Antidysrhythmic Drugs & Cardiac Cell Action Potential

• Antidysrhythmic drugs are used to treat and prevent disturbances in cardiac rhythm (dysrhythmias).
• Dysrhythmia: Any deviation from the normal rhythm of the heart.

Cardiac Cell Action Potential

• The resting membrane potential requires an energy-requiring pump to maintain an uneven distribution of ions, specifically the sodium-potassium adenosine triphosphatase (ATPase) pump.
• Inside a resting cardiac cell, there is a net negative charge relative to the outside due to the uneven distribution of ions (sodium, potassium, calcium) across the cell membrane, resulting in a resting membrane potential.
• A change in ion distribution causes cardiac cells to become excited, leading to an electrical impulse that spreads across the cells, causing myocardial muscle contraction.
• Four phases occur during action potential, sinoatrial node and Purkinje cells each have separate action potentials.
• Absolute or effective refractory period is part of action potential duration
• Relative refractory period is part of action potential duration.
• Threshold potential occurs during action potential.
• Automaticity or pacemaker activity occurs during action potential.

Common Dysrhythmias

• Supraventricular dysrhythmias.
• Ventricular dysrhythmias.
• Ectopic foci.
• Conduction blocks.

Vaughan Williams Classification of Antidysrhythmic Drugs

• System commonly used to classify antidysrhythmic drugs based on their electrophysiological effect on the action potential.
• Includes Class I (Ia, Ib, Ic), Class II, Class III, Class IV, and Unclassified drugs.

Vaughan Williams Classification: Mechanism of Action

• Class I drugs are membrane-stabilizing drugs and fast sodium channel blockers, divided into Ia, Ib, and Ic drugs according to their effects.
• Class Ia drugs (procainamide, quinidine, and disopyramide): block sodium (fast) channels, delay repolarization, and increase action potential duration (APD); used for atrial fibrillation, premature atrial contractions/ventricular contractions, ventricular tachycardia, and Wolff-Parkinson-White syndrome.
• Class Ib drugs (lidocaine hydrochloride): block sodium channels, accelerate repolarization, and increase or decrease APD; lidocaine is used for ventricular dysrhythmias only, and phenytoin is used for atrial and ventricular tachydysrhythmias caused by digitalis toxicity or long QT syndrome.
• Class Ic drugs (flecainide, propafenone): block sodium channels (more pronounced effect) with little effect on APD or repolarization; used for severe ventricular dysrhythmias and may be used in atrial fibrillation/flutter, Wolff-Parkinson-White syndrome, supraventricular tachycardia dysrhythmias.
• Class II drugs (ß-blockers): reduce or block sympathetic nervous system stimulation, reducing transmission of impulses in the heart’s conduction system; depress phase 4 depolarization and are general myocardial depressants for both supraventricular and ventricular dysrhythmias; also used as antianginal and antihypertensive drugs.
• Class III drugs (amiodarone, dronedarone, sotalol, ibutilide): increase APD and prolong repolarization in phase 3; used for dysrhythmias that are difficult to treat, including life-threatening ventricular tachycardia or fibrillation, and atrial fibrillation or flutter resistant to other drugs.
• Class IV drugs: Calcium channel blockers that inhibit slow channel (calcium-dependent) pathways, depress phase 4 depolarization, and reduce atrioventricular node conduction; used for paroxysmal supraventricular tachycardia (PSVT) and rate control for atrial fibrillation and flutter.

Specific Antidysrhythmic Drugs

• Procainamide hydrochloride: used for atrial and ventricular tachydysrhythmias; significant adverse effects include ventricular dysrhythmias and blood disorders; other adverse effects include hypotension, rash, diarrhea, nausea, vomiting, agranulocytosis, systemic lupus erythematosus (SLE)–like syndrome, and torsades de pointes resulting from prolongation of the QT interval; contraindications include known hypersensitivity, heart block, and SLE.
• Lidocaine (Xylocaine®): raises the ventricular fibrillation threshold; significant adverse effects on the central nervous system (CNS): twitching, convulsions, confusion, respiratory depression or arrest, hypotension, bradycardia, and dysrhythmias; contraindications include hypersensitivity, severe sinoatrial or atrioventricular intraventricular block, or Stokes-Adams or Wolff-Parkinson-White syndrome.
• Flecainide (Tambocor®): first-line drug in the treatment of atrial fibrillation; has a negative inotropic effect and depresses left ventricular function; adverse effects include dizziness, visual disturbances, and dyspnea; contraindications include hypersensitivity, cardiogenic shock, second-or third-degree atrioventricular block, and non–life-threatening dysrhythmias.
• Atenolol (Tenormin®): cardioselective ß-blocker that preferentially blocks the ß1-adrenergic receptors in the heart; noncardioselective ß-blockers block both the ß1-adrenergic receptors in the heart and the ß2-adrenergic receptors in the lungs and therefore can exacerbate pre-existing asthma or chronic obstructive pulmonary disease; uses include antidysrhythmic, hypertension, and angina; contraindications include severe bradycardia, second-or third-degree heart block, heart failure, cardiogenic shock, or a known hypersensitivity.
• Amiodarone hydrochloride (Cordarone®): markedly prolongs the action potential duration and the effective refractory period in all cardiac tissues; blocks both the α-and ß-adrenergic receptors of the sympathetic nervous system; uses: one of the most effective antidysrhythmic drugs for controlling supraventricular and ventricular dysrhythmias; the drug of choice for ventricular dysrhythmias; most serious effect: pulmonary toxicity; other adverse effects: corneal microdeposits, photosensitivity, and pulmonary toxicity; drug interactions: digoxin and warfarin sodium; contraindications: hypersensitivity, severe sinus bradycardia, or second-or third-degree heart block.
• Diltiazem (Cardizem®, Tiazac®): temporary control of a rapid ventricular response in patients with atrial fibrillation or flutter and PSVT; contraindications: hypersensitivity, acute myocardial infarction, pulmonary congestion, Wolff-Parkinson-White syndrome, severe hypotension, cardiogenic shock, sick sinus syndrome, or second-or third-degree AV block.
• Adenosine (Adenocard®): slows conduction through the atrioventricular node and is used to convert PSVT to sinus rhythm; very short half-life—less than 10 seconds; only administered as fast intravenous (IV) push; may cause asystole for a few seconds; other adverse effects are minimal.

Contraindications to Antidysrhythmic Drugs

• Known drug allergy.
• Second-or third-degree atrioventricular block, bundle branch block, cardiogenic shock, sick sinus syndrome, and any other ECG changes, depending on the clinical judgment of a cardiologist.
• Other antidysrhythmic drugs.

Adverse Effects of Antidysrhythmics

• All antidysrhythmics can cause dysrhythmias!.
• Hypersensitivity reactions.
• Nausea, vomiting, and diarrhea.
• Dizziness.
• Headache, and blurred vision.
• Prolongation of the QT interval.

Drug Interactions with Antidysrhythmics

• Warfarin sodium (Coumadin®): monitor international normalized ratio (INR).
• Grapefruit juice: amiodarone, disopyramide, and quinidine.

Nursing Implications for Antidysrhythmic Drugs

• Obtain a thorough drug and medical history.
• Measure baseline blood pressure, pulse, input and output, and cardiac rhythm.
• Measure serum potassium levels before initiating therapy.
• Assess for conditions that may be contraindications to the use of specific drugs.
• Assess for potential drug interactions.
• Instruct patients to report dosing schedules and adverse effects to physician
• During therapy, monitor cardiac rhythm, heart rate, blood pressure, general well-being, skin color, temperature, and heart and lung sounds.
• Assess plasma drug levels as indicated.
• Monitor for toxic effects.
• Instruct patients to take medications as scheduled and not to skip doses or double up for missed doses.
• Instruct patients to contact their physicians for instructions if a dose is missed.
• Instruct patients not to crush or chew oral sustained-release preparations.
• Monitor ECG for prolonged QT interval with use of antidysrhythmics, including amiodarone, procainamide, quinidine, sotalol, and flecainide.
• Administer IV infusions with an IV pump.
• Solutions of lidocaine that contain epinephrine should not be given intravenously; they are to be used only as local anesthetics.
• Ensure that the patient knows to notify the health care provider of any worsening of dysrhythmia or toxic effects.
• Teach patients taking ß-blockers, digoxin, and other drugs how to take their own radial pulse for 1 full minute and to notify their physician before taking the next dose if the pulse is less than 60 beats/min.
• Monitor for therapeutic response.
• Decreased blood pressure in hypertensive patients
• Decreased edema
• Decreased fatigue
• Regular pulse rate
• Pulse rate without major irregularities
• Improved regularity of rhythm
• Improved cardiac output