Brugada syndrome is an inherited cardiac arrhythmia condition characterized by (i) coved ST-elevation and J point elevation of at least 2 mm in at least two of the right precordial ECG leads (V1-V3) and (ii) ventricular arrhythmias, syncope, and sudden death. Patients with Brugada syndrome or suspected mutation carriers can have normal ECG recordings at other times. In these cases, a diagnostic challenge with a sodium channel blocker such as ajmaline, flecainide, or pilsicainide may induce the full-blown type 1 ECG pattern and support the diagnosis. However, recently, many other pharmacological agents not related to class I anti-arrhythmic agents have been reported to induce Brugada ECG patterns including tricyclic antidepressants, fluoxetine, lithium, trifluoperazine, antihistamines, and cocaine. As published reports of the drug-induced Brugada sign have become increasingly prevalent, there is growing interest in the mechanisms responsible for this acquired ECG pattern and its clinical significance. It is possible that drug-induced Brugada syndrome may be due to an individual susceptibility that favours drug-induced ECG abnormalities, possibly as a result of an increase in a latent ion channel dysfunction similar to that in drug-induced long QT syndrome. However, further evidence is needed to confirm this postulation. In this paper, we will review the cases and evidence of drug-induced Brugada syndrome reported in the literature.
Amiodarone (AD), a potent antiarrhythmic drug, is often associated with several adverse effects. It is shown to accumulate phospholipids in various tissues, and the impaired catabolism of phospholipids has been implicated in AD-induced phospholipidosis. The synthesis of phospholipids in tissues has not been dealt with. Hence, the incorporation of [14C]-acetate into phospholipids has been studied to understand the AD-induced phospholipidosis in lung and liver. A significant increase in lung and liver phospholipids was observed after 21 and 28 days of AD (175 mg/kg body weight/day) treatment. In the lung and liver, the incorporation of [14C]-acetate into all phospholipid fractions was elevated, while in the lung mitochondria phosphatidylcholine, phosphatidyl ethanolamine and the cardiolipin levels were significantly increased. The results indicate that, in addition to the impaired catabolism of phospholipid, AD treatment resulted in increased phospholipid synthesis.