arrhythmia - pathophysiology and treatment (pharmacotherapy)

Arrhythmia

ABDULLAH M.Pharm

(Pharmacy Practice) 1st SemFaculty of Pharmacy Jamia Hamdard

DEFINATION

Cardiac Arrhythmia is a condition in which the heart beats with an irregular or abnormal rhythm.

ABNORMAL RHYTHM

CAN BE OF TWO EXTREME FORMS

1. Bradycardia - Cardiac beats below 60 beats per minute .

2. Tachycardia – Cardiac beat above 100 beats per minute.

ETIOLOGY Coronary artery disease. Electrolyte imbalances in your blood

(such as sodium or potassium). Changes in your heart muscle. Injury from a heart attack.

Healing process after heart surgery. Irregular heart rhythms can also

occur in "normal, healthy" hearts. Ischemic Heart Disease Drugs related Others

Arrhythmia Presentation (SYMPTOMS)

Palpitation. Dizziness. Chest Pain. Dyspnea.

Fainting. Sudden cardiac death Swelling Shortness of Breath Exercise Intolerance

Mechanism of Arrhythmias Bradycardia1. SA node : Slowed / AbsentCauses• Decreased Sympathetic Signals• Increased Parasympathetic Signals• SA node Damage

2. Blockage of Conduction from SA node

AV node BlockageCauses• Ischemia • Fibrosis• Viral Infection

RESULTS in HEART ATTACK

LEFT BUNDLE BRUNCH BLOCK (LBBB)• No Impulse conduction through

Bundle Brunch• Action Potential transferred through

Right Ventricle to Left Ventricle

RESULTS in Wide QRS complex

Tachycardia1. Increased Pacemaker Activity (SA

Node)- Sinus Tachycardia Causes• Increased Sympathetic Signals• Decreased Parasympathetic Signals• SA node Dysfunction Example : Sick Sinus Syndrome

2.Re-entry Tachycardias Atrial Fibrillation

• loss of the normal organised propagation of electrical activity

• atria fibrillate, they no longer contract in a mechanically useful way

• a degree of stasis to blood flow and predisposing to clot (thrombus) formation within the chambers

Ventricular Fibrillation

•  Uncoordinated contraction of the Cardiac Muscle

• Quiver rather than contract properly

• Commonly identified arrhythmia in Cardiac Arrest patients

• As a consequence, Sudden Cardiac Death

Wolf Parkinson White Syndrome (WPW)

• WPW is caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles. 

• Electrical Signals through abnormal pathway  stimulate the ventricles to contract prematurely

• A unique type of supraventricular tachycardia referred to as an ”atrioventricular reciprocating tachycardia”.

Atrioventricular nodal re-entrant tachycardia

• Most common regular supraventricular tachycardia

•  Re-entry circuit forms within or just next to the atrioventricular node.

• Same as WPW except reentry is in or around AV node

3. Delayed Repolarization

Causes

• Ischemia • Drugs related (Potassium Blockers)• Electrolyte Imbalance

Effects

Long QT intervalR on T PhenomenonPremature Ventricular BeatVentricular Fibrillation

PHARMACOTHERAPY

Class Action Drugs

I A. Na Channel blockers Quinidine, procainamide

I B. Na Channel blockers Lidocaine

I C. Na Channel blockers Flecainide

II Beta-adrenergic blockers Propranolol, esmolol

III Prolong repolarization Amiodarone, Sotolol

Dofetalide, ibutilide

IV Calcium channel blockers Verapamil, diltiazem

Class I: Sodium Channel Blockers (Local Anesthetics)

Class 1A agents:• Procainamide• quinidine • disopyramide   Effects on cardiac activity• conduction

• refractory period ( (K+) and Na inactivation)

• automaticity • increase threshold (Na+)

Quinidine has anticholinergic (atropine like action) to speed AV conduction used with digitalis, β blocker or Ca channel blocker

• Quinidine is also an alpha receptor antagonist

Uses

Quinidine : maintain sinus rhythms in atrial fibrillation and flutter and to prevent recurrent tachycardia and fibrillation  

Procainamide: acute treatment of supraventricular and ventricular arrhythmias  

Side effects• Hypotension, reduced cardiac

output• Proarrhythmia (generation of a new

arrhythmia)• Dizziness, confusion, insomnia,

seizure (highdose)•  Gastrointestinal effects (common)

Class 1B agents: • Lidocaine • mexiletine • Henytoin

AdministrationLidocaine: iv only

      Tocainide and mexiletine: oral      

Effects on cardiac activity

• APD slightly decreased (normal tissue)

• increase threshold (Na+)

Uses• Acute : Ventricular tachycardia

and fibrillation (esp. during ischemia)

• Not used in atrial arrhythmias or AV junctional arrhythmias

      Side effects  CNS effects: dizziness, drowsiness

Class 1C agents:• Flecainide • propafenone              Effects on cardiac activity• automoticity ( threshold)

• APD (K+) and refractory period, especially in rapidly depolarizing atrial tissue.

Uses• Wide spectrum• Used for supraventricular

arrhythmias (fibrillation and flutter)

• Premature ventricular contractions (caused problems)

• Wolff-Parkinson-White syndrome

Side effects• Proarrhythmia and sudden

death especially with chronic use • increase ventricular response to

supraventricular arrhythmias• CNS and gastrointestinal effects

like other local anesthetics

CLASS II :BETA-ADRENOCEPTOR-BLOCKING DRUGS

Class II agents:• propranolol • acebutolol • esmolol

Administration Propranolol: oral, iv Esmolol: iv only (very short acting T½, 9 min)

Cardiac effects

• APD and refractory period in AV node to slow AV conduction velocity

Uses• Treating sinus and

catecholamine dependent tachyarrhythmias

• converting reentrant arrhythmias in AV

• protecting the ventricles from high atrial rates (slow AV

conduction)

Side effects

• bronchospasm•  hypotension• don’t use in partial AV block or

ventricular failure

CLASS III - Drugs That Prolong Effective Refractory Period By Prolonging the Action Potential

Class III agents:• amiodarone• sotalol • Ibutilide• dofetilide

Amiodarone

AdministrationOral or iv (T 1/2 about 3 months)

Cardiac effects

• increase refractory period and APD (K+)

•   conduction (Na+)•    (β block and Ca++ block)•   speed of AV conduction

Uses• Very wide spectrum: effective for most

arrhythmias

Side effects: Many serious that increase with time• Pulmonary fibrosis• Hepatic injury• Increase LDL cholesterol• Thyroid disease• Photosensitivity

Sotolol

Administration-oral

Cardiac effects• APD and refractory period in

atrial and ventricular tissue

Uses• Wide spectrum: supraventricular and

ventricular tachycardia              Side effects• Proarrhythmia, • Fatigue• insomnia

Ibutilide

Administration- iv infusion

Cardiac effects

• Result in APD

Uses• conversion of atrial fibrillation and

flutter         

Side effects• Torsades de pointes

Dofetilide

Administration- oral

Cardiac effects• APD and refractory period

Uses• maintain sinus rhythm in atrial

fibrillation               Side effects• restricted use• Torsades de pointes

CLASS IV- CALCIUM CHANNEL-BLOCKING DRUGS

Class IV agents: • verapamil • diltiazem

Administration verapamil: oral or i.v.diltiazem: oral

Cardiac effects

• slow conduction through AV (Ca++)• refractory period in AV node

Uses• control ventricles during

supraventricular tachycardia• convert supraventricular

tachycardia (re-entry around AV)

Side effects• Caution when hypotension,

decreased CO or sick sinus.Some gastrointestinal problems

ADDITIONAL ANTIARRYHTHMIC AGENTS

Adenosine

Adminsitration                     rapid i.v. bolus, very short T1/2 (seconds)

Cardiac effects• Slows AV conduction

Uses

• convert re-entrant supraventricular arrhythmias

• hypotension during surgery, diagnosis of CAD

Digioxin (cardiac glycosides)

Mechanism• Enhances vagal activity(10th

Cranial Nerve)• ( K+ currents, Ca++ currents,

refractory period• slows AV conduction and slows

HR

Uses

• Treatment of atrial fibrillation and flutter

AtropineMechanism• selective muscarinic antagonist Cardiac effects• block vagal activity to speed AV conduction and

increase HR

Uses• treat vagal bradycardia

Magnesium• treatment for tachycardia resulting from long QT

References

Basic and Clinical Pharmacology Katzung 13 Edition Pharmacotherapy Handbook - Ninth Edition by Barbara

G. Wells (Author), Joseph T. Dipiro (Author), Terry L. Schwinghammer (Author)

www.youtube.com - Pathophysiology of Cardiac Arrhythmias by Andrew Wolf

Wikipedia