Medicine chapters
Antiarrhythmic drugs, cardioversion and defibrillation
The Vaughan Williams classes with their key drugs, uses and side effects (amiodarone, digoxin, adenosine, flecainide, lidocaine, verapamil, sotalol), plus synchronised cardioversion vs defibrillation, ICDs and catheter ablation.
- Vaughan Williams: I sodium channel blockers (Ia quinidine, Ib lidocaine, Ic flecainide), II beta-blockers, III potassium channel blockers (amiodarone, sotalol), IV rate-limiting calcium channel blockers (verapamil, diltiazem); plus adenosine and digoxin.
- Key toxicities: amiodarone (thyroid, lungs, liver, skin, eyes), digoxin (nausea, yellow vision, any arrhythmia, worse with hypokalaemia), class Ic (deadly in structural heart disease), class Ia/III (long QT, torsades).
- Cardioversion is a shock synchronised to the QRS for organised rhythms (AF, flutter, SVT, VT with pulse); defibrillation is unsynchronised for VF and pulseless VT.
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Overview
Antiarrhythmic drugs change how heart cells fire and conduct. They are classed by their main action on the cardiac action potential (Vaughan Williams classification). All of them can cause arrhythmias (proarrhythmia) and many depress heart function, and none has been shown to prolong life except beta-blockers in some settings.
Electrical treatment is often safer and faster: synchronised cardioversion for organised tachycardias and defibrillation for VF and pulseless VT. Devices (pacemakers, ICDs) and catheter ablation have taken over much long-term care.
Vaughan Williams classification
| Class | Action | Effect on action potential | Drugs | Main uses |
|---|---|---|---|---|
| Ia | Na+ channel block (moderate) plus K+ block | Lengthens AP and QT | Quinidine, procainamide, disopyramide | AF, WPW (procainamide); rarely used now |
| Ib | Na+ channel block (weak, fast on-off) | Shortens AP | Lidocaine, mexiletine | Ventricular arrhythmias, especially ischaemic |
| Ic | Na+ channel block (strong) | No change in AP length; slows conduction | Flecainide, propafenone | AF and SVT in structurally normal hearts; WPW |
| II | β-adrenoceptor block | Slows phase 4 in the SA node; slows AV node | Propranolol, metoprolol, atenolol, bisoprolol, esmolol | Rate control, SVT prevention, post-MI, long QT |
| III | K+ channel block | Lengthens AP, refractory period and QT | Amiodarone, sotalol, dronedarone, dofetilide, ibutilide, vernakalant | AF, flutter, VT, VF |
| IV | L-type Ca2+ channel block (non-dihydropyridine) | Slows SA and AV nodal conduction | Verapamil, diltiazem | SVT, rate control in AF |
| Others | Adenosine (A1 receptor, K+ channel opening); digoxin (Na+/K+ ATPase, vagal); magnesium; atropine | — | — | SVT (adenosine); AF rate (digoxin); torsades (magnesium); bradycardia (atropine) |
"Some Block Potassium Channels": Sodium (I), Beta (II), Potassium (III), Calcium (IV).
Class I subgroups: "Double Quarter Pounder" (Ia: Disopyramide, Quinidine, Procainamide); "Lettuce, Mayo" (Ib: Lidocaine, Mexiletine); "Fries Please" (Ic: Flecainide, Propafenone).
Class I drugs
Ia: quinidine, procainamide, disopyramide
- Prolong QT, so risk torsades de pointes.
- Quinidine: cinchonism (tinnitus, headache, blurred vision), diarrhoea, thrombocytopenia.
- Procainamide: drug-induced lupus (anti-histone antibodies). Useful for AF in WPW.
- Disopyramide: anticholinergic effects (urinary retention, dry mouth), negative inotropy.
Ib: lidocaine
- Acts best on ischaemic, depolarised ventricular tissue; little effect on atria.
- Used IV for ventricular tachycardia, especially after MI; alternative to amiodarone in arrest.
- Not given orally because of extensive first-pass metabolism in the liver.
- Toxicity: CNS (perioral tingling, confusion, seizures), then bradycardia and hypotension.
A 2% solution = 2 g per 100 mL = 2000 mg ÷ 100 mL = 20 mg/mL
10 mL of 2% lidocaine = 10 × 20 = 200 mg
(1% = 10 mg/mL, so 10 mL of 1% = 100 mg)
Ic: flecainide, propafenone
- Strong sodium block; slow conduction; little effect on QT.
- Used for AF (including "pill-in-the-pocket"), SVT and WPW in patients with normal hearts.
- Contraindicated after MI, in coronary disease and in LV dysfunction: the CAST study showed increased mortality from proarrhythmia.
- Can convert AF to flutter with 1:1 conduction; give with an AV nodal blocker.
Flecainide is a good drug for a young person with a normal heart, and a dangerous one for a patient with a previous MI or poor LV function. In structural heart disease use amiodarone.
Class II: beta-blockers
- Block the effect of catecholamines; slow the SA node and AV node.
- Uses: rate control in AF, prevention of SVT, post-MI (reduce sudden death), heart failure, congenital long QT, thyrotoxicosis.
- Esmolol: very short-acting IV beta-blocker.
- Side effects: bradycardia, AV block, bronchospasm (avoid in asthma), fatigue, cold hands, masking of hypoglycaemia.
Class III: potassium channel blockers
They prolong repolarisation (phase 3), the refractory period and the QT interval.
Drugs that lengthen the action potential (class Ia and class III) lengthen the QT and can cause torsades de pointes; class Ib and Ic do not.
Amiodarone
The most effective antiarrhythmic and the safest in structural heart disease (low proarrhythmic risk), but with many non-cardiac side effects. Very long half-life (weeks to months), so effects persist after stopping. It also has class I, II and IV actions.
Uses: AF and flutter (cardioversion and rhythm control, especially with heart failure), stable VT, refractory VF or pulseless VT in arrest.
| System | Adverse effect |
|---|---|
| Thyroid | Hypothyroidism and hyperthyroidism (high iodine content); check TFTs before and during treatment |
| Lungs | Pulmonary fibrosis / pneumonitis |
| Liver | Raised enzymes, hepatitis |
| Skin | Photosensitivity, slate-grey (blue-grey) pigmentation |
| Eyes | Corneal microdeposits (usually harmless), optic neuropathy (rare) |
| Nerves | Peripheral neuropathy, tremor |
| Heart | Bradycardia, QT prolongation (torsades is uncommon) |
| Interactions | Raises digoxin and warfarin levels: reduce their doses and monitor |
Amiodarone checks before starting: "TFTs, LFTs, chest X-ray" (and ECG).
Sotalol
A beta-blocker with class III action. Used for AF prevention and ventricular arrhythmias, particularly with coronary disease. Main danger: long QT and torsades, worse with hypokalaemia (watch diuretics) and renal failure.
Dronedarone
Related to amiodarone with fewer side effects, but harmful in heart failure and LV dysfunction.
Class IV: verapamil and diltiazem
- Block L-type calcium channels in the SA and AV nodes.
- Uses: terminate or prevent AVNRT/AVRT; rate control in AF; verapamil-sensitive idiopathic VT.
- Side effects: bradycardia, AV block, hypotension, heart failure (negative inotropes), constipation (verapamil).
- Do not give verapamil: with or soon after IV beta-blockers (asystole risk); in broad-complex tachycardia (may be VT); in AF with WPW; in heart failure with poor LV function.
Dihydropyridines (amlodipine, nifedipine) have no antiarrhythmic use; only verapamil and diltiazem act on the nodes.
Other drugs
Adenosine
- Acts on A1 receptors: opens K+ channels and causes transient complete AV block for a few seconds (half-life under 10 seconds).
- Terminates AVNRT and AVRT; unmasks flutter waves; does not usually stop VT.
- Dose: 6 mg rapid IV, then 12 mg if needed.
- Effects: flushing, chest tightness, dyspnoea, sense of doom, brief asystole.
- Avoid in asthma (bronchospasm). Effect increased by dipyridamole and in heart transplant patients; reduced by theophylline/caffeine.
Digoxin
- Mechanism: inhibits Na+/K+ ATPase, so more intracellular Na+, less Ca2+ removal by Na+/Ca2+ exchange, more Ca2+ in the cell, stronger contraction. It also increases vagal tone, slowing AV conduction.
- Uses: rate control in AF, especially with heart failure or in sedentary elderly patients; add-on in heart failure.
Digoxin slows the ventricular rate in AF mainly through extra vagal tone at the AV node, which is why it works at rest but not during exercise.
- Narrow therapeutic range; excreted by the kidney (reduce dose in renal impairment and the elderly).
- Digoxin effect (not toxicity): sagging, "reverse tick" ST depression, short QT, flat T waves.
Toxicity
| Feature | Detail |
|---|---|
| GI | Anorexia, nausea, vomiting, diarrhoea |
| CNS and eyes | Confusion, yellow-green vision (xanthopsia), blurred vision |
| Heart | Almost any arrhythmia: ventricular ectopics, bigeminy, atrial tachycardia with block, AV block, VT, bradycardia |
| Electrolytes | Hyperkalaemia in acute overdose (pump blocked) |
Precipitating factors: hypokalaemia (often from loop or thiazide diuretics), hypomagnesaemia, hypercalcaemia, hypothyroidism, renal impairment, old age, and drugs that raise levels (amiodarone, verapamil, quinidine, macrolides).
Treatment: stop digoxin; correct potassium; atropine for bradycardia; digoxin-specific antibody (Fab) fragments for life-threatening arrhythmias, severe hyperkalaemia or haemodynamic compromise.
Hypokalaemia makes digoxin more toxic, although acute digoxin overdose itself causes hyperkalaemia.
Magnesium and atropine
- Magnesium sulphate IV: first-line for torsades de pointes; also for arrhythmias with low magnesium.
- Atropine: muscarinic blocker; raises SA rate and AV conduction in symptomatic bradycardia and nodal heart block.
Drug of choice summary
| Situation | First choice |
|---|---|
| Stable SVT (AVNRT/AVRT) | Vagal manoeuvres, then adenosine |
| SVT in asthmatic | Verapamil |
| AF rate control (active patient) | Beta-blocker or diltiazem/verapamil |
| AF rate control with heart failure | Beta-blocker plus digoxin |
| AF rhythm control, normal heart | Flecainide |
| AF rhythm control, structural disease | Amiodarone |
| AF with WPW (stable) | Procainamide or flecainide; avoid nodal blockers |
| Stable VT | Amiodarone (or lidocaine) |
| Torsades de pointes | Magnesium sulphate |
| Refractory VF/pulseless VT in arrest | Amiodarone after the third shock |
| Symptomatic bradycardia | Atropine |
| Digoxin toxicity with serious arrhythmia | Digoxin Fab fragments |
Cardioversion vs defibrillation
Both pass a direct current shock across the heart to depolarise all the myocardium at once, letting the sinus node take over. The key difference is timing.
| Feature | Synchronised cardioversion | Defibrillation |
|---|---|---|
| Timing | Shock synchronised to the R wave (QRS) | Unsynchronised: delivered at once |
| Why | Avoids a shock on the T wave (vulnerable period), which could cause VF | No QRS to sync with; delay is fatal |
| Rhythms | AF, atrial flutter, SVT, VT with a pulse | VF, pulseless VT |
| Patient | Conscious: needs sedation or short general anaesthesia | Unconscious (cardiac arrest) |
| Energy | Lower; flutter and SVT need less than AF | Biphasic 150–200 J (monophasic 360 J) |
| Setting | Elective or emergency (unstable tachycardia) | Emergency only |
Synchronised = organised rhythm with a pulse. Unsynchronised = VF or pulseless VT. An accidental unsynchronised shock in a patient who does not need it can itself trigger VF.
Practical points for elective cardioversion
- Anticoagulation: AF or flutter over 48 hours needs 3 weeks of anticoagulation before (or a TOE showing no clot) and at least 4 weeks after.
- Electrolytes: correct potassium.
- Digoxin: therapeutic levels do not add risk, but digoxin toxicity can lead to ventricular arrhythmias or asystole after a shock; it is customary to withhold digoxin for a few days before elective cardioversion.
- Pads: right of the upper sternum and over the apex, or front and back (anteroposterior).
- Biphasic defibrillators need less energy and work better than monophasic ones; success for AF is around 80%.
- Cardiac enzymes may rise slightly afterwards; skin burns can occur.
- Everyone must stand clear at the moment of the shock.
Pharmacological cardioversion
- Flecainide (or propafenone) IV or oral in normal hearts.
- Amiodarone IV in structural heart disease.
- Vernakalant or ibutilide in some countries.
The MCQ answer for VF is defibrillation, not "cardioversion". For unstable VT with a pulse it is synchronised cardioversion.
Devices and ablation
Automated external defibrillator (AED)
Analyses the rhythm, decides whether it is shockable and guides untrained rescuers. Placed in public areas.
Implantable cardioverter-defibrillator (ICD)
A device in the chest wall that detects VT or VF and treats it with overdrive (anti-tachycardia) pacing or an internal shock.
- Secondary prevention (first-line): survivors of VF or haemodynamically significant VT without a reversible cause.
- Primary prevention: heart failure with ejection fraction 35% or less; inherited conditions with high risk of sudden death (hypertrophic cardiomyopathy, long QT, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy).
- Combined with cardiac resynchronisation (CRT-D) in heart failure with LBBB.
- ICDs beat antiarrhythmic drugs at preventing sudden death.
Catheter ablation
Radiofrequency or cryo energy destroys the circuit or focus. Highly effective (often curative) for AVNRT, accessory pathways (WPW), typical atrial flutter, focal atrial tachycardia, idiopathic VT, and pulmonary vein isolation for paroxysmal AF.
Expect: classifying drugs by Vaughan Williams class; class III drugs prolong the action potential and QT; lidocaine as class Ib for ventricular arrhythmias and why it is not oral; flecainide avoided after MI; amiodarone side effects (thyroid both ways, lung fibrosis, liver, grey skin, corneal deposits) and its interaction with digoxin and warfarin; digoxin mechanism, toxicity (yellow vision, bigeminy) and the role of hypokalaemia; adenosine and asthma; verapamil contraindications; sotalol and torsades; and synchronised cardioversion vs unsynchronised defibrillation with their indications.
Quick revision
- I Na+ (Ia quinidine/procainamide, Ib lidocaine, Ic flecainide); II beta; III K+ (amiodarone, sotalol); IV verapamil/diltiazem.
- Lidocaine: IV only, ventricular arrhythmias, CNS toxicity.
- Flecainide: normal hearts only; never after MI or with LV dysfunction.
- Amiodarone: thyroid, lungs, liver, skin, eyes; raises digoxin and warfarin.
- Digoxin: Na+/K+ ATPase; toxicity with hypokalaemia; yellow vision, bigeminy; Fab fragments.
- Adenosine 6 then 12 mg for SVT; avoid in asthma.
- Verapamil: not with beta-blockers, not for broad complex, not in WPW with AF.
- Cardioversion is synchronised (AF, flutter, SVT, VT with pulse); defibrillation is unsynchronised (VF, pulseless VT).
- ICD for VF/VT survivors and EF 35% or less.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Why must cardioversion be synchronised?
A shock landing on the T wave, when the ventricles are partly repolarised, can trigger VF. Synchronising to the R wave avoids that vulnerable moment.
Why is flecainide dangerous after a myocardial infarction?
In patients with scarred or weak ventricles it can provoke fatal ventricular arrhythmias, and a large study showed increased deaths with class Ic drugs after MI.
Which electrolyte disturbance most often precipitates digoxin toxicity?
Hypokalaemia, often caused by diuretics, which increases digoxin binding to the sodium-potassium pump.
What should happen to digoxin when amiodarone is started?
Amiodarone raises digoxin levels, so the digoxin dose should be reduced and levels monitored.