Anti-arrhythmic Drugs

A very quick overview

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.

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

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.

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

Shockable rhythms

VT (sustained) VF AF

Atrial Arrythmia – Sinus Tachy

Metoprolol tartrate 25 to 100 mg orally twice daily 

OR 

Verapamil sustained-release 160 to 480 mg orally, daily

Atrial Arrythmia - Premature complexes

Metoprolol tartrate 25 to 100 mg orally twice daily 

OR 

Verapamil sustained-release 160 to 480 mg orally, daily

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

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

AF rhythm control

Cardioversion with Drugs Flecainide Amiodarone

Maintainance of sinus rhthym after cardioversion Flecainide Amiodarone Sotalol

AF rate control

Digoxin (rarely used alone in younger pt’s) Atenolol Metoprolol Diltiazem Verapamil

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

Ventricular Tachycardia

Lignocaine Amiodarone Sotalol Flecainide Atenolol/ Metoprolol only if significant

ventricular dysfunction is present

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

Cardiac Arrest recipe (20 to VT, VF or Asystole)

CPR DC Shock if 20

to VT/VF only Adrenaline and atropine for asystole Amiodarone/ Lignocaine for VT/ VF NaCO3 for acidosis if resus takes <10min

Amiodarone

MOADecreases 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.

Amiodarone

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

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.

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.

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.

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.

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.

Lignocaine

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

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.

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+

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).