arrhythmia - pathophysiology and treatment (pharmacotherapy)
TRANSCRIPT
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Arrhythmia
ABDULLAH M.Pharm
(Pharmacy Practice) 1st SemFaculty of Pharmacy Jamia Hamdard
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DEFINATION
Cardiac Arrhythmia is a condition in which the heart beats with an irregular or abnormal rhythm.
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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.
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ETIOLOGY Coronary artery disease. Electrolyte imbalances in your blood
(such as sodium or potassium). Changes in your heart muscle. Injury from a heart attack.
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Healing process after heart surgery. Irregular heart rhythms can also
occur in "normal, healthy" hearts. Ischemic Heart Disease Drugs related Others
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Arrhythmia Presentation (SYMPTOMS)
Palpitation. Dizziness. Chest Pain. Dyspnea.
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Fainting. Sudden cardiac death Swelling Shortness of Breath Exercise Intolerance
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Mechanism of Arrhythmias Bradycardia1. SA node : Slowed / AbsentCauses• Decreased Sympathetic Signals• Increased Parasympathetic Signals• SA node Damage
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2. Blockage of Conduction from SA node
AV node BlockageCauses• Ischemia • Fibrosis• Viral Infection
RESULTS in HEART ATTACK
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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
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Tachycardia1. Increased Pacemaker Activity (SA
Node)- Sinus Tachycardia Causes• Increased Sympathetic Signals• Decreased Parasympathetic Signals• SA node Dysfunction Example : Sick Sinus Syndrome
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2.Re-entry Tachycardias Atrial Fibrillation
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• 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
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Ventricular Fibrillation
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• Uncoordinated contraction of the Cardiac Muscle
• Quiver rather than contract properly
• Commonly identified arrhythmia in Cardiac Arrest patients
• As a consequence, Sudden Cardiac Death
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Wolf Parkinson White Syndrome (WPW)
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• 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”.
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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
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3. Delayed Repolarization
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Causes
• Ischemia • Drugs related (Potassium Blockers)• Electrolyte Imbalance
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Effects
Long QT intervalR on T PhenomenonPremature Ventricular BeatVentricular Fibrillation
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PHARMACOTHERAPY
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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
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Class I: Sodium Channel Blockers (Local Anesthetics)
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Class 1A agents:• Procainamide• quinidine • disopyramide Effects on cardiac activity• conduction
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• 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
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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
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Side effects• Hypotension, reduced cardiac
output• Proarrhythmia (generation of a new
arrhythmia)• Dizziness, confusion, insomnia,
seizure (highdose)• Gastrointestinal effects (common)
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Class 1B agents: • Lidocaine • mexiletine • Henytoin
AdministrationLidocaine: iv only
Tocainide and mexiletine: oral
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Effects on cardiac activity
• APD slightly decreased (normal tissue)
• increase threshold (Na+)
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Uses• Acute : Ventricular tachycardia
and fibrillation (esp. during ischemia)
• Not used in atrial arrhythmias or AV junctional arrhythmias
Side effects CNS effects: dizziness, drowsiness
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Class 1C agents:• Flecainide • propafenone Effects on cardiac activity• automoticity ( threshold)
• APD (K+) and refractory period, especially in rapidly depolarizing atrial tissue.
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Uses• Wide spectrum• Used for supraventricular
arrhythmias (fibrillation and flutter)
• Premature ventricular contractions (caused problems)
• Wolff-Parkinson-White syndrome
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Side effects• Proarrhythmia and sudden
death especially with chronic use • increase ventricular response to
supraventricular arrhythmias• CNS and gastrointestinal effects
like other local anesthetics
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CLASS II :BETA-ADRENOCEPTOR-BLOCKING DRUGS
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Class II agents:• propranolol • acebutolol • esmolol
Administration Propranolol: oral, iv Esmolol: iv only (very short acting T½, 9 min)
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Cardiac effects
• APD and refractory period in AV node to slow AV conduction velocity
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Uses• Treating sinus and
catecholamine dependent tachyarrhythmias
• converting reentrant arrhythmias in AV
• protecting the ventricles from high atrial rates (slow AV
conduction)
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Side effects
• bronchospasm• hypotension• don’t use in partial AV block or
ventricular failure
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CLASS III - Drugs That Prolong Effective Refractory Period By Prolonging the Action Potential
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Class III agents:• amiodarone• sotalol • Ibutilide• dofetilide
Amiodarone
AdministrationOral or iv (T 1/2 about 3 months)
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Cardiac effects
• increase refractory period and APD (K+)
• conduction (Na+)• (β block and Ca++ block)• speed of AV conduction
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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
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Sotolol
Administration-oral
Cardiac effects• APD and refractory period in
atrial and ventricular tissue
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Uses• Wide spectrum: supraventricular and
ventricular tachycardia Side effects• Proarrhythmia, • Fatigue• insomnia
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Ibutilide
Administration- iv infusion
Cardiac effects
• Result in APD
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Uses• conversion of atrial fibrillation and
flutter
Side effects• Torsades de pointes
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Dofetilide
Administration- oral
Cardiac effects• APD and refractory period
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Uses• maintain sinus rhythm in atrial
fibrillation Side effects• restricted use• Torsades de pointes
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CLASS IV- CALCIUM CHANNEL-BLOCKING DRUGS
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Class IV agents: • verapamil • diltiazem
Administration verapamil: oral or i.v.diltiazem: oral
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Cardiac effects
• slow conduction through AV (Ca++)• refractory period in AV node
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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
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ADDITIONAL ANTIARRYHTHMIC AGENTS
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Adenosine
Adminsitration rapid i.v. bolus, very short T1/2 (seconds)
Cardiac effects• Slows AV conduction
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Uses
• convert re-entrant supraventricular arrhythmias
• hypotension during surgery, diagnosis of CAD
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Digioxin (cardiac glycosides)
Mechanism• Enhances vagal activity(10th
Cranial Nerve)• ( K+ currents, Ca++ currents,
refractory period• slows AV conduction and slows
HR
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Uses
• Treatment of atrial fibrillation and flutter
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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
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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