Sildenafil citrate and Torsade de pointes

Sildenafil citrate is a drug used in the treatment of erectile dysfunction. It is an inhibitor of the enzyme phosphordiesterase-5; it slows down the breakdown of c-GMP and nitrous oxide. The cardiac effects associated with Sildenafil citrate have been extensively studied in medical literature, especially its potent vasodilatory effect when combined with nitrate-based medications, producing intractable hypotension, but a lesser known and potentially lethal side effect is prolonged cardiac repolarization when used at dosage greater than recommended, leading to QT prolongation that could theoretically lead to dangerous cardiac dysrrhythmias and sudden death in men with coronary artery disease. The authors present the case of a 49-year-old hypertensive Hispanic man who arrived to our emergency department with the chief complaint of acute epigastric pain for 3 hours of evolution after ingestion of Sildenafil citrate 50 milligrams (mg). The patient was found to have an acute ST elevation inferior myocardial infarction (STEMI). Shortly after diagnosis the patient developed a polymorphic ventricular tachycardia (Torsade de pointes) before thrombolytic administration. We present this case followed by a brief discussion, to heighten awareness of the possible association of acute inferior STEMI and the development of Torsade de Pointes after the use of Sildenafil citrate.

Sex difference in the repolarization currents of rabbit ventricular cells / 华中科技大学学报（医学）（英德文版）

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4+/-26.5 ms, n=15) than in male ones (489.0+/-20.7 ms, n = 14), P0.05). The lower IK.tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

Seventy-four defibrillations for sotalol-induced torsades de pointes.

We report a patient with sotalol-induced torsades de pointes episodes that did not respond to magnesium and amiodarone. Electrical defibrillation totaling 15,120 joules had to be applied. However, torsades de pointes episodes could be brought under control only after the induction of general anesthesia with pentothal.

Torsade de pointes probably induced by sparfloxacin.

Sparfloxacin is a new fluoroquinolone with potent antitubercular activity. We report a case of a 37 year old female who was on this drug as part of modified antitubercular therapy and developed torsade de pointes on this drug.

The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.