• 대한약리학회지
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• 제30권3호
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• pp.299-311
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• 1994

Pentazocine은 opioid 수용체에 대한 흥분작용과 길항작용을 겸유한 opioid계 약물로 알려져 있다. 본 연구에서 흰쥐 적출 관류부신으로 부터 pentazocine의 catecholamine(CA) 분비작용을 관찰하여 그 기전을 규명하고 또한 다른 opioid의 작용과 비교하여 얻어진 결과는 다음과 같다. Pentazocine$(30{\sim}300\;ug)$을 부신정맥내에 주사하였을때 현저한 용량의 존성의 CA 분비작용을 나타내었다. Pentazocine의 이러한 CA 분비작용은 chlorisondamine $(10^{-6}\;M)$, naloxone $(1.22{\times}10^{-7}\;M)$, morphine $(1.73{\times}10^{-5}\;M)$, enkephalin $(9.68{\times}10^{-6}\;M)$, nicardipine $(10^{-6}\;M)$ 및 TMB-8$(10^{-5}\;M)$등의 전처치로 뚜렷이 억제되었으나 pirenzepine (2과$10^{-6}\;M)$의 전처치에 의해서는 영향을 받지 않았다. $Ca^{++}$-free Krebs 용액으로 30분간 관류한 후에 pentazocine의 CA 분비작용은 현저한 감소를 나타냈었다. Pentazocine $(1.75{\times}10^{-4}\;M)$을 20분간 관류시킨 후에 ACh $(5.32{\times}10^{-3}\;M)$과 DMPP $(10^{-4}\;M)$에 의한 CA 분비작용이 의의 있게 감약되었다. 이상과 같은 연구결과를 종합하면, pentazocine은 횐쥐 적출 관류부신에 투여시 현저한 CA 분비작용을 일으키고 있는 칼슘의존성 exocytotic mechanism에 의한 것으로 생각되며, 이러한 pentazocine의 CA 분비작용은 부신 chromaffin cell에 있는 opioid 수용체의 활성화를 통하여 나타나며, 또한 부신의 nicotine 수용체의 흥분작용과도 관련성이 있는 것으로 사료된다.

• Journal of Hospice and Palliative Care
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• 제19권3호
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• pp.249-255
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• 2016

목적: 췌장암 환자의 90% 이상이 신경성 통증을 앓는 것으로 알려져 있으며 말기 췌장암 환자에서는 통증조절이 매우 중요한 목적 중 하나이다. 케타민은 NMDA 수용체 길항제로서 신경통에 효과가 있는 것으로 알려져 있으며 마약성 진통제의 요구를 감소시켜주는 효과에 대한 연구들이 앞서 진행된 바 있는 약물이다. 본 연구에서는 완화병동에 입원한 췌장암 환자들을 대상으로 케타민의 사용과 관련된 항목들을 알아보고 마약성 진통제를 줄여주는 효과를 나타내는지에 대해 진행한 연구이다. 방법: 2013년 1월부터 2014년 12월까지 서울성모병원완화의학과에 입원한 췌장암 환자 111명에 대한 의무기록을 통하여 케타민을 사용한 그룹(34명)과 사용하지 않은 그룹(77명)에 대해 케타민 사용과 관련된 요인 및 사용 후 모르핀을 포함한 마약성 진통제의 용량 변화를 분석하였다. 결과: 케타민을 사용한 군에서 사용하지 않은 군에 비하여 총 기본 마약성 진통제 사용량(P value 0.001), 하루에 사용한 마약성 진통제의 용량(P value<0.001), 평균 구제 약물의 용량(P value 0.001), 하루 평균 구제 약물 사용 횟수(P value 0.001), 하루 평균 구제 약물을 용량(P value<0.001)이 더 높게 나타났다. 케타민 사용 전후를 비교한 결과 마약성 진통제는 케타민 사용 전(76.1 (${\pm}64.5$))에 비하여 후(89.6 (${\pm}80.9$))에 유의하게 증가한 것으로 확인되었다. 결론: 후향적으로 의무기록 분석을 통해 이루어진 본 연구에서는 더 많은 용량의 마약성 진통제를 요한 환자들이 케타민을 사용한 경향이 확인되었다. 이와 더불어 케타민을 사용함으로 인해 마약성 진통제 요구량이 감소하는 경향은 확인할 수 없었다. 차후 더 많은 환자들과 다양한 종류의 암성 통증을 대상으로 한 완화의료적 목적의 케타민 사용에 대한 연구가 요할 것으로 생각되며 케타민의 사용에 관련된 가이드라인에 대한 논의가 요할 것으로 생각된다.

• The Korean Journal of Pain
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• 제13권2호
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• pp.202-207
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• 2000

Background: Superior hypogastric plexus block has been advocated as a useful technique for the treatment of cancer related pelvic pain. The aim of this study was to evaluate the effect of neurolytic trans-intervertebrodiscal superior hypogastric plexus block for pelvic cancer pain. Methods: Twenty-eight patients with gynecologic, colorectal or genitourinary cancer who suffered intractable pain were studied. We performed superior hypogastric plexus block by trans-intervertebrodiscal approach at L5/S1 level under the C-arm fluoroscopic guide unilaterally or bilaterally. Ten ml of 100% dehydrated alcohol was injected through each needle. We evaluated the change of visual analog pain score (VAS; 0~100 mm) and daily dose of oral morphine sulphate at the time of pre-block and 7 days after the block. Results: Fourteen patients (50%) had satisfactory pain relief (VAS<30) while five patients (18%) had moderate pain control (VAS 30~60). The remaining nine patients (32%) had mild or little pain relief (VAS>60) and their daily oral morphine doses were above 160 mg. Additional pain control method may be needed for those patients who received high dose of opioid before neurolytic block. Conclusions: We conclude trans-intervertebrodiscal neurolytic superior hypogastric plexus block was effective in relieving pelvic cancer pain. Neurolytic block, earlier stage, may provide better effects for more comfortable life at the end stage for cancer patients.

• Advances in Traditional Medicine
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• 제6권4호
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• pp.349-354
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• 2006

In the present study, three Malaysian Channa spp. fish Channa striatus, Channa micropeltes and Channa lucius were assessed for their analgesic activity. Distilled water and mixture of chloroform: methanol were used for extraction. The analgesic or antinociceptive activity was investigated by abdominal writhing and hot plate test. The water extract of Channa striatus and the chloroform: methanol extract Channa lucius produced potent antinociceptive effect when assessed with the abdominal writhing test. The activity was compared to morphine where the activity of the extracts was less potent than the opioid. In the hote plate test, water extract of Channa striatus revealed significant activity and chloroform:methanol extract of Channa micropeltes had moderate activity. However, these activities were statistically lower than morphine. Collectively, this study also showed that Channa striatus extract was more potent analgesic agent when compared to the other closely related snakehead Channa micropeltes and Channa lucius.

• 약학회지
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• 제49권5호
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• pp.370-374
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• 2005

Lactoferrin is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, it was reported that bovine milk-derived lacto­ferrin (BLF) produced analgesia via a $\mu$-opioid receptor-mediated response in the spinal cord. However the precise mech­anism of this analgesic effect is remains unclear. In Randall-Selitto paw pressure study, each single administration of morphine (10 mg/kg) and BLF (50, 100 and 200 mg/kg) induced analgesia, however, NMDA receptor antagonist MK-801 (0.1, 0.2 and 0.3 mg/kg), inhibited analgesia induced by BLF (100 mg/kg). Intracerebroventricular infusion (I.C.V.) of N­methyl-D-aspartic acid (NMDA) ($0.3\;{\mu}g/8.0\;{\mu}l/hr/day$), as a NMDA receptor agonist, reversed inhibition of MK-801 (0.3 mg/kg) on analgesia induced by BLF (100 mg/kg). These results suggest that BLF have analgesic effect, through NMDA recep­tor activation.

• The Korean Journal of Pain
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• 제22권1호
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• pp.68-73
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• 2009

Opioids profoundly inhibit evoked discharges of spinal nociceptive neurons, thereby inhibiting the transmission of pain. Intrathecal administration of opioids using implantable continuous infusion systems is an effective method of pain relief when other treatments have failed, as well as for patients with adequate analgesia on high dose therapy that produces unacceptable side effects. We report two cases of intrathecal pump implantation performed in patients suffering from intractable chronic pain. A test dose of 3 mg morphine was injected into the epidural space. No side effects were noted and patients experienced considerable pain relief. Implantation was performed one day after the test. The initial intrathecal morphine delivery dose was half of the equivalent dose of daily oral intake opioids and the infusion rate was increased gradually under close observation for opioid side effects. Two days post-implantation, both patients were discharged without any complications.

• The Korean Journal of Pain
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• 제11권2호
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• pp.214-219
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• 1998

Pain is one of the most frequent and disturbing symptom of cancer patients. And almost of cancer patients are afraid of a attacks of pain related to cancer. Caring for the cancer patient can be divided into two phases. The phase of "active treatment" involves various interventions-surgical, chemical or radiological- that are designed to prolong the patient's life. "Terminal care" is the period from the end of active treatment until the patient's death. But in the majority of clinical settings, cancer pain is not being managed adequately results from a lack of education about how to treat the cancer pain management in the safest and most effective way during terminal phase. Althought organic factors represent the most important cause of their pain, it is also important to deal with the patient's psychological reactions and to take account of his or her social and family environment if treatment for chronic cancer pain is to prove adequate. Thus we try to evaluate a kinds of cancer related to pain, degree of pain, effectiveness of drugs, and patient's responses to management. In regard to the satisfaction for pain relief in pain clinics at Pusan National University Hospital(PNUH) are about 70% in patients and 90% in family. Average life expectancy in cancer patients are about 140 days (3 days- 5.7 years). Cancer patients are complained of several discomfortness (above 30 kinds) such as, pain associated with cancer (75%), nausea and vomitting (38%), sleeping disorder (38%), anorexia (38%), dyspnea (32%), constipation (31%), etc. Distributions of cancer associated with pain are stomach cancer (21%), lung cancer (16%), cervix cancer (10%), anorectal and colon cancer (8.6%), hepatoma (8%), pancreatic cancer (3%). About 1/3 of patients are suffer from incident pain in 3~5 times in a day especially in moving, coughing, and exercise. Methods for drug delivering system before death are transdermal fentanyl patch (42%), intravenous PCA (21%), oral intake of opioid (17%), epidural PCA (14%), etc.

• 대한임상독성학회지
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• 제11권1호
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• pp.49-52
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• 2013

Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

• The Korean Journal of Pain
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• 제37권3호
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• pp.211-217
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• 2024

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

• 대한약리학회지
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• 제23권2호
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• pp.123-131
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• 1987

Morphine을 비롯한 opioid peptide가 말초 또는 중추에 투여시 혈압하강과 심박동수감소를 보이며 opiate 수용체 길항제인 naloxone에 의해 길항됨이 관찰되었던바 근래 몇몇 보고들은 중추신경내에서 adrenergic및 opioidergic system이 서로 관련되어 있음을 시사하고 있다. 이에 본 실험에서 고혈압 연구에 널리 사용되고 있는 2-kidney, 1-clip (2K1C) 방법으로 실험적 고혈압을 유발시킨 백서의 측뇌실내 clonidine또는 morphine의 심맥관계에 대한 효과와 각각의 차단제에 의한 영향 그리고 정상 및 고혈압상태 백서의 뇌내 ${\beta}-endorphin$의 함량과 specific opiate receptor binding을 정량하여 고혈압 유발에 따른 뇌내 opiate system의 변동을 관찰하였다. 2K1C 고혈압 또는 sham-operated대조백서에서 측뇌실내 clonidine $(3-30\;{\mu}g/kg)$은 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며 clonidine의 혈압강하 효과는 2K1C고혈압 백서에서 더욱 현저하였다. clonidine의 혈압강하효과는 고혈압 백서에서 측뇌실내 yohimbine 또는 naloxone 전처리에 의해 약화되었고 대조군에서는 yohimbine ($30\;{\mu}g/kg$, i.v.t.)에 의해 억제되었으나 naloxone ($50\;{\mu}g/kg$, i.v.t.)에 의해서는 영향 받지 않았다. clonidine과 마찬가지로 측뇌실내 morphine $(10-100\;{\mu}g/kg)$은 2K1C 고혈압 또는 sham-operated 대조백서에서 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며, morphine의 혈압강하효과는 2K1C 고혈압백서에서 더욱 현저하였다. 대조군과 고혈압군에서 morphine의 혈압강하효과는 naloxone 전처리에 의해 현저히 약화되었으나 yohimbine에 의해서는 영향 받지 않았다. 2K1C 시술익일부터 투여한 clonidine은 2K1C 시술에 의한 혈압 상승을 억제하였으며 naloxone (2 mg/kg, i.p.)에 의해 반전되었다. 2K1C 시술에 의해 고혈압이 유발된 백서의 뇌내 ${\beta}-endorphin$ 함량은 sham-operated 군에 비하여 유의하게 감소되어 있었고 (3H)-naloxone의 specific binding의 Bmax는 증가되었으나 Kd치는 변동되지 않았다. 이상의 실험 성적은 뇌내 opiate계가 혈압조절에 중요한 역할을 담당하고 있으며 2K1C 고혈압백서의 고혈압상태 유지에 뇌내 opiate계의 기능저하가 일부관여하고 있음을 강력히 시사한다.