Prolong QT interval and "torsades de pointes" associated with different group of drugs.
The problem of formation of cardiac arrhythmia such as "torsades de pointes" because of prolongation of the QT interval is discussed in this article. It is established 2 forms of the long QT syndrome, a congenital and an acquired one. The congenital form has seven different known predisposing genes, six of which are associated with the myocardial ion channels. The prevalence of the congenital form is estimated at less than 1/10000. The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current. Among the congenital forms, particularly interest is focused on the potassium channel coded by the HERG gene located on chromosome 7 and with a key role in the normal electric cardiac activity. The potassium channel coded by the HERG gene is partly responsible for the return of the electric cardiac activity to the resting phase before the next myocardial electric activation process. Disturbed function will prolong the return to resting phase, which is thought to be an essential part of the development mechanism of myocardial "torsades de pointes" tachycardia. There may also be correlation between the strength of binding of the medicinal substance to the potassium channel coded by the HERG gene and prolongation of the QT interval. The investigation revealed that different groups of drugs may produce an effect on the QT interval, such as some neuroleptics (haloperidol, droperidol, thioridazine) antidepressants (paroxetine), narcotic analgesics (methadone), antiarrhythmics (class I), antihistamines (H1 receptor blocking agents) and motility stimulants (domperidone and cisapride). For the prevention of cardiac arrhythmia such as "torsades de pointes".
Gongadze
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N
Tbilisi State Medical University, Department of Pharmacology.
Kezeli
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T
Antelava
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N
D004358:Drug Therapy / Q000145:classification*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology