2. Content
• Physiology of normal cardiac rhythm
• Definition and mechanisms of
arrhythmias
• Classification of drugs to treat
arrhythmias
• Important anti-arrhythmic drugs
(mechanism and pharmacological
characteristics)
• Arrhythmias in clinical practice
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3. Physiology of cardiac rate
and rhythm
• Cardiac myocytes are electrically excitable
• Resting intracellular voltage of myocardial
cells is negative -90mV (SA node is -40mV)
• Resting state - K+ inside and Na+ outside cell
(Na+/K+ pump)
• Action potential occurs when Na+ enters the
cell and sets up a depolarising current
• Stimulation of a single muscle fibre causes
electrical activity to spread across the
myocardium www.indiandentalacademy.com
4. Phases of action potential of
cardiac cells
•
•
•
•
•
•
Phase 0 rapid depolarisation
(inflow of Na+)
Phase 1 partial repolarisation
(inward Na+ current deactivated,
outflow of K+)
Phase 2 plateau (slow inward
calcium current)
Phase 3 repolarisation (calcium
current inactivates, K+ outflow)
Phase 4 pacemaker potential
(Slow Na+ inflow, slowing of K+
outflow) ‘autorhythmicity’
Refractory period (phases 1-3)
Phase 1
IV
Phase 2
0 mV
Phase 0
-80mV
I
Phase 4
II
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III
Phase 3
5. Sinus rhythm
• Sinoatrial node is
cardiac pacemaker
• Normal sinus rhythm
60-100 beats/min
• Depolarisation triggers
depolarisation of atrial
myocardium (‘forest
fire’)
• Conducts more slowly
through AV node
• Conducts rapidly
through His bundles
and Purkinje fibres
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6. Sinus rhythm
• Sinoatrial rate controlled by autonomic
nervous system
• Parasympathetic system predominates (M2
muscarinic receptors)
• Sympathetic system (ß1 receptors)
– Increased heart rate (positive chronotropic
effect)
– Increased automaticity
– Facilitation of conduction of AV node
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7. ECG
• Recording of electrical activity of the heart
• Net sum of depolarisation and repolarisation
potentials of all myocardial cells
• P-QRS-T pattern
• P - atrial depolarisation
• QRS - ventricular depolarisation
• T - ventricular repolarisation
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8. Definition of arrhythmia
• Cardiac arrhythmia is an abnormality of
the heart rhythm
• Bradycardia – heart rate slow (<60
beats/min)
• Tachycardia – heart rate fast (>100
beats/min)
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9. Clinical classification of
arrhythmias
• Heart rate (increased/decreased)
• Heart rhythm (regular/irregular)
• Site of origin (supraventricular /
ventricular)
• Complexes on ECG (narrow/broad)
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10. Mechanisms of arrhythmia
production
• Re-entry (refractory tissue reactivated due to
conduction block, causes abnormal
continuous circuit. eg accessory pathways
linking atria and ventricles in Wolff-ParkinsonWhite syndrome)
• Abnormal pacemaker activity in nonconducting/conducting tissue (eg ischaemia)
• Delayed after-depolarisation (automatic
depolarisation of cardiac cell triggers ectopic
beats, can be caused by drugs eg digoxin)
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11. Vaughan Williams classification
of antiarrhythmic drugs
•
•
•
•
Class I: block sodium channels
– Ia (quinidine, procainamide,
disopyramide) ↑AP
– Ib (lignocaine) ↓AP
– Ic (flecainide) ↔AP
Class II: ß-adrenoceptor
antagonists (atenolol, sotalol)
Class III: prolong action
potential and prolong refractory
period (suppress re-entrant
rhythms) (amiodarone, sotalol)
Class IV: Calcium channel
blockers. Impair impulse
propagation in nodal and
damaged areas (verapamil)
Phase 1
Phase 2
0 mV
Phase 0
-80mV
IV
I
Phase 4
II
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III
Phase 3
12. Management of arrhythmias
• Acute management (clinical
assessment of patient and diagnosis)
• Prophylaxis
• Non-pharmacological
• Pharmacological (some antiarrhythmics
are also proarrhythmic)
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17. Amiodarone
•
•
•
•
•
•
•
•
•
•
Class III - increases refractory period and AP
Major effect acutely is depression of AV node
Acute Rx/prophylaxis
Atrial and ventricular arrhythmias
Oral or IV (central line)
Loading and maintenance doses
T1/2 54 days
Large volume of distribution
Accumulates
Hepatic metabolism- biliary and intestinal
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excretion
19. Adenosine
• Not in Vaughan Williams class
• Purine nucleotide (activates adenosine
receptors)
• Slows AV nodal conduction
• Acute Rx
• Termination of SVT/ diagnosis of VT
• Given IV only (rapid bolus)
• T1/2 < 2 seconds
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21. Verapamil
• Class IV (calcium channel blocker)
• Prolongs conduction and refractoriness in AV
node, slows rate of conduction of SA node
• Acute Rx /prophylaxis
• Used IV/oral
• SUPRAVENTRICULAR NOT VENTRICULAR
ARRHYTHMIAS (cardiovascular collapse)
• Do not use IV verapamil with ß- blocker (heart
block)
• T1/2 6-8 hours
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23. Digoxin
• Not in Vaughan Williams class
• Cardiac glycoside (digitalis, foxglove)
• Acts on Na/K-ATPase of cell membrane
(inhibits Na+/K+ pump, increases intracellular
Na+ and calcium)/ increases vagal activity
• Increase cardiac contraction and slows AV
conduction by increasing AV node refractory
period
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24. Digoxin
• Atrial fibrillation or flutter (controls ventricular
rate)
• Acute Rx/prophylaxis
• Oral/IV
• Loading and maintenance doses
• T1/2 36 hours
• Excreted by kidneys
• Narrow therapeutic index
• Therapeutic drug monitoring
• Reduce dose in elderly/renal impairment
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28. 36 year old woman with asthma
has ‘thumping in chest’
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29. 76 year old man with
breathlessness
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30. 54 year woman collapses 24
hours post MI
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31. 60 year old man with recurrent
blackouts
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32. Summary
• Anti-arrhythmic drugs are classified by their
effect on the cardiac action potential
• Not all drugs fit this classification
• In clinical practice treatment of arrhythmias is
determined by the type of arrhythmia (SVT,
VT) and clinical condition of the patient
• Anti-arrhythmic drugs are efficacious but may
have serious adverse effects
• Not all arrhythmias are treated with drug
therapy alone
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33. Thank you
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Hinweis der Redaktion
Resting intracellular voltage of myocardial cell is –90mV (high intracellular K maintained by Na/K pump)
Sinoatrial node located at junction of superior vena cava and the right atrium.
Narrow originate in atria or AV node
Broad originate from ventricles or from atria or AV node wirh aberrant concuction to the ventricles (LBBB or RBBB)
Re-entry is when tisue that is usually refractory is reactivated. Occurs if there is a ring of tissue that does not conduct normally. Usually the two paths of action potentials meet and die out, but if they do not meet then a circuit is set up.
Abnormal pacemaker activity can occur if myocardial cells are damaged eg ischaemic heart disease also via catecholamine overactivity
Delayed after-depolarisation occurs when in cardiac tissue that usually has to wait for the initiation of an action potential from pacemaker tissue, the cardiac cell automatically depolarises. This leads to a repetitive discharge (triggers ectopic beats -‘R on T phenomenon’) (related to extent of inward Ca current) caused by cardiac glycosides eg digoxin
Re-entry (partial conduction block eg accessory pathways linking atria and ventricles eg Wolff-Parkinson-White syndrome) halted by drugs that prolong the refractory period
