Anti-arrhythmic Drugs Flashcards
Classification of anti-arrhythmic drugs?
Class 1 drugs (sub-categorised into) “Na+ Blockers”
- Class 1A = Quinidine, disopyramide and procainamide
- Class 1B = Lidocaine and mexiletine
- Class 1C = Flecainide and propafenone
Class 2 Drugs : Beta blocker agents “propranolol”
Class 3 Drugs : “Amiodarone” (K+ channel blocker)
Class 4 Drugs : “Verapamil” (Ca2+ channel blockers)
Other anti-arrhythmic : “Digoxin” sodium : potassium ATPase channel blocker.
MOA of class 1A drugs ?
They function to block sodium channels, preventing sodium influx, which in turn reduces the rate of phase 0 (Depolarisation in cardiac AP). Ca2+ blockage and inhibition of K+ channels. Overall effects are “reduced conduction velocity” and “increased refraction” (when the next AP is able to be produced) as a result.
Therapeutic uses of class 1A?
“Quinidine” is used for a wide range of arrhythmias such as atrial arrhythmia’s, AV junctional and ventricular arrhythmia’s.
“Procainamide” is only available through IV infusion hence it has a rapid acute effect, suitable for treatment of acute atrial and ventricular arrhythmias.
“Disopyramide” can be used as an alternative for the treatment of atrial fibrillation/flutter and ventricular arrhythmias.
Adverse effects of A1 drugs?
- Quinidine in high doses causes “cinchonism” symptoms.
- Disopyramide induces anti-cholinergic effects (Xerostomia, constipation, urinary retention e.t.c)
- Metabolism of procainamide leads to “NAPA” formation which has class 3 adverse effect activity that are pro-arrhythmic, can progress into ventricular fibrillation.
Pharmacokinetics of A1 drugs?
Quinidine has good oral absorption, hepatic metabolism into active metabolites via CYP3A4 isoenzyme.
Procainamide has IV administration, hepatic metabolism via CYP3A4 into NAPA, which has adverse effects of class 3 drugs of developing ventricular fibrillation.
Disopyramide is well absorbed after oral administration, hepatic metabolism by CYP3A4 isoenzyme into inactive metabolites, more than half of drug is excreted in the urine unchanged.
MOA of class 1B?
Blockage of sodium channels to prevent sodium influx (Normally sodium channels would open to allow entry into cell). Opening of the K+ channel (potassium efflux), this leads to “reduced duration of the action potential”. Phase 3 of cardiac AP is also shortened, as the low sodium influx required less ca2+ influx to achieve the rapid re-polarisation in phase 2, caused by the K+ efflux.
Therapeutic uses of class 1B?
Lidocaine is used as a alternative to “Amiodarone” for the treatment of ventricular flutter and VT, whereas the mexiletine is used for treatment of chronic ventricular arrhythmias.
Pharmacokinetics of class 1B?
Lidocaine like procainamide is give using IV administration due to extensive first pass metabolism. Lidocaine is metabolised by the isoenzyme CYP1A2, whereas mexiletine is acted on by CYP2D6 isoenzyme into active metabolites that are removed in the bile via feces.
Adverse effects of class 1B?
Lidocaine use leads to CNS penetration hence its related effects are (drowsiness, paresthesia and convulsions).
Mexelitene side effects are vomiting, nausea and dyspepsia (indigestion).
MOA of class 1C drugs?
Most potent sodium channel blockers out of the 3 class 1 drugs. They exhibit no effects on the K+ channels, therefore have little effect on the duration of the action potential and refraction. But Flecainide can close K+ channels which leads to prolonged action potential. Propafenone reduces conduction in the cardiac tissues but does not block K+ channels.
Therapeutic uses of class 1C?
Flecainide is used for maintaining “sinus rhythm” (atrial flutter/fibrillation) in patients with a structurally normal heart e.g without CAD. Due to the pro-arrhythmic and inotropic effects of these drugs, they are contraindicated in patients with CAD, left ventricular hypertrophy, heart failure e.t.c. Propafenone is restricted mostly to the use of atrial arrhythmias.
Adverse effects of class 1C?
Propafenone may cause broncho constriction, hence it is contra-indicated in patients with asthma.
Flecainide causes nausea, dizziness and blurred vision.
Pharmacokinetics of the class 1C drugs?
Flecainide undergoes metabolism via the isoenzyme CYP2D6 into multiple metabolites.
Propafenone undergoes metabolism via CYP2D6 into active metabolites that are excreted into the feces and urine.
Describe the type 2 anti-arrhythmic drugs.
They are beta-blockers, meaning that their effects are associated with reduced heart rate and contractility. The type 2 drugs also have other functions : reduced automaticity, prolonged AV conduction and to diminish the 4th phase of the cardiac AP (re-entry of sodium into the cardiac cells).
The main example is “Propranolol” which has CNS penetration as wells as metabolism by the CYP2D6 isoenzyme. The propranolol can be used to reduce the effects of bronchospasm (which was a side effect of the propafenone).
MOA of type 3 anti-arrhythmic drugs?
Amiodarone is the main example, its dominant effect is to block the K+ channels therefore having the effect of prolonging the duration of the AP and refractory period.
