Pharmacological Effects of Antiarrhythmic Drugs

Abstract

Most antiarrhythmic drugs are potent compounds with a relatively narrow therapeutic index. When prescribed judiciously, they can have a key role in enhancing or prolonging the lives of patients with most common arrhythmias. But when misprescribed, through selection of an inappropriate drug or dosage regimen, the end result may range from inadequate control of the arrhythmia to a proarrhythmic effect. Ultimately, the optimal use of antiarrhythmic drug therapy depends in large part on understanding the pharmacodynamics and pharmacokinetics of each antiarrhythmic drug. Despite the common classification of antiarrhythmic drugs into class I, II, III, or IV, each drug has a unique pharmacological profile and must not be considered interchangeable with other members of its class. Likewise, each patient is unique with respect to the innumerable factors that can alter the pharmacokinetics of an antiarrhythmic drug, including coexisting diseases, concurrent drug therapies, and endogenous or age-related metabolic variations. This article provides an overview of the key pharmacodynamic and pharmacokinetic characteristics of the major antiarrhythmic drugs in use. It also offers specific examples that may be used to ensure that patients receive the most appropriate therapy.

Type 1 Brugada pattern ECG due to supra-therapeutic phenytoin level

“…It decreases the maximum rate of depolarisation of the cardiac action potential and increases the effective refractory period. Therefore, it is useful in inhibiting ventricular ectopy, especially in an ischaemic or damaged myocardium 6. However, the emergence of newer and less toxic agents has led to the replacement of phenytoin as a first-line treatment.…”

Phenytoin as an effective treatment for polymorphic ventricular tachycardia due to QT prolongation in a patient with multiple drug intolerances

“…The elimination half-life is 16–24 h, with the major route of elimination being hepatic. Phenytoin has a 50–70% oral bioavailability and 90% protein binding 3. Phenytoin can be administered intravenously or orally 2…”

Mexiletine has a local anesthetic effect on sciatic nerve blockade in rats

“…Mexiletine has pharmacological effects similar to those of lidocaine. Both drugs have antiarrhythmic effects, especially for the ventricular tachyarrhythmia [Campbell and Williams, 2001;Kowey, 1998;Kowey et al, 2000] and both have Na 1 channel blocking and local anesthetic effects. The similarity in their chemical structures (Fig.…”

“…Mexiletine is an antiarrhythmic drug that has Na 1 channel blocking activity [Kowey et al, 2000] and has been widely used in the treatment of symptomatic and/ or life threatening ventricular arrhythmias, e.g., ventricular tachycardia [Campbell and Williams, 2001;Kowey, 1998;Kowey et al, 2000] and in the treatment of neuropathic pain including diabetic neuropathy, neuropathic cancer pain, among others [Jarvis and Coukell, 1998;Sloan et al, 1999]. Although mexiletine has been used clinically for more than 30 years [Labbé and Turgeon, 1999], its potential clinical use has not been fully explored, e.g., local anesthetic effect.…”

“…First, unlike most of the classical local anesthetics, mexiletine has limited cardiac-related side effects because it is a drug used in the treatment of cardiac rhythm disorders [Campbell and Williams, 2001;Kowey, 1998;Kowey et al, 2000]. Secondly, mexiletine has anticonvulsant activity and is effective in protecting the brain from ischemic insults [Hewitt et al, 2001;Stys and Lesiuk, 1996].…”