• Journal of The Korean Society of Clinical Toxicology
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• v.14 no.1
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• pp.26-32
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• 2016

Purpose: Aspiration pneumonia is an important complication of drug intoxication with decreased mental status. The purpose of the study is to investigate the risk factors of aspiration pneumonia in the patients of benzodiazepine overdose with or without co-ingestion of other drugs. Methods: A retrospective chart review of patients who visited the emergency department between January 2012 and December 2014 was conducted. Demographic data, time from ingestion to visit, initial vital signs, symptoms, mental status, medical history, laboratory results, chest radiological findings and co-ingested medications were recorded. Multiple logistic analyses were performed to verify the association between variables and the development of aspiration pneumonia. Results: A total of 249 patients presented to the emergency department with benzodiazepine overdose. Aspiration pneumonia had developed in 24 patients (9.6%). Univariate analysis revealed time from ingestion to visit was longer, Glasgow coma scale score was lower, hypoxia was presented, leukocytosis was shown, types of ingested drugs was high, less activated charcoal was applied and tricyclic antidepressants was taken in patients that developed aspiration pneumonia. Time from ingestion to visit (odds ratio (OR) 1.121, 95% confidence interval (CI), 1.057-1.189, p=0.000), GCS score (OR 0.724. 95% CI, 0.624-0.839, p=0.000), oxygen saturation (OR 0.895, 95% CI, 0.835-0.959, p=0.002), and co-ingestion of TCA (OR 4.595, 95% CI, 1.169-18.063, p=0.029) were identified as risk factors of morbidity of aspiration pneumonia upon multiple logistic regression analysis. Conclusion: Time from ingestion to visit, low GCS score, low oxygen saturation and co-ingestion of TCA were risk factors of the development of aspiration pneumonia in benzodiazepine overdose patients.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.14-20
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• 2000

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

• Korean Journal of Clinical Pharmacy
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• v.24 no.2
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• pp.115-125
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• 2014

Purpose: The purpose of the present study was to assess the incidence of the potentially inappropriate medication (PIM) use in Korean elderly patients with heart failure, and to evaluate factors that influence PIM use. Method: Korean National Health Insurance claims database between January 2009 and December 2009 was used. Using 2012 updated Beers criteria, PIM use in heart failure patients aged 65 years or older was examined. Result: The incidence of PIM use in elderly heart failure patients was higher than in overall elderly patients. Among the 12,759 elderly patients with heart failure, 46.2% of study subjects were prescribed PIM(s) at least once. The number of PIM per 10 medications that patients received per patient was 1.53. The most commonly used PIMs in elderly heart failure patients were benzodiazepines (30.9%), non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors (16.3%), digoxin (9.9%), and spironolactone (9.0%). Women (odds ratio, 1.20; 95% CI, 1.17-1.24), medical aid (odds ratio, 1.11; 95% CI, 1.08-1.13), and long-term facilities (odds ratio, 2.69; 95% CI, 2.44-2.96) were revealed to be important factors associated with PIM use. In addition, patient's age also seems to influence PIM use. Conclusion: Elderly heart failure patients are at a greater risk for adverse drug events attributed by inappropriate medication use. Efforts to increase awareness of PIM use in elderly heart failure patients are needed. In addition, various comprehensive strategies and policies to identify and prevent PIM use should be established nationwide.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.230-234
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• 2015

This paper includes a review of 555 drug-facilitated sexual assault (DFSA) cases analyzed at the National Forensic Service (NFS), South Korea, between 2006 and 2012. The results of toxicological analyses of blood and urine samples were also reported, and furthermore the results were interpreted with respect to the number of drugs detected. The number of DFSA cases was highest during warmer summer months and the mean age of the victims was 25 years, with 48% being between 20 and 29 years. Accommodations or entertainment places were the most frequent place of the sexual assault (57%); and the assailant was a stranger in 72% of the DFSA cases. Drugs were identified in the blood or urine samples in 145 cases (26%) and sedative-hypnotics, such as benzodiazepines and zolpidem, were the most commonly detected, along with sedative antihistamines such as doxylamine and diphenhydramine. The frequent presence of sedative drugs in biological samples tends to implicate their use in chemical submission. However, interpreting the analytical results in terms of voluntary vs. surreptitious administration of drugs requires further detailed investigation and knowledge of the victim's health status and medication used at the time of event.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.287-295
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• 1998

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol $(0.03{\sim}0.3\;{\mu}\;g/kg)$, diazepam $(10{\sim}100\;{\mu}\;g/kg)$ and pentobarbital $(1{\sim}10\;{\mu}\;g/kg)$ were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol ＞ pentobarbital ＞ diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam $(30\;{\mu}g/kg)$ augmented the effect of muscimol $(0.1\;{\mu}g/kg)$ in decreasing blood pressure and renal nerve activity, but pentobarbital $(3\;{\mu}g/kg)$ did not. Bicuculline $(0.5\;{\mu}g/kg)$, a GABAergic receptor blocker, significantly attenuated the effect of muscimol in decreasing BP and RNA, either alone or with diazepam, and that of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.361-382
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• 2022

The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α₂ agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.

• Journal of Korean Academy of Nursing
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• v.53 no.4
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• pp.371-384
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• 2023

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing delirium. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between participants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1-concentrations of urine EVs-were comparatively higher in participants with severe delirium than that in participants without delirium (p = .002 and p = .001, respectively). Conclusion: These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.

• Journal of the korean academy of Pediatric Dentistry
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• v.28 no.3
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• pp.441-446
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• 2001

Flumazenil is a competitive antagonist of benzodiazepines. It is usually administered intravenously. However, if the intravenous route is not available then other routes of drug administration should be considered. This study was designed to evaluate the reversal effects of flumazenil after nasal administration. Twenty-five young, healthy adult volunteers participated in this clinical trial. The dosage of 0.08mg/kg midazolam was administered intravenously to induce deep sedation. Ten minutes after midazolam administration, 0.5mg of flumazenil was dropped nasally, over a period of one minute. Blood samples were taken to measure the concentration of midazolam and flumazenil at 0, 5, 10, and 20min after nasal administration of flumazenil, using High Performance Liquid Chromatography. The degree of sedation was evaluated with sedation score and bispectral index (BIS), Statistical analysis was performed by multivariate ANOVA and correlation analysis (P<0.05). Peak serum flumazenil concentration was reached in 10min. Sedation score decreased after midazolam administration and showed a significant increase after flumazenil administration. However, BIS decreased during the first 10min after midazolam administration and then no significant changes after flumazenil administration. There were two instances representing rapid and complete reversal of midazolam after intranasal administration of flumazenil. In conclusion, intranasal flumazenil administration may be effective in some patients when intravenous route is not available in condition of benzodiazepine overdose.

• Sleep Medicine and Psychophysiology
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• v.8 no.2
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• pp.113-120
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• 2001

Objectives: Obstructive sleep apnea syndrome is common and may produce various symptoms and serious complications. A substantial number of research articles on obstructive sleep apnea syndrome have been published in Korea. However, we found such limitations as lack of sufficient sample size and lack of polysomnography-proven cases. Therefore, we aimed at studying clinical features and sleep structure in a sufficient number of Korean patients with obstructive sleep apnea syndrome diagnostically confirmed with polysomnography. Methods: We studied 801 subjects referred to the Division of Sleep Studies, Seoul National University Hospital, who were diagnosed as having obstructive sleep apnea syndrome with polysomnography. Subjects were excluded if they had central sleep apnea syndrome, periodic limb movement disorder, narcolepsy or REM sleep behavior disorder. Foreign patients were also excluded. First of all, we studied the clinical features of the subjects. Secondly, we compared sleep-related parameters of the study subjects with those of age/sex-matched normal values. Thirdly, correlations of respiratory disturbance index (RDI) with each of the sleep-related parameters were calculated. Results: Among the 801 subjects, 668 were male subjects (83.4%) and 133 female subjects (16.4%). Their mean age was 46.6 years (${\pm}13.5$). The mean body mass index (BMI) was 25.8 (${\pm}3.8$) and subjects with BMI was over 28.0 accounted for 22.8% of the total. Fifty subjects (6.2%) were found to take benzodiazepines. Mean RDI and mean nocturnal oxygen saturation of all subjects was 31.2 (${\pm}24.4$) and 94.5% (${\pm}3.6$), respectively. In comparison with normal values, the subjects showed longer sleep latency, lower sleep efficiency, decreased total slow wave sleep % (TSWS %), and decreased total REM sleep % (TREM %)(p<0.01 in all). RDI had a negative correlation with each TSWS % and TREM % (p<0.01, p<0.01). However, RDI did not have significant correlation with either sleep latency or sleep efficiency. Conclusion: In this study, 6.2% of patients diagnosed as having obstructive sleep apnea syndrome were found to take benzodiazepines, although they are generally considered to be of litte benefit or even dangerous because of the respiratory suppressing effect. The proportion of obese subjects was only 22.8% and Korean patients with obstructive sleep apnea syndrome seem to be less obese than those described in foreign journals. This study also suggests that the severity of obstructive sleep apnea syndrome may have a more significant effect on sleep architecture defined as TSWS % and TREM % than on sleep efficiency.

• Biomedical Science Letters
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• v.10 no.3
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• pp.299-303
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• 2004

The number of acute drug intoxication who visiting to emergency department which is located near urban and rural area concomitantly is inclined to increase slightly, The purpose of this study was the investigation of methods and strategies of management of acute drug intoxication in emergency department Clinical trials were done on 92 cases of acute drug intoxication visiting to Emergency Department of Chungnam National University Hospital during 4 months from April to July 2003. 1. The total number of acute drug intoxication during this period was 92 patients, which presented 0.95％ of all the emergency department visiting patients during the study. The intentional ingestions were observed in 84 cases (91.3％). 2. The maximal point of age distribution was 4th decade. The number of that was 21 cases (22.8％). 3. The number of patients who had ingested benzodiazepines and doxylamine succinates was 26 cases (28.2％), organophosphorus was 20 (21.7％), paraquat was 10 (10.8％), others were 36 (39.3％). 4. Five kinds of po1ydrug ingestion was observed in 3 cases, four kinds was observed in 3, three kinds was observed in 5 and co-ingestion of alcohol was observed in 28 cases (30.4％). 5. The mortality was occurred in 4 cases, 2 of them were caused by paraquat, 1 of them was caused by organophosphorus (OP), 1 of them was caused by acetic acid. 6. The gastric larvage as a mean of treatment modality was done in 57 cases (61.9％). The use of activated charcoal was done in 8 (8.69％). The maintenance of tracheal intubation was done in 6 (6.52％). 7. The mean observational period in emergency department was 8 hours 42 minutes in benzodiazepine and doxylamine succinate group, 21 hours 46 minutes in OP, 20 hours 39 minutes in other germicidal except OP, 23 hours 9 minutes in paraquat group. Without a drug information and intoxication center in Korea, We should minimize the exhaustion of medical resources by establishment of determinant criteria which can be seen in relatively less-complicated cases of acute drug intoxication. Thus, we should consider the introduction of simple toxicology treatment protocol and toxicologic observation unit in emergency department as possible means to reduce economical and social burdens.