drugs are explained. Supraventricular and ventricular arrhythmias as well as individual drug profiles are outlined in detail.

1. Cardiovascular System Module
By
Dr. Mohamed Farouk Ahmed, PhD
Assistant Professor of Clinical Pharmacology - Faculty of Medicine - University of Jeddah

2. LECTURE’S OUTLINES:
• Normal cardiac rhythm
• Action potential of cardiac cells
• Arrhythmia: definition, causes, types
• Anti-arrhythmic Drugs: Class I, II, III, IV,V

3. Normal cardiac rhythm

4. Action potential of cardiac cells

5. Arrhythmia
If the arrhythmia
arises from the
ventricles it is called:
Ventricular
arrhythmia
If the arrhythmia
arises from atria, SA
node, or AV node it is
called:
Supraventricular
arrhythmia
Causes of arrhythmia
Arteriosclerosis
Coronary artery
spasm
Heart block
Myocardial ischemia

6. Supraventricular Arrhythmias
 Sinus Tachycardia: high sinus rate of 100-180 beats/min, occurs
during exercise or other conditions that lead to increased SA
nodal firing rate.
 Atrial Tachycardia: a series of 3 or more consecutive atrial
premature beats occurring at a frequency >100/min.
 Paroxysmal Atrial Tachycardia (PAT): tachycardia which begins
and ends in acute manner.
 Atrial Flutter: sinus rate of 250-350 beats/min.
 Atrial Fibrillation: uncoordinated atrial depolarizations.
AV blocks
 A conduction block within the AV node , occasionally in the
bundle of His, that impairs impulse conduction from the atria to
the ventricles.
Types of Arrhythmia

7.  Ventricular Premature Beats (VPBs): caused by ectopic ventricular
foci; characterized by widened QRS.
 Ventricular Tachycardia (VT): high ventricular rate caused by
abnormal ventricular automaticity or by intraventricular reentry;
can be sustained or non-sustained (paroxysmal); characterized by
widened QRS; rates of 100 to 200 beats/min; life-threatening.
 Ventricular Flutter: ventricular depolarizations > 200/min.
 Ventricular Fibrillation: uncoordinated ventricular depolarizations.
Ventricular Arrhythmias

8. Pharmacologic Rationale & Goals
 The ultimate goal of antiarrhythmic drug therapy:
o Restore normal sinus rhythm and conduction.
o Prevent more serious and possibly lethal arrhythmias from
occurring.
 Antiarrhythmic drugs are used to:
 Decrease conduction velocity.
 Change the duration of the effective refractory period (ERP).
 Suppress abnormal automaticity.

9. Classification of antiarrhythmic drugs
Drugs
Actions
Class
Quinidine,
procainamide,
Moderate block activated Na+ channels
Block inactivated Na+ channels
Ⅰa
Lidocaine,
Phenytoin
Minimal block activated Na+ channels
Block mainly inactivated Na+ channels
Ⅰb
Encainide
Marked block activated Na+ channels
Ⅰc
Propranolol
Beta adrenergic blockers
Ⅱ
Amiodarone
Potassium channel blockers
Ⅲ
Diltiazem
Calcium channel blockers
Ⅳ
Adenosine
Miscellaneous Drugs
V
• They are classified according to Vaughan William into four classes according to their effects on the cardiac action potential

10. Quinidine
Actions:-
 Heart :
- direct myocardial depressant, atropine like effect.
 ANS :-
- It has atropine-like action & alpha-blocking action.
 ECG :-
- Q-T interval : prolonged
- P-R interval : prolonged
- T- wave : prolonged & inverted
Class 1a antiarrhythmic drugs

11. Quinidine (cont.)
Uses:
 Atrial extra systole.
 Paroxysmal supraventricular tachycardia.
 Atrial flutter.
 Recent atrial fibrillation: pretreated with
digitalis. (not used in old A.F.).
 Ventricular arrhythmia.
 Maintenance after DC.

12. Quinidine (cont.)
Contraindications:
►Allergy.
►Complete heart block.
►Old AF > 6 months.
►History of embolism.
►Subacute bacterial endocarditis.
►Pregnancy.
►Myasthenia gravis.
►Digitalis induced arrhythmia.

13. Quinidine (cont.)
Side effects and toxicity:
¤ Idiosyncratic, hypersensitivity reaction.
¤ Cinchonism.
¤ Embolism.
¤ Paradoxical ventricular tachycardia.
¤ Quinidine syncope.
¤ Hypotension.
¤ Cardiotoxicity.
¤ GIT upset.

14. ClassⅠb antiarrhythmic drugs
Members: lidocaine , phenytoin
 Minimal block activated Na+ channels.
 Mainly block inactivated Na+ channels.
 Activate K+ channels ↠ short APD & ERP.

15. Lidocaine
Dynamics:
 Cardiac effects:
- Mainly on ventricular muscle.
- Minimal effect on SAN, AVN, or contractility.
- Minimal effect on conductivity and excitability.
- ⇩ automaticity.
- Shorten A.P duration in purkinje fibers and ventricular muscles.
 No atropine like action.
 Local surface anesthetic.

16. Lidocaine (cont.)
Uses in arrhythmia:
• Ventricular tachyarrhythmias without heart block.
• Drug of choice in ventricular fibrillation.
Side effects and toxicity:
• CVS: least cardiotoxic than class I.
• GIT : Nausea of central origin.
• CNS: dizziness, slurred speech, hearing disturbances.
• Hypersensitivity reactions.

17. Encainide
Actions:
- It prolong conduction in atria , A-V node.
- less (-ve) inotropic action.
- ECG :- prolonged (P- R & QRS) interval.
Uses: Supraventricular & ventricular arrhythmia.
Side effects and toxicity:
(1) Headache , dizzness , tremor.
(2) Nausea , visual disturbances.
ClassⅠc antiarrhythmic drugs

18. Propranolol
Actions:
1- Class II antiarrhythmic drug (block -adrenergic receptors in
small dose).
2- Class I Activity In large dose (blocks Na+ channel).
3- Class IV Activity (block slow Ca++ channels).
Used in:
1- Sympathetic induce arrhythmia.
2- Supraventricular tachycardia.
Class II antiarrhythmic drugs

19. Class Ⅲ antiarrhythmic drugs
Members: Amiodarone, Sotalol, Bretylium.
Actions:
Prolong cardiac action potentials, resulting in an increase in
the effective refractory period. With the exception of ibutilide,
which slows outward Na+ currents during repolarization, the
class III drugs block potassium channels.

20. Amiodarone
(broad spectrum antiarrhythmic)
Dynamics:
 Class III: prolongs APD and ERP of HEART.
 Class I activity (block Na+ channels).
 Weak class II and IV activities.
-adrenergic block.
Uses:
 Recurrent ventricular arrhythmia.
 Supraventricular tachycardia.
 Angina.

21. Amiodarone (cont.)
Side effects and toxicity:
(1) Sinus bradycardia , A-V block.
(2) Corneal deposits which are reversible.
(3) Rash, photosensitivity, myopathy, pulmonary fibrosis.
Drug interactions:
 ⇈ effect of digoxin.
 ⇈ effect of warfarin.
 CCBs, β-blockers ⇈ depressant effect of amiodarone.

22. Diltiazem
Actions:
 This drug depress calcium-dependent action potentials in slow
channel tissues and thus decrease the rate of automaticity, slow
conduction velocity, and prolong refractoriness.
Used in:
• Supraventricular tachycardia.
• It’s the drug of choice in paroxysmal atrial tachycardia (PAT).
• Ventricular arrhythmias without heart block.
Class IV antiarrhythmic drugs

23. Miscellaneous antiarrhythmic Drugs
o Adenosine activates A1-purinergic receptors decreasing the SA
nodal firing and automaticity, reducing conduction velocity,
prolonging effective refractory period, and depressing AV nodal
conductivity.
o It is the drug of choice in the treatment of paroxysmal supra-
ventricular tachycardia.
o It is used only by slow intravenous bolus.
o It only has a low-profile toxicity (lead to bronchospasm) being
extremely short acting for 15 seconds only.
Adenosine

24.  All antiarrhythmic drugs are proarrythmatic, So, we should use
them causiously.
 Class Ic drugs are very effective in preventing atrial arrythmia
with structurally normal heart.
 Amiodarone has efficacy in preventing most of tacchyarrythmia.
 Among antiarrythmic drugs only beta blockers have mortality
benefit and less side effects.

25.  Lippincott illustrated reviews pharmacology 5th Edition.
 Basic and clinical pharmacology 12th edition.
 Rang & Dale's Pharmacology. 9th Edition.
 Goodman and Gilman's the pharmacological basis of therapeutics
13th edition.
 Katzung basic and clinical pharmacology 12th edition.