Anti-arrhythmic drugs
INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com

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Content
• Physiology of normal cardiac rhythm
• Definition and mechanisms of
arrhythmias
• Classification of drugs to trea...
Physiology of cardiac rate
and rhythm
• Cardiac myocytes are electrically excitable
• Resting intracellular voltage of myo...
Phases of action potential of
cardiac cells
•
•

•
•
•

•

Phase 0 rapid depolarisation
(inflow of Na+)
Phase 1 partial re...
Sinus rhythm
• Sinoatrial node is
cardiac pacemaker
• Normal sinus rhythm
60-100 beats/min
• Depolarisation triggers
depol...
Sinus rhythm
• Sinoatrial rate controlled by autonomic
nervous system
• Parasympathetic system predominates (M2
muscarinic...
ECG
• Recording of electrical activity of the heart
• Net sum of depolarisation and repolarisation
potentials of all myoca...
Definition of arrhythmia
• Cardiac arrhythmia is an abnormality of
the heart rhythm
• Bradycardia – heart rate slow (<60
b...
Clinical classification of
arrhythmias
• Heart rate (increased/decreased)
• Heart rhythm (regular/irregular)
• Site of ori...
Mechanisms of arrhythmia
production
• Re-entry (refractory tissue reactivated due to
conduction block, causes abnormal
con...
Vaughan Williams classification
of antiarrhythmic drugs
•

•
•

•

Class I: block sodium channels
– Ia (quinidine, procain...
Management of arrhythmias
• Acute management (clinical
assessment of patient and diagnosis)
• Prophylaxis
• Non-pharmacolo...
Non-pharmacological
treatment
• Acute
– Vagal manoeuvres
– DC cardioversion

• Prophylaxis
– Radiofrequency ablation
– Imp...
Pharmacological treatmentLignocaine (Lidocaine)
• Class Ib (blocks Na+ channels, reduces AP
duration)
• Ventricular arrhyt...
Flecainide
• Class Ic (block Na+ channels, no change to
AP)
• Slows conduction in all cardiac cells
• Acute Rx /prophylaxi...
Flecainide
• CAST (Cardiac Arrhythmia Suppression
Trial) 1989 – increased mortality post
MI (VF arrest)
• SE- cardiac fail...
Amiodarone
•
•
•
•
•
•
•
•
•
•

Class III - increases refractory period and AP
Major effect acutely is depression of AV no...
Amiodarone – adverse effects
•
•
•
•
•
•
•
•
•
•
•

Photosensitive rashes
Grey/blue discolouration of skin
Thyroid abnorma...
Adenosine
• Not in Vaughan Williams class
• Purine nucleotide (activates adenosine
receptors)
• Slows AV nodal conduction
...
Adenosine- adverse effects
• Feeling of impending doom!
• Flushing, dyspnoea, chest pain,
transient arrhythmias
• Contrain...
Verapamil
• Class IV (calcium channel blocker)
• Prolongs conduction and refractoriness in AV
node, slows rate of conducti...
Verapamil- adverse effects
•
•
•
•

Heart failure
Constipation
Bradycardia
Nausea

www.indiandentalacademy.com
Digoxin
• Not in Vaughan Williams class
• Cardiac glycoside (digitalis, foxglove)
• Acts on Na/K-ATPase of cell membrane
(...
Digoxin
• Atrial fibrillation or flutter (controls ventricular
rate)
• Acute Rx/prophylaxis
• Oral/IV
• Loading and mainte...
Atrial fibrillation

www.indiandentalacademy.com
Digoxin – adverse effects
• Arrhythmias, heart block, anorexia,
nausea, diarrhoea, xanthopsia,
gynaecomastia, confusion, a...
Clinical cases

www.indiandentalacademy.com
36 year old woman with asthma
has ‘thumping in chest’

www.indiandentalacademy.com
76 year old man with
breathlessness

www.indiandentalacademy.com
54 year woman collapses 24
hours post MI

www.indiandentalacademy.com
60 year old man with recurrent
blackouts

www.indiandentalacademy.com
Summary
• Anti-arrhythmic drugs are classified by their
effect on the cardiac action potential
• Not all drugs fit this cl...
Thank you
For more details please visit
www.indiandentalacademy.com

www.indiandentalacademy.com
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Anti arrhythmicdrugs

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  • 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
  • Multiple micro re-entry circuits within (often diseased) atrial tissue. Chaotic ventricular rhythm
  • Digoxin-specific binding (Fab) fragment, antibody to digoxin, neutralises digoxin in the plasma
  • Anti arrhythmicdrugs

    1. 1. Anti-arrhythmic drugs INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
    2. 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 www.indiandentalacademy.com
    3. 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. 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 www.indiandentalacademy.com III Phase 3
    5. 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 www.indiandentalacademy.com
    6. 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 www.indiandentalacademy.com
    7. 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 www.indiandentalacademy.com
    8. 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) www.indiandentalacademy.com
    9. 9. Clinical classification of arrhythmias • Heart rate (increased/decreased) • Heart rhythm (regular/irregular) • Site of origin (supraventricular / ventricular) • Complexes on ECG (narrow/broad) www.indiandentalacademy.com
    10. 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) www.indiandentalacademy.com
    11. 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 www.indiandentalacademy.com III Phase 3
    12. 12. Management of arrhythmias • Acute management (clinical assessment of patient and diagnosis) • Prophylaxis • Non-pharmacological • Pharmacological (some antiarrhythmics are also proarrhythmic) www.indiandentalacademy.com
    13. 13. Non-pharmacological treatment • Acute – Vagal manoeuvres – DC cardioversion • Prophylaxis – Radiofrequency ablation – Implantable defibrillator • Pacing (external, temporary, permanent) www.indiandentalacademy.com
    14. 14. Pharmacological treatmentLignocaine (Lidocaine) • Class Ib (blocks Na+ channels, reduces AP duration) • Ventricular arrhythmias (acute Rx) • IV infusion only (2 hour half life, high first pass metabolism) • Hepatic metabolism (inhibited by cimetidine, propranolol) • SE mainly CNS - drowsiness, disorientation, convulsions, hypotension www.indiandentalacademy.com
    15. 15. Flecainide • Class Ic (block Na+ channels, no change to AP) • Slows conduction in all cardiac cells • Acute Rx /prophylaxis • Supraventricular tachycardias • Paroxysmal atrial fibrillation • Ventricular tachycardias • Oral/IV • Long acting (T1/2 14 hours) • Hepatic metabolism, urinary elimination www.indiandentalacademy.com
    16. 16. Flecainide • CAST (Cardiac Arrhythmia Suppression Trial) 1989 – increased mortality post MI (VF arrest) • SE- cardiac failure, ventricular arrhythmias, blurred vision, abdominal discomfort, nausea, paraesthesia, dizziness, tremor, metallic taste www.indiandentalacademy.com
    17. 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 www.indiandentalacademy.com excretion
    18. 18. Amiodarone – adverse effects • • • • • • • • • • • Photosensitive rashes Grey/blue discolouration of skin Thyroid abnormalities 2% Pulmonary fibrosis Corneal deposits CNS/GI disturbance Pro-arrhythmic effects (torsades de pointes) Heart block Nightmares 25% Abnormal LFT 20% Interacts with digoxin, warfarin (reduces clearance) www.indiandentalacademy.com
    19. 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 www.indiandentalacademy.com
    20. 20. Adenosine- adverse effects • Feeling of impending doom! • Flushing, dyspnoea, chest pain, transient arrhythmias • Contraindicated in asthma, heart block www.indiandentalacademy.com
    21. 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 www.indiandentalacademy.com
    22. 22. Verapamil- adverse effects • • • • Heart failure Constipation Bradycardia Nausea www.indiandentalacademy.com
    23. 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 www.indiandentalacademy.com
    24. 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 www.indiandentalacademy.com
    25. 25. Atrial fibrillation www.indiandentalacademy.com
    26. 26. Digoxin – adverse effects • Arrhythmias, heart block, anorexia, nausea, diarrhoea, xanthopsia, gynaecomastia, confusion, agitation • AE potentiated by hypokalaemia and hypomagnesaemia • Overdose –Digibind (digoxin binding antibody fragments), phenytoin for ventricular arrhythmias, pacing, atropine www.indiandentalacademy.com
    27. 27. Clinical cases www.indiandentalacademy.com
    28. 28. 36 year old woman with asthma has ‘thumping in chest’ www.indiandentalacademy.com
    29. 29. 76 year old man with breathlessness www.indiandentalacademy.com
    30. 30. 54 year woman collapses 24 hours post MI www.indiandentalacademy.com
    31. 31. 60 year old man with recurrent blackouts www.indiandentalacademy.com
    32. 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 www.indiandentalacademy.com
    33. 33. Thank you For more details please visit www.indiandentalacademy.com www.indiandentalacademy.com

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