Class IB Antiarrhythmic Drugs

Class IB antiarrhythmic drugs block sodium channels with fast binding and unbinding, so they act mainly on depolarised, ischaemic or rapidly firing tissue and spare normal conduction at resting rates. They shorten the action potential and have little effect on the QT interval. Their use is for ventricular arrhythmia, and they are less proarrhythmic than class IA and IC drugs, though not free of risk.

Members. Lidocaine (lignocaine), mexiletine and phenytoin. Tocainide is obsolete because of marrow and lung toxicity.

Mechanism. Binding to the open and inactivated sodium channel is rapid and dissociation is quick (under 1 second), so block accumulates only when the heart rate is fast or the membrane is partly depolarised. The plateau of the action potential shortens through late sodium current block. Conduction velocity and refractoriness in normal tissue change little.

Pharmacokinetics. Lidocaine undergoes about 70% first pass hepatic metabolism, so it is given intravenously for arrhythmia. Half-life is 1.5 to 2 hours and is prolonged in heart failure, shock, cirrhosis and prolonged infusion. Hepatic blood flow drives clearance. Mexiletine is well absorbed orally, has a half-life of 10 to 14 hours and is metabolised mainly by CYP2D6 and CYP1A2. Phenytoin is metabolised in the liver by saturable kinetics, with a narrow therapeutic range.

Therapeutic range. Lidocaine 1.5 to 5 micrograms/mL. Mexiletine 0.5 to 2 micrograms/mL.

• Lidocaine: intravenous; ventricular tachycardia and ventricular fibrillation; also local anaesthetic.
• Mexiletine: oral; chronic ventricular arrhythmia, long QT syndrome type 3, myotonia, neuropathic pain.
• Phenytoin: historical use for digoxin-induced arrhythmia; now rare.

• Pulseless ventricular tachycardia or ventricular fibrillation: lidocaine 1 to 1.5 mg/kg intravenously as an alternative to amiodarone, with a second dose of 0.5 to 0.75 mg/kg if needed.
• Stable ventricular tachycardia: lidocaine 1 to 1.5 mg/kg intravenously over 2 to 3 minutes, repeated at half dose every 5 to 10 minutes to a maximum of 3 mg/kg, then infusion 1 to 4 mg/minute. Electrical cardioversion is preferred if unstable.
• Reduced infusion: halve the rate in heart failure, shock, cirrhosis or after 24 hours.
• Mexiletine: 150 to 200 mg three times daily, increasing to 200 to 300 mg three times daily. Take with food to reduce nausea. Use is usually as an add-on to a beta blocker or amiodarone for recurrent ventricular tachycardia, or alone in long QT syndrome type 3.
• Myotonia: mexiletine 200 mg three times daily.
• Selection: use after amiodarone fails or is unsuitable, and in ischaemia-related ventricular arrhythmia after revascularisation and electrolyte correction.

Contraindications. Second or third degree atrioventricular block without a pacemaker, Stokes-Adams attacks, severe sinoatrial disease, severe heart failure or shock, and hypersensitivity to amide anaesthetics. Mexiletine is also avoided in acute myocardial infarction outside specialist care.

Adverse effects. Lidocaine toxicity is dose related: perioral numbness, tinnitus, light-headedness, slurred speech, confusion, tremor, seizures, then bradycardia, hypotension and cardiac arrest. Mexiletine causes nausea, tremor, dizziness, ataxia, blurred vision, rash and hepatic enzyme rise.

Treatment of lidocaine toxicity. Stop the infusion, give oxygen, control seizures with a benzodiazepine, and give 20% lipid emulsion 1.5 mL/kg intravenously over 1 minute, then infusion 15 mL/kg/hour, if cardiovascular collapse follows.

Interactions. Beta blockers, cimetidine and propranolol reduce lidocaine clearance. Ciprofloxacin and fluvoxamine (CYP1A2 inhibitors) raise mexiletine levels. Rifampicin, carbamazepine and smoking lower mexiletine levels. Amiodarone and other antiarrhythmics add conduction effects. Mexiletine raises theophylline levels.

Monitoring. Electrocardiogram, blood pressure, neurological state, and levels in prolonged infusion, liver disease or heart failure.

Referral and escalation. Refer for implantable defibrillator and ablation assessment in recurrent ventricular tachycardia or electrical storm.

Special groups. Hepatic impairment and heart failure: reduce lidocaine doses by half. Older adults: higher neurological toxicity. Pregnancy: lidocaine is used as a local anaesthetic, and systemic antiarrhythmic use needs specialist input. Children: weight-based dosing.