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QT INTERVAL AND DRUG-INDUCED CHANGES
Souza, A. C.M., 1Grabe-Guimarães, A., 3Sales M. L., 1Leite, R., 2Guimarães,
H.N.,¹Laboratório de Farmacologia Experimental, Departamentoto de Farmácia, UFOP, MG,
Brazil,2Departamento de Engenharia Elétrica, UFMG, MG, Brazil, 3Departamento de Ciências
Médicas, UFOP, MG, Brazil.
1
Introduction: The electrocardiogram (ECG) is an important tool for the diagnosis of
cardiac abnormalities, as well as the monitoring of cardiac patients in treatment, among
other utilities. The QT interval, time since the beginning of the QRS complex to the end
of the T wave of ECG is a measure of the duration of depolarization and repolarization.
The QT interval prolongation can be induced by use of cardiotoxic drugs. Objectives:
Describe the QT interval and its prolongation induced by drugs. Methods and Results:
Literature research on Medline database using the keywords “QT interval prolongation”
and “cardiotoxic drugs”. Theoretical literature information was obtained after selection of
articles that describe ECG alterations induced by drugs with different therapeutic goals.
According to “FDA Guidance for Industry S7B Nonclinical Evaluation of the Potential for
Delayed Ventricular Repolarization (QT Interval Prolongation) by Human
Pharmaceuticals” when QT interval is prolonged, there is an increased risk of ventricular
tachyarrhythmia, particularly when combined with other risk factors (e.g., hypokalemia,
structural heart disease, bradycardia). Thus, much emphasis has been placed on the
potential proarrhythmic effects of pharmaceuticals that are associated with QT interval
prolongation. The rapidly and slowly activating components of the delayed rectifier
potassium current, IKr and IKs, have the most influential role in determining the duration
of the action potential, and so, the QT interval. The human ether-a-go-go-related gene
(hERG) and KvLQT1 gene encode pore-forming proteins KCNH2 and KCNQ1 that are
thought to represent the α-subunits of the human potassium channels responsible for
IKr and IKs, respectively. ECG abnormalities similar to those seen in patients carrying
mutations in the hERG gene can also be induced by direct blockade of hERG/IKr
channels by a large group of structurally diverse therapeutic compounds including many
antiarrhythmics, antihistamines, antipsychotics and antibiotics. The most common
mechanism of drug induced QT interval prolongation is inhibition of the delayed rectifier
potassium channel that is responsible for IKr. At least three therapeutic compounds
reduce hERG/IKr currents not by direct blockade but by inhibition of hERG/IKr trafficking
to the cell surface: (i) arsenic trioxide and and antimonial compounds, which are used to
treat acute promyelocytic leukaemia, (ii) the antiprotozoical agent pentamidine, and (iii)
cardiac glycosides, which are still used in heart failure. The antidepressive fluoxetine
represents the first member of a potentially large group of compounds that directly block
hERG and inhibit its traffic at the same time.(Biochemical Society Transactions 35:5,
2007). Conclusions: Therefore, it's important to investigate and understand the safety
of therapeutic drugs that may induce arrhythmias due the QT prolongation. Financial
Support: FAPEMIG; UFOP; UFMG