Prolongation of QT interval

BP, pulse, respiration, ECG intervals (PR, QRS, QT) at initiation of therapy and again after dosage increases prolongation of QT interval by greater than 0.52 sec predisposes to proarrythmia... 

Mechanism of Action An antiarrhythmicthat prolongs both atrial and ventricular action potential duration and increases the atrial and ventricular refractory period. Activates slow, inward current (mostly of sodium), produces mild slowing of sinus node rate and AV conduction, and causes dose-related prolongation of QT interval. Therapeutic Effect Converts arrhythmias to sinus rhythm. 

Prolongation of QT interval may produce torsades de pointes, a form of ventricular tachycardia. Patients with bradycardia, hypokalemia, or hypomagnesemia are at increased risk. 

In rabbits burned by an unknown amount of white phosphorus, electrocardiogram alterations (prolongation of QT interval, ST segment depression, T-wave changes, bradycardia, and low voltage QRS complex) indicative of myocardial damage were observed however, no histological alterations were observed in the heart (Bowen et al. 1971). 

Susceptibility factors genetic (long QT syndrome) altered physiology (hypokalemia) drug interactions (metabolism inhibitors drugs that prolong the QT interval) diseases (liver disease cardiac disease with prolongation of QT interval)... 

Sakabe M, Fujiki A, Inoue H. Propofol induced marked prolongation of QT interval in a patient with acute myocardial infarction. Anesthesiology 2002 97(l) 265-6. 

Retinoic acid-like syndrome (fever, dyspnea, pulmonary infiltrates, pleural effusions, peripheral edema, hypotension) fatigue musculoskeletal pain prolongation of QT interval and cardiac arrhythmias hyperglycemia... 

Halofantrine (Halfan) 250-mg tablet P. falciparum malaria Gl Abdominal pain, diarrhea Card. Prolongation of QT interval Should not be taken with fatty meals. Contraindication Preexisting conduction defects. 23,24,27... 

The emphasis, in terms of drug-induced prolongation of QT interval due to a decrease in the ability of myocytes to repolarize, has been squarely placed on the notion that this is due to the inhibition of (i.e., hERG potassium channel). However, an increase in the time constant for a myocyte to repolarize can also occur for reasons other than the inhibitimi of Other reasons for the prolongation... 

Drugs that prolor the QT interval + Other drugs that prolor the QT interval Amiodarone + Disopyramide Additive prolongation of QT interval, increased risk of torsade de pointes... 

Prolongation of QT interval may be predicted in vitro by patch clamp electrophysiology in mammalian cells transfected with the human ether-d-go-go-related gene (hERG), a subunit of the (cardiac rapidly activating delayed rectifier potassium channel), or by measuring a compound s abihty... 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

Elevated plasma concentrations of QT interval-prolonging drugs due to drug interactions or absence of dose adjustment for organ dysfunction... 

Domperidone minimally crosses the BBB it acts in the CTZ which lies outside of the BBB. As such, domperidone is less likely to cause the centrally-mediated adverse effects seen with metoclopramide and has an estimated overall incidence of 5% to 10%.1,30 However, domperidone has been associated with prolonged QT intervals, cardiac arrhythmias, and sudden death.31 It should not be used for patients with underlying long QT interval or for those on other medications that prolong the QT interval. Both metoclopramide and domperidone can cause hyperprolactinemia, galactorrhea, and gynecomastia. 

ECG changes include increased heart rate, flattened T waves, ST-segment depression, prolongation of QT and PR intervals, and torsade de pointes. Torsade de pointes has been reported with thioridazine, which may be a cause of cardiac sudden death. 

Several studies support the notion that the basic mechanism by which many drugs prolong the QT interval is related to blockade of potassium currents. For instance, several antihistamines, antibacterial macrolides, fluoroquinolones and antipsychotics were shown to inhibit the rapid component of the delayed rectifier K+ current (fKr) in electrophysiological studies and to block potassium channels encoded by hERG [37-42]. 

Davis, A.S. (1998) The pre-clinical assessment of QT interval prolongation a comparison of in vitro and in vivo methods. Human el Experimental Toxicology, 17, 677-680. 

De Ponti, F., Poluzzi, E., Cavalli, A., Recanatini, M. and Montanaro, N. (2002) Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsades de pointes an overview. Drug Safety, 25, 263-286. 

CPMP. Points to Consider The assessment of QT interval prolongation by noncardiovascular medicinal products... 

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