Displaying publications 21 - 40 of 136 in total

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  1. Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW
    J Clin Pharm Ther, 2004 Oct;29(5):455-63.
    PMID: 15482390
    Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage; Analgesics, Opioid/pharmacokinetics*
  2. O'Brien T, Ahn JS, Chye R, Le B, Lu H, Olarte G, et al.
    J Opioid Manag, 2019 7 26;15(2):147-158.
    PMID: 31343716 DOI: 10.5055/jom.2019.0496
    Transdermal buprenorphine (TDB) has demonstrated effectiveness in treating a range of chronic pain conditions, including cancer pain, nociceptive pain, and neuropathic pain and has a favorable safety profile. Worldwide, clinical experience of its use is relatively limited. There is considerable misunderstanding about the pharmacology, mechanism of action, and safety of buprenorphine. There is also limited guidance on the appropriate use of TDB for chronic pain management. This article presents an overview of TDB and also provides practical recommendations for its use as part of a multifaceted strategy in chronic cancer and non-cancer pain.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage*; Analgesics, Opioid/therapeutic use
  3. Sivakumar S, Venkiteswaran A, Roslan MA, Musa S
    J Clin Pediatr Dent, 2024 May;48(3):15-23.
    PMID: 38755977 DOI: 10.22514/jocpd.2024.054
    Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have been used in reducing the postoperative pain. In this review, the authors assessed various modalities used to alleviate postoperative pain in children's dental treatment under general anaesthesia. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol were strictly adhered to in this systematic review. Specific keywords including postoperative pain, general anaesthesia, children, and dental extraction were used in the search for relevant randomized control trial studies in Web of Science, Scopus and PubMed, and included articles published until June 2021. From a total of 191 abstracts, 21 were reviewed. From the six studies with the usage of non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with paracetamol, four observed that the preoperative use of NSAIDs alone or in combination was better than paracetamol alone, one discovered preoperative intravenous paracetamol was better than postoperative intravenous paracetamol, and the remaining study found no difference among various groups. Of two studies comparing the usage of non-steroidal anti-inflammatory drugs with opioid analgesics, one stated intravenous fentanyl in combination was better, while the other study found no difference among groups. The results obtained in this review can be utilized by physicians to control postoperative pain in children undergoing dental treatment under general anaesthesia.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage; Analgesics, Opioid/therapeutic use
  4. Hadi MA, Kamaruljan HS, Saedah A, Abdullah NM
    Med J Malaysia, 2006 Dec;61(5):570-6.
    PMID: 17623958
    The success of major surgery depends partly on providing effective post-operative pain relief, which can be commonly achieved by morphine administration via patient- controlled analgesic (PCA) system. Alternatively, tramadol which is a weak opioid analgesic, can be used for post operative pain relief. The purpose of this study was to evaluate the effectiveness of intravenous PCA tramadol in comparison with PCA morphine in term of analgesic properties, sedation and side effects. A randomized, double-blinded study was conducted on 160 ASA I and II patients who underwent major operations. Eighty of them received a loading dose of intravenous morphine 0.1 mg/kg followed by PCA morphine bolus of 1 mg (1 mg/ml) as required, while the other 80 patients received a loading dose of 2.5 mg/kg of intravenous tramadol followed by PCA infusion of 10 mg (10 mg/ml) as required. Patients were monitored for pain, sedation and side effects as well as respiratory rate, nausea, vomiting, pruritus, blood pressure and pulse rate. Patients were evaluated 30 minutes, 4 hours, 24 hours and 48 hours post operation. There were no differences in the demographic data between the two groups (p > 0.05). The overall mean pain score in tramadol group was 0.70 +/- 0.60 as compared to 0.75 +/- 0.67 for morphine group. The mean pain score for tramadol and morphine groups at 30 minutes, 4 hours, 24 hours and 48 hours post operation were 1.32 +/- 0.79, 104 +/- 0.79, 0.35 +/- 0.48, 0.09 +/- 0.33 and 1.35 +/- 0.99, 1.14 +/- 0.81, 0.40 +/- 0.54, 0.10 +/- 0.34 respectively. The overall mean sedation score in tramadol and morphine group was 0.39 +/- 0.44 as compared to 0.35 +/- 0.43 for morphine group. The mean sedation score for tramadol and morphine group at 30 minutes, 4 hours, 24 hours and 48 hours post operation were 0.90 +/- 0.74, 0.56 +/- 0.59, 0.075 +/- 0.27, 0.025 +/- 0.16 and 0.84 +/- 0.70, 0.46 +/- 0.64, 0.08 +/- 0.27, 0.01 +/- 0.11 respectively. There was no significant difference in the overall mean pain and sedation score between the two groups as well as for each duration assessed (p > 0.05). There were also no significant differences between the two groups with regard to the blood pressure and heart rate. The incidence of nausea, vomiting and pruritus were the same in the two groups. This study indicates that PCA tramadol is as equally effective as PCA morphine control following major surgery. The incidences of sedation, nausea or pruritus were the same in the two groups.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage; Analgesics, Opioid/therapeutic use*
  5. Yee A, Loh HS, Hisham Hashim HM, Ng CG
    Int J Impot Res, 2014 Sep-Oct;26(5):161-6.
    PMID: 24990199 DOI: 10.1038/ijir.2014.18
    Methadone maintenance treatment is proven to be effective treatment for opioid dependence. Of the many adverse events reported, sexual dysfunction is one of the most common side effects. However, there may be other clinical factors that are associated with sexual dysfunction among methadone users. We conducted a meta-analysis to examine the clinical factors associated with sexual dysfunction among male patients on methadone and buprenorphine treatments, of which eligible studies were selected using prior defined criteria. A total of 2619 participants from 16 eligible studies, published from inception till December 2012, were identified from the PubMed, OVID and EMBASE databases. The included studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval (CI), 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (odds ratio=4.01, 95% CI, 1.52-10.55, P=0.0049). Our study shows that eight clinical factors are associated with sexual dysfunction among men receiving opioid substitution treatment, namely age, hormone assays, duration of treatment, methadone dose, medical status, psychiatric illness, other current substance use and familial status, and methadone versus buprenorphine treatment. Despite the methodological limitations, the findings of this meta-analysis study may offer better insights to clinicians in dealing with both sexual dysfunction and its related problems.
    Matched MeSH terms: Analgesics, Opioid/adverse effects*; Analgesics, Opioid/therapeutic use
  6. Takayama H
    Chem Pharm Bull (Tokyo), 2004 Aug;52(8):916-28.
    PMID: 15304982
    The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.
    Matched MeSH terms: Analgesics, Opioid/pharmacology; Analgesics, Opioid/chemistry*
  7. Satyam SM, Bairy LK, Shetty P
    Neuroendocrinology, 2023;113(6):667-677.
    PMID: 36796342 DOI: 10.1159/000529761
    INTRODUCTION: Differences in pain thresholds may have implications in pain management, as they may account in part for the variability in analgesic requirements between individuals. We planned to investigate the influence of endogenous sex hormones on the analgesic modulation of tramadol in lean and high-fat diet-induced obese Wistar rats.

    METHODS: The whole study was carried out on 48 adult Wistar rats (24 male: 12 obese and 12 lean and 24 female: 12 obese and 12 lean). Each male and female rat group was further subdivided into two groups (n = 6/group) and treated with normal saline/tramadol for 5 days. On the fifth day, 15 min after tramadol/normal saline treatment, animals were tested for pain perception toward noxious stimuli. Later, endogenous 17 beta-estradiol and free testosterone levels in serum were estimated through ELISA methods.

    RESULTS: The present study revealed that female rats experienced more pain sensitivity to noxious stimuli compared to male rats. High-fat diet-induced obese rats experienced more pain sensations to noxious stimuli than lean rats. Obese male rats were found to have significantly low free testosterone and high 17 beta-estradiol levels compared to lean male rats. An increase in serum 17 beta-estradiol level led to increased pain sensation to noxious stimuli. While an increase in free testosterone level resulted in the lowering of pain sensation to noxious stimuli.

    CONCLUSION: The analgesic effect of tramadol was more pronounced in male rats compared to female rats. The analgesic effect of tramadol was more marked in lean rats compared to obese rats. Additional research to elucidate obesity-induced endocrine changes and the mechanisms driving sex hormones in pain perception is needed to foster future interventions to reduce disparities in pain.

    Matched MeSH terms: Analgesics, Opioid/pharmacology; Analgesics, Opioid/therapeutic use
  8. Kua, Vee May Dianne, Ng Woei Kean, Sreenivasan, Sasidharan, Lai, Ngit Shin
    MyJurnal
    Opioids are opium-like drugs which are commonly used as analgesics to treat moderate to severe pain. Apoptosis is a type of programmed cell death to remove unnecessary or damaged cells in an organism. Recently, the ability of opioids to induce apoptosis especially in cancer cell lines hasgained the interest of many researchers. This fascinating finding hasled to more testing of different kindsof opioids against different kindsof cancer cell lines in the course to search for the potential anticancer drugs. This review provides current information about opioids and apoptosis, and more importantly the compilations of researches over the years on how opioids are related to apoptotic cells death.
    Matched MeSH terms: Analgesics, Opioid
  9. Choy, Y.C., Wan Nuruddin Shah, W.J., Wong, Y.M., Boey, C.Y., Noor Zuhaily, M.N., Kumutha, T., et al.
    MyJurnal
    Effective management of cancer pain is often hampered by patients’ lack of knowledge regarding cancer pain management and other barriers related to ethnicity and religious beliefs. This cross sectional study was performed to determine the patient-related barriers to effective cancer pain management. One hundred patients receiving cancer pain management were studied. Inclusion criteria were: patients over the age of 18 years, able to communicate, with known diagnosis of cancer, experiencing persistent pain for the past two weeks. A modified version of the Barriers Questionnaire II (BQ-II) was used and a modified Brief Pain Inventory was used to assess the pain profile. Barriers such as, patient’s attitude and beliefs, communication skills and fear of side effects of pain medication were determined, given a score and the summation was recorded as the total patient related barriers score. Overall, 85% of respondents achieved more than 40% pain relief and the 72 of 100 patients reported low patient related barrier scores of 6 or less. Nevertheless, the main patient related barriers were: fear of tolerance to opioids (51%), ethnicity (p=0.003) and religious beliefs (p=0.002) which constituted the major components of the patient-related barriers score. Ethnicity and religious beliefs had significant influence on patient-related barriers score suggesting the need of further investigation into this area. In order to achieve a comprehensive view, other barriers to effective cancer pain management such as those related to the health systems and healthcare providers need to be assessed together.
    Matched MeSH terms: Analgesics, Opioid
  10. Lim SY, Tan AH, Lim JL, Ahmad-Annuar A
    J Mov Disord, 2018 May;11(2):87-88.
    PMID: 29860787 DOI: 10.14802/jmd.18004
    Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).
    Matched MeSH terms: Analgesics, Opioid
  11. Zahari Z, Inrahim MA, Tan SC, Mohamad N, Ismail R
    Turk J Med Sci, 2016 Dec 20;46(6):1743-1748.
    PMID: 28081321 DOI: 10.3906/sag-1507-132
    BACKGROUND/AIM: Sleep disturbances may contribute to poor treatment outcomes in opioid-dependent patients. The extent to which the sleep profiles of opioid-dependent patients differ from those of the general Malaysian population is not documented. This study compared opioid-naive subjects and opioid-dependent patients on methadone maintenance therapy (MMT) in terms of their sleep quality.

    MATERIALS AND METHODS: Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI).

    RESULTS: The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030].

    CONCLUSION: This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.

    Matched MeSH terms: Analgesics, Opioid
  12. Haerian BS, Haerian MS
    Pharmacogenomics, 2013 May;14(7):813-24.
    PMID: 23651028 DOI: 10.2217/pgs.13.57
    The OPRM1 gene encodes the µ-opioid receptor, which is the primary site of action of most opioids. Several studies and three meta-analyses have examined a possible link between the exonic OPRM1 A118G (rs1799971) polymorphism and opioid dependence; however, results have been inconclusive. Therefore, a systematic review and meta-analysis have been carried out to examine whether this polymorphism is associated with opioid dependence. Thirteen studies (n = 9385), comprising 4601 opioid dependents and 4784 controls, which evaluated association of the OPRM1 rs1799971 polymorphism with susceptibility to opioids, were included in this study. Our meta-analysis showed significant association between this polymorphism and susceptibility to opioid dependence in overall studies under a codominant model, as well as susceptibility to opioid dependence or heroin dependence in Asians under an autosomal dominant model. The nonsynonymous OPRM1 rs1799971 might be a risk factor for addiction to opioids or heroin in an Asian population.
    Matched MeSH terms: Analgesics, Opioid/adverse effects
  13. Lim KY, Lim TA, Wong WH
    Med J Malaysia, 2005 Dec;60(5):647-9.
    PMID: 16515119
    Anaesthetizing patients with Long QT Syndrome is a major challenge, as the potential for sudden catastrophic cardiovascular collapse is well known. We present a 15-year-old boy with Long QT Syndrome who presented for an elective renal transplant. All electrolyte concentration abnormalities were corrected preoperative and adequate beta-blockade was maintained. The patient was given a target controlled infusion of propofol, together with opioids and atracurium. Anaesthesia was uneventful and the patient was extubated at the end of the surgical procedure.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage
  14. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    J Pharm Pharm Sci, 2016;19(1):127-36.
    PMID: 27096697 DOI: 10.18433/J3NS49
    PURPOSE: This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects.

    METHODS: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose.

    RESULTS: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016).

    CONCLUSIONS: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.

    Matched MeSH terms: Analgesics, Opioid/administration & dosage*
  15. Chiu CK, Ng TS, Wazir NN, Bhurhanudeen KA
    Ulus Travma Acil Cerrahi Derg, 2015 Jan;21(1):63-7.
    PMID: 25779715 DOI: 10.5505/tjtes.2015.27475
    A rare case of bilateral anterior hip dislocation reduced under sedation was reported in this study. A 47-year-old man was knocked down by a car and sustained bilateral anterior hip dislocation which was reduced successfully with sedation using titrated dose of intravenous Midazolam in combination with Pethidine. A modified Lefkowitz maneuver using the manipulator's thigh as a fulcrum was used. Patient started weight bearing in the second month after injury and was walking without any hip pain at the twenty-fourth month follow-up. Thirteen case reports describing bilateral anterior hip dislocations were found while reviewing the literature and it was noticed that only one author had reported the usage of intravenous sedation (Propofol) for the reduction procedure. However, no author reported the use of Lefkowitz maneuver for this purpose. Consequently, reduction of a bilateral anterior hip dislocation is possible with sedation using a modified Lefkowitz maneuver.
    Matched MeSH terms: Analgesics, Opioid/administration & dosage*
  16. Saref A, Suraya S, Singh D, Grundmann O, Narayanan S, Swogger MT, et al.
    J Ethnopharmacol, 2019 Jun 28;238:111876.
    PMID: 31014959 DOI: 10.1016/j.jep.2019.111876
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) is a traditional medicinal plant widely used in Southeast Asia for its opioid-like effects. Although kratom produces analgesia through binding of mitragynine and other alkaloids at the mu-opioid receptor (MOR), the association of long-term kratom use with adverse opioid-like effects remains unknown.

    AIM OF THE STUDY: To determine the self-reported prevalence and severity of opioid-related adverse effects after kratom initiation in a cohort of illicit opioid users.

    MATERIALS AND METHODS: A total of 163 illicit opioid users with current kratom use history were recruited through convenience sampling from the northern states of Peninsular Malaysia. Face-to-face interviews were conducted using a semi-structured questionnaire.

    RESULTS: Respondents were all males, majority Malays (94%, n = 154/163), with a mean age of 37.10 years (SD = 10.9). Most were single (65%, n = 106/163), had 11 years of education (52%, n = 85/163) and employed (88%, n = 144/163). Half reported using kratom for over >6 years (50%, n = 81/163), and 41% consumed >3 glasses of kratom daily (n = 67/163). Results from Chi-square analysis showed kratom initiation was associated with decreased prevalence of respiratory depression, constipation, physical pain, insomnia, depression, loss of appetite, craving, decreased sexual performance, weight loss and fatigue.

    CONCLUSIONS: Our findings indicate that kratom initiation (approximately 214.29 mg of mitragynine) was associated with significant decreases in the prevalence and severity of opioid adverse effects.

    Matched MeSH terms: Analgesics, Opioid/adverse effects*
  17. 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: Analgesics, Opioid/adverse effects
  18. Ayoub R, Jarrar Q, Ali D, Moshawih S, Jarrar Y, Hakim M, et al.
    Eur J Pharm Sci, 2021 Aug 01;163:105865.
    PMID: 33979659 DOI: 10.1016/j.ejps.2021.105865
    BACKGROUND: Mefenamic acid (MFA), a commonly prescribed non-steroidal anti-inflammatory drug (NSAID), possesses a greater risk of dose-related central nervous system (CNS) toxicity than other NSAIDs. In this study, α-tocopherol and α-tocopherol acetate were selected as prodrug moieties for MFA in an attempt to reduce the CNS toxicity and enhance the therapeutic efficacy.

    METHOD: α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations.

    RESULTS: Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20 mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA.

    CONCLUSION: Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.

    Matched MeSH terms: Analgesics, Opioid/therapeutic use
  19. Chooi WT, Mohd Zaharim N, Desrosiers A, Ahmad I, Yasin MAM, Syed Jaapar SZ, et al.
    J Psychoactive Drugs, 2017 06 29;49(4):326-332.
    PMID: 28661714 DOI: 10.1080/02791072.2017.1342152
    Amphetamine-type stimulants (ATS) use is increasingly prevalent in Malaysia, including among individuals who also use opioids. We evaluated cognitive functioning profiles among individuals with co-occurring opioid and ATS dependence and their lifetime patterns of drug use. Participants (N = 50) enrolling in a clinical trial of buprenorphine/naloxone treatment with or without atomoxetine completed the Raven's Standard Progressive Matrices, Rey-Osterrieth Complex Figure Test, Digit Span, Trail Making and Symbol Digit Substitution tasks. Multidimensional scaling and a K-means cluster analyses were conducted to classify participants into lower versus higher cognitive performance groups. Subsequently, analyses of variance procedures were conducted to evaluate between group differences on drug use history and demographics. Two clusters of individuals with distinct profiles of cognitive performance were identified. The age of ATS use initiation, controlling for the overall duration of drug use, was significantly earlier in the lower than in the higher cognitive performance cluster: 20.9 (95% CI: 18.0-23.8) versus 25.2 (95% CI: 22.4-28.0, p = 0.038). While adverse effects of ATS use on cognitive functioning can be particularly pronounced with younger age, potentially related to greater vulnerability of the developing brain to stimulant and/or neurotoxic effects of these drugs, the current study findings cannot preclude lowered cognitive performance before initiation of ATS use.
    Matched MeSH terms: Analgesics, Opioid/adverse effects*
  20. Yusof SR, Abbott NJ, Avdeef A
    Eur J Pharm Sci, 2017 Aug 30;106:274-286.
    PMID: 28614733 DOI: 10.1016/j.ejps.2017.06.016
    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10-6cm·s-1. The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (pH-MME) analysis of the data indicated a smooth sigmoidal transition from a higher capacity uptake process affecting cationic naloxone (pH5.0-7.0) to a lower capacity uptake process affecting the neutral drug (pH8.0-8.5), with cross-over point near pH7.4. Evidently, measurements at multiple pH values can reveal important information about both cerebrovascular flow and BBB transport kinetics.
    Matched MeSH terms: Analgesics, Opioid/pharmacokinetics*
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