• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.96-99
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• 2004

Aminophylline, ceftriaxone 및 ampicillin/sulbactam (Unasyn)을 미숙아용 고영양수액제에 직접 첨가하거나 Y-site로 투여하는 경우의 안정성에 관해 조사하였다. Aminophylline 주사액 (25mg/mL) $300{\mu}l$와 ceftriaxone sodium (37.5 mg/mL) 2mL를 각각 고영양수액제 직접 첨가하였다. 또한 Y-site에서의 안정성 조사를 위해 ceftriaxone sodium (37.5 mg/mL)을 고영양수액제에 각각 1:1 및 1:2 부피비가 되도록 혼합하였고 Unasyn (25mg/mL)은 고영양수액제와 1:1의 부피비로 혼합하였다. 이상과 같이 조제한 혼합액을 $25^{\circ}C$와 $4^{\circ}C$에 보관하여 aminophylline은 48시간 동안 그리고 항생제들은 24시간 동안의 경시변화를 HPLC를 이용하여 분석하였다. Aminophylline은 위 보존조건에서 48시간동안 안정하였다(변화율 <$10{\%}$). Ceftriaxone sodium을 고영양수액제에 직접 첨가한 경우 ceftriaxone의 잔존률은 $25^{\circ}C$에서 4시간째에 $90.5{\pm}1.8{\%}$이었고 $4^{\circ}C$에는 $95.1{\pm}1.4{\%}$로 측정되었다. Y-site에서의 안정성과 관련하여 ceftriaxone sodium을 고영양수액제와 1:1로 혼합한 경우 양 보존조건에서 ceftriaxone은 24시간 동안 안정하였으나 1:2로 혼합한 경우에는 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$ 정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$에서는 안정하였으나 $25^{\circ}C$에서는 $30{\%}$까지 감소되는 것으로 분석되었고 sulbactam은 24시간째에 온도와 관계없이 안정한 것으로 나타났다. Ceftriaxone sodium을 TPN과 Y-site 혼합 후 1-2시간 이내에 침천이 형성되었고 Unasyn의 경우에는 12시간째에 침천이 형성되었다. 혼합액의 pH나 색상은 연구기간 동안 일정하였다. 이러한 연구결과에 기초할 때, aminophylline은 고영양수액제와 혼합가능하고 ceftriaxone과 Unasyn은 고양양수액제와 혼합시 최소 1시간 동안은 안정한 것으로 평가되었다.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.170-181
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• 2011

Purpose: There is considerable variability in rates of hospitalization for patients with community-acquired pneumonia (CAP) in part because of physicians' uncertainty in assessing the severity of illness at presentation. The purpose of the study was to examine the current treatment patterns and factors influencing the Pneumonia Severity Index (PSI) and clinical outcomes in the patient with CAP. Method: The retrospective data collection of the patients with CAP was conducted and the data were reviewed. The collected data included demographic, clinical, laboratory and microbiological medical information. All patients were stratified into three risk groups according to PSI: low risk (PSI score I-II), moderate risk (III) and high risk (IV-V) groups. The examined treatment patterns were the appropriateness of admissions, category of antibiotics used. The prognostic factors associated with PSI and clinical outcomes were examined. Results: One hundred and six patients' medical data were reviewed. The overall appropriateness of admissions was low presenting many of patients were admitted or intensely treated in the hospital despite of lower risk of prognosis and treated with intravenous antibiotics instead of oral fluoroquinolones. Primary pneumonia pathogens were Klebsiella pneumoniae (27%) and Streptococcus pneumoniae (21.6%). Mean LOS was 8.5 days and was significantly longer (10.0days) (p<0.001) in high risk group. The patients with age >65 (p<0.001), diabetes mellitus (p<0.001), mental alteration (p<0.001), and/or $PaO_2$ <60 mmHg (p<0.001) had a tendency to have higher PSI. The prognostic factors associated with longer LOS were age >65 years (p=0.008), mental status alteration (p<0.001), dyspnea (p=0.002) and PSI score (p=0.001). The prognostic factors associated with mortality were congestive heart failure (p=0.038), systolic blood pressure <90 mmHg (p=0.002) and arterial pH <7.35 (p=0.013). Conclusion: Most of patients were found to over-utilize medical service according to appropriateness of admissions. The elderly, mentally altered patients with low $PaO_2$ had higher PSI score with increased risk of LOS. The mortality could be increased in the patient with disease state of congestive heart failure, high blood pressure, and/or acidosis.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.122-130
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• 2011

Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<$240{\mu}g/dl$) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score ($R^2$=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.161-169
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• 2011

The purpose of this study is to survey on the pharmacists' medication teaching service for topical steroids in regions without separation of dispensary from medical practice. The questionnaire was sent to 199 pharmacists who work inregions without separation of dispensary from medical practice via mail, e-mail or fax. 112 out of 199 pharmacists requested have answered the survey (response rate 56.28%). The questionnaire was composed of 4 categories with demographic characteristics, generally explained contents, adverse effects and precaution in pregnancy, breastfeeding and children. We analyzed the questionnaire by the 6 items with reference to the practical guidelines for medication teaching service. The medication teaching service for topical steroids in terms of generic name, physical characteristics, efficacy, usage and dosage, warning and precaution has been well provided by pharmacists in regions without separation of dispensary except for means and duration of optimal storage. The majority of pharmacists provided their patients with 4 and more kinds of items (69.64%), but the generally recommended 4 kinds of items such as generic name, efficacy, usage and dosage, warning and precaution were provided in as low as 48.22% of the respondents. These results show that the medication teaching service for topical steroids in terms of means and duration of optimal storage (45.54%) and the generally recommended 4 kinds of items have not been enough provided by pharmacists in regions without separation of dispensary. Taken together pharmacists in these regions should make a proper guideline for medication teaching service that can prevent the adverse effects of topical steroids.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.106-114
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• 2011

While multiple medication is an important global medication safety issue, ununified concomitant medication by multiple prescriptions may cause more severe problems by the fact that those are neither intended nor watched. This could cause therapy duplication and severe drug interaction and etc. Korean Government made region wide scale programs twice to detect such problems and give warnings to pharmacists and doctors through the internet system in 2009-2010, which are called Drug Use Review Services Pilot Project. This study is an analysis and comparison of the results of the two DUR pilot projects. There were 5.0 and 4.2 cases of severe drug interaction by the concomitant medication of multiple doctors' prescriptions per 10 thousand prescriptions, while only 0.37 and 0 cases by the medication of same doctor's prescription(s). There were 426 and 381 cases of drug duplication by the concomitant medication of multiple doctors' prescriptions per 10 thousand cases, while only 197 and 23 cases by medication of same doctors' prescription(s). Doctors' participation to those projects improved at Jejudo the later one compared to Goyangsi the former, which means the efforts of them to make less prescription problems succeeded to decrease the number of cases caused from same doctor's prescription. But they could not decrease the number of problem cases caused from concomitant medication by multiple doctors prescriptions enough. The findings support the issue of strengthening and widening the project nation wide and the issue of recommending the patients to designate their own pharmacy, which can provide them counseling for unified and safety controlled medication.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.107-113
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• 2010

서 론: 중환자실에서 집중적 인슐린 요법에 의한 평균혈당강하는 사망률을 감소시키는 것으로 나타났으나 이로 인한 저혈당 및 혈당변동은 새로운 문제로 대두되고 있다. 본 연구에서는 혈당과 관련한 여러 요인들이 사망에 미치는 영향을 규명하고 적정 혈당치를 확인하고자 하였다. 연구방법: 2008년 2월부터 7월 사이인 6개월 동안 서울아산병원 외과계 중환자실에서 4일 이상 재실한 18세 이상의 성인 환자를 대상으로 전자 의무기록 조사를 통해 후향적으로 연구가 진행되었다. 연구를 위해 환자의 인구학적 특성, 수술의 종류, 중환자실에서의 재실기간, 사망여부, 스테로이드 사용 유무, 기계적 인공호흡기의 사용유무, 신대체요법의 사용유무, 혈당치, 재실기간 중 스테로이드 사용유무와 인슐린 양, 입원 후 첫 24시간 동안의 포도당 주입속도, 입원 후 2일 이내와 그 이후에 발생한 균혈증 감염, APACH II와 SOFA 점수를 조사하였다. 혈당수치는 각각의 환자에서 중환자실 입실 후 가장 처음 측정된 혈당, 재실기간 중 가장 높은 혈당과 가장 낮은 혈당수치를 조사하였고 중환자실 전체 재실기간 동안 혈당수치의 평균과 변동계수를 계산하였다. 이상의 혈당관련지표를 포함한 인자들이 일차 종속변수인 사망에 어떠한 영향을 주는지를 환자를 생존군과 사망군으로 나누어 분석하였고 ROC (receiver operator characteristic) 곡선을 사용하여 혈당지표와 APACH 및 SOFA 점수의 cut-off치를 구하여 이로부터 단변량 및 다변량 분석을 시행하였다. 결 과: 연구에 포함된 환자는 170명 이었고 그 중 23명이 연구 기간 중 중환자실에서 사망하였다. 생존자에 비해 사망자의 최대혈당은 유의적으로 높았고 최소혈당치는 유의적으로 낮아 높은 변동계수를 보였다. ROC곡선으로부터 산출된 혈당치들의 cut-off 수치는 최소혈당치 70 mg/dL, 변동계수 25%, 최대혈당치 250 mg/dL, 평균혈당치 150 mg/dL이었다. 다변량분석에서 최소혈당이 70 mg/dL 보다 큰 경우가 낮은 경우에 비해 오즈비가 0.922(95% 신뢰구간 0.881-0.965)로 유의성 있게 낮았으며 변동계수가 25% 보다 높은 집단의 경우 그보다 낮은 집단에 비해 오즈비가 1.121(95% 신뢰구간 1.017-1.236)로 유의성 있게 높았다. Kaplan-Meier 생존분석 결과 최소혈당치 70 mg/dL와 변동계수 25%에 따라 생존기간에 유의성 있는 차이가 나타났다.(각각 P < 0.001, P < 0.05) 결 론: 고혈당 발생의 감소뿐 아니라 최소혈당치를 70 mg/dL 이상으로 유지하면서 변동을 최소화하는 것이 외과계 중환자실에서의 사망률감소를 위한 중요한 요인임을 알 수 있었다.

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.159-164
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• 2010

Radiofrequency ablation (RA) is being used to manage atrial fibrillation (AF) with patients failed at the $1^{st}$-line anti-arrhythmic medications. Patients undergoing this procedure are at increased risk of thromboembolism after ablation, and anticoagulation management surrounding the ablation remains controversial. Although no conclusive recommendations can be made, published guidelines and data support therapeutic anticoagulation with warfarin. The purpose of this study was to analyze effectiveness of current therapy and to find factors fluctuate International Normalized Ratio (INR) values in patients undergone RA followed by anticoagulation service (ACS). Retrospective review was conducted utilizing database in a hospital. Among 110 patients under warfarin around ablation between January 2006 to September 2007, 54 patients were selected and allocated into 2 groups: Group A included 47 who discontinued warfarin after ablation, while 7 in B continued the medication. Information on demographics, amount and length of warfarin dosing, INR values and measuring frequencies, and the causing factors on INR fluctuation were abstracted. Differences were analyzed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. Mean amount of warfarin before and after surgery was 4.0 mg, 4.1 mg in Group A and was 5.1 mg, 4.6 mg in Group B, respectively. Average duration of warfarin doing before ablation was 73.7 days in Group A, 129.9 days in B with no significant difference (p = 0.312). The duration time of warfarin on groups after ablation lasted several months. The number of checking INRs was 4.1 and 7.6, respectively. Inter-individual variability of INR fluctuations were $2.1{\pm}0.6$ in Group A and $2.2{\pm}0.7$ in B which were not significantly different (p = 0.062). 164 cases of decreased INR were: 'omission in taking medication, stressfulness and headache, 'increased intake of high vitamin K foods', 'lifestyle change of increased physical activities', and 'increase of food-intakes'. To the contrary, 36 cases of increased INR were: 'reduce of food-intake', 'use of non-prescription drugs', 'reduction in physical activities', and 'excessive restriction on food-intake', consecutively. In conclusion, the study validated therapeutic outcomes of RA patients who we treated with standard guideline and demonstrated 9 factors of INR fluctuations in the patient. A well-trained, pharmacist-monitored anticoagulation service could reduce the risk of adverse effects and prevent complications in patients with AF around RA operation.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.696-700
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• 2009

Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.

• Archives of Pharmacal Research
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• v.28 no.6
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• pp.709-715
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• 2005

The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1$\mu$M, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the ${\alpha}_1$-adrenoreceptor. The $\beta$-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and $CaCl_2$ in $Ca^{2+}$-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular $Ca^{2+}$ influx through the receptor-operated calcium channels and intracellular $Ca^{2+}$ release from the $Ca^{2+}$ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular $Ca^{2+}$ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated $Ca^{2+}$-influx and $Ca^{2+}$-release, and partly from the endothelium mediated by EDHF.