Pharmacodynamics<unk>  acts as a blocker of voltage-gated sodium channels. Inhibition of the Nav1.5 channel is specifically involved in its antiarrhythmic effects as a class I antiarrhythmic agent.<unk>  also blocks certain voltage-gated potassium channels (e.g., Kv1.4, Kv4.2, hERG, among others), acts as an antimuscarinic and alpha-1 blocker, and is an antimalarial. Mechanism of action Like all other class I antiarrhythmic agents,<unk>  primarily works by blocking the fast inward sodium current (INa).<unk> 's effect on INa is known as a 'use dependent block'. This means at higher heart rates, the block increases, while at lower heart rates, the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the cardiac action potential to decrease (decreased Vmax). It seems still efficacious as an IV antimalarial against Plasmodium falciparum. This electrolyte dependent agent also increases action potentials and prolongs the<unk> T interval.<unk>  also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito. At micromolar concentrations,<unk>  inhibits Na+/K+-ATPase by binding to the same receptor sites as the digitalis glycosides such as ouabain. The effect of<unk>  on the ion channels is to prolong the cardiac action potential, thereby prolonging the<unk> T interval on the surface ECG. Other ECG effects include a wide notched P wave, wide<unk> RS complex, depressed ST segment, and U waves. These are the results of both slowed depolarization and repolarization. Pharmacokinetics Elimination The elimination half-life of oral<unk>  is 6 to 8 hours, and it is eliminated by the cytochrome P450 system in the liver. About 20% is excreted unchanged via the kidneys.
Quinidine
Lidocaine
Nortilidine
Colestilan
Ibutilide
Maprotiline
Etidocaine
Amiodarone