Anti-arrhythmic Drugs

1. Anti-arrhythmic Drugs A very quick overview

2. A few rules before prescribing All anti-arrhythmic drugs can actually have proarrhythmic effects. • increase in frequency or duration of the index arrhythmia • development of a novel arrhythmia • development of torsades de pointes (sotalol and amiodarone) Treatment should never be instituted for benign symptoms such as palpitations without an incriminating ECG. Underlying abnormalities of electrolytes such as hypokalaemia (especially in digoxin use - toxicity) should be corrected if present. Symptomatic hypoperfusion or hypotension associated with a tachyarrhythmia should always be regarded as a medical emergency - may require urgent electrical cardioversion.

3. VW Classification of Antiarrythmics Class 1 – Na+ channel blocker, thereby inhibiting phase 0, or depolarisation • Class IC agents have the slowest binding and dissociation from the receptor (quinidine, procainamide and disopyramide). • Class IB agents are the most rapid (lignocaine and mexilitine). • Class IA agents are intermediate (flecainide). During faster heart rates, less time exists for the drug to dissociate from the receptor, resulting in an increased number of blocked channels and enhanced blockade; resulting in a progressive decrease in impulse conduction velocity and a widening of the QRS complex. This use dependence is frequently seen with the class IC agents, less frequently with the class IA drugs, and rarely with the class IB agents

4. VW Classification of Antiarrythmics Class 2 - Beta blockers which reducing sympathetic effects on heart rate and force of contraction Class 3 - Block potassium channels to prolong repolarization, and the refractory period – which shows as prolongation of QT (>450 msec)interval setting up platform for torsade de pointes to take off (Sotalol and Amiodarone). Class 4 - Non-selective calcium channel blockers which act on channels in the AV nodes (Diltiazem and Verapamil) The Vaughan Williams classification system does not include Digoxin, Atropine or Adenosine.

5. The Ventricular AP Phase 0 depolarization: Sodium channels open allowing sodium entry into the cells Phase 1 Repolarization: Results after sodium channels are fully closed and potassium channels are opened. Phase 2 plateau: Reflects the slow entry of calcium into the cells, which counteracts the effect of potassium exit. Phase 4 recovery: Sodium leaves and potassium re enters the cells via the Na-K-ATPase

6. Shockable rhythms • VT (sustained) • VF • AF

7. Atrial Arrythmia – Sinus Tachy Metoprolol tartrate 25 to 100 mg orally twice daily  OR  Verapamil sustained-release 160 to 480 mg orally, daily

8. Atrial Arrythmia - Premature complexes Metoprolol tartrate 25 to 100 mg orally twice daily  OR  Verapamil sustained-release 160 to 480 mg orally, daily

9. Atrial flutter definitions • Usually 2:1 AV block and Ventricular rate of 150bpm with narrow QRS • VR of 100 is 3:1 AV block • VR of 75 is 4:1 AV block • VR of 300 is 1:1 AV block Atrial fibrillation definitions Irregular VR btw 160 – 180bpm Risk factors – mitral valve, ASD, thyrotoxicosis, HF, HTN

10. Atrial flutter and atrial fibrillation: rhythm control BUT FIRST!!!! Anticoagulation is needed for at least 4 weeks prior to cardioversion • Enoxaparin 1 mg/kg BD • Heparin 5000units bolus then infusion and monitor APTT • Warfarin 5mg daily for 2 days then as per INR result

11. AF rhythm control Cardioversion with Drugs • Flecainide • Amiodarone Maintainance of sinus rhthym after cardioversion • Flecainide • Amiodarone • Sotalol

12. AF rate control • Digoxin (rarely used alone in younger pt’s) • Atenolol • Metoprolol • Diltiazem • Verapamil

13. Paroxysmal SVT Conversion to sinus rhythm (after non-drug manoeuvres) • Adenosine IV • Verapamil IV Prophylaxis of SVT • Atenolol/ Metoprolol • Sotalol • Flecainide • Verapamil SR • Amiodarone if all above fail

14. Ventricular Tachycardia • Lignocaine • Amiodarone • Sotalol • Flecainide • Atenolol/ Metoprolol only if significant ventricular dysfunction is present

15. Torsades de pointes • Atropine IV if underlying bradycardia present • Magnesium IV • Isoprenaline IV • Lignocaine IV amiodarone, disopyramide, flecainide or sotalol should be avoided in patients with torsades as long QT interval perpetuates arrythmia

16. Cardiac Arrest recipe(20 to VT, VF or Asystole) • CPR • DC Shock if 20to VT/VF only • Adrenaline and atropine for asystole • Amiodarone/ Lignocaine for VT/ VF • NaCO3 for acidosis if resus takes <10min

17. Amiodarone MOA Decreases nodal automaticity, slows AV conduction and prolongs refractory period of myocardial tissues; also has weak beta-blocker activity. Precautions • Contraidicated with allergy to iodine (200mg tablet is nearly 40% iodine). • Thyroid dysfunction, including goitre or nodules—increases risk of hypo- or hyperthyroidism. • Lung disease (particularly with reduced diffusion capacity)—less reserve to cope with pulmonary adverse effects. • Contraindicated in 2nd/ 3rd degree block, symptomatic bradycardia or sick sinus syndrome (when no pacemaker). • Amiodarone is the least negatively inotropic antiarrhythmic and is therefore usually well tolerated in HF. • Check QT interval is <450 milliseconds before use as amiodarone may increase risk of arrhythmia by prolonging the QT interval.

18. Amiodarone ADE’s • Metallic taste • Increased LFT’s • Blue/ grey skin pigmentation • Pulmonary fibrosis/ Pulmonary inflammation • Hypotention • AV block • Torsade de pointes

19. Amiodarone Acute treatment of tachyarrhythmias • Emergency, IV 150–300 mg over 1–2 minutes (monitor clinical signs and ECG very closely). • Loading, IV infusion 5 mg/kg over 20 minutes to 2 hours. • Maintenance, IV infusion 15–20 mg/kg over 24 hours; begin oral treatment as soon as possible, overlapping oral and IV treatment by 2 days. Chronic treatment of tachyarrhythmias • Oral, 200–400 mg 3 times daily for 1 week, followed by 200–400 mg twice daily for 1 week. • Maintenance, 100–400 mg once daily. Concentration monitoring • Therapeutic range 1–2.5 mg/L although rarely done. • The maximum effect of dosage change is not seen for 1–3 months or more because half-life is 27–107 days.

20. Atropine MOA – Removes the PNS stimulation of heart Precautions – Acute MI – may worsen ischemia IV Dose • 1 mg; repeat prn until desired rate is achieved - Max 3mg Intratracheal dose is venous route not available • Bradycardia, 1 mg; repeat prn until desired rate is achieved to 3mg Max • Asystole, 6 mg once only.

21. Adenosine MOA – short acting drug (also endogenous) depresses sinus and AV node activity/ conduction; also produces peripheral and coronary vasodilation. Is blocked by caffeine! Precautions - Contraindicated in 2nd/ 3rd degree heart block or sick sinus syndrome (without pacemaker). Dose for SVT, diagnostic aid for tachycardia • Rapid IV bolus, initially 3 mg; if unsuccessful within 1–2 minutes, give 6 mg; if still unsuccessful within 1–2 minutes give 12 mg.

22. Flecainide MOA - Slows cardiac conduction and to a lesser extent, increases refractory period in all myocardial tissues (esp in the His-Purkinje conduction system). Also has negative inotropic activity. Precautions • Contraindicated in 2nd/ 3rd degree heart block, increased risk of 1st degree block • Increased risk of ventricular arrhythmias in structural heart disease or chronic AF. • Increases risk of significant bradyarrhythmia in sick sinus syndrome. • Heart failure may worsen. Dose • IV, 2 mg/kg/dose over at least 10 minutes to a maximum of 150 mg. • Oral, 50–100 mg twice daily; increase by 50 mg every 4 days up to a maximum of 400 mg daily.

23. Lignocaine MOA - Reduces automaticity of myocardial tissue with little effect on cardiac conduction. It has a mild negative inotropic effect and weak neuromuscular blocking activity. Precautions • Safe to use in pregnancy • Contraindicated in 2nd/ 3rd degree heart block or severe SA block (without pacemaker). • Bradycardia or cardiogenic shock increases risk of arrhythmia; correct before starting treatment if possible. • Heart failure may worsen Dose Initially, IV injection 1 mg/kg (in adults usually 75–100 mg) over 1–2 minutes, repeated after 5 minutes if necessary.Maintenance, IV infusion 10–50 micrograms/kg/minute.

24. Lignocaine ADE’s • Headache • Dizziness • Drowsiness • Paraesthesia • Hypotension • Bradycardia • Cardiac arrest • Muscle twitching • Seizures • Coma • Respiratory depression

25. Sotalol MOA - nonselective beta-blocker (class 2) that ALSO prolongs the refractory period of atria, ventricles and bypass tract (class 3). It has no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic doses. Precautions • Phaeochromocytoma (may exacerbate hypertension since is not complete antagonist) • Diabetes (may cause hypoglycaemia) • Heart failure (may worsen) • Peripheral vascular disease – raynauds’ • Contraindicated in 2nd/ 3rd degree heart block or severe SA block (without pacemaker) Dose • IV, initially 0.5–1.5 mg/kg (20–120 mg) over at least 10 minutes; repeat every 6 hours if necessary, or infuse 80–160 mg over 12 hours. • Oral, initially 40–80 mg twice daily; increase according to response to 160 mg twice daily.

26. Digoxin MOA - Increases force of myocardial contraction and decreases AV nodal conduction, predominantly by PNS effect on the heart, also slowing the heart rate. It can increase the excitability of cardiac muscle, particularly at higher doses. Precautions • Contraindicated in 2nd/ 3rd degree heart block (without pacemaker), Wolff-Parkinson-White syndrome, VF/VT, cor pulmonale/ constrictive pericarditis and hypertrophic obstructive cardiomyopathy. • Predominately renally cleared (70%) so reduce dose in renal failure • Safe is pregnancy (even used to treat some fetal arrythmias) • Narrow therapeutic range; trough level (or at least 6 hours after dose) 0.8 – 1.2 micrograms/L. Steady state is reached after about 5 days if renal function is normal (half-life is 36 hours). • ECG effect is prolonged PR interval, ST depression or T wave inversion. Apart from the effect on the PR interval, which is a sign of toxicity, the other ECG changes do not necessarily indicate digoxin toxicity or myocardial ischaemia. • Hypokalemia may lead to digoxin toxicity – monitor and correct K+

27. Digoxin ADE’s anorexia, N&V, diarrhoea, blurred vision, visual disturbances, drowsiness, dizziness, nightmares, agitation, depression, acute psychosis,, shortened QRS complex, atrial or ventricular extra systoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block, gynaecomastia (long-term use) Dose Loading, oral/IV 250–500 micrograms every 4–6 hours, to a maximum of 1.5 mg. Maintenance, oral 125–250 micrograms once daily (rarely increased up to 500 micrograms daily).