• Title/Summary/Keyword: Drug-associated

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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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    • v.15 no.3
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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.

Hepatotoxic Events Associated with Herbal Medicinal Products, Folk Remedies and Food Supplements in Korea (국내에서 보고된 한약 및 민간요법, 건강식품 관련 약인성간손상에 대한 체계적 고찰)

  • Park, Hae-Mo;Jang, In-Soo;Lee, Sun-Dong
    • The Journal of Korean Medicine
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    • v.26 no.2 s.62
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    • pp.152-165
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    • 2005
  • Background: The use of herbal preparations as remedies for various medical conditions has continuously increased in Korea Large proportions of Korean patients use herbal medicinal products, folk remedies, and food supplements. However, studies on the safety of herbal products arc conducted on a less than sufficient basis even in the countries like Korea where herbal medicine is being used extensively. Some of the reports on the safety of herbs were done by the doctors of western medicine but lack of knowledge and misclassification led to misunderstandings. Objecitves: This study aims to review the recent evidences on hepatotoxic events associated with the use of herbal medicinal products, folk remedy, and food supplements. In the process, this review will grasp trends in this field of studies and will direct further researches into the right direction. Methods: Systematic literature searches were performed on MedRic and MEDLIS in Korea. Screening and selection of the articles and the extraction of data were performed independently by two of authors. There were no restrictions regarding the published date. In order to avoid bias, the articles written by medical doctors, not by oriental doctors were selected. 43 journals were chosen for the review. Results: Analyzing the number of journals, studies on the drug-induced liver injury were increased after the year 2000. The proportion of herbal and folk remedy associated hepatotoxic injuries in all drug-induced liver injury was $21.0\%-30.0\%$. But criterion for herbal medicine is rather vague and limited objective data hindered objectiveness. Few of single medicinal herbs and combination preparations were associated with hepatotoxic injuries. But because of lack of objectivity, further researches must be conducted to yield more concrete results. Conclusions: yield more concrete results. Incidence figures are largely unknown, and in most cases a causal attribution is not established. The challenge for the future is to systematically research this area, educate all parties involved, and minimize patient risks.

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Incidence and Severity of Weight Gain Associated with the Use of Olanzapine for the Treatment of Schizophrenia (올란자핀의 체중증가 부작용 발생율 및 체중변화량)

  • Lee, Kyung-Hee;Shanmugam, Srinivasan;Baskaran, Rengarajan;Nagayya-Sriraman, Santhoshkumar;Yong, Chul-Soon;Choi, Han-Gon;Woo, Jong-Soo;Yoo, Bong-Kyu
    • YAKHAK HOEJI
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    • v.52 no.4
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    • pp.288-292
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    • 2008
  • Olanzapine, an atypical antipsychotic, has been widely used for the treatment of schizophrenia and bipolar disease. Although olanzapine is less associated with extrapyramidal symptoms and neuroleptic malignant syndrome compared to existing typical antipsychotics, the use of this drug has a problematic side effect of weight gain, which may cause metabolic syndrome such as type 2 diabetes. However, there are few hospitals practicing body weight monitoring of the patients on olanzapine or other atypical antipsychotics. The goal of this study was to identify the incidence and severity of weight gain associated with the use of the drug in Korea. We performed body weight monitoring of the patients who were on the drug in a hospital setting. Mean of the weight gain (as of one-month-transformation) was 4.33 and 3.39 kg for the male and female patients, respectively. The incidence in the young patients was higher than that observed in the old patients, and the severity was the highest in patients in their thirties followed by twenties or younger. This result suggests that the pattern of the weight gain associated with the use of olanzapine in Korea is similar to the reports performed and documented in US and European countries. Therefore, it appears that healthcare professionals in Korea should also watch on the weight gain issue in patients who are on olanzapine or other atypical antipsychotics.

Analysis of Perceptions and Behaviors Associated with Health Functional Food Use: a cross-sectional survey (건강기능식품에 관한 인식도 및 소비양식의 분석)

  • Chun, Pusoon
    • Korean Journal of Clinical Pharmacy
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    • v.24 no.1
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    • pp.53-61
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    • 2014
  • Background: The use of health functional food (HFF) is increasing and will continue to rise worldwide. Concerns about HFF-drug interactions are increasing as HFF are becoming more widely used. Therefore, awareness of consumers' perceptions and behaviors associated with HFF use may help health care providers improve their communications with patients. Purpose: The aim of this study was to assess the characteristics, perceptions, and behaviors associated with HFF use in South Korea. Method: The online survey was conducted from September 21th to October 7th, 2013. With the aid of Social Network Service (SNS) and google, the questionnaire was posted online on internet website targeting people aged 15 years or older so that self-reported data covering 4 domains were collected from 257 Koreans. Results: A total of 257 people responded the questionnaire. Among them, 81.3% reported experiences of HFF use. Female were more likely than male to use HFFs. There were no differences in demographic characteristics between HFF users and non-users in relation to age, education, and household income. Higher level of education was associated with high-level perception of HFF function (OR 3.9, 95% CI 1.48, 10.1) and a positive relationship was observed between the maximum number of HFFs used concurrently and age of the respondents. Among the HFF users, 42.6% reported concurrent HFF-medication use. However 73.3% of them did not disclose their use to physician or pharmacist and only 30.2% were informed about potential drug-HFF interactions. Pharmacy was most commonly reported as the source from which the respondents were informed about potential interactions. Conclusion: Many people had used HFF and medications concurrently while not being informed about potential HFF-drug interactions. Pharmacists and physicians should be vigilant for risk of the interactions and actively determine whether the patient is using an HFF before prescribing and administrating medications.

Awareness on expiration date of repackaged prescription medications and pulverization of solid pills: A questionnaire study (소분조제된 처방약의 사용기한과 성인 산제조제에 대한 인식)

  • Kim, So Yeon;Choi, Yeo Jin;Sohn, Hyun Soon
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.2
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    • pp.96-103
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    • 2021
  • Background: The number of elderly people with comorbidities who experience dysphagia associated with geriatric disorders, such as stroke, Parkinson's disease, and Alzheimer's dementia, is increasing. Consequently, the demand for long-term prescriptions of powdered medications is expected to rise. Most patients procure repackaged prescription medications from pharmacies; however, the guidelines regarding their expiration dates are unclear. Objectives: The aim of this study was to assess awareness among adults regarding the expiration dates and drug stability issues associated with repackaged prescription medications, including powdered medications. Methods: A questionnaire with 16 components was designed and distributed online (August 1-September 1, 2019) to adults aged 19 years or older. Statistical analyses, including descriptive analysis and chi-square test, were conducted on the obtained data. A p-value <0.05 was considered significant. Results: Data from 254 respondents were analyzed; 191 (75.20%) respondents worked in non-healthcare-related fields. A significant number of healthcare workers recognized the stability issues associated with powdered medications (p<0.001). However, a large proportion of healthcare workers were not aware of the expiration dates (p>0.05). Conclusions: More than half of the total respondents, including healthcare workers, were not familiar with the appropriate expiration dates of repackaged prescription medications. The establishment of evidence-based guidelines regarding drug expiration dates and the dissemination of awareness among patients are required. Furthermore, clinical practices including repackaging or pulverizing medications for long-term prescriptions should be avoided owing to the associated drug stability issues.

Long Non-coding RNAs and Drug Resistance

  • Pan, Jing-Jing;Xie, Xiao-Juan;Li, Xu;Chen, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8067-8073
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    • 2016
  • Background: Long non-coding RNAs (lncRNAs) are emerging as key players in gene expression that govern cell developmental processes, and thus contributing to diseases, especially cancers. Many studies have suggested that aberrant expression of lncRNAs is responsible for drug resistance, a substantial obstacle for cancer therapy. Drug resistance not only results from individual variations in patients, but also from genetic and epigenetic differences in tumors. It is reported that drug resistance is tightly modulated by lncRNAs which change the stability and translation of mRNAs encoding factors involved in cell survival, proliferation, and drug metabolism. In this review, we summarize recent advances in research on lncRNAs associated with drug resistance and underlying molecular or cellular mechanisms, which may contribute helpful approaches for the development of new therapeutic strategies to overcome treatment failure.

Theoretical and Experimental Considerations for Improving Elastomer Drug Infusers (탄성체 약물주입기 개선을 위한 이론적·실험적 고찰)

  • Kim, Dong Hoon;Kang, Taewon
    • Journal of the Korean Society of Manufacturing Technology Engineers
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    • v.26 no.3
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    • pp.320-327
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    • 2017
  • The main function of an infuser is to ensure constant dosage of a drug. Elastomer drug infusers have been used widely owing to their economic advantages. The mechanism of the device is primarily based on the pressure created from the elastic material that contains the drugs. However, as the drug is infused and the internal pressure is reduced, the drug is not linearly infused at all times. This study involves investigating factors to improve the design of the infuser. The first factor is the range of proper deformation, which does not affect a significant amount of stress variation during infusion. The second is concerned with the flow restrictor and the associated design variables are recommended by employing finite element analysis and the factorial experiment technique. The last factor is related to the spring device connected to balloon. The results showed that the drug reservoir can compensate for unexpected pressure gradient drops.

The Comparative Efficacy of Colistin Monotherapy and Combination Therapy Based on in vitro Antimicrobial Synergy in Ventilator-associated Pneumonia Caused by Multi-drug Resistant Acinetobacter baumannii (다제내성 Acinetobacter baumannii 에 의한 인공호흡기연관 페렴에서 Colistin 단독요법과 시험관 내 상승작용에 근거한 병합요법간의 효능 비교)

  • Jang, Hang Jea;Kim, Mi-Na;Lee, Kwangha;Hong, Sang-Bum;Lim, Chae-Man;Koh, Younsuck
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.3
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    • pp.212-220
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    • 2009
  • Background: Ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii has been increasing and growing as a threat in intensive care units. Limited therapeutic options have forced clinicians to choose colistin with or without combination of other antibiotics. We tried to compare the effectiveness between colistin monotherapy and combination therapy based on in vitro synergistic tests. Methods: From January 2006 to December 2007 in medical ICU of a tertiary care hospital in Korea, We reviewed the medical records of patients treated with intravenous colistin due to ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. Results: A total of 41 patients were analyzed. 22 patients had been treated with colistin monotherapy and 19 patients with colistin and combination antibiotics that were found to have in vitro synergistic effects. Baseline characteristics were similar in both groups but the mean duration of colistin administration was significantly longer in the combination group (19.1${\pm}$11.2 days vs. 12.3${\pm}$6.8 days, p=0.042). There were no significant differences in outcome variables between the two groups. Conclusion: Combination treatment based on the in vitro antimicrobial synergy test did not show better outcomes compared with colistin monotherapy in VAP caused by multi-drug resistant A. baumannii.

Differences in Gene Expression Profiles Reflecting Differences in Drug Sensitivity to Acetaminophen in Normal and Transformed Hepatic Cell Lines In vitro

  • Jeong, Youn-Kyoung;Kang, Jin-Seok;Kim, Joo-Whan;Suh, Soo-Kyung;Lee, Michael;Kim, Seung-Hee;Lee, Sang-Kook;Park, Sue-Nie
    • Molecular & Cellular Toxicology
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    • v.5 no.1
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    • pp.32-43
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    • 2009
  • Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea

  • Yang, Jeong Seong;Kim, Kyung Jong;Choi, Hongjo;Lee, Seung Heon
    • Annals of Laboratory Medicine
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    • v.38 no.6
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    • pp.563-568
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    • 2018
  • Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ${\leq}0.025$ to >1.6 mg/L, ${\leq}0.0312$ to >4 mg/L, and ${\leq}0.125$ to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.