• Title/Summary/Keyword: opioid system

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Evaluating Appropriateness of Medication Use in the Operating Rooms of a Tertiary Hospital: Based on Survey (일개 병원의 수술실 약제관련 업무 적정화 방안연구: 설문조사를 중심으로)

  • Lee, Ye Ji;Jeong, Kyeong Hye;Kim, Young Nam;Kim, Eun Young
    • Korean Journal of Clinical Pharmacy
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    • v.26 no.3
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    • pp.230-237
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    • 2016
  • Background: Since the use of opioid analgesics is frequent in operation rooms (OR), the risk of medication error is high; however the use of medication in the OR has been operating independently with the hospital pharmacy. Therefore, the assessment on management of medication use in operation and the pharmacist's role is needed. Methods: We conducted the literature review and survey from anesthesiologists, operating nurses at Chung-Ang Hospital on management of medication for operation use, awareness on need for medication management efficiency, need for satellite pharmacy in the operating room and its effect. Results: 56% of medical staffs responded that management of medication in the operating room is efficient; however, 82.6% responded that they felt the inconvenience in medication delivery to the OR when additional prescription was ordered. 51.5% also responded that extra time was required for management of narcotics and inventory/record keeping. 80% agreed that there could be lost costs due to prescription missed. Medical staffs responded improving the drug management system could increase the OR efficiency (87%), and eventually bring the increase in hospital revenue (80.4%). Those who responded that implementation of OR satellite pharmacy was needed include physicians (84.6%), nurses (63.6%), and also responded that it'd bring more profit to the hospital by increasing the efficiency in OR (60.9%). Conclusion: For efficient management of medications, implementation of OR satellite pharmacy would lead to improved drug management and increased efficiency in OR and reduced cost and improved patient care.

Effect of NMDA Receptor on Analgesic Effect of Bovine Milk-derived Lactoferrin (BLF) (우유속 락토페린의 NMDA 수용체를 통한 진통효과)

  • Jeon, Yong-Joon;Yun, Jae-Suk;Lim, Hwa-Kyung;Park, Ki-Suk;Na, Han-Kang;Kim, Dong-Sup;Kim, Joo-il;Yoon, Yea-Chang;Choi, Ki Hwan
    • YAKHAK HOEJI
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    • v.49 no.5
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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.

Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs -Analgesic effects of toad cake-

  • Inoue, Eiji;Shimizu, Yasuharu;Masui, Ryo;Usui, Tomomi;Sudoh, Keiichi
    • Journal of Pharmacopuncture
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    • v.17 no.1
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    • pp.74-79
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    • 2014
  • Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug ${\alpha}$-methyl-DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

Implantation of an Intrathecal Drug Administration System -A report of two cases- (척수강 내 약물 주입기의 이식 -증례보고-)

  • Lee, Sang Jin;Nam, Sang Kun;Kim, Jang Hyun;Kim, Hyun Joo;Lee, Sang Chul;Kim, Yong Chul
    • The Korean Journal of Pain
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    • v.22 no.1
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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 antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems

  • Dehkordi, Faraz Mahdian;Kaboutari, Jahangir;Zendehdel, Morteza;Javdani, Moosa
    • The Korean Journal of Pain
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    • v.32 no.3
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    • pp.160-167
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    • 2019
  • Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

Remifentanil promotes osteoblastogenesis by upregulating Runx2/osterix expression in preosteoblastic C2C12 cells

  • Yoon, Ji-Young;Kim, Tae-Sung;Ahn, Ji-Hye;Yoon, Ji-Uk;Kim, Hyung-Joon;Kim, Eun-Jung
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.19 no.2
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    • pp.91-99
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    • 2019
  • Background: The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods: The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results: ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions: We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing.

The analgesic efficacy of the continuous adductor canal block compared to continuous intravenous fentanyl infusion with a single-shot adductor canal block in total knee arthroplasty: a randomized controlled trial

  • Kim, Min Kyoung;Moon, Hyoung Yong;Ryu, Choon Gun;Kang, Hyun;Lee, Han Jun;Shin, Hwa Yong
    • The Korean Journal of Pain
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    • v.32 no.1
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    • pp.30-38
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    • 2019
  • Background: The adductor canal block (ACB) is an effective intervention for postoperative analgesia following total knee arthroplasty (TKA). However, the ideal ACB regimen has not yet been established. We compared the analgesic effects between a continuous ACB group and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) with a single-shot ACB group. Methods: Patients who underwent TKA were randomly allocated to either a continuous ACB group (Group CACB) or IV-PCA with a single-shot ACB group (Group IVACB). Before the surgery, ultrasound guided ACB with 0.5% ropivacaine 20 cc was provided to all patients. Before skin incision, the infusion system (0.2% ropivacaine through an adductor canal catheter in group CACB vs. intravenous fentanyl in group IVACB) was connected. The postoperative pain severity; the side effects of local anesthetics and opioids; administration of rescue analgesics and anti-emetics; and sensorimotor deficits were measured. Results: Postoperative pain severity was significantly higher in the IVACB group at 30 min, 4 h, 24 h, and 48 h after surgery. The averages and standard deviations (SD) of the NRS score of postoperative pain were $0.14{\pm}0.37$, $4.57{\pm}2.37$, $6.00{\pm}1.63$, and $4.28{\pm}1.49$, respectively in the IVACB group. Rescue analgesic requirements and quadriceps muscle strength were not statistically different between the groups throughout the postoperative period. Moreover, rescue antiemetic requirements were higher in group IVACB than group CACB. Conclusions: In this study, the continuous ACB provided superior analgesia and fewer side effects without any significant motor deficit than the IV-PCA with a single-shot ACB.

Transcriptional Regulatory Role of NELL2 in Preproenkephalin Gene Expression

  • Ha, Chang Man;Kim, Dong Hee;Lee, Tae Hwan;Kim, Han Rae;Choi, Jungil;Kim, Yoonju;Kang, Dasol;Park, Jeong Woo;Ojeda, Sergio R.;Jeong, Jin Kwon;Lee, Byung Ju
    • Molecules and Cells
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    • v.45 no.8
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    • pp.537-549
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    • 2022
  • Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

Effect of Ondansetron Alone and Combination of Naltrexone and Ondansetron on Alcohol Intake in C57BL/6 Mice (Naltrexone과 ondansetron의 병합투여가 C57BL/6형 생쥐의 알코올 섭취량에 미치는 영향)

  • Kim, Hyeun-Kyeung;Kim, Sung-Gon;Kang, Cheol-Joong;Park, Sang-Ick;Kim, Won-Ho
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1576-1581
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    • 2007
  • Dopamine reward pathway projecting from ventral tegmental area to nucleus accumbens is well known as playing an important role in alcohol dependence. It is supposed that this dopamine pathway is modulated by $5-HT_3$ nervous system, and it was reported that ondansetron (OND), $5-HT_3$ receptor antagonist, reduced drinking amount and increased abstinence rate in alcohol-dependent patients. The purpose of this study is to investigate the effect of combination of OND and naltrexone (NTX), non-specific opioid receptor antagonist, on alcohol intake in C57BL/6 mice. In 40 C57BL/6 mice in the state of alcohol dependence, vehicle, while OND 0.01 mg/kg, or NTX 1.0 mg/kg administrated respectively, or OND 0.01 mg/kg and NTX 1.0 mg/kg administrated simultaneously for ten days, medication effects on 2-hr alcohol, 22-hr water, 24-hr food intake and body weight were studied. When vehicle group was compared with 3 medication groups respectively, using a repeated measure ANOVA, NTX alone and vehicle groups showed a significant medication by time interaction (p=0.042) in 2-hr alcohol intake, but in the other 2 groups, OND and NTX combination group and OND alone group, there was no significant interaction with vehicle group in 2-hr alcohol intake. From these results, it is suggested that there is no effect on alcohol intake in mice treating with OND, and naltrexone#s suppression effect on alcohol intake in mice is attenuated when treating with OND and NTX simultaneously. It is supposed that a further study looking at the interactions of serotonin, dopamine and opioid nerves systems will be needed.

Regulator of G-Protein Signaling 4 (RGS4) Controls Morphine Reward by Glutamate Receptor Activation in the Nucleus Accumbens of Mouse Brain

  • Kim, Juhwan;Lee, Sueun;Kang, Sohi;Jeon, Tae-Il;Kang, Man-Jong;Lee, Tae-Hoon;Kim, Yong Sik;Kim, Key-Sun;Im, Heh-In;Moon, Changjong
    • Molecules and Cells
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    • v.41 no.5
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    • pp.454-464
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    • 2018
  • Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown. The present study used a short hairpin RNA (shRNA)-mediated knock-down of RGS4 in the NAc of the mouse brain to investigate the relationship between the activation of ionotropic glutamate receptors and RGS4 in the NAc during morphine reward. Additionally, the shRNA-mediated RGS4 knock-down was implemented in NAc/striatal primary-cultured neurons to investigate the role that striatal neurons have in the morphine-induced activation of ionotropic glutamate receptors. The results of this study show that the NAc-specific knock-down of RGS4 significantly increased the behaviors associated with morphine and did so by phosphorylation of the GluR1 (Ser831) and NR2A (Tyr1325) glutamate receptors in the NAc. Furthermore, the knock-down of RGS4 enhanced the phosphorylation of the GluR1 and NR2A glutamate receptors in the primary NAc/striatal neurons during spontaneous morphine withdrawal. These findings show a novel molecular mechanism of RGS4 in glutamatergic transmission that underlies the negative symptoms associated with morphine administration.