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Prevention, diagnosis, and treatment of opioid use disorder under the supervision of opioid stewardship programs: it's time to act now

  • Kim, Eun-Ji;Hwang, Eun-Jung;Yoo, Yeong-Min;Kim, Kyung-Hoon
    • 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.

Effects of opioid and non-opioid antagonists, pH and enzymes on Corchorus olitorius antinociception in mice

  • Zakaria Zainul Amiruddin;Neelendran M;Pubalan S;Sulaiman MR;Fatimah CA
    • Advances in Traditional Medicine
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    • v.6 no.3
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    • pp.186-195
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    • 2006
  • The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.

Opioid-induced constipation: a narrative review of therapeutic options in clinical management

  • Lang-Illievich, Kordula;Bornemann-Cimenti, Helmar
    • The Korean Journal of Pain
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    • v.32 no.2
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    • pp.69-78
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    • 2019
  • Pain therapy often entails gastrointestinal adverse events. While opioids are effective drugs for pain relief, the incidence of opioid-induced constipation (OIC) varies greatly from 15% to as high as 81%. This can lead to a significant impairment in quality of life, often resulting in discontinuation of opioid therapy. In this regard, a good doctor-patient relationship is especially pivotal when initiating opioid therapy. In addition to a detailed history of bowel habits, patient education regarding the possible gastrointestinal side effects of the drugs is crucial. In addition, the bowel function must be regularly evaluated for the entire duration of treatment with opioids. Furthermore, if the patient has preexisting constipation that is well under control, continuation of that treatment is important. In the absence of such history, general recommendations should include sufficient fluid intake, physical activity, and regular intake of dietary fiber. In patients of OIC with ongoing opioid therapy, the necessity of opioid use should be critically reevaluated in terms of an with acceptable quality of life, particularly in cases of non-cancer pain. If opioids must be continued, lowering the dose may help, as well as changing the type of opioid. If these measures do not suffice, the next step for persistent OIC is the administration of laxatives. If these are ineffective as well, treatment with peripherally active ${\mu}$-opioid receptor antagonists should be considered. Enemas and irrigation are emergency measures, often used as a last resort.

Prescribing Patterns of Pain Medication in Hospitalized Elderly Patients with Non-Cancer Pain (노인 입원 환자의 비암성 통증에 대한 약물 처방 현황)

  • Nam, Ki Nam;Choi, Eun Ok;Kim, Beam Hae;Seong, Sae Ra;Heo, Yoo Jeong;Lee, Kyeong Ju;Lee, Yu Jeung
    • Korean Journal of Clinical Pharmacy
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    • v.25 no.3
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    • pp.145-150
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    • 2015
  • Objective: Pain is very common in the elderly, so there is a high prevalence of analgesic use among this population. The purpose of this study was to assess patterns of analgesic use and evaluate factors associated with analgesic use in elderly patients. Method: The subjects of this study were patients over 65 years old hospitalized in a teaching hospital located in Chuncheon-si, Korea between January 1, 2014 and March 31, 2014. Data collection regarding analgesic prescriptions and baseline characteristics was conducted using computerized hospital database by medical information team. Logistic regression analysis was used to identify factors related to analgesic use. Results: A total of 2,394 patients were finally included. Among these patients, 700 (29.2%) took analgesics; 521 (74.4%) out of these 700 patients were received opioid analgesics and 179 (25.6%) were received only non-opioid analgesics. The most frequently prescribed opioid analgesic was pethidine (45.7%), and the most frequently prescribed non-opioid analgesic was acetaminophen (44.1%). Fracture was associated with increased odds of opioid analgesic prescriptions (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001) and any analgesic prescriptions (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001). Stroke or cerebral infarction was associated with decreased odds of opioid analgesic prescriptions (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003). Conclusion: A significant proportion of hospitalized elderly patients use analgesics. Health care professionals should consider factors associated with analgesic use in this population to improve pain management.

Trends in the Consumption of Opioid Analgesics in a Tertiary Care Hospital from 2000 to 2012 (단일 상급종합병원에서 마약성 진통제의 최근 13년간 사용 경향 조사)

  • Cho, Yoon Sook;Lee, Ju-Yeun;Kim, Hyang Sook;Kwon, Kyenghee
    • YAKHAK HOEJI
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    • v.58 no.4
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    • pp.268-276
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    • 2014
  • Background: World Health Organization considers opioid analgesic use as an important measure in the treatment of pain relief. However, there are limited data about the pattern of opioid analgesic use in tertiary care hospitals in Korea. The aim of this study was to describe the trends in the prescribed amount of the opioid for 13 years from 2000 to 2012 in a single tertiary care hospital. Methods: The data from the prescribed amount of opioid use in patients aged over 18 years were retrieved from medical charts and longitudinal pharmacy records of Seoul National University Hospital. Yearly prescribed amount of opioids were calculated using defined daily dose adjusted by hospital stay (DDD/1000${\bullet}$HS). Results: Over the 13 years of the study period, overall use of opioid has increased by 64.1%. Although, the opioid use by hospitalized patients comprised 98%~99% of total amount of opioid use, the proportions of opioid use by outpatient and by cancer patient increased from 1.1% to 2.2% and from 60.5% to 69.3%, respectively. The use of non-injectable opioids has increased by 47% and that of injectables has increased by 70%. While the amount of codeine and morphine use has decreased, the use of both transdermal and injection formulation of fentanyl has increased dramatically. Also, the use of oxycodone has increased, especially in outpatient setting. Conclusion: This longitudinal study showed that opioid analgesic use in tertiary hospital, especially in outpatient is continuously increasing. Improvement in pain management in tertiary care hospital can be cautiously inferred based on this results.

3D Quantitative and Qualitative Structure-Activity Relationships of the δ -Opioid Receptor Antagonists

  • Chun, Sun;Lee, Jee-Young;Ro, Seong-Gu;Jeong, Ki-Woong;Kim, Yang-Mee;Yoon, Chang-Ju
    • Bulletin of the Korean Chemical Society
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    • v.29 no.3
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    • pp.656-662
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    • 2008
  • Antagonists of the d -opioid receptor are effective in overcoming resistance against analgesic drugs such as morphine. To identify novel antagonists of the d -opioid receptor that display high potency and low resistance, we performed 3D-QSAR analysis using chemical feature-based pharmacophore models. Chemical features for d -opioid receptor antagonists were generated using quantitative (Catalyst/HypoGen) and qualitative (Catalyst/HipHop) approaches. For HypoGen analysis, we collected 16 peptide and 16 non-peptide antagonists as the training set. The best-fit pharmacophore hypotheses of the two antagonist models comprised identical features, including a hydrophobic aromatic (HAR), a hydrophobic (HY), and a positive ionizable (PI) function. The training set of the HipHop model was constructed with three launched opioid drugs. The best hypothesis from HipHop included four features: an HAR, an HY, a hydrogen bond donor (HBD), and a PI function. Based on these results, we confirm that HY, HAR and PI features are essential for effective antagonism of the d -opioid receptor, and determine the appropriate pharmacophore to design such antagonists.

Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions?

  • Ok, Hwoe Gyeong;Kim, Su Young;Lee, Su Jung;Kim, Tae Kyun;Huh, Billy K;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • v.31 no.2
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    • pp.73-79
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    • 2018
  • All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to ${\mu}$ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the ${\beta}$-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the ${\beta}$-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the ${\mu}$ receptor G protein pathway selective (${\mu}$-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased ${\mu}$ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.

Comparison of Propacetamol plus Fentanyl and Fentanyl alone with Patient Controlled Analgesia after Total Knee Arthroplasty (수술 후 자가통증조절장치 사용 환자에서 propacetamol과 fentanyl 복합제 및 fentanyl 단일제제의 효과 비교)

  • Kim, Minhyung;Jeong, Hyokeun;Park, Sohyun;Rhie, Sandy Jeong
    • Korean Journal of Clinical Pharmacy
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    • v.28 no.1
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    • pp.17-23
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    • 2018
  • Objective: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. Methods: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. Results: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. Conclusion: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

Successful Treatment with Transdermal Buprenorphine Patch in Opioid-Dependent Cancer Patients: Case Series (암환자의 마약성 진통제에 대한 신체적 의존을 경피적 Buprenorphine 패취를 통해 성공적으로 치료한 증례보고)

  • Go, Se-Il;Kim, Jung Hoon;Lee, Gyeong-Won;Kang, Jung Hun
    • Journal of Hospice and Palliative Care
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    • v.21 no.4
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    • pp.152-157
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    • 2018
  • Opioid aberrant behavior is an emerging problem as strong opioid is increasingly used to alleviate cancer pain in patients with cancer. Although the treatment of opioid addiction and physical dependence for non-cancer pain is well known, few studies have been conducted with cancer patients, particularly in the Korean population. Presented here are ten cases of cancer patients who were physically dependent on strong opioid and successfully treated with a partial mu-opioid receptor agonist, buprenorphine. This is the first report showing the efficacy of transdermal buprenorphine as a treatment for physical dependence on opioid medication in cancer patients.

Effects of Ginseng Total Saponin on Stress-Induced Analgesia (스트레스로 유도된 진통력에 미치는 인삼의 효과)

  • Kim, Hack-Seang;Chung, Myeon-Woo;Jang, Choon-Gon;Park, Woo-Kyu;Oh, Ki-Wan
    • Journal of Ginseng Research
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    • v.17 no.1
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    • pp.22-28
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    • 1993
  • This study was undertaken to determine the effects of ginseng total saponin (GTS) on stress- induced analgesia (SIA) in mice. intermittent foot shock (FS)-SIA was antagonized not by on but by naloxone in the tail flick FS-SIA which was not antagonized by naloxone in the T.F. test. On the other hand, GTS did not antagonize the continuous FS-SIA naloxone antagonized in the T.P. test. Also GTS antagonized psychological (PSIF)-SIA which was not antagonized by naloxone in the T.F. test. However, GTS did not antagonize the PSY-SIA which naloxone antagonized in the T.P. test. Forced swimming (FSIP)-SIA was not affected by both GTS and naloxone. These results suggest that the antapeonisms of intermittent FS-SIA in the T.F. test, continuous FS-SIA and PSY-SIA by GTS are mediated by non-opioid mechanisms but the antagonism of intermittent FS-SIA in the T.P. test by GTS is mediated by opioid mechanism.

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