Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Anti-arrhythmic drugs www.freelivedoctor.com
Content <ul><li>Physiology of normal cardiac rhythm </li></ul><ul><li>Definition and mechanisms of arrhythmias </li></ul><...
  Physiology of cardiac rate and rhythm <ul><li>Cardiac myocytes are  electrically excitable </li></ul><ul><li>Resting int...
Phases of action potential of cardiac cells <ul><li>Phase 0  rapid depolarisation (inflow of Na +) </li></ul><ul><li>Phase...
Sinus rhythm <ul><li>Sinoatrial node is cardiac pacemaker </li></ul><ul><li>Normal sinus rhythm 60-100 beats/min </li></ul...
Sinus rhythm <ul><li>Sinoatrial rate controlled by autonomic nervous system </li></ul><ul><li>Parasympathetic system predo...
ECG <ul><li>Recording of electrical activity of the heart </li></ul><ul><li>Net sum of depolarisation and repolarisation p...
Definition of arrhythmia <ul><li>Cardiac arrhythmia is an abnormality of the heart rhythm </li></ul><ul><li>Bradycardia  –...
Clinical classification of arrhythmias <ul><li>Heart rate (increased/decreased) </li></ul><ul><li>Heart rhythm (regular/ir...
Mechanisms of arrhythmia production <ul><li>Re-entry  (refractory tissue reactivated due to conduction block, causes abnor...
Vaughan Williams  classification of antiarrhythmic drugs <ul><li>Class I :  block sodium channels  </li></ul><ul><ul><li>I...
Management of arrhythmias <ul><li>Acute management (clinical assessment of patient and diagnosis) </li></ul><ul><li>Prophy...
Non-pharmacological treatment <ul><li>Acute </li></ul><ul><ul><li>Vagal manoeuvres </li></ul></ul><ul><ul><li>DC cardiover...
Pharmacological treatment-Lignocaine (Lidocaine)  <ul><li>Class Ib  (blocks Na +  channels, reduces AP duration) </li></ul...
Flecainide <ul><li>Class Ic  (block Na +  channels, no change to AP) </li></ul><ul><li>Slows conduction in all cardiac cel...
Flecainide <ul><li>CAST (Cardiac Arrhythmia Suppression Trial) 1989 – increased mortality post MI (VF arrest) </li></ul><u...
Amiodarone <ul><li>Class III  - increases refractory period and AP </li></ul><ul><li>Major effect acutely is depression of...
Amiodarone – adverse effects <ul><li>Photosensitive rashes </li></ul><ul><li>Grey/blue discolouration of skin </li></ul><u...
Adenosine <ul><li>Not in Vaughan Williams class </li></ul><ul><li>Purine nucleotide (activates adenosine receptors) </li><...
Adenosine- adverse effects <ul><li>Feeling of impending doom! </li></ul><ul><li>Flushing, dyspnoea, chest pain, transient ...
Verapamil <ul><li>Class IV  (calcium channel blocker) </li></ul><ul><li>Prolongs conduction and refractoriness in AV node,...
Verapamil- adverse effects <ul><li>Heart failure </li></ul><ul><li>Constipation </li></ul><ul><li>Bradycardia </li></ul><u...
Digoxin <ul><li>Not in Vaughan Williams class  </li></ul><ul><li>Cardiac glycoside (digitalis, foxglove) </li></ul><ul><li...
Digoxin <ul><li>Atrial fibrillation or flutter (controls ventricular rate) </li></ul><ul><li>Acute Rx/prophylaxis </li></u...
Atrial fibrillation www.freelivedoctor.com                                                                                ...
Digoxin – adverse effects <ul><li>Arrhythmias, heart block, anorexia, nausea, diarrhoea, xanthopsia, gynaecomastia, confus...
Clinical cases www.freelivedoctor.com
36 year old woman with asthma has ‘thumping in chest’ www.freelivedoctor.com
76 year old man with breathlessness www.freelivedoctor.com
54 year woman collapses 24 hours post MI www.freelivedoctor.com
60 year old man with recurrent blackouts www.freelivedoctor.com
Summary <ul><li>Anti-arrhythmic drugs are classified by their effect on the cardiac action potential </li></ul><ul><li>Not...
Upcoming SlideShare
Loading in …5
×

Antiarrhythmicdrugs

4,247 views

Published on

  • Be the first to comment

Antiarrhythmicdrugs

  1. 1. Anti-arrhythmic drugs www.freelivedoctor.com
  2. 2. Content <ul><li>Physiology of normal cardiac rhythm </li></ul><ul><li>Definition and mechanisms of arrhythmias </li></ul><ul><li>Classification of drugs to treat arrhythmias </li></ul><ul><li>Important anti-arrhythmic drugs (mechanism and pharmacological characteristics) </li></ul><ul><li>Arrhythmias in clinical practice </li></ul>www.freelivedoctor.com
  3. 3. Physiology of cardiac rate and rhythm <ul><li>Cardiac myocytes are electrically excitable </li></ul><ul><li>Resting intracellular voltage of myocardial cells is negative -90mV (SA node is -40mV) </li></ul><ul><li>Resting state - K + inside and Na + outside cell (Na + /K + pump) </li></ul><ul><li>Action potential occurs when Na + enters the cell and sets up a depolarising current </li></ul><ul><li>Stimulation of a single muscle fibre causes electrical activity to spread across the myocardium </li></ul>www.freelivedoctor.com
  4. 4. Phases of action potential of cardiac cells <ul><li>Phase 0 rapid depolarisation (inflow of Na +) </li></ul><ul><li>Phase 1 partial repolarisation (inward Na + current deactivated, outflow of K + ) </li></ul><ul><li>Phase 2 plateau (slow inward calcium current) </li></ul><ul><li>Phase 3 repolarisation (calcium current inactivates, K + outflow) </li></ul><ul><li>Phase 4 pacemaker potential (Slow Na + inflow, slowing of K + outflow) ‘autorhythmicity’ </li></ul><ul><li>Refractory period (phases 1-3) </li></ul>www.freelivedoctor.com Phase 4 Phase 0 Phase 1 Phase 2 Phase 3 0 mV -80mV II I III IV
  5. 5. Sinus rhythm <ul><li>Sinoatrial node is cardiac pacemaker </li></ul><ul><li>Normal sinus rhythm 60-100 beats/min </li></ul><ul><li>Depolarisation triggers depolarisation of atrial myocardium (‘forest fire’) </li></ul><ul><li>Conducts more slowly through AV node </li></ul><ul><li>Conducts rapidly through His bundles and Purkinje fibres </li></ul>www.freelivedoctor.com
  6. 6. Sinus rhythm <ul><li>Sinoatrial rate controlled by autonomic nervous system </li></ul><ul><li>Parasympathetic system predominates (M2 muscarinic receptors) </li></ul><ul><li>Sympathetic system (ß1 receptors) </li></ul><ul><ul><li>Increased heart rate (positive chronotropic effect) </li></ul></ul><ul><ul><li>Increased automaticity </li></ul></ul><ul><ul><li>Facilitation of conduction of AV node </li></ul></ul>www.freelivedoctor.com
  7. 7. ECG <ul><li>Recording of electrical activity of the heart </li></ul><ul><li>Net sum of depolarisation and repolarisation potentials of all myocardial cells </li></ul><ul><li>P-QRS-T pattern </li></ul><ul><li>P - atrial depolarisation </li></ul><ul><li>QRS - ventricular depolarisation </li></ul><ul><li>T - ventricular repolarisation </li></ul>www.freelivedoctor.com
  8. 8. Definition of arrhythmia <ul><li>Cardiac arrhythmia is an abnormality of the heart rhythm </li></ul><ul><li>Bradycardia – heart rate slow (<60 beats/min) </li></ul><ul><li>Tachycardia – heart rate fast (>100 beats/min) </li></ul>www.freelivedoctor.com
  9. 9. Clinical classification of arrhythmias <ul><li>Heart rate (increased/decreased) </li></ul><ul><li>Heart rhythm (regular/irregular) </li></ul><ul><li>Site of origin (supraventricular / ventricular) </li></ul><ul><li>Complexes on ECG (narrow/broad) </li></ul>www.freelivedoctor.com
  10. 10. Mechanisms of arrhythmia production <ul><li>Re-entry (refractory tissue reactivated due to conduction block, causes abnormal continuous circuit. eg accessory pathways linking atria and ventricles in Wolff-Parkinson-White syndrome) </li></ul><ul><li>Abnormal pacemaker activity in non-conducting/conducting tissue (eg ischaemia) </li></ul><ul><li>Delayed after-depolarisation (automatic depolarisation of cardiac cell triggers ectopic beats, can be caused by drugs eg digoxin) </li></ul>www.freelivedoctor.com
  11. 11. Vaughan Williams classification of antiarrhythmic drugs <ul><li>Class I : block sodium channels </li></ul><ul><ul><li>Ia (quinidine, procainamide, disopyramide)  AP </li></ul></ul><ul><ul><li>Ib (lignocaine)  AP </li></ul></ul><ul><ul><li>Ic (flecainide)  AP </li></ul></ul><ul><li>Class II : ß-adrenoceptor antagonists (atenolol, sotalol) </li></ul><ul><li>Class III : prolong action potential and prolong refractory period (suppress re-entrant rhythms) (amiodarone, sotalol) </li></ul><ul><li>Class IV : Calcium channel blockers. Impair impulse propagation in nodal and damaged areas (verapamil) </li></ul>Phase 4 Phase 0 Phase 1 Phase 2 Phase 3 0 mV -80mV II I III IV www.freelivedoctor.com
  12. 12. Management of arrhythmias <ul><li>Acute management (clinical assessment of patient and diagnosis) </li></ul><ul><li>Prophylaxis </li></ul><ul><li>Non-pharmacological </li></ul><ul><li>Pharmacological (some antiarrhythmics are also proarrhythmic) </li></ul>www.freelivedoctor.com
  13. 13. Non-pharmacological treatment <ul><li>Acute </li></ul><ul><ul><li>Vagal manoeuvres </li></ul></ul><ul><ul><li>DC cardioversion </li></ul></ul><ul><li>Prophylaxis </li></ul><ul><ul><li>Radiofrequency ablation </li></ul></ul><ul><ul><li>Implantable defibrillator </li></ul></ul><ul><li>Pacing (external, temporary, permanent) </li></ul>www.freelivedoctor.com
  14. 14. Pharmacological treatment-Lignocaine (Lidocaine) <ul><li>Class Ib (blocks Na + channels, reduces AP duration) </li></ul><ul><li>Ventricular arrhythmias (acute Rx) </li></ul><ul><li>IV infusion only (2 hour half life, high first pass metabolism) </li></ul><ul><li>Hepatic metabolism (inhibited by cimetidine, propranolol) </li></ul><ul><li>SE mainly CNS - drowsiness, disorientation, convulsions, hypotension </li></ul>www.freelivedoctor.com
  15. 15. Flecainide <ul><li>Class Ic (block Na + channels, no change to AP) </li></ul><ul><li>Slows conduction in all cardiac cells </li></ul><ul><li>Acute Rx /prophylaxis </li></ul><ul><li>Supraventricular tachycardias </li></ul><ul><li>Paroxysmal atrial fibrillation </li></ul><ul><li>Ventricular tachycardias </li></ul><ul><li>Oral/IV </li></ul><ul><li>Long acting (T1/2 14 hours) </li></ul><ul><li>Hepatic metabolism, urinary elimination </li></ul>www.freelivedoctor.com
  16. 16. Flecainide <ul><li>CAST (Cardiac Arrhythmia Suppression Trial) 1989 – increased mortality post MI (VF arrest) </li></ul><ul><li>SE- cardiac failure, ventricular arrhythmias, blurred vision, abdominal discomfort, nausea, paraesthesia, dizziness, tremor, metallic taste </li></ul>www.freelivedoctor.com
  17. 17. Amiodarone <ul><li>Class III - increases refractory period and AP </li></ul><ul><li>Major effect acutely is depression of AV node </li></ul><ul><li>Acute Rx/prophylaxis </li></ul><ul><li>Atrial and ventricular arrhythmias </li></ul><ul><li>Oral or IV (central line) </li></ul><ul><li>Loading and maintenance doses </li></ul><ul><li>T1/2 54 days </li></ul><ul><li>Large volume of distribution </li></ul><ul><li>Accumulates </li></ul><ul><li>Hepatic metabolism- biliary and intestinal excretion </li></ul>www.freelivedoctor.com
  18. 18. Amiodarone – adverse effects <ul><li>Photosensitive rashes </li></ul><ul><li>Grey/blue discolouration of skin </li></ul><ul><li>Thyroid abnormalities 2% </li></ul><ul><li>Pulmonary fibrosis </li></ul><ul><li>Corneal deposits </li></ul><ul><li>CNS/GI disturbance </li></ul><ul><li>Pro-arrhythmic effects (torsades de pointes) </li></ul><ul><li>Heart block </li></ul><ul><li>Nightmares 25% </li></ul><ul><li>Abnormal LFT 20% </li></ul><ul><li>Interacts with digoxin, warfarin (reduces clearance) </li></ul>www.freelivedoctor.com
  19. 19. Adenosine <ul><li>Not in Vaughan Williams class </li></ul><ul><li>Purine nucleotide (activates adenosine receptors) </li></ul><ul><li>Slows AV nodal conduction </li></ul><ul><li>Acute Rx </li></ul><ul><li>Termination of SVT/ diagnosis of VT </li></ul><ul><li>Given IV only (rapid bolus) </li></ul><ul><li>T1/2 < 2 seconds </li></ul>www.freelivedoctor.com
  20. 20. Adenosine- adverse effects <ul><li>Feeling of impending doom! </li></ul><ul><li>Flushing, dyspnoea, chest pain, transient arrhythmias </li></ul><ul><li>Contraindicated in asthma, heart block </li></ul>www.freelivedoctor.com
  21. 21. Verapamil <ul><li>Class IV (calcium channel blocker) </li></ul><ul><li>Prolongs conduction and refractoriness in AV node, slows rate of conduction of SA node </li></ul><ul><li>Acute Rx /prophylaxis </li></ul><ul><li>Used IV/oral </li></ul><ul><li>SUPRAVENTRICULAR NOT VENTRICULAR ARRHYTHMIAS (cardiovascular collapse) </li></ul><ul><li>Do not use IV verapamil with ß- blocker (heart block) </li></ul><ul><li>T1/2 6-8 hours </li></ul>www.freelivedoctor.com
  22. 22. Verapamil- adverse effects <ul><li>Heart failure </li></ul><ul><li>Constipation </li></ul><ul><li>Bradycardia </li></ul><ul><li>Nausea </li></ul>www.freelivedoctor.com
  23. 23. Digoxin <ul><li>Not in Vaughan Williams class </li></ul><ul><li>Cardiac glycoside (digitalis, foxglove) </li></ul><ul><li>Acts on Na/K-ATPase of cell membrane (inhibits Na + /K + pump, increases intracellular Na + and calcium)/ increases vagal activity </li></ul><ul><li>Increase cardiac contraction and slows AV conduction by increasing AV node refractory period </li></ul>www.freelivedoctor.com
  24. 24. Digoxin <ul><li>Atrial fibrillation or flutter (controls ventricular rate) </li></ul><ul><li>Acute Rx/prophylaxis </li></ul><ul><li>Oral/IV </li></ul><ul><li>Loading and maintenance doses </li></ul><ul><li>T1/2 36 hours </li></ul><ul><li>Excreted by kidneys </li></ul><ul><li>Narrow therapeutic index </li></ul><ul><li>Therapeutic drug monitoring </li></ul><ul><li>Reduce dose in elderly/renal impairment </li></ul>www.freelivedoctor.com
  25. 25. Atrial fibrillation www.freelivedoctor.com                                                                                                                                                      
  26. 26. Digoxin – adverse effects <ul><li>Arrhythmias, heart block, anorexia, nausea, diarrhoea, xanthopsia, gynaecomastia, confusion, agitation </li></ul><ul><li>AE potentiated by hypokalaemia and hypomagnesaemia </li></ul><ul><li>Overdose –Digibind (digoxin binding antibody fragments), phenytoin for ventricular arrhythmias, pacing, atropine </li></ul>www.freelivedoctor.com
  27. 27. Clinical cases www.freelivedoctor.com
  28. 28. 36 year old woman with asthma has ‘thumping in chest’ www.freelivedoctor.com
  29. 29. 76 year old man with breathlessness www.freelivedoctor.com
  30. 30. 54 year woman collapses 24 hours post MI www.freelivedoctor.com
  31. 31. 60 year old man with recurrent blackouts www.freelivedoctor.com
  32. 32. Summary <ul><li>Anti-arrhythmic drugs are classified by their effect on the cardiac action potential </li></ul><ul><li>Not all drugs fit this classification </li></ul><ul><li>In clinical practice treatment of arrhythmias is determined by the type of arrhythmia (SVT, VT) and clinical condition of the patient </li></ul><ul><li>Anti-arrhythmic drugs are efficacious but may have serious adverse effects </li></ul><ul><li>Not all arrhythmias are treated with drug therapy alone </li></ul>www.freelivedoctor.com

×