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내성 및 의존성 형성 약물의 약효 검색

  • 김학성;오기완
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.77-77
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    • 1993
  • 약물 내성 (tolerance) 및 의존성 (dependence)은 그 약물이 지니고 있는 여러 가지 약리작용과 관련되어 형성된다. 약물의 반복투여 후, 나타나는 작용이 처음의 반응 (response) 보다 감소되어 나타나는 현상 즉, 내성과, 이와는 반대로 약물반복 투여 후 나타나는 작용이 처음의 반응보다 점점 증가하는 역내성 (reverse tolerance 또는 sensitization) 측정에 있어서 약물에 따라 적절한 검색 방법을 설명한다. 의존성에 있어서 약물 섭취 결과 mood가 변하거나 도취감 또는 만족감을 일으키게 되면 그 감각을 재 경험하고 싶다는 욕구가 일어나게 되는 정신적 의존성(psychic dependence)과, 약물을 반복 투여하다가 갑자기 투여를 중단 했을때 여러가지 생리학적인 또는 행동적인 변화가 급격히 증가하여 금단증상을 나타내는 신체적 의존성 (physical dependence) 측정 방법을 제시한다. 내성과 의존성은 근본적으로 다르지만 대부분의 경우 내성이 형성되면 의존성이 형성된다. 여기서는 주로 morphine과 psychostimulants를 투여한 후 나타나는 약리작용에 대한 내성과 opioids (마약성 진통제)의 의존성 평가 방법에 대한 model을 설명하고자 한다 진통성 내성(analgesic tolerance)에 있어서 진통제의 진통력은 진통력 측정 방법(tail pinch, paw-withdrawal, tail flick, tail-withdrawal, hot plate, writhing, etc)에 따라 차이가 있기 때문에 각각의 진통제의 정합한 내성 측정 방법을 결정할 필요가 있다. 역내성 (roversetolerance)은 cocaine, amphetamine, opioids둥의 만성투여에서 일어난다. 이들 역내성을 측정하는 한 방법으로 자발운동을 측정하는데 locomotor activity cage나 tilting cage를 이용한다. 정신적 의존성(psychic dependence)은 약물 섭취 욕구를 이용한 CPP (conditioned place preference)법을 소개한다. 신체적 의존성 (physical dependence)은 opioids를 만성적으로 투여한 후 naloxone으로 precipitation하여 나타난 여러 가지 금단증상을 측정하고 몇몇 평가 model을 제시한다.

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The in Vivo Distribution of $^{99m}Tc-Phytate$ IL-2 Complex on Selective Splenic Arterial Injection (비장동맥에 선택적으로 투여한 Interleukin-2와 $^{99m}Tc-Phytate$ 혼합물의 생체내 분포)

  • Zeon, Seok-Kil;Lee, Hee-Jung;Sohn, Soo-Sang
    • The Korean Journal of Nuclear Medicine
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    • v.26 no.1
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    • pp.124-126
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    • 1992
  • Interleukin-2 (IL-2)는 많은 immunoenhancing lymphokine의 한 종류로서 lymphokine activiated killer (LAK) cell의 생성을 자극시켜 흑종의 종양세포를 죽인다고 알려져 있다. 최근 간종양에서 비장동맥 또는 간동맥으로 투여한 IL-2가 비장의 임파계를 자극하여 LAK cell을 생성하여 어느정도효과가 있음이 밝혀지면서, 여러가지의 투여 방법이 시도되고 있다. 그러나 각종의 투여 방법에서 실제로 투여한 IL-2의 인체내 분포에 관한 연구는 없다. 저자들은 비정맥과 간문맥에 이상이 없는 증례의 비동맥에 IL-2와 $^{99m}Tc-phytate$ 혼합물을 투여하고, IL-2의 생체에서의 비장과 간에 어떻게 분포하는지 알아보기 위하여 $^{99m}Tc$의 radioactivity를 계측하여 보았다. 6예의 간세포암과 3예의 위암으로부터의 전이성간암에서 동맥조영술적방법을 이용하여 초선택적 비장동맥에 투여한 IL-2와 $^{99m}Tc-phytate$ 혼합물이 비장 27%, 간73%의 분포를 보여 비장을 거쳐온 $^{99m}Tc$의 방사능이 간에 많이 침착함을 확인하였고 간과 비장이외의 부위 즉 골수, 복수 또는 폐장이나 늑막에는 전혀 방사능 분포가 없음을 알 수 있었다. 따라서 비정맥이나 간문백에 이상이 없는 증례에서 IL-2의 비장동맥 투여는 목적하는 바 IL-2의 생체내 분포를 이룩할 수 있을 것으로 사료된다.

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EFFECT OF ADMINSTRATION METHOD OF FLUMAZENIL ON THE PLASMA CONCENTRATION AND THE REVERSAL OF SEDATION INDUCED BY MIDAZOLAM (Flumazenil의 투여 방법에 따른 혈장내 농도와 midazolam에 의해 유도된 진정 상태의 환원 효과)

  • Park, Seong-Kyu;Lee, Sang-Ho;Lee, Chang-Seop;Lee, Nan-Young;Oh, You-Hyang
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.3
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    • pp.499-508
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    • 2005
  • The purpose of this study were to evaluate the effect on the reversion of sedation induced by midazolam with flumazenil and to determine the plasma concentration of flumazenil according to the method of administration. Intranasal and intravenous flumazenil were administered to sedated health volunteers aged from 23 to 25 years, in doses typical of those used clinically to induce sedation with midazolam and for reversal with flumazenil. Objective assessment for degree of sedation and vital signs, plasma concentration were made for 2 hours period. 1. Systolic and diastolic blood pressure, $SpO_2$ were not changed by adminstration of flumazenil in sedated subject with midazolam, but pulse rate was increased temporarily. 2. Flumazenil showed the reversal of the sedative effect induced by midazolam regardless of administration methods. But intravenous administration showed more effect on the degree and the duration of reversion than intranasal administration with the exception of on set time. 3. Peak plasma concentration of flumazenil administered by intranasal route reached after 2 min and that of flumazenil administered by intravenous route was 4 min. Thus uptake of flumazenil did not showed any difference in accordance with the adminstration route. 4. Administration of flumazenil resulted in the temporary increase of midazolam plasma concentration.

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그라프트중합에의한 다공성 폴리아미드막의 공경의 조절

  • 임성윤;김진홍;이영무
    • Proceedings of the Membrane Society of Korea Conference
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    • 1992.10a
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    • pp.45-46
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    • 1992
  • 최근들어 많은 연구자들에 의해서 고분자 재료를 이용하여 약물의 방출속도를 조절하며 이를 통해서 장기간에 걸쳐 치료 유효농도이상의 혈중농도를 유지 함으로써 치료효과를 극대화 하려는 연구가 진행되고 있다. 특히 고분자 재료를 이용한 macromolecular drug의 방출조절에 관한 연구가 활발히 진행되고 있다. Macromolercular drug은 인슐린, 알부민등의 단밸질과 유로키나제등의 효소와 같이 약효는 매우 높으나 적절한 투여 수단이 발견되지 않아 투여가 매우 번거로운 단점을 가지고 있다. 이와같은 macromolecular drug의 대부분은 구강을 통해서 투여하는 것은 거의 불가능하며 체내 반감기도 매우 짧아서 절절한 투여방법의 개선이 필요하다. 따라서 본 연구실에서는 macromolecular drug의 투여방법을 개선하고자 다공성 고분자막을 이용하였으며 생체 환경의 변화에 대해서 투과속도가 변화하는 자극감응성 고분자 막을 개발하고저 기질로 사용한 고분자 막의 표면에 기능성 모노머를 그라프트 반응을 통해서 도입하고 이의 이용 가능성을 확인하였다.

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Change of neutrophil count after treatment of intravenous immunoglobulin in children with idiopathic thrombocytopenic purpura (소아 특발혈소판감소자색반병에서 면역글로불린 투여 후 호중구수치의 변화)

  • Park, Jun Young;Park, Ji Ae;Park, Seong Shik;Lim, Young Tak
    • Clinical and Experimental Pediatrics
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    • v.51 no.2
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    • pp.204-208
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    • 2008
  • Purpose : The aim of this study was to investigate the incidence and course of neutropenia following intravenous immunoglobulin (IVIG) therapy in children with idiopathic thrombocytopenic purpura (ITP). Methods : From January 2001 to June 2006, fifty-four patients with ITP were enrolled in this study. Forty-two of 54 patients were treated with IVIG, while the other 12 were treated with anti-D immunoglobulin (Anti-D Ig). Post-treatment absolute neutrophil counts (ANC) were compared between patients who received IVIG and those who received Anti-D Ig. Comparison of post-treatment ANC between patients who treated with two different IVIG regimens (400 mg/kg/day for 5 days and 1 g/kg/day for 2 days) was also performed. Results : Pretreatment ANC were not significantly different between the two treatment groups. After treatment with IVIG, 32 out of 42 patients (76.2%) showed more than 50% decrease of ANC from the baseline. On the other hand, only 2 out of 12 patients (16.7%) showed more than 50% decrease of ANC from the baseline after treatment Anti-D Ig. No significant difference was observed in the decline of ANC between the first IVIG treatment (42 patients) and repeated IVIG treatment groups (7 patients). There was no statistical difference in post-treatment ANC between patients who treated with two different IVIG regimens. The neutropenia induced by IVIG had resolved spontaneously in 38 out of 39 patients (97%) after several days. Conclusion : Neutropenia following IVIG administration may not be an uncommon finding in children with ITP. It seems to be transient and self limited.

THE COMPARATIVE STUDY ON THE SEDATIVE EFFECT OF ORAL MIDAZOLAM AND INTRAMUSCULAR MIDAZOLAM IN SEDATING YOUNG PEDIATRIC DENIAL PATIENTS (소아 환자에서 미다졸람의 경구 투여와 근육 투여에 의한 진정 효과의 비교 연구)

  • Min, Yu-Jin;Yu, Seung-Hoon;Kim, Jong-Soo
    • Journal of the korean academy of Pediatric Dentistry
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    • v.33 no.1
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    • pp.53-61
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    • 2006
  • When routine behavior control is impossible, midazolam is often used for sedation, because it has wide margin of safety, relatively few side-effects and multiple route of administration. Although intramuscular administration of all administration route is frequently used, it is a major source of anxiety, discomfort, and trauma in children. To the contrary, oral administration of midazolam is easily administered and accepted by children. But, it's therapeutic drug concentration has not been established. The purpose of this study was to compare sedation effect and physiologic parameter of oral midazolam which palliate demerits of intramuscular administration in sedating young pediatric patients with intramuscular midazolam Twelve negative children, mean age 62.5 months, who needed at least two separate restorative visits, requiring local anesthesia participated in this study On every visit, one of the following 2 different sedative regimen was given : (1) 0.30mg/kg midazolam by intramuscular administration (2) 0.75mg/kg by oral administration. Physiologic parameter(oxygen saturation, heart rate) was recorded by ten procedure and behavior was videotaped and rated using Ohio State University Behavior Rating Scale and Automated Counting System by one investigator, blind to administration route The analyzed sedative effect of oral midazolam resulted in good sedative effect, comparing to intramuscular route, And there is no statistically difference between oral and intramuscular administration of midazolam (p>0.05).

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Differences in Thrombolytic Effects in Accordance with Dosing-regimens of Tissue-type Plasminogen Activator in Experimental Pulmonary Embolism (실험적 폐색전증에서 조직형플라스미노겐활성체의 투여방법에 따른 혈전용해효과의 차이)

  • Chung, Hee-Soon;Kim, Ho-Jung;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.123-134
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    • 1993
  • Background: Tissue-type plasminogen activator is a physiologic activator, which has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA has the potential to induce effective thrombolysis without producing a systemic lytic state. In practice, however, therapeutically efficacious doses of t-PA has been associated with the development of a systemic lytic state. As experience with t-PA has accumulated, it has suggested that the fibrin selectivity is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optimize the duration of t-PA regimen. Methods: This study was designed to assess the thrombolytic efficacy of t-PA and the differences of two dosing regimens of t-PA (infusion of 1 mg/kg t-PA over 15 or 180 minutes) in a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots. By continuously counting over both lung fields with a external gamma counter, we correlated rate and extent of pulmonary thrombolysis with corresponding pulmonary hemodynamics in addition to the gas analyses of arterial and mixed venous blood. Results: 1) While total clot lysis was similar ($36.2{\pm}3.3%$ and $39.6{\pm}2.3%$ respectively, p>0.05) when t-PA was infused over 15 or 180 minutes, the rate of lysis during infusion was markedly increased with the shorter infusion ($81.4{\pm}16.8%/hr$ vs $37.3{\pm}2.4%/hr$, p<0.05). 2) The duration of thrombolysis was $63.3{\pm}22.2$ minutes although t-PA was administered over 15 minutes, and it was only $148.5{\pm}14.0$ minutes in case of the infusion over 180 minutes (p<0.05). 3) The increased rate of thrombolysis with the shorter infusion was accompanied by a faster amelioration of cardiopulmonary impairment from pulmonary embolism (p<0.05). Conclusion: It is concluded that the shorter (15 minutes) infusion of t-PA is superior to the longer (180 minutes) infusion when the dose is equal, in consideration of the faster improvement in cardiopulmonary impairment from pulmonary embolism.

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Ov-Synch 처리시 bST, HCG, Progesterone 투여가 수태율에 미치는 영향

  • 박정준;이명식;박수봉;임석기;전기준;정영훈;서국현;나기준;고대환
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.265-265
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    • 2004
  • 한우번식우 사육농가와 사육규모가 확대와 소 값 상승으로 인하며 인공수정 및 수정란 이식에 대한 수태율 향상에 많은 관심이 집중되고 있다. 이러한 수태율 향상을 위하여 한우 암소에 배란동기화 처리 후 인공수정 시 황체기능 강화제인 등을 투여하여 황체기능을 강화시키고, 투여시기에 따라 개체에 대한 신체충실지수(BCS)와 혈중요소태질소화합물(BUN)을 분석하였으며, 또한 투여시기에 따른 혈중 Progesteroner의 변화를 조사하였다. 황체기능강화제의 투여 방법은 HCG 투여구는 배란동기화 처리 후 6일째와 7일째에 각각 1500 IU와 3000 IU를 투여하였고, 투여 후 14일째에 혈액을 채취하여 혈중 P4 분석하였다. (중략)

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