Other Drugs Acting on Nervous System Associated with QT-Interval Prolongation

Abstract

Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some preparations used for treatment of cough. These drugs have a narrow therapeutic interval or possible drug interactions that lead to clinical toxicity manifested by arrhythmias. They share the ability to block potassium channels (HERG), prolong the action potential and QT interval, and generate arrhythmias and Torsades de Pointes like other typicality recognized like antiarrhythmics, antihistamines, prokinetics, psychotropics and anti-infectives agents. Muscle relaxants like alcuronium, pancuronium and atracurium associated with or without atropine prolong significantly the QT interval. Methadone is the opiod most tightly associated with QTc prolongation; with much lesser potency buprenorphine and oxycodone can block HERG channels and depress the IKr current in vitro.Antineoplastic chemotherapy like anthracyclines, alkylating drugs, alkilants and cisplatin are associated with electrocardiographic alterations including prolongation of QT and emesis of different grades. It's very important take in account the synergic effects over the QT prolongation when effective antiemetics like 5-HT3 receptor antagonist (granisetron, ondansetron, and dolasetron) are administered. The Knowledge of their pharmacological properties is of vital importance to avoid exposing particularly vulnerable individuals as those with congenital long QT syndrome, and even the general public to unnecessary risk of potentially fatal arrhythmias.

Ion channel trafficking: A new therapeutic horizon for atrial fibrillation

“…It has been well established that non-antiarrhythmic drugs can have proarrhythmic effects through off target inhibition of cardiovascular ion channel currents. This has been reported for psychiatric drugs, antihistamines, antimicrobials and other compounds, many of which can induce QT prolongation with subsequent risk of torsade de pointes 92. As a result, pharmaceutical companies and regulatory agencies mandate that cardiac ion channel testing be part of the drug safety profiling of all new compounds.…”

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

“…We identified three patient cases (0.8 %) of methadone-associated QT interval prolongation [30, 31] of the 392 patients in methadone treatment ( p  = 0.008; FDR = 0.02), verified by manual chart review.…”

Symptomatic Management for Gastroparesis

“…QTc prolongation also has been attributed to other antiemetic and neuromodulatory drugs used for gastroparesis, including 5-HT 3 receptor antagonists and tricyclic antidepressants. 43 Although increases in sudden cardiac death have been reported, no similar black box warnings have been issued for these medications. Consideration has been advocated for surveillance monitoring of electrolytes and electrocardiographic testing in selected clinical settings during use of some of these drugs.…”