Anti-arrhythmic Drugs Overview Review causes and features of cardiac arrhythmia The Vaughan-Williams classification of anti-arrhythmic drugs. Emergency Rx of arrhythmias Summary Drugs of choice for common arrhythmias Definitions Arrhythmia is a deviation from the normal rate or sinus rhythm of the heart Bradycardia (<60) Tachycardia (>100) Common Tachyarrhythmias Atrial fibrillation Atrial Flutter Supraventricular (atrial) tachycardia Ventricular tachycardia Common Bradyarrhythmias Sick Sinus Syndrome AV Conduction block Causes: Cardiac Disease of heart muscle:- Cardiomyopathy Ischaemia Post MI Chronic disease Infection: - Pericarditis Myocarditis Arterial Pathology: - Atheroma Structural Pathology Mitral stenosis Congenital abnormal conduction pathways Causes: Non-Cardiac/Systemic Metabolic Disturbance: K+ Ca2+ Mg2+ Hypoxia/Hypercapnia Acidosis Thyroid disease Pneumonia www.askdoctorclarke.com 1
Causes: Drugs Inhalers (B2-A) Digoxin L-Dopa Tricyclics Caffeine/Smoking/Alcohol Clinical Features Symptoms Palpitations Symptoms of impaired blood supply: - Chest pain Syncope / funny turn Angina attacks Signs Hypotension Pulmonary Oedema NB: - Often asymptomatic or found incidentally Questions on Hx General Framework Medication Hx Smoking/Alcohol Existing heart disease FHx heart disease Investigations Bloods:- FBC (anaemia) U + E (K+, Ca 2+) Glucose Thyroid Function ABG: - Hypoxia / hypercapnia ECG (often 24 hr) Echo- looking for evidence of structural disease Vaughan-Williams Classification Drugs classified according to their effect they have on cardiac conduction cycle- see below This classification is of little clinical value as most cardiologist rely on experience, current practice and personal preference when prescribing anti-arrhythmics. Nevertheless, it is widely quoted in textbooks. Class I Fast Sodium Channel Inhibitors Class II Beta Blockers Class III Amiodarone Class IV Calcium Channel Blockers www.askdoctorclarke.com 2
Cardiac Conduction Phase 0- Action Potential Na+ enters cardiac cells through fast channels Phase 1- Early/1 st repolarisation Na+ channels close and K+ channels open, K+ leaves cells Phase 2 - Plateau Only in cardiac muscle, balance between Ca2+ inflow and K+ outflow, to allow heart time to carry out its function Phase 3 Late/2 nd repolarisation Closure of Ca2+ channels. K+ continues to exit cells to cause more repolarisation. Phase 4 Slow depolarisation All ion concentrations are restored. Na+ enters through slow channels to create next conduction cycle Myocardial Cell Action Potential 1 2 0 3 4 4 Class I Fast Na+ Channel Inhibitors Blocks fast Na+ channels Therefore slowing phase 0 of conduction cycle Cardiac conduction is prolonged and heart rate is decreased. Can be further divided into three sub-groups 1a Disopyramide Inhibits fast Na+ channels and prolongs the action potential. Useful for both atrial AND ventricular arrhythmias. Can be given IV (for rx) or orally (prophylaxis). Not to be used in heart block pts, or pts with severe heart failure. Can itself lead to arrhythmia as a side effect as well as anticholinergic adverse effects. 1b - Lidocaine Inhibits fast Na+ channels but shortens action potential Useful in Rx of ventricular arrhythmias ONLY as it particularly slows conduction through purkinje fibres. Can only be given IV, but has a short half life (2 hrs), so can be used acutely to rx VT post MI. Can lead to drowsiness, paraesthesia and convulsions in overdose. Not to be used in AV node block or any SA node disorders. Important to have patient on an ECG monitor when giving this drug. www.askdoctorclarke.com 3
1c - Flecanide Inhibits Na+ channels, no effect on action potential BUT prolongs QRS complex. Can be used in BOTH atrial and ventricular arrhythmias (broad spectrum AA). NOT to be used in existing heart failure, past MI, or chronic, untreated ATRIAL FIBRILLATION. Use in caution in pts with heart block. Can cause marked GI upset and arrhythmia as an adverse effect. Monitor plasma drug levels if pt in renal failure, and have pt on ECG if giving IV. Interacts with other AA s, increases digoxin levels, and can cause myocardial depression with B-Blockers and Verapamil. Class II B-Blockers Have very little affect on the actual conduction cycle. Slows conduction through AV node, prolonging stage 4 and lengthening time before next action potential is generated. Atenolol and sotalol are most commonly used. Used for atrial arrhythmias only Not to be used in asthmatics, pts with uncontrolled heart failure or heart block Can slow heart rate too much and cause bradycardia, heart failure and hypotension Class III - Amiodarone Prolongs action potential, and inhibits repolarisation, by affecting K+ channels, also prolongs refractory period between conduction cycles. Can be used in ALL tachyarrhythmias, (broad spectrum). Not to be used in bradycardia, heart block or SA node disease but CAN be used in heart failure pts. However, has significant adverse effects including arrhythmia, N & V (if used acutely), lung disease/fibrosis, decreased HR/BP, hepatitis, hypo/hyper thyroidism, photosensitivity Monitor development of side effects using TFT s, LFT s and CXR. Warn the pt to avoid sunlight/use sunscreen Has many drug interactions including increasing effect of Warfarin Class IV - Verapamil Dihydropyridine group NOT used, verapamil only drug of use in arrhythmia, (as it primarily affects heart, not peripheries) Inhibits influx of Ca2+ into cells therefore prolonging plateau phase, therefore slowing conduction and HR. Given orally or IV to rx atrial arrhythmias only. (not to be used in VT) Not to be used in bradycardias, HF or heart block as it is significantly negatively inotropic Interacts with b-blockers, to cause severe decreased HR Other AA s: Atropine Used to treat bradycardias Anti-cholinergic: so blocks vagal tone, therefore encouraging sinus node to act automatically Speeds AV node conduction, to increase HR Given IV to rx acute bradycardia Always to be used if pts condition life-threatening regardless of any CI/SE s www.askdoctorclarke.com 4
Other AA s: Adenosine Acts on adenosine receptors in SA node to slow conduction through AV node, therefore causing bradycardia Used in acute atrial tachyarrhythmias (IV) NOT to be used in asthmatics as also acts on airway receptors to cause bronchospasm (use verapamil instead) Warn patient may cause SOB, chest pain and flushing when given. Other AA s: Digoxin Used exclusively in atrial fibrillation Rx Slows conduction through AV node by blocking Na+/K+ exchange AND also increases vagal tone to decrease heart rate. Used in treatment and prophylaxis of atrial fibrillation Not to be used in acute MI, heart block pts and pts with severe renal disease (as highly nephrotoxic) Use in caution in pts with potassium level imbalance as toxicity risk increases. Adverse effects can occur if digoxin is given in large doses. These include GI upset, visual disturbance, neuro effects (headache, fatigue etc.) and arrhythmias Very narrow therapeutic index so monitor U+E s and digoxin plasma levels. Emergency Rx of arrhythmia Give amiodarone in any patient who presents to A+E with arrhythmia of unknown cause or origin Management:- Assess pulse (if absent CPR) High flow O 2 - monitor SATS Monitor vital signs (BP, HR, RR) Look for adverse signs of heart failure / haemodynamic instability If no signs heart failure, give amiodarone 150mg IV. If adverse signs present, consider, ALS (shock protocol), correct any K+ imbalance, and call for expert help. Once stable give amiodarone. After initial rx with amiodarone, establish cause / origin using hx taking and ix and start appropriate therapy. Drugs of choice for Rx of common arrhythmias NB No drug rx usually needed if ECG normal during palpitations and pt is asymptomatic. Re-assurance is often all that is required. Atrial Fibrillation/Flutter DIGOXIN to control rate or DISOPYRAMIDE (1a) or AMIODARONE (III) to convert back to sinus rhythm. Ventricular Tachycardia LIDOCAINE (1b) or AMIODARONE (III) SVT/Atrial Arrhythmia ADENOSINE or VERAPAMIL (IV) for Rx. SOTALOL (II) or VERAPAMIL (IV) for prophylaxis www.askdoctorclarke.com 5
Acute Bradycardia ATROPINE Emergency Rx AMIODARONE If drug therapy fails to prevent arrhythmia recurring, then consider:- Cardiac Pacemaker Implanted defibrillator Please Note These notes were compiled by Stewart Hale as a medical student in 2007. They are presented in good faith and every effort has been taken to ensure their accuracy. Nevertheless, medical practice changes over time and it is always important to check the information with your clinical teachers and with other reliable sources. Disclaimer: no responsibility can be taken by either the author or publisher for any loss, damage or injury occasioned to any person acting or refraining from action as a result of this information. Please give feedback and report any inaccuracies or ambiguities www.askdoctorclarke.com 6