Class I Antiarrhythmic Drugs

Class I antiarrhythmic drugs block fast sodium channels, slowing conduction velocity and reducing excitability in atria, ventricles and accessory pathways. They are divided by their effect on action potential duration and by how quickly they unbind from the channel. They can be proarrhythmic and are avoided in structural heart disease, coronary disease and heart failure.

Subclasses. IA (quinidine, procainamide, disopyramide) lengthen action potential duration and QT. IB (lidocaine, mexiletine, phenytoin) shorten it. IC (flecainide, propafenone) strongly slow conduction with little change in duration.

Mechanism. Blockade of the Nav1.5 channel in open and inactivated states lowers the rate of phase 0 rise. Block is use dependent, so it increases at fast rates and in depolarised, ischaemic tissue. IB drugs unbind quickly and act mainly on diseased tissue. IC drugs unbind slowly and affect normal conduction at resting rates.

Proarrhythmia. In patients after myocardial infarction, flecainide-type drugs raised mortality. IC drugs can convert atrial fibrillation to flutter with 1 to 1 conduction, so they are combined with an atrioventricular node blocker. IA drugs cause torsades.

Pharmacokinetics. Flecainide has a half-life of 12 to 27 hours, with kidney and CYP2D6 clearance. Propafenone depends on CYP2D6. Lidocaine has high first pass metabolism and is given intravenously. Mexiletine is well absorbed orally.

• Quinidine, procainamide, disopyramide (IA): atrial and ventricular arrhythmia, accessory pathway block.
• Lidocaine, mexiletine (IB): ventricular arrhythmia; mexiletine also treats myotonia and neuropathic pain.
• Flecainide, propafenone (IC): supraventricular arrhythmia in a structurally normal heart.
• Ajmaline, flecainide, procainamide: provocation of the Brugada pattern when the diagnosis is suspected.

• Atrial fibrillation or supraventricular tachycardia, structurally normal heart: flecainide 50 to 150 mg twice daily (maximum 300 mg daily), or propafenone 150 to 300 mg 3 times daily, with a beta blocker or rate-limiting calcium channel blocker.
• Pill-in-the-pocket cardioversion: a single dose of flecainide 200 mg (under 70 kg) or 300 mg (70 kg or more), or propafenone 450 mg (under 70 kg) or 600 mg (70 kg or more), taken once after the first test in a monitored setting and only in selected patients.
• Ventricular arrhythmia: lidocaine 1 to 1.5 mg/kg intravenously, then 1 to 4 mg/minute; mexiletine 150 to 200 mg 3 times daily, increased to 200 to 300 mg.
• Myotonia: mexiletine 200 mg 3 times daily.
• Pre-excited atrial fibrillation: procainamide intravenously, or electrical cardioversion. Avoid nodal blockers.
• Brugada test: ajmaline 1 mg/kg intravenously over 5 minutes or flecainide 2 mg/kg (maximum 150 mg) over 10 minutes, with resuscitation ready.
• Selection: class IC only when the heart is structurally normal and coronary disease is excluded.

Contraindications. Structural heart disease, coronary disease, previous infarction, heart failure with reduced ejection fraction, left ventricular hypertrophy (flecainide), second or third degree atrioventricular block, bifascicular block, sick sinus syndrome, cardiogenic shock, and Brugada syndrome.

Adverse effects. Proarrhythmia, QRS widening, negative inotropy, dizziness, blurred vision (flecainide), metallic taste (propafenone), tremor and seizures (lidocaine), lupus-like syndrome (procainamide), diarrhoea and cinchonism (quinidine), and anticholinergic effects (disopyramide).

Interactions. CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, bupropion) raise flecainide and propafenone levels. Propafenone raises digoxin and warfarin effect. Beta blockers and calcium channel blockers add negative inotropy. Amiodarone and QT-prolonging drugs add risk.

Monitoring. Electrocardiogram at baseline and after dose changes, with stopping or dose reduction if QRS widens by over 25% or reaches 120 ms or more, echocardiogram before starting, potassium and magnesium, and trough levels where used (flecainide 0.2 to 1.0 micrograms/mL).

Referral and escalation. New heart failure symptoms, syncope or wide-complex rhythm needs stopping the drug and urgent review.

Special groups. Pregnancy: flecainide is used for foetal supraventricular tachycardia under specialist care. Renal impairment: flecainide 100 mg daily when creatinine clearance is under 35 mL/min. Hepatic impairment: reduce doses. Older adults: start low. Poor CYP2D6 metabolisers: higher flecainide and propafenone levels.