• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.138-144
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• 2015

Objective: It is to evaluate the drug interaction monitoring program as a pilot project to develop a pharmaceutical care model in a medical intensive care unit and to analyze the influencing factors of drug interactions. Method: Electronic medical records were retrospectively investigated for 116 patients who had been hospitalized in a medical intensive care unit from October to December in 2014. The prevalence of adverse reaction with risk rating higher than 'D' was investigated by Lexi-$Comp^{(R)}$ Online database. The factors related with potential drug interaction and with treatment outcomes were analyzed. Results: The number of patients with a potential interaction of drug combination was 92 (79.3%). Average ages, the length of stay in the intensive care unit and the numbers of prescription drugs showed significant differences between drug interaction group and non-drug interaction group. Opioids (14.4%), antibiotics (7.2%), and diuretics (7.2%) were most responsible drug classes for drug interactions and the individual medications included furosemide (6.4%), tramadol (4.9%), and remifentanil (4.5%). There were 950 cases with a risk rating of 'C' (84.6%), 142 cases with a risk rating of 'D' (12.6%), and 31 cases with a risk rating of 'X' (avoid combination) (2.8%). The factors affecting drug interactions were the number of drugs prescribed (p < 0.0001) and the length of stay at intensive care unit (p < 0.01). The patients in intensive care unit showed a high incidence of adverse reactions related to potential drug interaction. Therefore, drug interaction monitoring program as a one of pharmaceutical care services was successfully piloted and it showed to prevent adverse reaction and to improve therapeutic outcomes. Conclusion: Active participation of a pharmacist in the drug management at the intensive care unit should be considered.

• Korean Journal of Clinical Pharmacy
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• v.26 no.2
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• pp.97-106
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• 2016

Background: Sevelamer is associated with reduced complications of chronic kidney disease-mineral bone disorder (CKD-MBD) resulted from hyperphosphatemia, which may contribute mortality, in CKD patients with dialysis. So far clinical outcomes of sevelamer on mortality and risk of cardiovascular mortality related to CKD-MBD are debating. Purpose of this study was to evaluate the effectiveness of sevelamer HCl on mortality of secondary hyperparathyroidism (SHPT), risk of cardiovascular mortality and, frequency of osteopathy in end stage renal disease (ESRD) patients with dialysis. Methods: We retrospectively reviewed the electronic medical records of 536 patients with ESRD, who were admitted for moderate to severe SHPT, for 36 months. 75 patients who met inclusion criteria were evaluated for the efficacy of sevelamer (mean serum iPTH = 487.5 pg/mL). Results: Sevelamer intervention was not associated with increased three-year survival time compared with non-sevelamers group [average survival month: 30.4 months in sevelamer group, 26.8 months in non-sevelamer group, p = 0.463]. Sevelamer intervention was not associated with significant mortality benefit and cardiovascular mortality benefit as compared to non-sevelamer group [sevelamer group: non-sevelamer group, all-cause mortality (iPTH > 600 pg/mL): 14.3% (1/34): 20% (1/41) p = 0.962, OR = 0.935, 95% CI, 0.058-14.98, heart disease mortality: 6.67% (2/30): 0% (0/32) p = 0.138]. Sevelamer was not associated with significantly lower cumulative incidence of osteopathy compared to non-sevelamer group (sevelamer group: non-sevelamer group, 5.9% (2/34):9.8% (4/41); p = 0.538; OR = 0.578; 95% CI, 0.099-3.367). Conclusion: Sevelamer was not associated with decreased all-cause mortality and risk of cardiovascular mortality compared to non-sevelamer group in ESRD patients with SHPT.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.513-519
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• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.345-351
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• 2009

Organic cation transporters (OCTs) are important for absorption, elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is located in a cluster on chromosome 6 and OCTs are in major organs such as intestine, liver, kidney, brain and placenta. Therefore, expression levels and function of OCTs directly affect plasma levels and intracellular concentrations of drugs and thereby determine therapeutic response. The aim of this study was to investigate the frequency of the SNPs on OCT1 (C181T and C1022T) and OCT2 (G808T) to analyze haplotype frequency in healthy Korean population. Human subjects have been genotyped for OCT1 (C181T for 195 subjects and C1022T for 825 subjects), using polymerase chain reaction-based diagnostic tests (RFLP). And for OCT2 (G808T), a total of 861 subjects have been genotyped, using pyrosequencing method. Haplotype was statistically inferred using an algorithm based on the expectation-maximization (EM). OCT1 C181T genotyping showed 100% homozygous wild-type (C/C). OCT1 C1022T genotyping showed wild-type (C/C), heterozygous (C/T) and homozygous mutant-type (T/T) and each accounted for 72.1, 24.5 and 3.4%, respectively. OCT2 G808T genotyping results also showed homozygous wild-type (G/G), heterozygous (G/T) and homozygous mutant-type (T/T) and each took 81.8, 17.9 and 0.3%, respectively. Based on these genotype data, haplotype analysis between OCT1 C181T and OCT1 C1022T has proceeded. The result has revealed that linkage disequilibrium between alleles is not obvious (P=0.0122).

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5121-5126
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• 2016

Objective: To investigate the impact of chemotherapy on quality of life (QoL) among breast cancer patients and to evaluate the relationship with age, cancer stage and presence of any comorbidity. Methods: A prospective study was conducted among breast cancer patients receiving chemotherapy in Hospital Melaka from 1st January 2014 to 31st July 2014. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was given to patients to fill in prior chemotherapy (baseline) and after the third cycle of chemotherapy. Socio-demographic and clinical data were collected and analyzed using SPSS version 20. Result: Respondents were 32 female patients [mean age (SD): 49.7(9.93) years]. They reported a significant lower global health status (P < 0.01) and significant higher symptoms of nausea and vomiting (P < 0.01), loss of appetite (P = 0.028) and diarrhea (P = 0.026) after the third cycle of chemotherapy as compared to baseline. Compare to, this study showed significant better emotional functioning (P < 0.01) and social functioning (P < 0.01) than the EORTC QLQ-C30 Reference Values 2008 for breast cancer cases. Under symptom scales higher scores were noted for appetite loss (P = 0.017), nausea and vomiting (P < 0.01). Age, stage and comorbidity had no clear associations with global health status in our patients (P > 0.05). Conclusion: Chemotherapy did reduce the QoL of breast cancer patients. Management of chemotherapy-induced loss of appetite, diarrhea, nausea and vomiting should be improved for a better outcome.

• YAKHAK HOEJI
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• v.58 no.5
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• pp.328-336
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• 2014

Anticholinergic drugs are included in the efficacy group of various antidepressants, antihistamines, antispasmodics like skeletal muscle relaxants. Elderly patients are often taking anticholinergic drugs due to various diseases such as sleep disorders and dysuria. But the use of anticholinergic drugs is restricted in guidelines such as Beers Criteria or STOPP due to the anticholinergic adverse effects including dry mouth, constipation, difficult urination, delirium, hallucinations and especially cognitive impairment. In this study, we investigated the usage of anticholinergic drugs in out-of-hospital prescription of 4,442 elderly patients. Results of the study were obtained that 32% (n=1,421) of overall patients were prescribed with 1~6 products (average 1.37) of anticholinergic drugs. 70.9% of the 1,421 patients (n=1,007) were prescribed with one drug, 22.7% (n=323) were two drugs and 4.9% (n=70) were three drugs. 27.1% of the 1,421 patients (n=430) were 70~74 years old patients who were the most commonly prescribed with anticholinergic drugs. Amitriptyline, chlorpheniramine, dimenhydrinate and quetiapine were most frequent component of ACB Score 3 drugs and amantadine, baclofen, carbamazepine, cyproheptadine and oxcarbazepine were most frequent of ACB Score 2 drugs. Anticholinergic Drug Scale (ADS) of individual patients presented one point (48.5%, n=689), 2 points (15.4%, n=219), more than 3 points (36.1%, n=513), and up to maximum 12 point (n=1). More than 2 points were more than half (51.5%, n=732). Therefore, additional prospective study in the use and adverse effects of anticholinergic drugs for elderly patients will be required. And national management such as DUR program will be required for elderly drug administration from now on.

• Journal of Clinical Nutrition
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• v.10 no.2
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• pp.31-37
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• 2018

Recently, in Korea, the importance of preparation and use of injectable drugs has been emphasized due to successive fatal accidents caused by injection infections. Parenteral nutrition (PN) has also been identified as a cause of infection. Cases of infection due to PN have been reported not only in Korea, but also abroad, and contamination occurs mainly during the preparation of PN. Because sterile preparation and compounding of injections are very important for infection control and patient safety, this article reviews the major guidelines outlined thus far. The Korea Ministry of Food and Drug Safety in 2006 published guidelines and the KSHP (Korean Society of Health-System Pharmacists) recently issued guidelines for the aseptic preparation of injections. In addition, as US guidelines, the ASHP (American Society of Health-System Pharmacists) guidelines and United States Pharmacopeia (USP) <797> are also reviewed. The recent guidelines published by the KSHP have significance in that they were adopted in accordance with the domestic reality, even though they conform to foreign guidelines, and are expected to be guidelines for hospital pharmacists performing aseptic preparation work. In addition, the Korea Ministry of Health and Welfare is considering appropriate guidelines for the safe management of medications, training staff for infection prevention and strengthening staff capacity. Furthermore, the gradual expansion of aseptic compounding facilities and human resources, as well as the provision of adequate medical costs are also considered. Based on the establishment and standardization of injectable drugs compounding guidelines for Korean hospitals, it is believed that if human resources and facilities are supported and medical charges are improved, it will be possible to expect the safer preparation and use of injections.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.155-165
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• 2022

Background: Chronic obstructive pulmonary disease (COPD) is not completely reversible and requires long-term management with appropriate treatment. This study aimed to analyze trends in treatment regimens and medication costs for COPD patients using a national claims database. Methods: We conducted this analysis using National Patient Sample data from the Health Insurance Review and Assessment Service covering the period from 2015 to 2018. We have constructed a dataset comprising COPD disease classification codes J43.x and J44.x (based on KCD-7 code, J43.0 was excluded) and compiled a list of drugs fitting current guidelines. To identify trends, we calculated frequency, ratio, and compound annual growth rate (CAGR) using the numbers of prescriptions and patients. Results: The number of COPD patients was 7,260 in 2018, slightly decreased from 2015. Most of these COPD patients were aged 60 or older and included a high proportion of males (72.2%; 2018). The number of patients prescribed inhaled medications increased gradually from 2015 to 2018 (9,227 (47.1%); 2015, 9,285 (51.5%); 2018), while the number of patients prescribed systemic beta-agonists and Xanthines has decreased since 2015 (CAGR -14.7; systemic beta-agonist, -5.8; Xanthines). The per capita cost of medication has increased by 0.4% (KRW 206,667; 2018, KRW 204,278; 2015) annually during the study period. Conclusion: This study showed that treatment with inhaled medications had continuously increased in accord with changing guidelines, but oral medications were still widely used. It is necessary to emphasize the importance of inhaled medications in treating COPD to reduce additional economic burden through appropriate medication use.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.311-318
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• 2022

Background: Ketamine is widely used in infants and young children for procedural sedation and anesthesia. The aim of this study was to evaluate the efficacy and safety of low dose oral ketamine to control pain and distress in children during intravenous (IV) cannulation. Methods: This is a prospective, randomized, double-blind study, including children aged between 3 and 6 years requiring a non-emergent IV-line placement. Children were randomly assigned to two groups, treated either with oral ketamine or a placebo. All patients were monitored for vital signs. Pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wong-Baker Faces Pain Rating Scale (WBFS) scales and sedation using a 5-point sedation score. The facility of IV-line placement was measured by a 3-point scale. Adverse effects were recorded after 1 and 24 hours. Results: A total of 79 and 81 children were entered in the ketamine and placebo groups, respectively. The heart and respiratory rates increased significantly in the placebo group. The median CHEOPS 4 (95% confidence interval [CI]: 3, 4, P < 0.001) and WBFS 6 (95% CI: 4, 6, P < 0.001) scores decreased statistically in the ketamine group. IV-line placement was 50% easier in the ketamine group (95% CI: 37%, 63%, P < 0.001). No serious adverse effects were observed in all cases. Conclusions: Low dose oral ketamine effectively decreased the pain and distress during IV cannulation in children without any significant adverse reactions.