Displaying publications 1 - 20 of 76 in total

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  1. Lim RBL, Yeat CL, Vighneshvaran R, Kasinathan N, Ahmad Subki SZ, Singh AHS, et al.
    J Pain Symptom Manage, 2023 Sep;66(3):221-229.
    PMID: 37295564 DOI: 10.1016/j.jpainsymman.2023.05.017
    INTRODUCTION AND OBJECTIVES: This national audit involving Ministry of Health (MOH) Hospitals aimed to map out the levels of development of palliative care services and essential palliative medication availability in Malaysia.

    MATERIALS AND METHODS: An online survey coupled with manual follow up was conducted throughout all MOH hospitals in Malaysia. Data collected described elements of the palliative care service(PCS) based on the WHO public health model. Data was computed using a novel matrix to determine three key indices which were the 1) palliative care development score (PCDS), 2)essential medications availability score (EMAS) and 3) opioid availability score (OAS). These scores then allowed mapping of PCS according to scores of 1-4 (1=least developed, 4=most developed).

    FINDINGS: Out of all 140 MOH hospitals 88.6% (124) completed the PCDS survey, 120(85.7%) for the EMAS survey and 140 (100%) for the OAS survey. A total of 32(25.8%) hospitals had formal PCS with 8(25%) having resident palliative physicians (RPP), 8(25%) visiting palliative physicians(VPP) and 16(50%) no palliative physician (NPP). Out of these services, 17 (53%) had dedicated palliative care beds. In the PCDS survey, hospitals with PCS had significantly higher mean PCDS of 2.59 compared to 1.02 for non-PCS hospitals (P<0.001). The EMAS survey showed 109(90.8%) hospitals had EMAS of four and the OAS survey showed that 135(96.4%) hospitals had oral morphine available.

    CONCLUSION: This study shows that palliative care service development in MOH hospitals is still very limited however, majority of MOH hospitals in Malaysia have all the essential medications and oral morphine available.

    Matched MeSH terms: Morphine Derivatives
  2. Hasan MS, Abdul Razak N, Yip HW, Lee ZY, Chan CYW, Kwan MK, et al.
    BMC Anesthesiol, 2023 May 24;23(1):177.
    PMID: 37226107 DOI: 10.1186/s12871-023-02127-8
    BACKGROUND: The liberal use of remifentanil in spine surgery has been associated with an increased incidence of postoperative hyperalgesia. Nevertheless, controversies remain as the existing evidence is inconclusive to determine the relationship between remifentanil use and the development of opioid-induced hyperalgesia. We hypothesized that intraoperative infusion of higher dose remifentanil during scoliosis surgery is associated with postoperative hyperalgesia, manifesting clinically as greater postoperative morphine consumption and pain scores.

    METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group.

    RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively.

    CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.

    Matched MeSH terms: Morphine Derivatives
  3. Japarin RA, Harun N, Hassan Z, Shoaib M
    Behav Pharmacol, 2023 Apr 01;34(2-3):123-130.
    PMID: 36752325 DOI: 10.1097/FBP.0000000000000715
    Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.
    Matched MeSH terms: Morphine/pharmacology
  4. Basheer M, Hassan Z, Gam LH
    Int J Med Sci, 2023;20(1):102-113.
    PMID: 36619231 DOI: 10.7150/ijms.78861
    Background: Mitragyna speciosa Korth or Kratom is widely used traditionally for its medicinal values. The major alkaloid content of kratom leaves is mitragynine, which binds to opioid receptors to give opioid-like effects. This study aimed to analyse the brain proteome of animals that displayed addictive behaviors. Design and Methods: Six groups (n=6-8) of rats made up of negative control, positive control using morphine (10 mg/kg), and treatment groups at low (1mg/kg) and high doses of mitragynine (30 mg/kg) for 1 and 4 days. The rats' behaviors were evaluated and subsequently the rats' brains were harvested for proteomic analysis that was performed by using 2D gel electrophoresis and LC/MS/MS. Results: The rats developed physical dependence only on day 4 following morphine and mitragynine (1 and 30mg/kg) treatments. Among the proteins that were up-regulated in treatment groups were four calcium-binding proteins, namely calretinin, F-actin, annexin A3 and beta-centractin. Conclusions: Upregulation of calretinin acted as low Ca2+ buffering upon the blockage of Ca2+ ion channel by mitragynine in the brain, which subsequently caused a reduction of GABA released and inversely increased the dopamine secretions that contributed to dependence indicators.
    Matched MeSH terms: Morphine
  5. You CY, Hassan Z, Müller CP, Suhaimi FW
    Psychopharmacology (Berl), 2022 Jan;239(1):313-325.
    PMID: 34693456 DOI: 10.1007/s00213-021-05996-4
    RATIONALE: The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g., methadone, may further exacerbate the cognitive deficits. Growing evidence suggests that mitragynine, the primary alkaloid from the Kratom (Mitragyna speciosa) leaves, may serve as a promising alternative therapy for opiate addiction. However, the knowledge of its health consequences is still limited.

    OBJECTIVES: We aimed to examine the cognitive effects of mitragynine substitution in morphine-withdrawn rats. Furthermore, we asked whether neuronal addiction markers like the brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent kinase II alpha (αCaMKII) might mediate the observed effects.

    METHODS: Male Sprague-Dawley rats were given morphine at escalating doses before treatment was discontinued to induce a spontaneous morphine withdrawal. Then, vehicle or mitragynine (5 mg/kg, 15 mg/kg, or 30 mg/kg) substitution was given for 3 days. A vehicle-treated group was used as a control. Withdrawal signs were scored after 24 h, 48 h, and 72 h, while novel object recognition (NOR) and attentional set-shifting (ASST) were tested during the substitution period.

    RESULTS: Discontinuation of morphine significantly induced morphine withdrawal signs and cognitive deficit in the ASST. The substitution with mitragynine was able to alleviate the withdrawal signs. Mitragynine did not affect the recognition memory in the NOR but significantly improved the reversal learning deficit in the morphine-withdrawn rats.

    CONCLUSIONS: These data support the idea that mitragynine could be used as safe medication therapy to treat opiate addiction with beneficial effects on cognitive deficits.

    Matched MeSH terms: Morphine/pharmacology
  6. Barratt DT, Sia AT, Tan EC, Somogyi AA
    Pain Med, 2021 Nov 26;22(11):2648-2660.
    PMID: 34015137 DOI: 10.1093/pm/pnab172
    OBJECTIVE: Pain severity and opioid requirements in the postoperative period show substantial and clinically significant inter-patient variation due mainly to factors such as age, surgery type, and duration. Genetic factors have not been adequately assessed except for the neuronal OPRM1 rs1799971 and COMT rs4680, whereas the contribution of innate immune signaling pathway genetics has seldom been investigated.

    SETTING: Hospital surgical ward.

    SUBJECTS: Women (107 Indian, 184 Malay, and 750 Han Chinese) undergoing total hysterectomy surgery.

    METHODS: Morphine consumption, preoperative pain, and postoperative pain were evaluated in relation to genetic variability comprising 19 single-nucleotide polymorphisms (SNPs) in 14 genes involved in glial activation, inflammatory signaling, and neuronal regulation, plus OPRM1 (1 SNP) and COMT (3 SNPs).

    RESULTS: Pre- and postoperative pain and age were associated with increased and decreased morphine consumption, respectively. In Chinese patients, only 8% of the variability in consumption could be explained by these nongenetic and genetic (BDNF, IL1B, IL6R, CRP, OPRM1, COMT, MYD88) factors. However, in Indian patients, 41% of morphine consumption variability could be explained by age (explaining <3%) and variants in OPRM1 rs1799971, CRP rs2794521, TLR4 rs4986790, IL2 rs2069762, COMT rs4818, TGFB1 rs1800469, and IL6R rs8192284 without controlling for postoperative pain.

    CONCLUSIONS: This is the highest known value reported for genetic contributions (38%) to morphine use in the acute postoperative pain setting. Our findings highlight the need to incorporate both genetic and nongenetic factors and consider ethnicity-dependent and nonadditive genotypic models in the assessment of factors that contribute to variability in opioid use.

    Matched MeSH terms: Morphine*
  7. Lee MT, Chen YH, Mackie K, Chiou LC
    J Pain, 2021 03;22(3):300-312.
    PMID: 33069869 DOI: 10.1016/j.jpain.2020.09.003
    Analgesic tolerance to opioids contributes to the opioid crisis by increasing the quantity of opioids prescribed and consumed. Thus, there is a need to develop non-opioid-based pain-relieving regimens as well as strategies to circumvent opioid tolerance. Previously, we revealed a non-opioid analgesic mechanism induced by median nerve electrostimulation at the overlaying PC6 (Neiguan) acupoint (MNS-PC6). Here, we further examined the efficacy of MNS-PC6 in morphine-tolerant mice with neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Daily treatments of MNS-PC6 (2 Hz, 2 mA), but not electrostimulation at a nonmedian nerve-innervated location, for a week post-CCI induction significantly suppressed established mechanical allodynia in CCI-mice in an orexin-1 (OX1) and cannabinoid-1 (CB1) receptor-dependent fashion. This antiallodynic effect induced by repeated MNS-PC6 was comparable to that induced by repeated gabapentin (50 mg/kg, i.p.) or single morphine (10 mg/kg, i.p.) treatments, but without tolerance, unlike repeated morphine-induced analgesia. Furthermore, single and repeated MNS-PC6 treatments remained fully effective in morphine-tolerant CCI-mice, also in an OX1 and CB1 receptor-dependent fashion. In CCI-mice receiving escalating doses of morphine for 21 days (10, 20 and 50 mg/kg), single and repeated MNS-PC6 treatments remained fully effective. Therefore, repeated MNS-PC6 treatments induce analgesia without tolerance, and retain efficacy in opioid-tolerant mice via a mechanism that involves OX1 and CB1 receptors. This study suggests that MNS-PC6 is an alternative pain management strategy that maybe useful for combatting the opioid epidemic, and opioid-tolerant patients receiving palliative care. PERSPECTIVE: Median nerve stimulation relieves neuropathic pain in mice without tolerance and retains efficacy even in mice with analgesic tolerance to escalating doses of morphine, via an opioid-independent, orexin-endocannabinoid-mediated mechanism. This study provides a proof of concept for utilizing peripheral nerve stimulating devices for pain management in opioid-tolerant patients.
    Matched MeSH terms: Morphine/administration & dosage; Morphine/pharmacology*
  8. Japarin RA, Yusoff NH, Hassan Z, Müller CP, Harun N
    Behav Brain Res, 2021 02 05;399:113021.
    PMID: 33227244 DOI: 10.1016/j.bbr.2020.113021
    Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.
    Matched MeSH terms: Morphine/administration & dosage; Morphine/pharmacology*
  9. Sivalingam M, Ogawa S, Parhar IS
    Sci Rep, 2020 11 11;10(1):19569.
    PMID: 33177592 DOI: 10.1038/s41598-020-76287-9
    The habenula is an evolutionarily conserved brain structure, which has recently been implicated in fear memory. In the zebrafish, kisspeptin (Kiss1) is predominantly expressed in the habenula, which has been implicated as a modulator of fear response. Hence, in the present study, we questioned whether Kiss1 has a role in fear memory and morphine-induced fear memory impairment using an odorant cue (alarm substances, AS)-induced fear avoidance paradigm in adult zebrafish, whereby the fear-conditioned memory can be assessed by a change of basal place preference (= avoidance) of fish due to AS-induced fear experience. Subsequently, to examine the possible role of Kiss1 neurons-serotonergic pathway, kiss1 mRNA and serotonin levels were measured. AS exposure triggered fear episodes and fear-conditioned place avoidance. Morphine treatment followed by AS exposure, significantly impaired fear memory with increased time-spent in AS-paired compartment. However, fish administered with Kiss1 (10-21 mol/fish) after morphine treatment had significantly lower kiss1 mRNA levels but retained fear memory. In addition, the total brain serotonin levels were significantly increased in AS- and Kiss1-treated groups as compared to control and morphine treated group. These results suggest that habenular Kiss1 might be involved in consolidation or retrieval of fear memory through the serotonin system.
    Matched MeSH terms: Morphine/toxicity
  10. Wasli NS, Ridzwan IE, Azzubaidi MS, Kasmuri AR, Ahmed QU, Ming LC, et al.
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S826-S830.
    PMID: 33828384 DOI: 10.4103/jpbs.JPBS_379_19
    Introduction: κ-opioid receptor (KOPr) system has been linked to relapse to many substances, especially opioids. Positive responses were recently reported in morphine and methamphetamine (polydrug)-dependent mice treated with buprenorphine and naltrexone, a functional κ antagonist.

    Objectives: This study aimed to determine the specific brain region that is responsive to KOPr treatment following polydrug dependence.

    Materials and Methods: The polydrug-dependent mice model was developed using conditioned place preference (CPP) method. Following successful withdrawal phase, the mice were treated with 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone. Four brain regions (hippocampus, prefrontal cortex, amygdala, and striatum) were investigated using immunohistochemistry technique. This is to quantify the changes in KOPr expression in each major brain region that was primarily involved in addiction neurocircuits of many substances. Unpaired Student's t test was used to analyze all results, where P < 0.05 is considered significant.

    Results: The results showed that treatment with buprenorphine and naltrexone successfully attenuated relapse in 60% of mice (n = 14). A significant upregulation of KOPr was detected in striatum at the end of post-withdrawal phase (P < 0.01, n = 12). This treatment successfully suppressed KOPr in striatum (P < 0.001, n = 12), which supports the positive results seen in the CPP setting. No significant changes were observed in other brain regions studied.

    Conclusion: The hyperactivity of striatum suggests that the affected brain region following KOPr antagonist treatment is the region that primarily controls the drug rewarding activity, in which nucleus accumbens is located. This indicates that manipulation of KOPr system is one of the potential targets to treat morphine- or methamphetamine-dependence problem.

    Matched MeSH terms: Morphine
  11. Zin CS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S841-S845.
    PMID: 33828387 DOI: 10.4103/jpbs.JPBS_251_19
    Background: Analgesic is commonly used in children but little is known about its patterns of utilization. This study explored the patterns of analgesic prescribing in children.

    Materials and Methods: This cross-sectional study used prescription databases of tertiary hospital settings in Malaysia from 2010 to 2016. Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged <18 years were included. Number of annual patients and prescriptions were measured and analyzed using Stata v15.

    Results: During a 7-year study period, a total of 5040 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 2460 pediatric patients (81.8% NSAIDs patients, 17.9% tramadol patients, and 0.3% opioid patients). Ibuprofen was the primary analgesic in young children less than 12 years old (≤2 years old [y.o.] [75%], 3-5 y.o. [85%], and 6-12 y.o. [56.3%]). However, there was a wide range of analgesics used in older children (>12 y.o.) with the majority for naproxen (13-15 y.o. (28.2%) and 16-17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12-15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16-17 y.o.

    Conclusion: Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol.

    Matched MeSH terms: Morphine
  12. Zin CS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S846-S851.
    PMID: 33828388 DOI: 10.4103/jpbs.JPBS_252_19
    Background: It was reported that opioid consumption in developing countries was stagnated or decreased, but precise data on the consumption are unclear. This study examined the trends and patterns of opioid consumption in Malaysia and other four Southeast Asian countries.

    Materials and Methods: Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) was used for calculating the annual amount of opioid use.

    Results: The total consumption of five strong opioids was increased in all five Southeast Asian countries during a 10-year study period. Malaysia was recorded with the largest increase of the opioid consumption (993.18%), followed by Indonesia (530.34%), Vietnam (170.17%), Singapore (116.16%), and Thailand (104.66%). Malaysia also had the highest total strong opioid consumption (11.2 DDD/1000 inhabitants/day), primarily for methadone. Among the opioids used for pain management, fentanyl was primarily used in Malaysia and Singapore but the greatest increase in these two countries was for oxycodone. Fentanyl was also primarily used in Indonesia while morphine was predominantly used in Thailand and Vietnam.

    Conclusion: Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain.

    Matched MeSH terms: Morphine
  13. Ho JFV, Yaakup H, Low GSH, Wong SL, Tho LM, Tan SB
    Palliat Med, 2020 May;34(5):619-629.
    PMID: 32103707 DOI: 10.1177/0269216320904905
    BACKGROUND: The prevalence of undertreated cancer pain remains high. Suboptimal pain control affects quality of life and results in psychological and emotional distress. Barriers to adequate pain control include fear of opioid dependence and its side effects.

    AIM: To investigate the attitudes and perceptions of morphine use in cancer pain in advanced cancer patients and their caregivers and to examine the influence of caregivers' attitudes and perceptions on patients' acceptance of morphine.

    DESIGN: Qualitative study involving semi-structured individual interviews transcribed verbatim and analyzed thematically.

    SETTING/PARTICIPANTS: A total of 18 adult opioid-naïve patients with advanced cancer and 13 caregivers (n = 31) were recruited at a private tertiary hospital via convenience sampling.

    RESULTS: Attitudes and perceptions of morphine were influenced by previous experiences. Prevalent themes were similar in both groups, including perceptions that morphine was a strong analgesic that reduced suffering, but associated with end-stage illness and dependence. Most participants were open to future morphine use for comfort and effective pain control. Trust in doctors' recommendations was also an important factor. However, many preferred morphine as a last resort because of concerns about side effects and dependence, and the perception that morphine was only used at the terminal stage. Caregivers' attitudes toward morphine did not affect patients' acceptance of morphine use.

    CONCLUSION: Most participants were open to future morphine use despite negative perceptions as they prioritized optimal pain control and reduction of suffering. Focused education programs addressing morphine misperceptions might increase patient and caregiver acceptance of opioid analgesics and improve cancer pain control.

    Matched MeSH terms: Morphine/therapeutic use*
  14. Ng KT, Yap JLL, Izham IN, Teoh WY, Kwok PE, Koh WJ
    Eur J Anaesthesiol, 2020 Mar;37(3):212-223.
    PMID: 31977626 DOI: 10.1097/EJA.0000000000001164
    BACKGROUND: Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain.

    OBJECTIVES: The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery.

    DESIGN: Systematic review and meta-analysis with trial sequential analysis.

    DATA SOURCES: MEDLINE, EMBASE, CENTRAL from their inception until January 2019.

    ELIGIBILITY CRITERIA: All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded.

    RESULTS: Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of -5.6 mg (-7.54 to -3.66, P 

    Matched MeSH terms: Morphine*
  15. Kan E, Mustafa S, Chong WW, Premakumar CM, Mohamed Shah N
    Patient Prefer Adherence, 2020;14:1411-1419.
    PMID: 32848370 DOI: 10.2147/PPA.S255289
    Context: Pain is a common and distressing symptom among cancer patients. Opioid analgesics are the mainstay of cancer pain management, and adequate adherence plays an important role in achieving good pain control.

    Purpose: To determine the level of adherence to opioid analgesics in patients with cancer pain and to identify factors that may influence the adherence.

    Patient and Methods: This was a cross-sectional study conducted from March to June 2018 at two tertiary care hospitals in Malaysia. Study instruments consisted of a set of validated questionnaires; the Medication Compliance Questionnaire, Brief Pain Inventory and Pain Opioid Analgesic Beliefs─Cancer scale.

    Results: A total of 134 patients participated in this study. The patients' adherence scores ranged from 52-100%. Factors with a moderate, statistically significant negative correlation with adherence were negative effect beliefs (rs= -0.53, p<0.001), pain endurance beliefs (rs = -0.49, p<0.001) and the use of aqueous morphine (rs = -0.26, p=0.002). A multiple linear regression model on these predictors resulted in a final model which accounted for 47.0% of the total variance in adherence (R2 = 0.47, F (7, 126) = 15.75, p<0.001). After controlling for other variables, negative effect beliefs were the strongest contributor to the model (β = -0.39, p<0.001) and uniquely explained 12.3% of the total variance.

    Conclusion: The overall adherence to opioid analgesics among Malaysian patients with cancer pain was good. Negative effects beliefs regarding cancer pain and opioids strongly predicted adherence.

    Matched MeSH terms: Morphine
  16. Hassan R, Pike See C, Sreenivasan S, Mansor SM, Müller CP, Hassan Z
    Front Psychiatry, 2020;11:411.
    PMID: 32457670 DOI: 10.3389/fpsyt.2020.00411
    Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts.

    Methods: Based on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated.

    Results: The morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5-30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5-2 mg/kg; i.p.) and buprenorphine (0.4-1.6 mg/kg; i.p.) were necessary to mitigate these effects.

    Conclusions: These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.

    Matched MeSH terms: Morphine; Morphine Dependence
  17. Davoudi M, Vijeepallam K, Azizi H, Mirnajafi-Zadeh J, Semnanian S
    J Neural Transm (Vienna), 2019 11;126(11):1425-1435.
    PMID: 31493096 DOI: 10.1007/s00702-019-02064-2
    The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14-P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.
    Matched MeSH terms: Morphine/administration & dosage
  18. Gan CY, Zainuddin Z, Muhamad Noh H, Rahmat R, Mohd Akir F, Mahad NH, et al.
    Forensic Sci Int, 2019 Sep;302:109865.
    PMID: 31279278 DOI: 10.1016/j.forsciint.2019.06.023
    Consumption of curry containing poppy seeds has raised an issue concerning the opiate content in the urine that might exceed the cut-off value (300ng/mL). The main objective of this study was to examine the morphine and codeine contents in the urine of the consumers after partaking poppy seed-enriched curry in. The volunteers were asked to partake: (a) a single meal and their urines were collected within 24h, or (b) Two meals a day for three consecutive days and their urines were collected within 72h. Two different dosages were also tested in this study: (a) low dosage: 1g/100ml curry (containing 138μg of morphine and 66μg of codeine) and (b) high dosage: 5g/100ml curry (containing 690μg of morphine and 330μg of codeine). The subjects were randomised into the groups using the method of stratified randomization with age and gender groups as covariates. A total of 6 subjects was allocated for each group and placebos were used as control. Results showed that all subjects who consumed low dosage of poppy seeds either in single meal or multiple meals experiment were found negative. However, 1 out of 6high dosage subjects was confirmed positive at a period of 3-6h after the consumption of curry in the single meal study. This outlier maybe due to the lack of water consumption after consuming the curry, thus the low volume of urine was collected and the opiate was concentrated in the urine. On the other hand, 5 out of 6high dosage subjects in the multiple meals experiment were found positive. Majority of these subjects were found positive on the second and third day of the experiment after the second curry meal was consumed. The outlier (negative) in this group might be due to the high consumption of water throughout the experiment and the subject's urine volumes and frequency of urine collection were much higher compared to other subjects. From the result of this study, it can be concluded that partaking high dosages of poppy seed in curry could give a positive response (>300ng/ml+uncertainty of measurement) in the urine, and the water consumption after partaking curry has significant influence for the opiate contents in the urine.
    Matched MeSH terms: Morphine/urine*
  19. Ali Khan MS, Misbah, Ahmed N, Arifuddin M, Rehman A, Ling MP
    Food Chem Toxicol, 2018 Jun 05.
    PMID: 29883785 DOI: 10.1016/j.fct.2018.06.007
    Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.
    Matched MeSH terms: Morphine
  20. Kampitak W, Tanavalee A, Ngarmukos S, Amarase C, Songthamwat B, Boonshua A
    Malays Orthop J, 2018 Mar;12(1):7-14.
    PMID: 29725506 DOI: 10.5704/MOJ.1803.002
    Introduction: Total knee arthroplasty (TKA) is associated with intense postoperative pain for which effective analgesia is essential to facilitate early postoperative recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) have become increasingly involved in postoperative pain management after TKA. We aimed to compare their efficacy and outcomes in patients undergoing TKA. Materials and Methods: Sixty patients undergoing unilateral TKA were randomized to receive either postoperative single-injection ACB (Group A) or LIA (Group L) during the operation. All patients received spinal anaesthesia. Primary outcome was total morphine consumption over postoperative 24 hours. Visual analog pain scale, time to first and total dosage of rescue analgesia, performance-based evaluations [timed-up and go (TUG) test, quadriceps strength], side-effects, length of hospital stay and patient satisfaction were measured. Results: Fifty-seven patients were available for analysis. Median total morphine consumption over 24 and 48 postoperative hours of Group A were significantly less than Group L (6/10 mg vs 13/25 mg, p, 0.008 and 0.001, respectively). Similarly, Group A had significantly lower VAS at postoperative 6, 12 and 18 hours, VAS at ambulation on postoperative (POD) 1-3, better TUG tests on POD 2 and during POD 3 than those of Group L. However, quadriceps strength and patient satisfaction were not different between both groups. Conclusion: Patients undergoing TKA with single-injection ACB required less postoperative opioids than those with LIA. Furthermore, multimodal analgesia using ACB provided better postoperative analgesia, as well as performance-based activities, than those with LIA.
    Matched MeSH terms: Morphine
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