## Class I Antiarrhythmics — Subclassification and Pharmacokinetics **Key Point:** Class I agents are subdivided into Ia, Ib, and Ic based on their effect on action potential duration and conduction velocity. Class Ic agents (flecainide, propafenone) have the most marked effect on conduction velocity with minimal APD change, slow onset, and long half-lives — ideal for chronic prophylaxis. ### Class I Subclassification | Subclass | Drugs | APD Effect | Conduction Velocity | Onset | Half-Life | Clinical Use | | --- | --- | --- | --- | --- | --- | --- | | **Ia** | Quinidine, Procainamide, Disopyramide | Prolongs | Slows | Moderate | 3–8 hrs | Acute/chronic (limited use now) | | **Ib** | Lidocaine, Mexiletine | Shortens | Minimal effect | Rapid (IV) | 1–2 hrs | Acute VT/VF (IV); oral less common | | **Ic** | **Flecainide, Propafenone** | Minimal | **Markedly slows** | **Slow** | **12–27 hrs** | **Chronic AF prophylaxis** | **High-Yield:** Flecainide is the prototypical Class Ic agent — it has: - **Slow onset of action** (takes days to reach steady state) - **Long half-life** (12–27 hours; flecainide ~20 hrs) - **Minimal APD prolongation** but **marked conduction slowing** - **Excellent oral bioavailability** and **long duration of action** → once or twice daily dosing **Mnemonic:** **"Fle-CAIN-ide is SLOW"** — Flecainide is Class Ic (slow conduction), slow onset, long half-life. **Clinical Pearl:** Flecainide is FDA-approved for chronic AF prophylaxis in structurally normal hearts. However, the CAST trial (1989) showed increased mortality with flecainide in post-MI patients with reduced ejection fraction — it is now contraindicated in structural heart disease. **Warning:** Lidocaine (Class Ib) has rapid onset but very short half-life (1–2 hrs) — unsuitable for chronic oral therapy. Procainamide and quinidine (Class Ia) have intermediate half-lives (3–8 hrs) and require more frequent dosing than flecainide.
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