• Title/Summary/Keyword: Cardiovascular drug

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약물대사효소의 유전적 다형성 및 임상적 응용 (Clinical Pharmacogenomics of Drug Metabolizing Enzymes and its Clinical Application)

  • 김경임;김승희;박지은;채한정;최지선;신완균;손인자;오정미
    • 한국임상약학회지
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    • 제16권2호
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    • pp.155-164
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    • 2006
  • Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

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심장내 이물질: 선행 원인이 불분명한 환자에서 발견된 우심실내 봉합침 (Intracardiac Foreign Body: A Sewing Needle in Right Ventricle of Unknown Etiology)

  • 김경환;장지민;안혁
    • Journal of Chest Surgery
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    • 제33권8호
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    • pp.681-683
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    • 2000
  • A 34 year-old woman was hospitalized with anterior chest pain and indigestion. Chest radiograph and computed tomogram revealed a sewing needle in the cardiac cavity. She had no histories of surgical intervention, drug abuse, or acupuncture. We removed the needle from the right ventricle under cardiopulmonary bypass.

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METHODS FOR ASSESSMENT OF GASTROINTESTINAL DRUG ACTIONS

  • Burks, Thomas F.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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    • pp.113-125
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    • 1994
  • Many types of drugs affect functions of tile gastrointestinal tract. Investigators may be interested in discovery or pharmacological characterization of drugs as therapeutic agents intended for treatment of gastrointestinal disorders or in identification of gastrointestinal side effects of drugs intended for non-gastrointestinal indications. Examples of drug categories often associated with significant gastrointestinal side effects include cardiovascular drugs, antibiotics (erythromycin in particular), anti-inflammatory drugs, antiemetics, analgesics (especially opiates), antihistamines, antidepressants, and antipsychotics. Whether tile objective is development of gastrointestinal therapeutic agents or evaluation of gastrointestinal side effects, appropriate laboratory models for experimentation are essential.

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iPSC technology-Powerful hand for disease modeling and therapeutic screen

  • Kim, Changsung
    • BMB Reports
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    • 제48권5호
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    • pp.256-265
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    • 2015
  • Cardiovascular and neurodegenerative diseases are major health threats in many developed countries. Recently, target tissues derived from human embryonic stem (hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes (CMs) or neurons, have been actively mobilized for drug screening. Knowledge of drug toxicity and efficacy obtained using stem cell-derived tissues could parallel that obtained from human trials. Furthermore, iPSC disease models could be advantageous in the development of personalized medicine in various parts of disease sectors. To obtain the maximum benefit from iPSCs in disease modeling, researchers are now focusing on aging, maturation, and metabolism to recapitulate the pathological features seen in patients. Compared to pediatric disease modeling, adult-onset disease modeling with iPSCs requires proper maturation for full manifestation of pathological features. Herein, the success of iPSC technology, focusing on patient-specific drug treatment, maturation-based disease modeling, and alternative approaches to compensate for the current limitations of patient iPSC modeling, will be further discussed. [BMB Reports 2015; 48(5): 256-265]

신약개발과 안전성약리시험 가이드라인 (Drug Development and Guideline for Safety Pharmacology Studies)

  • 최기환;박인숙;임화경;오우용;왕소영;김소희;김주일;김동섭
    • 약학회지
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    • 제47권2호
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    • pp.104-109
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    • 2003
  • The present paper reviews the notion and comparison of the Korea Food and Drug Administration(KFDA) general pharmacology and the International Conference on Harmonisation (ICH) safety pharmacology. General pharmacology or safety pharmacology is termed the study to determine the potential of a compound to induce adverse pharmacological effects. KFDA general pharmacology studies have been considered an important component in drug safety assessment and these were originally referred to those designed to examine effects other than the primary therapeutics effect of a drug candidate. The KFDA notified the Guideline for General Pharmacology in 1997. Safety pharmacology studies were focused on identifying adverse effects on physiological functions. In the ICH came into place S7A Safety Pharmacology Studies for Human Pharmaceuticals in 2001. A new chemical entity should be assessed for its side effects, initially in those physiological systems which are generally agreed to be the key systems that are essential for life; these "core system" include the central nervous system, cardiovascular system and respiratory system in safety pharmacology studies. These studies should be performed in compliance with Good Laboratory Practice (GLP).

The Study on Association of Calcium Channel SNPs with Adverse Drug Reaction of Calcium Channel Blocker in Korean

  • Chung, Myeon-Woo;Bang, Sy-Rie;Jin, Sun-Kyung;Woo, Sun-Wook;Lee, Yoon-Jung;Kim, Young-Sik;Lee, Jong-Keuk;Lee, Sung-Ho;Roh, Jae-Sook;Chung, Hye-Joo
    • Biomolecules & Therapeutics
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    • 제15권3호
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    • pp.156-161
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    • 2007
  • Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

Analysis of erectile dysfunction drugs and their analogues in counterfeit drugs and herbal medicines by LC-ESI-MS/MS

  • Lee, Ji Hyun;Jeong, Ji Hye;Park, Hyoung-Joon;Do, Jung Ah;Heo, Seok;Cho, Sooyeul;Yoon, Chang-Yong
    • 분석과학
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    • 제29권4호
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    • pp.155-161
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    • 2016
  • Distribution of various illegal or counterfeit drugs of seven approved erectile dysfunction drugs and their analogues has been increased, causing health problems such as cardiovascular disorder, tachycardia, headache, or vision disturbance. We used liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to determine the erectile dysfunction drugs and their analogues in various counterfeit drugs. Eleven erectile dysfunction drugs and their analogues were detected, with sildenafil and its analogues being the most counterfeited compounds (73.8 %), followed by tadalafil and its analogues (25.4 %). The limits of detection (LOD) and the limits of quantitation (LOQ) of liquid-type and solid-type negative samples ranged from 0.1 to 3.3 ng/mL or ng/g and from 0.3 to 10.0 ng/mL or ng/g, respectively. The recoveries ranged from 84.3 to 112.3 % and 83.2 to 110.2 %, respectively. The contents of sildenafil and tadalafil in the various counterfeit drugs ranged from 21.0 to 947.5 mg/g and from 0.2 to 170.2 mg/g, respectively.

Isofourane으로 마취된 개에 medetomidine, medetomidine-buprenorphine, medetomidine-fentanyl의 경막외 투여 시 심혈관계 반응과 진통효과의 비교 (Comparision of cardiovascular and analgesic effects of epidural administration of medetomidine, medetomidine-buprenorphine and medetomidine-fentanyl in dogs anesthetized with isoflurane)

  • 장화석;김혜진;최치봉;이정선;김휘율
    • 대한수의학회지
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    • 제47권1호
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    • pp.103-115
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    • 2007
  • The aim of this study was to compare the reaction of the cardiovascular system, and the anesthetic effect among 3 experimental groups, epidural administration of medetomidine as a single agent, the combination of buprenorphine and medetomidine, and the combination of fentanyl and medetomidine. Twenty one dogs were anesthetized with isoflurane and allowed to breathe spontaneously. Epidural, arterial, and venous catheters were inserted. The tip of epidural catheter was positioned at the level of the space between the sixth and seventh lumbar vertebra. After a stable plane of anesthesia was achieved, these dogs were each administered one of the following treatments epidurally : medetomidine $10{\mu}g/kg$ (Group M), a combination of medetomidine $5{\mu}g/kg$ and buprenorphine $10{\mu}g/kg$ (Group M/B), and a combination of medetomidine $5{\mu}g/kg$ and fentanyl $10{\mu}g/kg$ (Group M/F). Heart rate (HR), Respiratory rate (RR), End-tidal carbon dioxide (EtCO2), and arterial blood pressure were measured before drug administration (base line) and 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 min postinjection. Blood gas analysis was performed before injection and 5, 15, 25, 35, 45, 60 min postinjection. Isoflurane was discontinued 80 min postinjection and pain/motor function were evaluated up to 260 min postinjection every 15 min. At the early stage of drug introduction (until 5 min), the HR was decreased significantly in all 3 groups compared with base line. In Group M, HR was significantly decreased compared with the other 2 groups. With time (starting 20 min after drug introduction), the HR was decreased significantly in Group M/B in respect to base line. However, no significant difference was seen number-wise in all 3 groups. During 60 min after drug introduction, the systolic, diastolic and mean arterial pressures were highest in Group M and lowest in Group M/F. Among 3 groups, drug action and motor loss duration were longest in Group M/F. Analgesic effect observed in the M/F group was the most prominent and long-lasting, compared to those seen in the other 2 groups. Given the fact that the recovery of motor function takes place in a short period of time after analgesic effects disappeared, additional use of M/F depending on the patient's condition would be a good way to achieve effective pain management. However, proper care should be taken to ensure the function of cardiovascular system in the patient because the administration of M/F under isoflurane anesthesia results in a significant decline in arterial blood pressure ($65{\pm}10mmHg$).

결핵성 파괴폐의 수술적 치료에 대한 술후 이환율과 사망률에 영향을 미치는 위험 인자에 대한 임상고찰 (Clinical Evaluation of Risk Factors Affection Postoperative Morbidity and Mortality in the Surgical Treatment of Tuberculous Destroyed Lung)

  • 신성호;정원상;지행옥;강정호;김영학;김혁
    • Journal of Chest Surgery
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    • 제33권3호
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    • pp.231-239
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    • 2000
  • Background: This retrospective study tries to identify specific risk factors that may increase complication rates after the surgical treatment of tuberculous destroyed lung. Material and method: A retrospective study was performed on forty-seven patients, who received surgical treatment for tuberculous destroyed lung in the Department of Thoracic and Cardiovascular Surgery at Hanyang University Hospital from 1988 to 1998, to identify specific preoperative risk factors related to postoperative complications. Fisher's exact test was used to identify the correlations between the complications and right pneumonectomy, preoperative FEV1, predicted postoperative FEV1, massive hemoptysis, postoperative persistent empyema. Result: Hospital mortality and morbidity rates of the patients who received surgical treatment for tuberculous destroyed lung were 6.4% and 29.7%, respectively. In view of the hospital mortality and morbidity rates as a whole, predicted postoperative FEV1 less than 0.8L(p<0.005), preoperative FEV1 less than 1.8L(p=0.01), massive hemoptysis(p<0.005), postoperative persistent positive sputum cultures(p<0.0005), and the presence of multi drug resistant tuberculosis(p<0.05) presented statistically significant correlations. Among the postoperative complications, bronchopleural fistula, the most common complication, was found to have statistically significant corrleations with the preoperative empyema(p<0.05) and postoperative persistent positive sputum cultures(p<0.05). Conclusion: Although mortality and morbidity rates after surgical treatment of tuberculous destroyed lung were relatively low, when predicted postoperative FEV1 was less than 0.8L, when preoperative FEV1 was less than 1.8L, when massive hemoptysis was present, when postoperative sputum cultures were persistently positive, and when multi drug resistant tuberculosis was present, the rates were significantly higher.

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Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

  • Ko, Moon-Jeong;Ahn, Joon-Ik;Shin, Hee-Jung;Kim, Hye-Soo;Chung, Hye-Joo;Jeong, Ho-Sang
    • Genomics & Informatics
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    • 제8권1호
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    • pp.41-49
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    • 2010
  • Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.