• 대한소아치과학회지
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• 제47권2호
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• pp.228-234
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• 2020

Chloral hydrate(CH)는 100년이상 동안 진정용 약물로 이용되어 왔다. CH는 1832년 처음 합성되었고, 1861년에는 진정제의 특성이 소개되었으며, 1869년 이후부터는 합성기술의 발달로 이용 빈도가 증가되었다. 1894년 소아에게 CH를 사용하기 시작한 기록이 있다. CH는 최근까지도 안정성에 관한 많은 논란들이 있었음에도 저렴한 가격과 비교적 안전하다는 경험적 이유로 어린이의 치과 진정법에 여전히 사용되고 있다. 그러나, 2006년 미국 FDA의 권고 이후, 2012년부터 미국내 제약회사는 CH를 더 이상 생산하지 않고 있다. 그럼에도 여전히 미국 내 여러 지역에서는 CH 원재료를 이용하여 조제한 현탁액 형태로 진정법에 사용하고 있으며, 2012년 이후에도 사망과 관련한 부작용의 보고는 계속되고 있다. CH는 현재까지 한국에서 소아 진정법에 가장 많이 이용되고 있는 약제이며, 최근 한국에서도 다수의 부작용에 관련한 보고들이 있었다. 최근 진정법을 이용한 소아의 치과치료에, CH를 대신하여 dexmedetomidine, propofol 등 여러 약물들이 소개되었다. 다만 이들을 소아치과 영역에서 사용하는데 있어서는 여러 가지 제한점이 있으며 고려해 볼 사항들도 많다. 이에 CH와 관련된 합병증들과 한국에서의 사용 실태, 그리고 CH를 대체할 수 있는 약물에 대해 알아보고자 한다.

• 한국임상수의학회지
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• 제33권4호
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• pp.234-236
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• 2016

A 14 kg, 9-year-old, spayed female, Cocker Spaniel was presented to the Veterinary Medical Teaching Hospital of Seoul National University with a history of head tilt and circling. Otitis externa and media were diagnosed by computerized tomography, and total ear canal ablation was performed. In preanesthetic evaluation, systemic hypertension and second-degree atrioventricular block were observed, but there was no regurgitation through the heart valves. Systemic hypertension was managed with amlodipine (0.1 mg/kg, PO, BID) for the anesthesia. The dog was premedicated with cefazolin (22 mg/kg, IV) and midazolam (0.2 mg/kg, IV). Anesthesia was induced with alfaxalone (2 mg/kg, IV) and maintained with isoflurane and 100% oxygen following intubation. During surgery, vital signs (heart rate, respiratory rate, blood pressure, end tidal carbon dioxide partial pressure and body temperature) were maintained within normal ranges, but bradycardia was observed and corrected with glycopyrrolate (5 ug/kg IV, twice). During subcuticular suture, electrohemostasis was applied at the incision line, which was close to the trigeminal nerve. In no time at all, heart rate dramatically decreased from 110 to 60 beats per minute. No additional treatment was done because mean blood pressure was maintained above 70 mmHg. The heart rate recovered according to the decrease of end tidal isoflurane concentration and there were no complications associated with the anesthesia and surgery. Sudden bradycardia after electrical stimulation around the trigeminal nerve was considered as trigeminocardiac reflex (TCR). It is recommended to be careful of bradycardia from TCR when electrocautery is used in the craniofacial area during surgery.

• Tuberculosis and Respiratory Diseases
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• 제73권3호
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• pp.151-161
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• 2012

Background: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. Methods: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. Results: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, $1.3{\pm}0.5{\mu}g/kg/min$; day 2, $0.9{\pm}0.4{\mu}g/kg/min$; p<0.01), and was significantly lower than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; $r_s$=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; $r_s$=0.77), and RASS and BIS ($r_s$=-0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. Conclusion: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability.

• 대한간호학회지
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• 제31권2호
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• pp.304-314
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• 2001

Major purposes of this study were to investigate the administration patterns of analgesics and sedatives in SICU and to identify the factors influencing the use of prn analgesics and sedatives by ICU nurses. The sample of this descriptive study was 50 adult patients in SICU and 53 ICU nurses. Patient's medical records were reviewed to investigate names, doses, the routes of administration, the interval of administration, and the type of prescription of sedatives and analgesics administered. Study medications were narcotics, hypnotics, and antipsychotics. To identify the factors influencing the use of prn analgesics and sedatives, 53 ICU nurses checked 9 items, and rank them from first to fifth. The selection of items was based on the previous studies and the experience of the investigator. The results of the study are as follows: 1. The mean age of the subjects was 53 years, 24 patients out of 50 subjects had received mechanical ventilation therapy. Most of the patients received neurosurgeries and abdominal surgeries. 2. For 4 days, 13 total study medications and combination of these were administered to the patients. Commonly prescribed drugs were Ketoprofen and Midazolam. Twenty six to fourty two percent of the patients did not receive any drugs for at least one day during the four days. 3. On the average, the study drugs were administerd 1.4 to 2.6 times per day during 4 days. 4. More than 50 percent of the prescription was as-needed (prn) except those of the POD 3. Fourteen percent of the patients did not have any prescription for sedation and pain control after surgery. 5. Examination of the frequency of sedatives and analgesics bolus administration revealed that a greater number of doses were given during daytime (from 7 am. to 7 pm.) than nighttime (from 7 pm. to 7 am.). The difference was significant at Alpha, .05. 6. First factor that most influenced nurses to administer sedatives and analgesics for intubated patients was the evaluation of patient's vital signs (51%). For non- intubated patients, the factors that nurses considered important were the patients' complaints of pain (64%) and evaluations of patients' vital signs (23%). In conclusion, the results of this study indicate that patients in SICU might not receive enough analgesics and sedatives to feel completely free from pain during the post operational period. Future study should be focused on the evaluation of the adequacy of current practice for pain and anxiety control in terms of the SICU patient's response.

• The Korean Journal of Pain
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• 제12권1호
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• pp.36-42
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• 1999

Background: The current maximal recommended doses of lidocaine are 7 mg/kg with $5\;{\mu}g/ml$ of epinephrine. But in clinical practice, sometimes more doses of lidocaine are required to produce adequate regional anesthesia. Method: Twenty-two healthy women patients were divided into two groups and pretreated with valium 5 mg p.o., morphine 5 mg i.m., and midazolam 2 mg i.v. before operation. Of these, 7 mg/kg of 2% lidocaine with $5\;{\mu}g/ml$ of epinephrine were given to 11 patients epidurally. Initial 3 ml of epinephrine mixed lidocaine was given as a test dose and remaining doses were given 5 ml/30 sec with 3 min intervals. Radial arterial blood were drawn at 5, 10, 15, 20, 30, 45, 60, 90, 120 min to measure plasma lidocaine concentrations. After confirming all of the peak plasma concentrations of 7 mg/kg lidocaine were absolutely under $5\;{\mu}g/ml$, the other 11 patients were given 10 mg/kg of 2% lidocaine with $5\;{\mu}g/ml$ of epinephrine epidurally and blood samplings were taken according to the same method of 7 mg/kg group. The peak plasma concentration ($C_{max}$), time to reach to $C_{max}$ ($T_{max}$), time to reach to $T_4$, maximal sensory block level, systemic toxicity, and vital sign changes were investigated. Result: $C_{max}$ was significantly higher in 10 mg/kg group ($5.1{\pm}1.3\;{\mu}g/ml$) than 7 mg/kg group($3.3{\pm}0.5\;{\mu}g/ml$), but $T_{max}$ ($10.5{\pm}2.7$ min vs $10.9{\pm}3.1$ min) was not different. Time to reach $T_4$ was significantly shorter in 10 mg/kg group ($9.5{\pm}2.7$ min) than 7 mg/kg group ($12.7{\pm}3.2$ min) but maximal sensory block level ($T_{3.7{\pm}0.7}$ vs $T_{2.7{\pm}1.0}$) was not different. In four patients of 10 mg/kg group, peak plasma concentrations exceeded $5\;{\mu}g/ml$, but no systemic toxicities appeared. No significant vital sign changes were observed. Conclusion: The current maximal recommended doses of lidocaine, merely based on body weight are not always appropriate. Further studies are needed to determine more precise guideline of maximal doses that include various pharmacokinetic components.

• Molecules and Cells
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• 제38권12호
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• pp.1064-1070
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• 2015

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO ($0.1-0.5{\mu}m$), a specific mitochondrial antioxidants, and cyclosporin A ($1-5{\mu}m$), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam ($1-50{\mu}m$), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.

• Journal of Microbiology and Biotechnology
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• 제22권12호
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• pp.1659-1664
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• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

• 생명과학회지
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• 제17권3호통권83호
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• pp.334-339
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• 2007

본 연구는 우황청심원을 비롯한 상용되는 20종의 한약제제를 대상으로 9종의 시토크롬 동종효소에 대한 대사능의 저해정도를 고속 스크리닝 기법을 이용하여 탐색함으로써, 한약제제와 약물의 병용으로 인한 약물 상호작용 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 9종의 주요 시토크롬 약물대사효소의 지표약물과NADPH-generating system및 한약제제(500 ${\mu}g/ml$)를 첨가한 후 $37^{\circ}C$에서 15분간 반응시켜 생성된 각각의 대사물을 LC/MS/MS를 이용하여 정량하여 시토크롬 동종효소 활성의 변화를 평가하였다. 그 결과 우황청심원 현탁액 및 황련해독탕 물 추출물이 각각 CYP2B6 및 CYP2D6 효소 활성을 선택적으로 강력하게 저해하였다. 이러한 결과는 약국에서 쉽게 구입할 수 있는 한약제제들 중 일부는 인체 간 시토크롬 활성 저해능을 가지고 있고, 이들 효소에 의해 대사되는 약물과의 병용 복용시 약물상호작용 발생 가능성이 있음을 의미한다. 향후 한약제제에서 저해능을 나타내는 주된 성분을 규명하여 이 성분의 저해능과 저해 기전을 살피는 노력이 필요할 것이다.

• Journal of Dental Anesthesia and Pain Medicine
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• 제23권2호
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• pp.101-110
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• 2023

Background: Dentists make various efforts to reduce patients' anxiety and fear associated with dental treatment. Dental sedation is an advanced method that dentists can perform to reduce patients' anxiety and fear and provide effective dental treatment. However, dental sedation is different from general dental treatment and requires separate learning, and if done incorrectly, can lead to serious complications. Therefore, sedation is performed by a limited number of dentists who have received specific training. This study aimed to investigate the proportion of dentists who practice sedation and the main sedatives they use in the context of the Republic of Korea. Methods: We used the customized health information data provided by the Korean National Health Insurance. We investigated the number of dental hospitals or clinics that claimed insurance for eight main sedatives commonly used in dental sedation from January, 2007 to September, 2019 at the Health Insurance Review and Assessment Service. We also identified the changes in the number of dental medical institutions by region and year and analyzed the number and proportion of dental medical institutions prescribing each sedative. Results: In 2007, 302 dental hospitals prescribed sedatives, and the number increased to 613 in 2019. In 2007, approximately 2.18% of the total 13,796 dental institutions prescribed sedatives, increasing to 3.31% in 2019. In 2007, 168 institutions (55.6%) prescribed N₂O alone, and in 2019, 510 institutions (83.1%) made claims for it. In 2007, 76 (25.1%) hospitals made claims for chloral hydrate, but the number gradually decreased, with only 29 hospitals (4.7%) prescribing it in 2019. Hospitals that prescribed a combination of N₂O, chloral hydrate, and hydroxyzine increased from 27 (8.9%) in 2007 to 51 (9%) in 2017 but decreased to 38 (6.1%) in 2019. The use of a combination of N₂O and midazolam increased from 20 hospitals (6.6%) in 2007 to 51 hospitals (8.3%) in 2019. Conclusion: While there is a critical limitation to the investigation of dental hospitals performing sedation using insurance claims data, namely exclusion of dental clinics providing non-insured treatments, we found that in 2019, approximately 3.31% of the dental clinics were practicing sedation and that N₂O was the most commonly prescribed sedative.

• Journal of Dental Anesthesia and Pain Medicine
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• 제24권3호
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• pp.187-193
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• 2024

Background: Patients with autism spectrum disorder (ASD) present challenges in dental treatment cooperation owing to deficits in communication skills and social interaction. Behavioral guidance, sedation, and general anesthesia may be employed to ensure the quality of dental care for individuals with ASD. This study aimed to examine the trends in dental treatment for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital, an oral health center for the disabled in the Gyeonggi region, over the past 10 years. Methods: This study utilized the order communication system to gather data on sex, age, cooperation level, number of quadrants treated, and administration of sedation or general anesthesia for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital between January 2013 and December 2022. Results: The total number of patients with ASD increased annually, possibly due to an increase in ASD prevalence and the hospital's designation as a center for disabled oral health. General anesthesia was predominant before 2017, with a shift towards N₂O-O₂ sedation. The most common age group for sedation or general anesthesia was 6-9 years, with a higher prevalence in males than in females. Notably, N₂O-O₂ and midazolam sedation resulted in better cooperation and fewer treated teeth than general anesthesia. Conclusion: This study highlights the evolving trends in dental treatment for individuals with ASD, indicating a shift towards outpatient methods, particularly N₂O-O₂ sedation. The sex distribution aligns with national statistics, emphasizing a higher prevalence of ASD in males than in females. These findings underscore the need for further research to establish evidence-based guidelines for optimal dental care strategies tailored to the unique needs of individuals with ASD.