General characteristics and limitations
The mechanism of action of drugs in this group is based on sodium channel blockade. Like subclass IA representatives, they predominantly affect the ventricles and cardiac pacemakers.
The main feature of class IC is its narrow clinical niche. They are used exclusively to manage life-threatening ventricular arrhythmias when other agents have proven ineffective.
Such caution is associated with severe limiting factors:
- Proarrhythmic effect: the drugs frequently provoke rhythm disorders themselves.
- Cardiodepression: most of them depress myocardial contractility.
- Conduction block: marked suppression of atrioventricular (AV) conduction.
Propafenone and Flecainide
Propafenone has a complex mechanism of action: in addition to its primary sodium channel blockade, it moderately blocks calcium channels and exhibits $\beta$-adrenolytic activity. It is well absorbed orally, but due to the intensive "first-pass" hepatic effect, its bioavailability varies widely (from 4 to 40%). Side effects include dyspepsia, sleep disturbances, bradycardia, and bronchospasm (a consequence of $\beta$-blockade).
Flecainide (used as acetate) strongly depresses conduction in the AV node and the His-Purkinje system, but has almost no effect on the effective refractory period of the ventricles. Unlike propafenone, it is not degraded during the first pass through the liver, and peak plasma concentrations are reached in 3–4 hours. It frequently causes neurological disorders (dizziness, visual disturbances) and proarrhythmic effects (in 5–15% of cases).
Phenothiazine derivatives: Moracizine and Etacizine
Moracizine (ethmozine) is unique in combining the properties of all three subclasses of sodium channel blockers (IA, IB, IC). It depresses impulse conduction in the AV node and Purkinje fibers, but has a weak effect on the sinus node. Despite its potential efficacy in supraventricular arrhythmias, in practice it is used only for resistant ventricular arrhythmias due to the high risk of arrhythmogenicity. The elimination half-life is only 2 hours.
Its chemical analogue, etacizine, additionally blocks calcium channels. However, its safety profile is inferior: adverse reactions occur more frequently and are more severe, especially when administered intravenously.
Herbal medication — Lappaconitine hydrobromide
Lappaconitine hydrobromide (allapinin) is derived from the alkaloid of Aconitum leucostomum (whitish-lip monkshood). It is a drug with a "mild" hemodynamic profile that stands out among the entire class IC.
Its key advantages are:
- It practically does not depress AV conduction (it slows only intra-atrial and intraventricular conduction).
- It is inotropically neutral (does not reduce myocardial contractility).
- It does not lower blood pressure.
Due to the absence of cardiodepressive action, it is the only drug among those reviewed that can be used during myocardial infarction to treat both ventricular and supraventricular extrasystoles. Notable side effects include central nervous system symptoms (diplopia, dizziness, headache) as the drug crosses the blood-brain barrier. These phenomena are dose-dependent and disappear when the dose is reduced.
Briefly: answers to topical questions
Which drugs belong to class IC antiarrhythmic agents?
According to the cited sources, class IC antiarrhythmic agents include: propafenone, flecainide, moracizine (ethmozine), etacizine, and lappaconitine hydrobromide (allapinin). The primary effect indicated for class IC is sodium channel blockade; sodium channel blockade is explicitly stated for propafenone and etacizine, and sodium channel-blocking properties are indicated for moracizine.
What are the absolute contraindications to prescribing propafenone?
Propafenone has a number of strict contraindications and limitations similar to other sodium channel blockers. These include:
- SA block (SA-blockade) — grade II–III SA block.
- AV block (AV-blockade) — grade II–III AV block.
- Sinus bradycardia (sinus bradycardia) — in the absence of an artificial pacemaker.
- Intraventricular conduction disturbances (intraventricular conduction disturbances) — severe disturbances (QRS > 140 ms).
- Atrial flutter (atrial flutter) — in the absence of therapy with AV nodal blocking agents.
- CAD (coronary artery disease) — coronary artery disease.
- Post-MI cardiosclerosis (post-myocardial infarction cardiosclerosis) — post-myocardial infarction cardiosclerosis.
- Left ventricular hypertrophy (left ventricular hypertrophy) — LVH > 1.4 cm.
- Decreased contractility (decreased contractility) — reduced ejection fraction.
In which supraventricular arrhythmias is flecainide used?
In the cited sources, flecainide is indicated for rhythm restoration in atrial fibrillation/atrial flutter: cardioversion of AF/AFl with class Ic drugs, including flecainide, is permitted only in "healthy hearts." Additionally, class IC agents in general are indicated for the prevention of AF/AFl recurrence in the absence of contraindications and when catheter ablation is ineffective, unfeasible, or declined.
With which drugs does propafenone clinically interact significantly?
Propafenone interacts clinically in a significant manner with immunosuppressants such as cyclosporine, tacrolimus, and sirolimus via inhibition of CYP3A4 enzymes and P-glycoprotein, leading to increased blood concentrations of these drugs. Furthermore, propafenone is contraindicated for co-administration with nirmatrelvir in combination with ritonavir.
To remember the safety profile of lappaconitine, use the mnemonic: "Lappaconitine is 'gentle' (Lasdovy/Gentle)." It is "gentle" on the myocardium: it does not lower blood pressure, does not depress contractility, and is approved for use in myocardial infarction, unlike harsh synthetic analogues.
Class and exam questions
Why are class IC drugs not prescribed as first-line agents?
Due to their pronounced arrhythmogenic activity and ability to suppress myocardial contractility. They are used only as a reserve for life-threatening ventricular arrhythmias refractory to other medications.
What causes the risk of bronchospasm when taking propafenone?
Propafenone has a complex mechanism of action that includes $\beta$-adrenolytic activity. It is precisely the blockade of $\beta$-receptors in the bronchi that can trigger a spasm.
Which class IC drug can be prescribed to a patient with myocardial infarction?
Lappaconitine hydrobromide. It exhibits inotropic neutrality, meaning it does not depress heart muscle contractility and does not lower blood pressure.
Why is the oral bioavailability of propafenone and lappaconitine relatively low?
Both drugs undergo intensive presystemic biotransformation (the hepatic "first-pass" effect), which significantly reduces the proportion of the active substance entering the systemic circulation.
What else to study on this topic
- Electrophysiological differences among subclasses IA, IB, and IC
- The mechanism of the hepatic "first-pass" effect and its impact on dosing
- Blood-brain barrier permeability for antiarrhythmics and neurological side effects
- Characteristics of intravenous administration of etacizine and moracizine
- Comparative characteristics of the effect of antiarrhythmics on the effective refractory period (ERP)
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