• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.215-220
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• 2009

Chlorpheniramine is a potent first-generation histamine $H_1$ receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The $IC_{50}$ of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the $H_1$ antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.

• Journal of Dental Anesthesia and Pain Medicine
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• 제23권1호
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• pp.45-51
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• 2023

Andersen-Tawil syndrome (ATS) is a rare genetic disease characterized by a triad of episodic flaccid muscle weakness, ventricular arrhythmias, and physical anomalies. ATS patients have various cardiac arrhythmias that can cause sudden death. Implantation of an implantable cardioverter-defibrillator (ICD) is required when life-threatening cardiac arrhythmias do not respond to medical treatment. An 11-year-old girl underwent surgery for an ICD implantation. For general anesthesia in ATS patients, anesthesiologists should focus on the potentially difficult airway, serious cardiac arrhythmias, such as ventricular tachycardia (VT), and delayed recovery from neuromuscular blockade. We followed the difficult airway algorithm, avoided drugs that can precipitate QT prolongation and fatal cardiac arrhythmias, and tried to maintain normoxia, normocarbia, normothermia, normoglycemia, and pain control for prevention of sympathetic stimulation. We report the successful application of general anesthesia for ICD implantation in a pediatric patient with ATS and recurrent VT.

• 대한수의학회지
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• 제52권3호
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• pp.163-167
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• 2012

Mosapride stimulated dietary motility was introduced because of the arrhythmogenic effect of cisapride. Cisapride, 5-HT receptor agonist, induces prolongation of QT interval. Additionally, this condition can raise the possibility of acute, "malignant" arrhythmias such as torsade de pointes. It is hard to find any reports about effects of mosapride on cardiac parameters in dogs. By confirming electrocardiogram (ECG) parameters, the surface extremity leads ECG that was obtained from the four-limb electrodes and which was recorded by an ECG recorder after administration of mosapride 3 mg/kg PO b.i.d, and mosapride 3 mg/kg with itraconazole 5 mg/kg PO b.i.d, respectively. QT interval was shortened on the days of 3, 5, and post-day 1 in both mosapride 3 mg/kg administrated group and mosapride with itraconazole group. Heart rate increased significantly. QTc was slightly prolonged in mosapride administration group and mosapride with itraconazole group. However, all dogs of QTc were in normal variation (150~250 msec). Besides, the dogs showed no side effects reported in human medicine during the administration with these drugs. Although mosapride can increase the heart rate, this study suggest that mosapride may be useful for the dogs with disorders of gastrointestinal motility because of no fatal arrhythmogenic effect inspite of administration with itraconazole in dogs.

• 한국임상약학회지
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• 제11권2호
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• pp.89-96
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• 2001

Ziprasidone is equally effective as haloperidol in treating schizophrenia with fewer side effects and drug interactions. Ziprasidone is an atypical antipsychotic agent and works by blocking serotonin and dopamine receptors in the central nervous system, specifically 5-HT2A and D2 receptors. Low anticholinergic side-effects and low EPS would recommend the drug for use in the elderly. Ziprasidone inhibits reuptake of norepinephrine and serotonin at neurojunction sites in vitro, indicating a potential efficacy for depression and negative symptoms which often follow after exacerbation of schizophrenia. Patients with recent acute myocardial infarction and uncompensated heart failure are contraindicated to the drug due to a possibility of QT prolongation. Although ziprasidone is metabolized by cytochrome P450 3A4, there is no significant drug interaction with the drugs that induce or inhibit the isoenzyme. Ziprasidone is safe with coadministration of lithium and there has been no significant drug interaction reported with oral birth control pills.

• 대한수의학회지
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• 제48권4호
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• pp.493-500
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• 2008

A 2-year-old female Pekingese dog was presented with primary complaints including exercise intolerance and neurological sign associated with hepatic encephalopathy. The major findings in clinical examination included an intermittent seizure, a slow heart rate with pulse deficit, leukocytosis and anemia in hemogram, elevated pre- and post-prandial serum bile acid and hepatic enzymes, hypoproteinemia, coagulopathy, ammonium urate crystaluria and bilirubinuria. Diagnostic tests revealed an intrahepatic portosystemic shunt complicated with a second degree atrioventricular block and QT prolongation. The case was successfully treated with a transvenous coil embolization. Clinical signs were gradually improved and cardiac bradyarrhythmia disappeared. This case is a rare case of intrahepatic portosystemic shunts complicated with a cardiac bradyarrhythmia in a small breed dog fixed by a transvenous coil embolization.

• 대한임상독성학회지
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• 제3권1호
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• pp.67-70
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• 2005

Pimozide and haloperidol are typical antipsychotics. They share a similarity in pharmacotherapeutic and adverse effect profiles. Cardiovascular effects may be seen as alterations in heart rate, blood pressure, and cardiac conduction. Conduction disturbances may occur ranging from asymptomatic prolongation of the QT interval to fatal ventricular arrhythmia. So in the case of anti psychotics overdose, the patient must be carefully monitored by continuous electrocardiography (ECG). We experienced a 34-year-old woman of schizophrenia with recurrent ventricular tachycardia after pimozide and haloperidol overdose. Initially she was slightly drowsy, however her ECG showed normal sinus rhythm. After 6 hours on emergency department entrance, her ECG monitoring showed ventricular tachycardia and we successfully defibrillated. There were five times events of ventricular arrhythmia during the in-hospital stay. She was discharged 5 days later without any other complications.

• 대한수의학회지
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• 제23권1호
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• pp.17-23
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• 1983

Experimental hypocalcemia was induced in normal goats by intravenous infusion with various concentration of $Na_2$-EDTA solution. 1. Progressive depression of reflexes and body temperature, paresis, and cardiac arrest were observed in two groups infused with 4% and 8% EDTA solution, whereas paresis and cardiac arrest were not observed in 3% EDTA group. 2. The patterns of electrocardiogram were changed according to the decrease of plasma Ca level in all of 7 goats. When plasma Ca decreased to 6mg per 100ml or below, sinus bradycardia or tachycardia and prolongation of QT interval were showed, while atrioventricular block was noted in case which the plasma Ca level decreased to 4mg per 100ml or below. Fibrillation and cardiac arrest were evident in case which the plasma Ca level decreased to as low as 3mg per 100ml.

• Translational and Clinical Pharmacology
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• 제26권4호
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• pp.145-149
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• 2018

Cases of drug-induced QT prolongation and sudden cardiac deaths resulted in market withdrawal of many drugs and world-wide regulatory changes through accepting the ICH guidelines E14 and S7B. However, because the guidelines were not comprehensive enough to cover the electrophysiological changes by drug-induced cardiac ion channel blocking, CiPA was initiated by experts in governments and academia in the USA, Europe, and Japan in 2013. Five years have passed since the launch of the CiPA initiative that aimed to improve the current ICH guidelines. This report reviews the current achievements of the CiPA initiative and explores unresolved issues.

• 대한임상독성학회지
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• 제17권1호
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• pp.28-31
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• 2019

Glyphosate herbicides, which are widely used worldwide, are known to have low toxicity. However, excessive intake may cause serious life-threatening complications; therefore, caution is needed when using them. A 51-year-old man visited the hospital after ingesting glyphosate herbicide. At the time of admission, his vital signs were 80/60 mmHg-115/min-20/min-$37.3^{\circ}C$. Electrocardiogram (ECG) showed QRS widening and corrected QT (QTc) prolongation, and blood tests showed metabolic acidosis. Treatment with gastric lavage, activated charcoal, sodium bicarbonate and intravenous lipid emulsion therapy was performed. After 2 hours, his blood pressure increased to 130/90 mg, and no QRS widening was observed on ECG.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.90.3-91
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• 2003

The most commonly proposed mechanism for QT interval prolongation(LQT) by pharmaceuticals is inhibition of the rapid delayed rectifier potassium channel (I$\_$Kr/). The LQT potency of pharmaceuticals can be effectively evaluated by examining the effect on hERG channels expressed in CHO cells, known to be equal to I$\_$Kr/. But, It was known that hERG channels according to increase the bath temperature have several changes, including a marked increase in the amplitude of the outward and tail currents, and acceleration of the rates of activation, recovery from inactivation, and deactivation. (omitted)