Class 1A:Sodium channel blockers Drugs • Quinidine • Disopyramide • Procainamide Mechanism of action • Binds to both active and inactivated Na+ channels • Reduce slope of phase 4 depolarization • Inhibits K+ channels • Increases duration of AP
Quinidine metabolism and adverse effects:
Liver CYP3A4
Cinchonism (dry lips, mouth, tinitius)
Drugs of class 1B:
Lidocaine
Mexiletine
Tocainide
Mechanism of class 1b
shorten phase 3 - repol
decrease action potential duration
Lidocaine metabolism and AE:
Metabolised by CYP3A4 but estensive FPE so IV preferred
AE: Nystagmus, confusion, negative inotrope
Slope showing effect of which class:
Class 1b due to reduced duration of action potential and shortening of phase 3
Class 1c
Flecainide
Propafenone
Class 1c MOA:
Significantly slow phase 0 depolarization
• Strong effect on Na+ channels
• Increase in threshold potential
• Blockade of K+ channels (Flecainide)
Flecanide useful for atrial flutter and fibrillation
Flecainide is restricted to use in structurally normal hearts
Beta blockers diminish phase 4 and have a negative inotropic effect
Indications of beta blockers
Treatment of supraventricular tachy-arrhythmias (AF, atrial flutter)
• Increase survival in patients with heart failure and myocardial infarction
Metoprolol is B1 selective e.g. reduced risk of bronchospasm
Esmolol is ultra short acting and has a rapid onsent (selective B1)
Class 3 agents include Amiodarone • Dronedarone • Sotalol, Ibutilide which are potassium channel blockers
class 3 prolong phase 3 repolarization therefore prolonging duration of AP
Amiodarone adverse effects
Has iodine ions
Thyroid disorders
Pulmonary fibrosis
hepatotoxicity , skin discoloration
Class 3 Dronedarone contraindications
Heart failure
Permanent AF
Class 4 are CCBs and the non dihydropyridines include
Diltiazem and Verapamil
CCBs MOA:
Prevent depolarization
BUT AVOID IN HF
Digoxin MOA
Inhibits Na-K Atpase preventing Na out and Calcium in