Class 1 Antiarrhythmics Flashcards
What is the primary mechanism of action of Class I antiarrhythmics?
Block sodium channels to inhibit phase 0 depolarization, reducing excitability and conduction in cardiac tissue. Binding is dependent on the rate of depolarization. Each causes a different level of sodium binding (C > A > B). They work via “use dependency” and bind more regularly to on/off channels rather than resting channels.
How do Class I antiarrhythmics affect cardiac conduction?
They slow conduction velocity and reduce the automaticity of cardiac cells.
How are Class I antiarrhythmics subdivided?
Into Class Ia, Class Ib, and Class Ic based on their effects on the action potential duration and their binding affinity to sodium channels.
What is state-dependent binding in Class I antiarrhythmics?
Class I drugs preferentially bind to sodium channels in their open or inactivated states, making them more effective at higher heart rates.
What are the primary Class Ia antiarrhythmics?
Quinidine, procainamide, and disopyramide.
What is the mechanism of action of Class Ia drugs?
Moderate sodium channel blockade, slowing phase 0 depolarization, and potassium channel blockade, prolonging the action potential and refractory period.
How does Class Ia prolong the action potential?
By blocking potassium channels, leading to prolonged repolarization (phase 3) and an increased refractory period.
What ECG changes are seen with Class Ia antiarrhythmics?
Prolonged QRS duration and prolonged QT interval, increasing the risk of torsades de pointes.
What arrhythmias are treated with Class Ia antiarrhythmics?
Supraventricular tachyarrhythmias, ventricular arrhythmias, and Wolff-Parkinson-White syndrome.
What are the major side effects of quinidine?
- Cinchonism (tinnitus, headache, dizziness)
- Thrombocytopenia
- QT prolongation
What symptoms are seen in quinidine-induced cinchonism?
Tinnitus, headache, dizziness, nausea, and blurred vision.
What is a rare hematologic adverse effect of quinidine?
Thrombocytopenia.
What are the major side effects of procainamide?
Drug-induced lupus erythematosus with antihistone antibodies, presenting as rash, arthralgia, pericarditis, pleuritis, and other systemic symptoms.
What are the common manifestations of drug-induced lupus erythematosus from procainamide?
Rash, fever, joint pain, serositis (pericarditis, pleuritis), and positive antihistone antibodies.
What is the major side effect of disopyramide?
Negative inotropic effect, which can precipitate heart failure.
Which Class Ia antiarrhythmic can lead to anticholinergic symptoms?
disopyramide
What are the primary Class Ib antiarrhythmics?
Lidocaine, mexiletine, and phenytoin.
What is the mechanism of action of Class Ib drugs?
Mild sodium channel blockade with preferential binding to depolarized or ischemic tissue, shortening phases 2 and 3 of the action potential.
Why are Class Ib antiarrhythmics selective for ischemic tissue?
They preferentially bind to depolarized sodium channels, which are more common in ischemic and infarcted tissue.
How do Class Ib antiarrhythmics affect the action potential duration?
They shorten the action potential duration by shortening phase 3 repolarization.
What ECG changes are seen with Class Ib antiarrhythmics?
Minimal to negligible effect on the PR interval, QRS duration, and QT interval.
What arrhythmias are treated with Class Ib antiarrhythmics?
Ventricular arrhythmias, particularly those associated with ischemic heart disease or myocardial infarction. Ironically these can cause ventricular arrhythmias.
What are the major side effects of Class Ib antiarrhythmics (Lidocaine, mexiletine, and phenytoin)?
Neurologic symptoms including paresthesia, tremors, and convulsions.
What is the most common side effect of lidocaine toxicity?
Seizures due to central nervous system excitation.
Why does lidocaine cause seizures in high doses?
It suppresses inhibitory neurons in the central nervous system, leading to excitatory symptoms such as tremors and convulsions.
What are the primary Class Ic antiarrhythmics?
Flecainide and propafenone.
What is the mechanism of action of Class Ic drugs?
Strong sodium channel blockade causing significant slowing of phase 0 depolarization and prolongation of QRS duration.
How do Class Ic antiarrhythmics affect the action potential duration?
They have little to no effect on the action potential duration.
What ECG changes are seen with Class Ic antiarrhythmics?
Prolonged QRS duration WITHOUT significant changes in the PR or QT intervals.
What arrhythmias are treated with Class Ic antiarrhythmics?
Supraventricular and ventricular arrhythmias, including atrial fibrillation and atrial flutter.
Why are Class Ic antiarrhythmics contraindicated in patients with structural or ischemic heart disease?
Class IC antiarrhythmics are contraindicated in patients with structural or ischemic heart disease due to their strong sodium channel blockade, which can exacerbate conduction abnormalities and promote fatal reentrant arrhythmias, as demonstrated by increased mortality in the CAST trial.
What is the proarrhythmic effect of Class Ic drugs?
Excessive sodium channel blockade can cause life-threatening ventricular arrhythmias.
Why do Class Ic antiarrhythmics exhibit strong use dependence?
They bind sodium channels most avidly in their open state, making them more effective at higher heart rates.
Which Class I antiarrhythmic subclass exhibits the strongest sodium channel binding?
Class Ic (flecainide, propafenone).
Which Class I antiarrhythmics are most effective for ischemia-induced arrhythmias?
Class Ib, such as lidocaine and mexiletine, because they preferentially target ischemic myocardium.
Which Class I antiarrhythmics are best for rhythm control in atrial fibrillation?
Class Ic, such as flecainide and propafenone, but only in patients without structural heart disease.
Which Class I antiarrhythmics prolong the QT interval and why?
Class Ia (quinidine, procainamide, disopyramide) due to potassium channel blockade that prolongs repolarization.
Which Class I antiarrhythmics have minimal effect on ECG intervals?
Class Ib (lidocaine, mexiletine) because they have minimal effect on conduction in normal cardiac tissue.
Which Class I antiarrhythmics are most potent in slowing conduction?
Class Ic (flecainide, propafenone) because they cause the most significant phase 0 upstroke delay.
