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Sample records for methadone morphine oxycodone

  1. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges. PMID:18295434

  2. Evaluation of Ongoing Oxycodone Abuse among Methadone-Maintained Patients

    PubMed Central

    Dunn, Kelly E.; Sigmon, Stacey C.; McGee, Mark R.; Heil, Sarah H; Higgins, Stephen T.

    2008-01-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. The current study presents results from an internal quality-assurance project conducted by an outpatient methadone-maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis testing methods. One-hundred and five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic’s usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, while the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. While future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication dosing decisions, and determining patient eligibility for methadone take-home privileges. PMID:18295434

  3. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    PubMed

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol. PMID:26689063

  4. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice

    PubMed Central

    Ueberall, Michael A; Eberhardt, Alice; Mueller-Schwefe, Gerhard HH

    2016-01-01

    Objective To compare the quality of life of patients with moderate-to-severe chronic low back pain under treatment with the WHO-step III opioids oxycodone/naloxone, oxycodone, or morphine in routine clinical practice. Study design Prospective, 12-week, randomized, open-label, blinded end-point study in 88 medical centers in Germany. Patients and methods A total of 901 patients requiring around-the-clock pain treatment with a WHO-step III opioid were randomized to either morphine, oxycodone, or oxycodone/naloxone (1:1:1). Changes from baseline to week 12 in quality of life were assessed using different validated tools (EuroQoL-5 Dimensions [EQ-5D], Short Form 12 [SF-12], quality of life impairment by pain inventory [QLIP]). Results EQ-5D weighted index scores significantly improved over the 12-week treatment period under all three opioids (P<0.001) with significantly greater improvements under oxycodone/naloxone (65.2% vs 49.6% for oxycodone and 48.2% for morphine, P<0.001). The proportion of patients without EQ-5D complaints was also significantly higher under oxycodone/naloxone (P<0.001). Although quality of life ratings with the QLIP inventory showed significant improvements in all the three treatment arms, improvements were significantly higher under oxycodone/naloxone than under oxycodone and morphine (P<0.001): 90.7% of all oxycodone/naloxone patients achieved ≥30% improvements in quality of life, 72.8% had ≥50%, and 33.2% ≥70% improvements. Similarly, both physical and mental SF-12 component scores showed significantly greater improvements under oxycodone/naloxone with both scores close to the German population norm after 12 weeks. Conclusion Treatment with morphine, oxycodone, or oxycodone/naloxone under routine daily practice conditions significantly improved state of health and quality of life of patients with moderate-to-severe low back pain over a 12-week treatment period. Comparison between the treatment groups showed significantly greater

  5. Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.

    PubMed

    Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Gray, Andrew; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Howes, John; Weis, Holger; Friedhoff, Lawrence

    2016-08-01

    The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine. PMID:26763764

  6. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats

    PubMed Central

    Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

    2012-01-01

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

  7. Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study

    PubMed Central

    Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

    2004-01-01

    Aims The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). Methods The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg−1 oral morphine sulphate, 0.5 mg kg−1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg−1 morphine sulphate with 0.25 mg kg−1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. Results The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. Conclusions These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. PMID:15327582

  8. Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

    PubMed Central

    Posa, Luca; Accarie, Alison; Marie, Nicolas

    2016-01-01

    Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

  9. Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

    PubMed Central

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B.; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  10. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    PubMed

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  11. Oxycodone

    MedlinePlus

    ... tablets, extended-release capsules, and concentrated solution should only be used to treat people who are tolerant ( ... XR, others); aspirin (Percodan); and ibuprofen. This monograph only includes information about the use of oxycodone alone. ...

  12. Oxycodone

    MedlinePlus

    ... this type of medication for at least one week. Oxycodone is in a class of medications called ... have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), ...

  13. Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine

    PubMed Central

    2010-01-01

    Background Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring. Methods Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g. Results Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals. Conclusions Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher

  14. Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial

    PubMed Central

    Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

    2016-01-01

    Background and Aims: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. Methods: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. Results: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4–8, 8–12 and 12–24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. Conclusion: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period. PMID:27053782

  15. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    PubMed Central

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  16. RAPID DOPAMINE TRANSMISSION WITHIN THE NUCLEUS ACCUMBENS DRAMATICALLY DIFFERS FOLLOWING MORPHINE AND OXYCODONE DELIVERY

    PubMed Central

    Mabrouk, Omar S.; Lovic, Vedran; Singer, Bryan F.; Kennedy, Robert T.; Aragona, Brandon J.

    2014-01-01

    While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with mass spectrometry. In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites, and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior. PMID:25208732

  17. Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line

    PubMed Central

    Tian, Mi; Jin, Li; Li, Renqi; Zhu, Sihai; Ji, Muhuo; Li, Weiyan

    2016-01-01

    The present study aimed to compare the effects of oxycodone and morphine hydrochloride on the proliferation, apoptosis and migration of A549 lung cancer cells. A549 human lung cancer cells were cultured in vitro and treated with oxycodone or morphine at various concentrations (10, 20 and 40 µg/ml). Cell migration was determined using a wound healing assay, whereas apoptosis was detected using flow cytometry. Reverse transcription quantitative-polymerase chain reaction was performed in order to assess the apoptosis-related gene expression levels, including p53, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax). The levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) were detected using enzyme-linked immunosorbent assays. The expression levels of intercellular cell adhesion molecule (ICAM)-1 were determined by immunofluorescence. In the present study, oxycodone and morphine induced apoptosis in A549 lung cancer cells with similar potency; however, >20 µg/ml oxycodone was more effective at inhibiting cell proliferation (P<0.05) and migration (P<0.05), as compared with morphine at the same concentration. Oxycodone induced a dose-dependent increase in the expression levels of p53 and Bax apoptosis-related genes, whereas it decreased the gene expression levels of Bcl-2. Furthermore, oxycodone decreased, whereas morphine increased, the expression levels of ICAM-1 in a concentration-dependent manner. In addition, at 40 µg/ml, the expression levels of VEGF and uPA in the morphine group were significantly higher than those demonstrated in the oxycodone group (P<0.05). In conclusion, oxycodone was more effective in inhibiting the proliferation and migration of A549 lung cancer cells, as compared with morphine. PMID:27446244

  18. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  19. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  20. G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

    PubMed Central

    Nakamura, Atsushi; Fujita, Masahide; Ono, Hiroko; Hongo, Yoshie; Kanbara, Tomoe; Ogawa, Koichi; Morioka, Yasuhide; Nishiyori, Atsushi; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku; Kato, Akira; Hasegawa, Minoru

    2014-01-01

    BACKGROUND AND PURPOSE Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (KIR3 also known as GIRK) channels in their antinociceptive effects. EXPERIMENTAL APPROACH Opioid-induced antinociceptive effects were assessed in mice, using the tail-flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of KIR3.1 channels with tertiapin-Q (30 pmol per mouse, i.c.v. and i.t.) and KIR3.1-specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin-Q administration in the mouse femur bone cancer and neuropathic pain models. KEY RESULTS The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by KIR3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by KIR3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin-Q. CONCLUSION AND IMPLICATIONS These results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone. PMID:24117458

  1. Azole antifungal inhibition of buprenorphine, methadone and oxycodone in vitro metabolism.

    PubMed

    Moody, David E; Liu, Fenyun; Fang, Wenfang B

    2015-06-01

    Opioid-related mortality rates have escalated. Drug interactions may increase blood concentrations of the opioid. We therefore used human liver microsomes (HLMs) and cDNA-expressed human cytochrome P450s (rCYPs) to study in vitro inhibition of buprenorphine metabolism to norbuprenorphine (CYP3A4 and 2C8), oxycodone metabolism to noroxycodone (CYP3A4 and 2C18) and oxymorphone (CYP2D6), and methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP; CYP3A4 and 2B6). In this study, we have examined the inhibitory effect of 12 (mostly antifungal) azoles. These compounds have a wide range of solubility; to keep organic solvent ≤1%, there was an equally wide range of highest concentration tested (e.g., itraconazole 5 µM to fluconazole 1000 µM). Inhibitors were first incubated with HLMs at three concentrations with or without preincubation of inhibitor with reducing equivalents to also screen for time-dependent inhibition (TDI). Posaconazole displayed evidence of TDI; metronidazole and albendazole had no significant effect. Azoles were next screened at the highest achievable concentration for non-CYP3A4 pathways. IC50 values (µM) were determined for most CYP3A4 pathways (ranges) and other pathways as dictated by screen results: clotrimazole (0.30 - 0.35; others >30 µM); econazole (2.2 - 4.9; 2B6 R-EDDP - 9.5, S-EDDP - 6.8; 2C8 - 6.0; 2C18 - 1.0; 2D6 - 1.2); fluconazole (7.7 - 66; 2B6 - 313, 361; 2C8 - 1240; 2C18 - 17; 2D6 - 1000); itraconazole (2.5 to >5; others >5); ketoconazole (0.032 - 0.094; 2B6 - 12, 31; 2C8 - 78; 2C18 - 0.98; 2D6 - 182); miconazole (2.3 - 7.6; 2B6 - 2.8, 2.8; 2C8 - 5.3; 2C18 - 3.1; 2D6 - 5.9); posaconazole (3.4 - 20; 2C18 - 3.8; others >30); terconazole (0.48 to >10; 2C18 - 8.1; others >10) and voriconazole (0.40 - 15; 2B6 - 2.4, 2.5; 2C8 - 170; 2C18 - 13; 2D6 >300). Modeling based on estimated Ki values and plasma concentrations from the literature suggest that the orally administered azoles, particularly

  2. Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats

    PubMed Central

    Fadaei-Kenarsary, Meisam; Farbood, Yaghoob; Taghi Mansouri, Seyed Mohammad; Fathi Moghaddam, Hadi

    2015-01-01

    Introduction: Methadone has been used as a drug to detoxify opioid tolerance. Naloxane precipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant. On the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the present study aimed to examine the effects of chronic methadone (70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) and their combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity. Methods: Twenty eight young male Sprague-Dawley rats were randomly divided into 4 groups: control, venlafaxine treated, methadone treated and venlafaxine + methadone treated. Morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. Then primary withdrawal behaviours and tail flick test were performed. The test was then followed by methadone or its vehicle administration. Second intervention was venlafaxine or its vehicle injection. Then final withdrawal behaviours and tail flick test were performed. Results: Combination of chronic methadone substitution and venlafaxine administration, significantly reduced freezing behaviour of spontaneous morphine withdrawal syndrome (P<0.01, 379±144%). Chronic methadone administration (P<0.05, 35±8% difference with venlafaxine treated group) induced hyperalgesia. A positive correlation (P=0.001, +63%) was observed between the animals final freezing scores and their response latencies to the painful stimulus. Discussion: Combination of chronic methadone and venlafaxine administrations reduces freezing withdrawal behaviour. Further investigations on analgesic interventions are needed to overcome this hyperalgesia.

  3. Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine.

    PubMed

    Lemaire, Eric; Schmidt, Carl; Denooz, Raphael; Charlier, Corinne; Boxho, Philippe

    2016-07-01

    Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution. PMID:27364283

  4. Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model

    PubMed Central

    Nakamura, Atsushi; Hasegawa, Minoru; Minami, Kazuhisa; Kanbara, Tomoe; Tomii, Takako; Nishiyori, Atsushi; Narita, Minoru; Suzuki, Tsutomu; Kato, Akira

    2013-01-01

    Background and Purpose Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. Experimental Approach To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the μ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. Key Results In the FBC model, the Bmax of [3H]-DAMGO binding was reduced by 15–45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10−8–10−5 M) and morphine (10−8–10−5 M) activated [35S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [35S]-GTPγS binding was quite limited (9–26%) in comparison with that of morphine (46–65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02–1.0 μg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05–2.0 μg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. Conclusion and Implications These results show that μ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the μ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. PMID:22889192

  5. [Electrodermal activity in heroin addicts and patients with methadone and morphine substitution].

    PubMed

    Linzmayer, Leopold; Boeck, Gerda; Fischer, Gabriele

    2003-01-01

    In the present investigation we tried to answer the question whether differences between heroin-dependent patients (n = 26, age: M = 24.96, SD = 6.30 years), a methadone substitution group (n = 20, age: M = 30.92, SD = 8.21 years) and a morphine substitution group (n = 20, age: M = 33.25, SD = 4.59 years) and healthy normals (n = 31, age: M = 25.07, SD = 4.62 years) could be found by means of measurement of electrodermal activity (SC, SCR, habituation of the SCR). Concerning "basal" skin conductance reflecting sympathetic activity, no significant differences were obtained. The methadone substitution group showed slight shortened onset latencies (information processing). In the morphine substitution group as compared to the other groups a small increase of the amplitude was observed indicating a slight increase in cognitive emotional intensity of appraisal after presentation of an acoustic stimulus. This small changes could be mediated by adaptation processes of the vegetative nervous system to the opioid, which occur "below" of those neuronal networks connected directly with the emotional stimuli processing. Concerning the speed of habituation no significant differences between the groups could be obtained. This indicates that no psychovegetative attenuation could be observed. The morphine substitution group as compared to the other groups was characterized by a longer persistence and a small increase of the intensity of excitement. However these variables ranged within normal limits and did not reach the level of statistical significance. This could be mediated by the effects of the opioid on the vegetative nervous system. PMID:12658967

  6. Methadone

    MedlinePlus

    Methadone is used to relieve severe pain in people who are expected to need pain medication around ... stop taking or continue not taking the drugs. Methadone is in a class of medications called opiate ( ...

  7. Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

    ClinicalTrials.gov

    2012-11-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  8. The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid.

    PubMed

    Jones, Joseph; Tomlinson, Kimberly; Moore, Christine

    2002-04-01

    Recently, the abuse of prescription opiates as alternatives to heroin has become a national concern. The determination of a six-drug opiate panel, codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, and oxycodone, in hair and oral fluid using solid-phase extraction and capillary gas chromatography-mass spectrometry (GC-MS) is described. Oral fluid was obtained from the donor by insertion of absorptive collectors into the mouth. Hair was collected from the patient and powdered using stainless steel ball bearings in a mini bead-beater apparatus. Opiates present in the samples were extracted from a buffered, aqueous matrix using a solid-phase cartridge. The extracts were concentrated and the methoxime/BSTFA derivatives prepared in order to eliminate interference from the keto-opiates. The extracts were separated by GC-MS in electron impact mode. By utilizing methoxyamine, we were able to produce the methoxime derivatives required for single derivative production and chromatographically separate all six opiates. The routine analysis of these opiates in hair and oral fluid using GC-MS is described for the first time. PMID:11991534

  9. Perioperative dilemma: challenges of the management of a patient on mega doses of morphine and methadone.

    PubMed

    Kaye, Alan David; Alian, Aymen A; Vadivelu, Nalini; Chung, Keun Sam

    2014-01-01

    High doses of opioids are often needed in the management of cancer-related pain. A discussion of a patient's perioperative opioid management and mechanisms contributing to opioid-induced hyperalgesia (OIH) are presented. In the present case report, a patient on high doses of opioids, including morphine and methadone, with severe worsening back pain and a history of increasing opioid requirements for the last 2 months due to metastatic leiomyosarcoma to the femur, spine, and neck is described. Use of high dose opioids is associated with numerous challenges, including tolerance. The successful management of this patient was multimodal and included the use of potent analgesics, N-methyl-D-aspartatereceptor antagonists, and the α-2 agonist clonidine. PMID:24604572

  10. Methadone but not morphine inhibits lubiprostone-stimulated Cl- currents in T84 intestinal cells and recombinant human ClC-2, but not CFTR Cl- currents.

    PubMed

    Cuppoletti, John; Chakrabarti, Jayati; Tewari, Kirti; Malinowska, Danuta H

    2013-05-01

    In clinical trials, methadone, but not morphine, appeared to prevent beneficial effects of lubiprostone, a ClC-2 Cl(-) channel activator, on opioid-induced constipation. Effects of methadone and morphine on lubiprostone-stimulated Cl(-) currents were measured by short circuit current (Isc) across T84 cells. Whole cell patch clamp of human ClC-2 (hClC-2) stably expressed in HEK293 cells and in a high expression cell line (HEK293EBNA) as well as human CFTR (hCFTR) stably expressed in HEK293 cells was used to study methadone and morphine effects on recombinant hClC-2 and hCFTR Cl(-) currents. Methadone but not morphine inhibited lubiprostone-stimulated Isc in T84 cells with half-maximal inhibition at 100 nM. Naloxone did not affect lubiprostone stimulation or methadone inhibition of Isc. Lubiprostone-stimulated Cl(-) currents in hClC-2/HEK293 cells, but not forskolin/IBMX-stimulated Cl(-) currents in hCFTR/HEK293 cells, were inhibited by methadone, but not morphine. HEK293EBNA cells expressing hClC-2 showed time-dependent, voltage-activated, CdCl2-inhibited Cl(-) currents in the absence (control) and the presence of lubiprostone. Methadone, but not morphine, inhibited control and lubiprostone-stimulated hClC-2 Cl(-) currents with half-maximal inhibition at 100 and 200-230 nM, respectively. Forskolin/IBMX-stimulated hClC-2 Cl(-) currents were also inhibited by methadone. Myristoylated protein kinase inhibitor (a specific PKA inhibitor) inhibited forskolin/IBMX- but not lubiprostone-stimulated hClC-2 Cl(-) currents. Methadone caused greater inhibition of lubiprostone-stimulated currents added before patching (66.1 %) compared with after patching (28.7 %). Methadone caused inhibition of lubiprostone-stimulated Cl(-) currents in T84 cells and control; lubiprostone- and forskolin/IBMX-stimulated recombinant hClC-2 Cl(-) currents may be the basis for reduced efficacy of lubiprostone in methadone-treated patients. PMID:22918821

  11. [Pupillary diameter and pupillary reactions in heroin dependent patients and in patients participating in a methadone and morphine replacement program].

    PubMed

    Linzmayer, L; Fischer, G; Grünberger, J

    1997-01-01

    The computer-assisted static and dynamic light evoked pupillometry (TV-pupillometer 1050, Whittaker Corp.) had been proved to be a sensitive procedure for assessment of the effect of psychoactive drugs. Therefore, this method was used in 26 heroin dependent patients (mean age 24.42 years), 20 methadone substituted patients (mean age 29.75), and 20 morphine-substituted patients (mean age 30.65 years) to answer the question whether there were no differences within the patient groups but significant differences between the patients and healthy normals. Indeed, pupillary diameter (vegetative activation) as well as relative change (pupillary reagibility) showed no significant differences between the heroin dependents, the methadone substitution group and the morphine substitution group. However concerning pupillary diameter and relative change the patient groups differed significantly from the healthy controls. Onset latency revealed no differences within the patient groups and between patient groups and healthy controls respectively. Thus the variable pupillary diameter and relative change could be used to assess the additional application of opiates in patients participating in a substitution program. PMID:9173676

  12. Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.

    PubMed

    Destro, Massimo; Ottolini, Luca; Vicentini, Lorenza; Boschetti, Silvia

    2012-10-01

    The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness. PMID:22252547

  13. Oxycodone controlled release in cancer pain management.

    PubMed

    Biancofiore, Giuseppe

    2006-09-01

    Oral opioids are the treatment of choice for chronic cancer pain. Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines from the World Health Organization (WHO). This recommendation by the WHO was derived from availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It was not based on proven therapeutic superiority over other options. Patients who experience inadequate pain relief or intolerable side effects with one opioid may often be successfully treated with another agent or with the same agent administered by a different route. Opioid rotation, or switching to an alternative opioid, helps some patients achieve better pain control with fewer associated adverse effects. Oxycodone is a mu-opioid receptor specific ligand, with clear agonist properties. It is an active potent opioid, which is in part a kappa-receptor agonist. Like morphine and other pure agonists, there is no known ceiling to the analgesic effects of oxycodone. The active metabolites of oxycodone (eg, oxymorphone) could be important in oxycodone-mediated analgesia. The main pharmacokinetic difference between oxycodone and morphine is in oral bioavailability. The bioavailability of oxycodone is >60% and the bioavailability of morphine is 20%. Controlled-release oxycodone is absorbed in a bi-exponential fashion. There is a rapid phase with a mean half-life of 37 min, accounting for 38% of the dose, and a slow phase with a half-life of 6.2 h, which accounts for the residual 62%. Oxycodone elimination is impaired by renal failure because there are both an increased volume of distribution and reduced clearance. A lot of studies prove that the efficacy of controlled-release oxycodone in cancer-pain control is at least the same as morphine, immediate-release oxycodone and hydromorphone. Its toxicity profile seems better than that of morphine. There are actually several

  14. The effect of chronic morphine or methadone exposure and withdrawal on clock gene expression in the rat suprachiasmatic nucleus and AA-NAT activity in the pineal gland.

    PubMed

    Pačesová, D; Novotný, J; Bendová, Z

    2016-07-18

    The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine. PMID:27070740

  15. Role of oxycodone and oxycodone/naloxone in cancer pain management.

    PubMed

    Leppert, Wojciech

    2010-01-01

    Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient analgesia and/or intense adverse effects such as sedation, hallucinations and nausea/vomiting a switch from another opioid to oxycodone might be beneficial. Oxycodone is administered to opioid-naive patients with severe pain and to patients who were unsuccessfully treated with weak opioids, namely tramadol, codeine and dihydrocodeine. Oxycodone effective analgesia may be attributed to its affinity to μ and possibly κ opioid receptors, rapid penetration through the blood-brain barrier and higher concentrations in brain than in plasma. Oxycodone displays high bioavailability after oral administration and may be better than morphine in patients with renal impairment due to the decreased production of active metabolites. Recently an oral controlled-release oxycodone formulation was introduced in Poland. Another new product that was launched recently is a combination of prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone tablets). The aim of this review is to outline the pharmacodynamic and pharmacokinetic properties, drug interactions, dosing rules, adverse effects, equianalgesic dose ratio with other opioids and clinical studies of oxycodone in patients with cancer pain. The potential role of oxycodone/naloxone in chronic pain management and its impact on the bowel function is also discussed. PMID:20884999

  16. Intravenous Methadone for Severe Cancer Pain: A Presentation of 10 Cases

    PubMed Central

    Lossignol, D.; Libert, I.; Michel, B.; Rousseau, C.; Obiols-Portis, M.

    2013-01-01

    Purpose. Methadone, a synthetic opioid agonist, is an effective alternative to strong opioids (morphine, hydromorphone, oxycodone, and buprenorphine) and is widely available as an oral formulation. Few data have been published so far on the use of intravenous (i.v.) methadone for the management of severe or refractory cancer pain. Methods. We followed 10 consecutives cancer patients with severe pain, treated with IV methadone. All had advanced disease and had already received strong opioids, some in association with ketamine. Pain was assessed at T0, T24 hours, and at the end of the treatment. Results. All patients benefited from the switch to IV methadone with a reduction of pain on VAS after 24 hours (median: 4/10; range 0–5) until the end of the treatment (all cases <3/10). The median starting dose was 100 mg/day (range 20–400) and the final dose remained stable with a median of 100 mg/day (range 27–700). The median duration of IV methadone was 11 days (range 2–59). No cardiac toxicity had been observed. Conclusions. IV methadone is an effective pain relieving alternative for the treatment of severe cancer pain, especially in refractory pain syndrome. Moreover, we did not observe any toxicity (neurological or cardiac) or any other major side effects and the treatment was overall well tolerated. More extensive comparative studies should be planned. PMID:27335869

  17. Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM).

    PubMed

    Rendig, S V; Amsterdam, E A; Henderson, G L; Mason, D T

    1980-10-01

    Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol), at concentrations from 10(-8) to 10(-4) M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10(-8) to 10(-6) M except for small but significant (P < .05) increases in all three parameters at 10(-6) M fentanyl, and small but significant increases in dT/dt at 10(-8) to 10(-6) M meperidine. At 10(-5) M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-alpha-acetylmethadol (-11%). For all six narcotics, the 10(-4) M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10(-4) M) did not prevent this reduction of contractile performance except at the highest concentration (10(-4) M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-alpha-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 X 10(-7) M) elicited a positive inotropic response whether administered in the presence of 10(-4) M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and

  18. Inhibition by morphine and morphine-like drugs of nicotine-induced emesis in cats.

    PubMed

    Beleslin, D B; Krstić, S K; Stefanović-Denić, K; Strbac, M; Mićić, D

    1981-05-01

    The effect of morphine, methadone and pethidine injected into the cerebral ventricle of the unanesthetized cat upon emesis produced by nicotine induced similarly was investigated. Morphine and morphine-like drugs depress or abolish the emetic effect of nicotine. The inhibitory effect of morphine, methadone and pethidine is observed after a transient emetic action of these drugs. The emetic and anti-emetic action of morphine, methadone and pethidine can perhaps be ascribed to an agonist/antagonist activity. Further, the possible site of inhibitory action of morphine and morphine-like drugs on the emesis produced by nicotine may be the area postrema of fourth ventricle. PMID:7248811

  19. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  20. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease.

    PubMed

    Tran, Bryant W; Kohan, Lynn R; Vorenkamp, Kevin E

    2015-02-15

    We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted. PMID:25689360

  1. Effect of morphine and morphine-like drugs on carbachol-induced fighting in cats.

    PubMed

    Krstić, S K; Stefanović-Denić, K; Beleslin, D B

    1982-08-01

    In the present experiments, morphine, methadone or pethidine was injected into the cerebral ventricle of the unanesthetized cat after fighting was induced with carbachol injected previously. The fighting evoked by carbachol was sensitive to the depressant action of morphine or pethidine but not to the depressant effect of methadone. The most likely explanation of the depressant effects of the former compounds is that they act on the postsynaptic receptors of central cholinergic neurons. PMID:6890210

  2. Synthetic substances with morphine-like effect

    PubMed Central

    Braenden, Olav J.; Eddy, Nathan B.; Halbach, H.

    1955-01-01

    For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

  3. Methadone overdose

    MedlinePlus

    ... strong painkiller. It is also used to treat heroin addiction. Methadone overdose occurs when someone accidentally or ... A.M. Editorial team. Related MedlinePlus Health Topics Heroin Pain Relievers Browse the Encyclopedia A.D.A. ...

  4. Optimum Methadone Compliance Testing

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this analysis was to determine the diagnostic utility of oral fluid testing collected with the Intercept oral fluid collection device. Clinical Need: Target Population and Condition Opioids (opiates or narcotics) are a class of drugs derived from the opium poppy plant that typically relieve pain and produce a euphoric feeling. Methadone is a long-acting synthetic opioid used to treat opioid dependence and chronic pain. It prevents symptoms of opioid withdrawal, reduces opioid cravings and blocks the euphoric effects of short-acting opioids such as heroin and morphine. Opioid dependence is associated with harms including an increased risk of exposure to Human Immunodeficiency Virus and Hepatitis C as well as other health, social and psychological crises. The goal of methadone treatment is harm reduction. Treatment with methadone for opioid dependence is often a long-term therapy. The Ontario College of Physicians and Surgeons estimates that there are currently 250 physicians qualified to prescribe methadone, and 15,500 people in methadone maintenance programs across Ontario. Drug testing is a clinical tool whose purpose is to provide objective meaningful information, which will reinforce positive behavioral changes in patients and guide further treatment needs. Such information includes knowledge of whether the patient is taking their methadone as prescribed and reducing or abstaining from using opioid and other drugs of abuse use. The results of drug testing can be used with behavior modification techniques (contingency management techniques) where positive reinforcements such as increased methadone take-home privileges, sustained employment or parole are granted for drug screens negative for opioid use, and negative reinforcement including loss of these privileges for drug screens positive for opioid used. Body fluids including blood, oral fluid, often referred to as saliva, and urine may contain metabolites and the

  5. Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

    PubMed

    Błaszczyk, Feliks; Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  6. Opioid Use and Neural Tube Defects

    MedlinePlus

    ... study include codeine, oxycodone, hydrocodone, morphine, propoxyphene, meperidine, methadone, tramadol, hydromorphone, butorphanol, heroin, fentanyl, buprenorphine, nalbuphine, and diphenoxylate. Making Treatment Decisions When making treatment decisions just before or ...

  7. Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain.

    PubMed

    Auret, Kirsten; Roger Goucke, C; Ilett, Kenneth F; Page-Sharp, Madhu; Boyd, Fiona; Oh, Teik E

    2006-06-01

    Racemic methadone is increasingly used to manage cancer pain. The authors studied 13 terminally ill patients with cancer pain, who underwent switching (rotation) from morphine to methadone. The relationship between initial morphine dose and final methadone dose, the pharmacokinetics of R- and S- methadone, and the degree of pain control and side effects were investigated. Preswitching serum morphine concentrations and second daily plasma concentrations of methadone were measured. The brief pain inventory (BPI) was used to assess pain every second day. "Worst pain" as measured by the BPI improved by >/=20% in 6 of the 13 patients. The mean morphine to methadone conversion ratio was 5.2 with wide interpatient variability (range 1.3 to 11). Average steady-state concentrations were 197 (98 to 379) mug/L and 272 (55 to 378) mug/L for R- and S-methadone, respectively. Mean population pharmacokinetic parameters for a 1-compartment model were 455 L and 338 L for apparent volume of distribution and 53.3 hours and 31.5 hours for half-life for R- and S- methadone, respectively. Bayesian estimates of apparent oral clearance for individual patients were 0.082 (0.052 to 0.112) L/kg/h and 0.117 (0.061 to 0.173) L/kg/h for R- and S- methadone, respectively (mean and 95% confidence interval). The low and variable clearance values generally resulted in slow achievement of steady-state concentrations over several days; inappropriately high plasma methadone levels occurred in 1 patient. Whereas optimal pain control was achieved in 46% of patients, there was no relationship with plasma concentrations of methadone. Best practice for methadone use in this patient group should include monitoring of both pain and methadone concentration. PMID:16778720

  8. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  9. Topical methadone and meperidine analgesic synergy in the mouse

    PubMed Central

    Kolesnikov, Yuri A.; Oksman, Galina; Pasternak, Gavril W.

    2010-01-01

    Topical analgesics have many potential advantages over systemic administration. Prior work has shown potent analgesic activity of a number of topical opioids in the radiant heat tailflick assay. The current study confirms the analgesic activity of morphine and extends it to two other mu opioids, methadone and meperidine. Combinations of topical morphine and lidocaine are synergistic. Similarly, the combination of methadone and lidocaine is synergistic. While there appeared to be some potentiation with the combination of meperidine and lidocaine, it did not achieve significance. Systemically, prior studies have shown that co-administration of morphine and methadone was synergistic. The combination of morphine and methadone was also synergistic when given topically. In contrast, the combination of morphine and meperidine was not synergistic systemically and it was not synergistic topically. Thus, the pharmacology of topical opioids mimics that seen with systemic administration. Their activity in the topical model supports their potential utility while the local limitation of their actions offers the possibility of a reduced side-effect profile. PMID:20433826

  10. [Opium (heroin * morphine)].

    PubMed

    Hiramatsu, Masayuki

    2010-08-01

    The number of people dependent on opiate drugs, including heroin, is still high, and these abused drugs are major social issues, both in the social science and medically. The mechanisms of physical dependence and withdrawal symptoms in laboratory animals are becoming clear; however, no useful method to detoxify abusers with opioid dependence in clinical situation has been established, and alternative therapy with methadone, used in Europe and America, cannot be used in Japan. Here, I will outline the global trend of opium abuse, including heroin and morphine, and summarize the problems of heroin abuse. PMID:20715484

  11. Neonatal abstinence syndrome

    MedlinePlus

    ... takes drugs such as heroin, codeine, oxycodone (Oxycontin), methadone or buprenorphine. These and other substances pass through ... babies with severe symptoms need medicines such as methadone and morphine to treat withdrawal symptoms. These babies ...

  12. Oxycodone accumulation in a hemodialysis patient.

    PubMed

    Foral, Pamela A; Ineck, Joseph R; Nystrom, Kelly K

    2007-02-01

    Oxycodone and oxycodone-containing analgesics are often used for the relief of pain. In the presence of renal dysfunction, the half-life of oxycodone and metabolites can be prolonged. We describe the case of a 41-year-old chronic hemodialysis patient who received multiple doses of oxycodone/acetaminophen resulting in accumulation of the medication and consequent lethargy, hypotension and respiratory depression. These adverse effects were reversed with multiple bolus doses of naloxone, followed by a continuous infusion administered for 45 hours. Utilizing the Naranjo probability scale, the patient had a "probable" adverse drug reaction to the oxycodone. Oxycodone should be used with caution in patients with chronic renal failure. PMID:17330696

  13. Narcotics

    MedlinePlus

    ... heroin and pharmaceutical drugs like OxyContin ® , Vicodin ® , codeine, morphine, methadone, and fentanyl. Street names Big H, Black ... synthesized from naturally occurring opium products, such as morphine and codeine, and include heroin, oxycodone, hydrocodone, and ...

  14. Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist

    PubMed Central

    Doi, Seira; Mori, Tomohisa; Uzawa, Naoki; Arima, Takamichi; Takahashi, Tomoyuki; Uchida, Masashi; Yawata, Ayaka; Narita, Michiko; Uezono, Yasuhito; Suzuki, Tsutomu

    2016-01-01

    Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. PMID:27317580

  15. Morphine Oral

    MedlinePlus

    ... relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used to relieve severe ( ... use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat ...

  16. Pain therapy with oxycodone/naloxone prolonged-release combination: case report

    PubMed Central

    Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  17. Fatal methadone intoxication in an infant listed as a homicide.

    PubMed

    Bonsignore, Alessandro; Groppi, Angelo; Ventura, Francesco; De Stefano, Francesco; Palmiere, Cristian

    2016-09-01

    Voluntary methadone administration for the purpose of sedation eventually resulting in the infant's death is extremely infrequent, though it has been observed. In this report, we describe an autopsy case pertaining to a 32-month-old infant who was repeatedly exposed to methadone by his parents. Autopsy revealed a coarctation of the aorta with a focal stenosis located at the junction of the distal aortic arch and the descending aorta. Left ventricular hypertrophy was also observed. Both these findings were considered to not have played a role in the child's death. Methadone was detected in the femoral blood (0.633 mg/l), urine (5.25 mg/l), bile (2.64 mg/l), and gastric contents (1.08 mg). A segmental hair analysis showed the presence of methadone and morphine in both the proximal and distal portion of the lock. Methadone was also detected in nail samples. A segmental hair analysis performed on the younger brother of the deceased revealed the presence of methadone and morphine in both the proximal and distal segments, as well as the presence of 6-monoacetylmorphine exclusively in the distal portion. Though the parents denied any involvement in methadone administration or exposure for the purpose of sedation, the manner of death was listed as homicide. The case emphasizes the usefulness of hair analysis to identify threatening situations for the children of drug-dependent parents and possibly support measures by the authorities to recognize and intervene in these potentially fatal situations. PMID:26500092

  18. Use of Methadone for Prevention of Opioid Withdrawal in Critically Ill Children

    PubMed Central

    Jeffries, Sonia A; McGloin, Rumi; Pitfield, Alexander F; Carr, Roxane R

    2012-01-01

    Background Opioids are commonly administered to critically ill children for analgesia and sedation, but many patients experience opioid withdrawal upon discontinuation. The authors’ institution developed a protocol for using methadone to prevent opioid withdrawal in children who have received morphine by continuous IV infusion for 5 days or longer in the pediatric intensive care unit (PICU). Objectives The primary objectives were to determine if opioids were tapered according to the protocol and to determine the conversion ratio for IV morphine to oral methadone that was used. Secondary objectives were to describe the methadone dosage used and the clinical outcomes, to evaluate adjustments to methadone dosing, and to report the incidence of adverse effects. Methods A retrospective analysis of charts was conducted for pediatric patients who had received morphine by continuous IV infusion for 5 days or longer followed by methadone in the PICU between May 2008 and August 2009. Validated scoring systems (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to assess symptoms of withdrawal and degree of sedation, respectively. Results Forty-three patients were included in the study, with median age of 8 months (range 0.25–201 months). For 31 patients (72%), the protocol was not used, and there were no patients for whom the protocol was followed to completion. The median duration of weaning was 10 days (range 0–91 days). The conversion ratio for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and 1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18 patients (42%) experienced withdrawal symptoms. The methadone dose was increased for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day (range 0–9 days), were comfortable for a median of 6.5 days (range 1–64 days), and were agitated for a median of 2.5 days (range 0–23 days). Naloxone was required for 2 patients. Conclusions

  19. Changes to the daily pattern of methadone-related deaths in England and Wales, 1993-2003.

    PubMed

    Morgan, O W; Johnson, H; Rooney, C; Seagroatt, V; Griffiths, C

    2006-12-01

    Previous studies suggest that fatal poisoning deaths involving methadone occur more frequently on the weekends. We assessed changes in the daily pattern of mortality because of methadone poisoning following a review of drug misuse services in 1996 and publication of revised clinical guidelines in 1999. We also compared this to the daily pattern of deaths involving heroin/morphine. The Office for National Statistics provided data on all deaths in England and Wales between 1993 and 2003 for which methadone and heroin/morphine were mentioned on the coroner's certificate of death registration after inquest, with or without alcohol or other drugs. There were 3098 deaths involving methadone. The death rate increased up to 1997 and then declined. Initially, there was a marked excess of deaths occurring on Saturdays. The rate of decline was greatest for deaths occurring on Saturdays. As a result, the Saturday peak disappeared (P = 0.006). There were 6328 deaths involving heroin/morphine. No change in the daily pattern of heroin/morphine deaths was observed during the study period. Although the marked change in the epidemiology of methadone deaths coincided with recommendations for service redevelopment and clinical management of methadone treatment, the contribution of improved prescribing practice or treatment services is unclear. PMID:17060353

  20. Specific serum binding of morphine, levorphanol and heroin

    PubMed Central

    Herndon, B. L.; Baeder, D. H.; Ringle, D. A.

    1976-01-01

    Effects of repeated subcutaneous pellet implantation of a series of narcotic drugs on the serum binding of [14C]morphine was studied in rabbits. Three of the compounds, morphine, heroin and levorphanol, elicited production of a morphine-binding globulin in the implanted rabbits. This serum response did not occur with several other compounds tested, including the potent analgesic methadone, and the narcotic antagonist naloxone. The time course of production of this globulin response, as well as the specificity of the binding for the drug that induced the response are both characteristic of an immunological reaction.

  1. Patterns of Care and Side Effects for Patients Prescribed Methadone for Treatment of Chronic Pain

    PubMed Central

    Macey, Tara A.; Weimer, Melissa B.; Grimaldi, Elizabeth M.; Dobscha, Steven K.; Morasco, Benjamin J.

    2014-01-01

    Objectives This manuscript evaluates physician monitoring practices and incidence of cardiac side effects following initiation of methadone for treatment of chronic pain as compared to patients who began treatment for chronic pain with morphine sustained release (SR). Design We retrospectively reviewed medical record data on all new initiations of methadone and compared results of physician monitoring practices to patients with new initiations of morphine SR. A standardized chart tool was used to capture clinical data. Data related to health service utilization and clinical diagnoses were obtained from the VA clinical information system. Setting A single VA medical center in the Pacific Northwest. Patients Chronic pain patients prescribed methadone (n=92) or morphine (n=90) in the calendar year 2008. Results There was no difference between patients prescribed methadone versus patients prescribed morphine SR in the likelihood of receiving an electrocardiogram (ECG) prior to initiating medication (53% versus 54%) or in the year after opioid initiation (37% versus 40%). The two groups also did not differ in rates of developing prolonged QTc intervals (>450 ms) (11% versus 17%). Seventy-two percent of all patients discontinued their long-acting opioid regimens before 90 days due to adverse effects or insufficient pain relief. Conclusion Despite recommendations for standardized assessment and cardiac risk monitoring, few patients prescribed methadone received an ECG, and this occurred at a rate that did not differ from patients prescribed morphine SR. Patients discontinued both medications at high rates. Further research is needed to evaluate the clinical significance of QTc prolongation in patients treated with methadone. PMID:24353045

  2. Out-of-Hospital Mortality among Patients Receiving Methadone for Non-Cancer Pain

    PubMed Central

    Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Cooper, William O.; Hall, Kathi; Stein, C. Michael

    2014-01-01

    Importance Growing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone may increase risk for both lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias. Objective To compare risk of out-of-hospital death in users of methadone for non-cancer pain to that for comparable users of sustained-release (SR) morphine. Design Retrospective cohort study. Setting Tennessee Medicaid, 1997 through 2009. Participants Cohort included current users of morphine SR or methadone 30–74 years of age without cancer or other life-threatening illness and not in a hospital or nursing home. At cohort entry, 32,742 and 6,014 had filled a prescription for morphine SR or methadone, respectively. The median age was 48 years, 58% were female, and comparable proportions had received cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90% of patients received the opioid for either back or other musculoskeletal pain. The median daily doses prescribed for morphine SR and methadone were 90mg and 40mg, respectively. Main Outcomes and Measures The primary study endpoint was out-of-hospital mortality, given that opioid-related deaths typically occur outside the hospital. Results There were 477 deaths during 28,699 person years of followup, or 166 deaths per 10,000 person-years. After control for study covariates, current methadone users had a 46% increased risk of death during followup, with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval 1.17–1.83, p = .0008), resulting in 72 (27–130) excess deaths per 10,000 person-years. Methadone users of doses ≤20mg/day, the lowest dose quartile, had increased risk (HR =1.59 [1.01–2.51], p = .0461) relative to a comparable dose of morphine SR (<60mg/day). Conclusions and Relevance The increased risk of death observed for users of methadone, even for low doses, supports recommendations that it

  3. Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

    PubMed

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

    2015-03-01

    In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of

  4. The Methadone Illusion

    ERIC Educational Resources Information Center

    Lennard, Henry L.; And Others

    1972-01-01

    Methadone treatment for heroin addiction does not touch the roots of the drug problem" and to think that the use of another drug can solve the profound and complex task facing us is indeed an illusion." (Author/AL)

  5. Methadone for Pain Relief.

    PubMed

    Johnson, Joseph; Sheth, Samir

    2016-06-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. In reply to a question, the authors discuss the use of methadone for pain management, outline how the body processes methadone, list interactions and side effects, and emphasize the importance of taking the medication as prescribed. PMID:27159280

  6. Opioid intoxication

    MedlinePlus

    ... use of opioid-based drugs. These include morphine, heroin, oxycodone, and synthetic (man-made) opioid narcotics. Prescription ... United States, the most commonly abused opioids are heroin and methadone. People who become addicted to these ...

  7. Methadone Treatment: Overview and Bibliography.

    ERIC Educational Resources Information Center

    Greenfield, Lawrence; Tang, Beth Archibald

    This overview focuses on methadone treatment. Briefly, it describes the clinical uses of methadone for substance abuse treatment, explores dosage guidelines, and discusses counseling components. This overview also reviews research data on the application of methadone treatment to special populations, such as pregnant women, polydrug users, and…

  8. An update on oxycodone: lessons for death investigators in Australia.

    PubMed

    Pilgrim, Jennifer L; Yafistham, Sabrina Putrianita; Gaya, Sanjeev; Saar, Eva; Drummer, Olaf H

    2015-03-01

    Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies. PMID:25403552

  9. Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord

    PubMed Central

    de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A liquid chromatography mass spectrometric selected reaction monitoring mode (SRM) method for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), 6-acetylmorphine, morphine and codeine quantification in human umbilical cord was developed and fully validated. Analytes were extracted from homogenized tissue (1 g) by solid phase extraction. Linearity was 2.5–500 ng/g, except for methadone (10–2000 ng/g). Method imprecision was <12.7%CV with analytical recovery 85.9–112.7%, extraction efficiency >59.2%, matrix effect 4.5–39.5%, process efficiency 48.6–92.6% and stability >84.6%. Analysis of an umbilical cord following controlled methadone administration and illicit drug use contained in ng/g, 40.3 morphine, 3.6 codeine, 442 BE, 186 methadone and 45.9 EDDP. PMID:19656745

  10. Analgesic efficacy of controlled-release oxycodone in postoperative pain.

    PubMed

    Sunshine, A; Olson, N Z; Colon, A; Rivera, J; Kaiko, R F; Fitzmartin, R D; Reder, R F; Goldenheim, P D

    1996-07-01

    The efficacy and safety of graded doses (10, 20, and 30 mg) of controlled-release (CR) oxycodone was compared with that of immediate-release (IR) oxycodone (15 mg), immediate-release oxycodone 10 mg in combination with acetaminophen 650 mg (APAP), and placebo in a single-dose, double-blind, randomized, parallel-group study. The participants, 182 inpatients experiencing moderate to severe pain after abdominal or gynecologic surgery, provided hourly ratings of pain intensity and relief for 12 hours after administration. All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences (SPID) and total pain relief (TOTPAR). A dose response was found among the three levels of CR oxycodone for pain relief and peak pain intensity difference (PID), with the 20- and 30-mg doses being significantly better than the 10-mg dose. For all active treatments, peak PID and peak pain relief occurred approximately 2 to 4 hours after administration. The median time to onset of relief was 32 minutes for oxycodone plus APAP, 41 minutes for IR oxycodone, and 46 minutes for CR oxycodone 30 mg. Duration of pain relief showed that the 10-, 20-, and 30-mg doses of CR oxycodone had durations of action of 10 to 12 hours compared with IR oxycodone and oxycodone plus APAP (both approximately 7 hours). Typical adverse events, particularly somnolence, occurred in all active treatment groups. Treatment with CR oxycodone was safe and effective in this study, and its characteristics will be beneficial in the treatment of pain. PMID:8844441

  11. Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?

    ERIC Educational Resources Information Center

    Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.

    2005-01-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…

  12. Oxycodone with an opioid receptor antagonist: A review.

    PubMed

    Davis, Mellar P; Goforth, Harold W

    2016-01-01

    The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome. PMID:26908305

  13. Methadone and prescription drug overdose.

    PubMed

    Hendrikson, Hollie; Hansen, Melissa

    2014-12-01

    (1) Methadone accounted for 2 percent of painkiller prescriptions and more than 30 percent of prescription painkiller deaths in 2009. (2) Data suggest that the rise in deaths from methadone overdose is not related to its use in treating drug abuse but, rather, to its use for pain management. (3) Preferred drug lists in most Medicaid programs identify methadone as a preferred drug for managing chronic pain, but most experts do no recommend it as a first choice. PMID:25556261

  14. Categorising methadone: Addiction and analgesia.

    PubMed

    Keane, Helen

    2013-11-01

    While methadone was first developed as an analgesic, and used for this purpose before it was adopted as a therapy for drug dependence, it is this latter use which has saturated its identity. Most of the literature and commentary on methadone discusses it in the context of methadone maintenance therapy (MMT). But one of the effects of the liberalization of opiate prescription for chronic pain which took place in the 1990s was the re-emergence of methadone as a painkiller. This article examines the relationship between methadone the painkiller and methadone the addiction treatment as it is constituted in recent medical research literature and treatment guidelines. It highlights the way medical discourse separates methadone into two substances with different effects depending on the problem that is being treated. Central to this separation is the classification of patients into addicts and non-addicts; and pain sufferers and non-pain sufferers. The article argues that despite this work of making and maintaining distinctions, the similarities in the way methadone is used and acts in these different medical contexts complicates these categories. The difficulties of keeping the 'two methadones' separate becomes most apparent in cases of MMT patients also being treated for chronic pain. PMID:23768774

  15. Relative abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers

    PubMed Central

    Comer, Sandra D; Sullivan, Maria A; Whittington, Robert A; Vosburg, Suzanne K; Kowalczyk, William J

    2013-01-01

    Abuse of prescription opioid medications has increased dramatically in the U.S. during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled inpatient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses [30 mg q.i.d.]). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as “I feel a good drug effect” and “I like the drug.” In general, the order of potency in producing these effects, from most to least potent, was: fentanyl > buprenorphine ≥ heroin > morphine = oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of “I feel a bad drug effect” and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions. PMID:17581533

  16. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    PubMed Central

    Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

    2015-01-01

    Objective To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. Methods This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN. PMID:26185466

  17. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.

    PubMed

    Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

    2016-02-01

    Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

  18. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine

    PubMed Central

    Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

    2016-01-01

    Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

  19. Evaluation of the analgesic effect of subcutaneous methadone after cesarean section

    PubMed Central

    Jabalameli, Mitra; Kalantari, Forough

    2014-01-01

    Background: Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control. Materials and Methods: Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean. Inclusion criteria: Prime gravid candidate of elective cesarean and spinal anesthesia class 1 or 2. Known case of drug allergy and methadone interaction, addiction, uncontrolled medical disease excluded. Case group injected 10 mg of subcutaneous methadone in the site of incision before final suture. Morphine was a pain reliever in follow up examination. Data include mean of pain, nausea and vomiting, MAP, etc., collected and analyzed by independent-T test and Man Whitney test. Results: Although mean usage of morphine between groups was not significant statistically but the mean pain severity (P value < 0.05) and mean satisfactory (P value = 0.02) was statistically significant between groups. Other parameters were not statistically significant. Conclusion: We suggest subcutaneous methadone as a safe pain reliever in post cesarean section patients. PMID:25337527

  20. Epidural methadone results in dose-dependent analgesia in cancer pain, further enhanced by epidural dexamethasone

    PubMed Central

    Lauretti, G R; Rizzo, C C; Mattos, A L; Rodrigues, S W

    2013-01-01

    Background: This study was designed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone. Methods: In all, 72 cancer patients, 32- to 67-year-old were randomized to six groups (n=12) and prospectively studied to examine analgesia and adverse effects for 3 weeks. Patients received single-dose protocol epidural test drugs: Control group (CG) received epidural 40-mg lidocaine diluted to 10-ml volume with saline. Dexamethasone group (DG) 40-mg lidocaine plus 10-mg dexamethasone. The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine; the 5MetG, 5-mg epidural methadone plus 40-mg lidocaine, the 7.5MetG, 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG, 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone. Results: Groups CG, DG and 2.5MetG were similar regarding analgesia and side effects. Patients from 5MetG and 7.5MetG took 3±1 and 5±1 days, respectively, to restart oral morphine. Patients from 7.5MetDG took 14±2 to restart oral morphine (P<0.001). Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation (P<0.005). Fatigue improved for both DG and 7.5MetDG during 2-week evaluation (P<0.005). By the third week of evaluation, all patients were similar. Conclusions: Epidural methadone plus lidocaine resulted in dose-dependent analgesia, further improved by epidural dexamethasone, which also improved fatigue. PMID:23322191

  1. Factors Associated with Methadone Treatment Duration: A Cox Regression Analysis

    PubMed Central

    Peng, Ching-Yi; Chao, En; Lee, Tony Szu-Hsien

    2015-01-01

    This study examined retention rates and associated predictors of methadone maintenance treatment (MMT) duration among 128 newly admitted patients in Taiwan. A semi-structured questionnaire was used to obtain demographic and drug use history. Daily records of methadone taken and test results for HIV, HCV, and morphine toxicology were taken from a computerized medical registry. Cox regression analyses were performed to examine factors associated with MMT duration. MMT retention rates were 80.5%, 68.8%, 53.9%, and 41.4% for 3, 6, 12, and 18 months, respectively. Excluding 38 patients incarcerated during the study period, retention rates were 81.1%, 73.3%, 61.1%, and 48.9% for 3 months, 6 months, 12 months, and 18 months, respectively. No participant seroconverted to HIV and 1 died during the 18-months follow-up. Results showed that being female, imprisonment, a longer distance from house to clinic, having a lower methadone dose after 30 days, being HCV positive, and in the New Taipei city program predicted early patient dropout. The findings suggest favorable MMT outcomes of HIV seroincidence and mortality. Results indicate that the need to minimize travel distance and to provide programs that meet women’s requirements justify expansion of MMT clinics in Taiwan. PMID:25875531

  2. Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment Patients in Dehong Prefecture of Yunnan Province, China

    PubMed Central

    Duan, Song; Ye, Runhua; Yang, Yuecheng; Wang, Jibao; Tang, Renhai; Gao, Meiyang; He, Na

    2015-01-01

    Objective Methadone maintenance treatment (MMT) was introduced to China in 2004 to reduce the harm of injecting drug users (IDUs). However, little is known about continued drug use, especially methamphetamine (MAMP), among MMT patients. Methods A survey was conducted among patients attending five major MMT clinics in Dehong Prefecture in 2014 to investigate the heroin and MAMP use and their associated risk factors. Participants were administered with face-to-face interviews, and urine tests for morphine and MAMP. Results A total of 2,121 were eligible and participated in the study. Among them, 220 (10.4%) were only positive for morphine, 12.9% were only positive for MAMP, and 196 (9.2%) were positive for both morphine and MAMP. Compared with neither use of heroin nor MAMP during MMT, heroin use (not using MAMP) was associated with ethnicity, shorter duration of MMT, lower dose of methadone, and having had no more than two sex partners in the past year; MAMP use (not using heroin) was associated with ethnicity, longer duration of MMT, higher dose of methadone and being aged <30 years (vs. ≥50 years); use of both heroin and MAMP was associated with being Dai minority (vs. Han), a marital status of divorced or widowed, having used drugs for ≥10 years and shorter duration of MMT. Conclusion These findings indicate the complexity in the treatment of heroin users and underscore the importance in prescribing appropriate methadone dosages in order to reduce both heroin and MAMP use. PMID:26196394

  3. Morphine: Myths and Reality

    MedlinePlus

    ... and Families Take the Quiz Morphine: Myths and Reality February, 2013 The mere mention of “Morphine” can ... due to misinformation and lack of training. The reality is that Morphine (and other opiates that work ...

  4. Serotonin syndrome probably triggered by a morphine-phenelzine interaction.

    PubMed

    Mateo-Carrasco, Hector; Muñoz-Aguilera, Eva María; García-Torrecillas, Juan Manuel; Abu Al-Robb, Hiba

    2015-06-01

    Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. Evidence supporting an association between nonserotonergic opiates, such as oxycodone or morphine, and serotonin syndrome is very limited and even contradictory. In this case report, we describe a patient who developed serotonergic-adverse effects likely precipitated by an interaction between morphine and phenelzine. A 57-year-old woman presented to the emergency department with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, confusion, sweating, tachycardia, and nausea over the previous week. On admission, her blood pressure was 185/65 mm Hg, and clonus was noted in the lower extremities. The patient was hospitalized 10 days earlier for cellulitis of the left breast secondary to a left mastectomy 5 months earlier, and a short course of oral morphine was prescribed for pain control. Her routine medications consisted of aspirin, atorvastatin, bisoprolol, clopidogrel, gabapentin, omeprazole, phenelzine, and ramipril. Supportive measures were initiated on admission. Phenelzine and morphine were discontinued immediately, leading to a progressive resolution of symptoms over the next 48 hours. Phenelzine was restarted on discharge without further complications. Use of the Drug Interaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of serotonin syndrome and the combination of morphine and phenelzine. The mechanism underlying this interaction, however, remains unclear and warrants further investigation. Clinicians should carefully weigh the risk and benefits of initiating morphine in patients taking monoamine oxidase inhibitors or any other serotonin-enhancing drugs. PMID:25903219

  5. Enhanced development of dispositional tolerance to methadone by desipramine given together with methadone

    SciTech Connect

    Liu, S.J.; Wang, R.I.H.

    1985-02-25

    Rats given 2-day oral administration of methadone (15 mg/kg, twice on day 1 and once on day 2) by gastric tube developed dispositional tolerance to methadone analgesia as demonstrated by a decrease in analgesic response and by an increase in methadone metabolism. The increased metabolism of methadone was evidenced by a decrease in brain concentration of /sup 14/C-methadone and increases in the percentages of total /sup 14/C in liver or urine as /sup 14/C-water-soluble metabolites (/sup 14/C-WSM) after the rats were challenged with a test dose of /sup 14/C-methadone. Two-day pretreatment with a combination of desipramine (DMI) (10 mg/kg, ip) and methadone (15 mg/kg, po) enhanced the development of dispositional tolerance to methadone analgesia which was evidenced by a greater decrease in the brain concentration of methadone and a greater increase in methadone metabolism as compared to those changes in rats pretreated with only methadone. Repeated treatment with DMI alone neither decreased the analgesic effect of methadone nor stimulated methadone metabolism. It is suggested that DMI given together with methadone promoted the induction of methadone metabolism in the liver by prolonging the enzyme-stimulating state of methadone, thus enhancing the development of dispositional tolerance to methadone. 20 references, 1 figure, 1 table.

  6. Metabolism of Oxycodone in Human Hepatocytes from Different Age Groups and Prediction of Hepatic Plasma Clearance

    PubMed Central

    Korjamo, Timo; Tolonen, Ari; Ranta, Veli-Pekka; Turpeinen, Miia; Kokki, Hannu

    2012-01-01

    Oxycodone is commonly used to treat severe pain in adults and children. It is extensively metabolized in the liver in adults, but the maturation of metabolism is not well understood. Our aim was to study the metabolism of oxycodone in cryopreserved human hepatocytes from different age groups (3 days, 2 and 5 months, 4 years, adult pool) and predict hepatic plasma clearance of oxycodone using these data. Oxycodone (0.1, 1, and 10 μM) was incubated with hepatocytes for 4 h, and 1 μM oxycodone also with CYP3A inhibitor ketoconazole (1 μM). Oxycodone and noroxycodone concentrations were determined at several time points with liquid chromatography–mass spectrometry. In vitro clearance of oxycodone was used to predict hepatic plasma clearance, using the well-stirred model and published physiological parameters. Noroxycodone was the major metabolite in all batches and ketoconazole inhibited the metabolism markedly in most cases. A clear correlation between in vitro oxycodone clearance and CYP3A4 activity was observed. The predicted hepatic plasma clearances were typically much lower than the published median total plasma clearance from pharmacokinetic studies. The data suggests that there are no children-specific metabolites of oxycodone. Moreover, CYP3A activity seems to be the major determinant in metabolic clearance of oxycodone regardless of age group or individual variability in hepatocyte batches. PMID:22291644

  7. Simultaneous Quantification of Methadone, Cocaine, Opiates, and Metabolites in Human Placenta by Liquid Chromatography–Mass Spectrometry*

    PubMed Central

    de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A validated method for quantifying methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, cocaine, benzoylecgonine, 6-acetylmorphine, morphine, and codeine in human placenta by liquid chromatography–ion trap mass spectrometry is described. Specimens (1 g) were homogenized and subjected to solid-phase extraction. Chromatographic separation was performed on a Synergi Polar RP column with a gradient of 0.1% formic acid and acetonitrile. The method was linear from 10 to 2000 ng/g for methadone and 2.5 to 500 ng/g for other analytes. Limits of detection were 0.25–2.5 ng/g, imprecisions < 9.1%CV, analytical recoveries 84.4–113.3%, extraction efficiencies > 46%, matrix effects −8.0–129.9%, and process efficiencies 24.2–201.0%. Method applicability was demonstrated by analysis of five placenta specimens from opioid-dependent women receiving methadone pharmacotherapy, with methadone doses ranging from 65 to 95 mg on the day of delivery. These are the first data on placenta concentrations of methadone and metabolites after controlled drug administration. Detection of other common drugs of abuse in placenta will also improve our knowledge of the usefulness of this matrix for detecting in utero drug exposure and studying disposition of drugs in the maternal-fetal dyad. PMID:19671243

  8. Drug Abuse: Methadone Becomes the Solution and the Problem

    ERIC Educational Resources Information Center

    Bazell, Robert J.

    1973-01-01

    Methadone is used to divert heroin addicts from using stronger drugs. Rate of crimes committed by drug addicts has fallen considerably after putting them on methadone. Despite criticisms, methadone use seems to be encouraging for the future. (PS)

  9. A new therapeutic option for postoperative pain management with oxycodone HCI injection.

    PubMed

    Choi, Byung Moon

    2016-06-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  10. A new therapeutic option for postoperative pain management with oxycodone HCI injection

    PubMed Central

    2016-01-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  11. Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers

    PubMed Central

    Kleykamp, Bethea A.; Vandrey, Ryan G.; Bigelow, George E.; Strain, Eric C.; Mintzer, Miriam Z.

    2016-01-01

    Background Methadone maintenance patients (MMP) often abuse other drugs, including alcohol. The combined use of methadone and alcohol could impair performance and daily functioning. Objective To examine the effects of methadone in combination with alcohol, as well as acute increases in methadone, on performance outcomes. Method This double blind, double-dummy, crossover study included 8 opioid dependent participants stabilized on methadone. Participants completed 6 inpatient sessions corresponding to methadone (100% or 150% of daily dose) and beverage (placebo, 0.25 or 0.50 g/kg alcohol). Performance tasks were completed before and after drug administration. Area under the timecourse values were analyzed by a 2 (methadone dose) by 3 (alcohol dose) repeated measures analysis of variance. Results Main effects of methadone were observed for two attention outcomes, suggesting reduced accuracy and slowed responding at an elevated methadone dose. In addition, main effects of alcohol were observed for episodic memory (false alarms and response bias) suggesting more impulsive responding as alcohol dose increased. No robust interactions of methadone and alcohol were observed for any outcome. Conclusions Study findings indicate that an acute increase in methadone (150%) and a moderate dose of alcohol (2–3 drinks) can impair distinct aspects of performance, although no significant interactive effect between methadone and alcohol was found. Future studies with larger sample sizes, larger doses, and more clinically informative tasks could expand on the present findings and further explore the cognitive consequences of concurrent opioid and alcohol use. PMID:25584897

  12. User views on supervised methadone consumption.

    PubMed

    Stone, Elizabeth; Fletcher, Keron

    2003-03-01

    To assess the views of opiate-dependent individuals about supervised methadone consumption. Three groups of opinions were sought: (i). new patients referred for assessment and treatment, using rating scales; (ii). the consensus view of the Methadone Alliance (a national users' forum); and (iii). the consensus view of a local service users' forum. All three groups expressed the view that supervised consumption has an important place in methadone treatments. Users understand the need for daily supervision of methadone and are generally willing to accept it. Users' views provide support for the introduction of flexible methadone prescribing regimes incorporating supervised consumption. Privacy in pharmacies and the possibility of moving away from supervision are important elements in an acceptable programme. Supervised consumption is an important component of safe, effective and responsible methadone prescribing. PMID:12745415

  13. Morphine: Myths and Reality

    MedlinePlus

    ... ve heard that Morphine has lots of side effects, and I feel bad enough already.” All opiates can cause nausea, drowsiness and constipation. However, all side effects will generally stop after a few days, as ...

  14. ROLE OF MENINGEAL MAST CELLS IN INTRATHECAL MORPHINE EVOKED GRANULOMA FORMATION

    PubMed Central

    Yaksh, Tony L.; Allen, Jeffery W.; Veesart, Samantha L.; Horais, Kjersti A; Malkmus, Shelle A.; Scadeng, Miriam; Steinauer, Joanne J.; Rossi, Steve S

    2013-01-01

    Background Intrathecal morphine forms granulomas that arise from the adjacent arachnoid membrane. We propose that these inflammatory cells exit the meningeal vasculature secondary to meningeal mast cell degranulation. Methods Three sets of experiments were accomplished in dogs. 1) Ex vivo Meningeal mast cell degranulation. Histamine release was measured ex vivo from canine dura incubated with opiates. 2) In vivo cutaneous mast cell degranulation. Flare areas on the dog abdomen were measured after subcutaneous opiates. 3) In vivo granuloma pharmacology. Dogs with lumbar intrathecal catheters received infusion of intrathecal saline or intrathecal morphine. Intrathecal morphine dogs received: i) No other treatment (Control); ii) Twice daily subcutaneous naltrexone; iii) Intrathecal co-infusion of cromolyn; or, iv) Twice daily subcutaneous cromolyn for the 24–28 day study course. Results 1) Morphine but not fentanyl evoked dural histamine release, which was blocked by cromolyn but not naloxone. 2) Wheal/flare was produced by subcutaneous morphine, methadone, hydromorphone, but not fentanyl, and was unaffected by naltrexone but prevented by cromolyn. 3) Granulomas occurred in all dogs receiving intrathecal morphine (15/15); subcutaneous naltrexone had no effect on granulomas (6/6), but was reduced by concurrent intrathecal cromolyn (0/5) or twice daily subcutaneous cromolyn (1 of 5). Conclusions The pharmacology of cutaneous/dural MC degranulation and intrathecal granulomas are comparable, not mediated by opioid receptors, and reduced by agents preventing MC degranulation. If an agent produces cutaneous MC degranulation at concentrations produced by intrathecal delivery, the agent may initiate granulomas. PMID:23426209

  15. Sex differences in responsiveness to the prescription opioid oxycodone in mice.

    PubMed

    Collins, Devon; Reed, Brian; Zhang, Yong; Kreek, Mary Jeanne

    2016-09-01

    Over-prescription and increased nonmedical use of oxycodone has become a major concern. Despite its increased use, preclinical data concerning oxycodone's effects are still limited, especially in rodent models. To address this, we examined oxycodone's effects on place preference, locomotor activation, corticosterone levels, and thermal analgesia across a range of doses (between 0.3 and 10mg/kg) in gonadally intact, adult male and female C57BL/6J mice. Males and females showed oxycodone-induced conditioned place preference and did not show significant between-sex differences in their place preference behavior. During both CPP conditioning sessions and open field assay, locomotor activity was increased by 1, 3, and 10mg/kg oxycodone in females and by 3 and 10mg/kg oxycodone in males. Plasma corticosterone levels were higher in females (compared to males) at baseline as well as following acute oxycodone injection and open field testing. The time course of oxycodone-induced analgesia was similar in males and females, however the total antinociceptive effect (AUC0-120min) was larger in males compared to females at the highest dose tested (10mg/kg). Taken together, these data suggest that male and female mice are modestly different in their responses to oxycodone. PMID:27316549

  16. The effect of sertraline on methadone plasma levels in methadone-maintenance patients.

    PubMed

    Hamilton, S P; Nunes, E V; Janal, M; Weber, L

    2000-01-01

    The authors examine methadone plasma levels in 31 depressed methadone-maintained opiate addicts enrolled in a 12-week placebo-controlled, double-blind study of sertraline. Between baseline and week 6, patients on sertraline showed a mean increase in methadone plasma level/dose (P/D) ratio of 26% (SD = 43%, range -32% to +118%), while patients on placebo showed a mean decrease of 16% (SD = 27%, range -62% to +50%). This difference was significant (p < 0.02). The sertraline and placebo groups did not differ in reported side effects or methadone dose adjustments. Between weeks 6 and 12, methadone P/D in the sertraline group decreased back towards baseline, and the treatment groups did not differ significantly at week 12. The results suggest sertraline may produce a modest increase in methadone serum levels over the first six weeks of treatment. Depression and anxiety disorders are common in methadone-maintained patients. Serotonin uptake inhibitors are attractive choices for treatment due to their low toxicity and low abuse potential, but these agents variously inhibit isoenzymes responsible for the metabolism of methadone. Clinicians treating depressed or anxious methadone patients with second-generation antidepressants should monitor for clinical signs of increased or decreased methadone levels and consider monitoring serum methadone levels. PMID:10914294

  17. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  18. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  19. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  20. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  1. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  2. Experience-Seeking Characteristics of Methadone Clients.

    ERIC Educational Resources Information Center

    Kohn, Paul M.; And Others

    1979-01-01

    Methadone clients scored higher than controls on measures reflecting boredom, desire for change and attraction to physically thrilling activities. Correlations of these measures with length of most recent dependency before treatment, time on program, and time since initial dependency suggest peculiarities of methadone clients antedated involvement…

  3. Methadone Medical Maintenance: An Early 21st-Century Perspective.

    PubMed

    Novick, David M; Salsitz, Edwin A; Joseph, Herman; Kreek, Mary Jeanne

    2015-01-01

    Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians' offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended. PMID:26110221

  4. Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain.

    PubMed

    Johnson, G H; Van Wagoner, J D; Brown, J; Cooper, S A

    1997-01-01

    The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study. PMID:9220215

  5. Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

    PubMed

    Frampton, James E

    2015-06-01

    An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted. PMID:26135898

  6. Markers for detection of supplementation in narcotic programs--deuterium-labeled methadone.

    PubMed

    Hsia, J C; Tam, J C; Giles, H G; Leung, C C; Marcus, H; Marshman, J A; Leblanc, A E

    1976-08-01

    Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs. PMID:941022

  7. Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants.

    PubMed

    Madadi, Parvaz; Kelly, Lauren E; Ross, Colin J; Kepron, Charis; Edwards, James N; Koren, Gideon

    2016-03-01

    There is a paucity of data to aid in assessing whether postmortem methadone findings in breastfed infants are clinically and/or toxicologically significant. Two cases are reported in which methadone was detected in deceased neonates whose mothers were enrolled in methadone maintenance programs and were breastfeeding. In addition to a complete autopsy and toxicological testing for alcohol, prescription medications, and drugs of abuse, pharmacogenetic analysis was performed for variants in genes related to methadone metabolism and response. In both cases, the postmortem methadone concentration measured in neonatal heart blood was higher than the maximum serum methadone concentration reported in living breastfed infants whose mothers were receiving methadone. However, additional analysis of antemortem blood indicated postmortem redistribution of methadone. Pharmacogenetic results were suggestive of a potential predisposition to methadone toxicity based on studies in adults; the significance of these findings in breastfed neonates requires further research. The medical cause of death was unascertained in both cases. PMID:26513313

  8. The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia.

    PubMed

    Chen, Suchang; Hui, Hui; Zhang, Deren; Xue, Yanzhi

    2010-12-01

    Post-herpetic neuralgia (PHN) is a devastating complication of shingles. The treatment of PHN with traditional pharmaceutical agents has various side effects. Therefore, the treatment of intractable PHN is often very time consuming, mainly because the available treatments often lead to intolerable side effects before the efficient dose can be reached. Opioids such as morphine and oxycodone are the most widely used drugs for the alleviation for severe chronic pain. A number of high quality studies demonstrated that opioids are effective in relieving neuropathic pain including PHN. Yet concerns of misuse, abuse and tolerance of opioids have, however, severely influenced their contribution to neuropathic pain, especially the tolerance that resulted in a loss of drug effect or the necessity for escalating doses to produce pain relief. The glia cells, particularly microglia and astrocytes are thought to play an important role in central sensitization. It is known that activated microglia cells produce NO, cytokines, and cyclooxygenase. All of these chemicals regulate synaptic transmissions in the central nervous system. Additionally, glia modulations showed antiallodynic and antihyperalgesic properties in various experimental pain models. Minocycline, a semisynthetic, second-generation tetracycline can potently inhibit microglial activation and proliferation. Also, the growing body of recent evidence indicates that minocycline attenuates morphine tolerance in neuropathic mice with a mechanism related to microglia. The combination of morphine and minocycline has synergetic effect. This can prevent the development of intractable PHN and attenuate morphine antinociceptive tolerance and further improve the efficacy of morphine and therefore reducing its dosage and side effects. We thereby hypothesize that the combination of morphine and minocycline may produce a duel effect of morphine antinociceptive and minocycline selectively inhibiting the activation of microglia. PMID

  9. Pharmacokinetic Interaction between Voriconazole and Methadone at Steady State in Patients on Methadone Therapy▿

    PubMed Central

    Liu, Ping; Foster, Grover; LaBadie, Robert; Somoza, Eugene; Sharma, Amarnath

    2007-01-01

    This trial was aimed to estimate the pharmacokinetic interaction between voriconazole and methadone at steady state in male patients on methadone therapy and to characterize the safety and tolerability profile during the coadministration. Twenty-three patients on individualized methadone therapy (30 to 100 mg once daily) were enrolled into this randomized, patient- and investigator-blind, placebo-controlled, parallel-group study. Methadone pharmacokinetic samples were collected from patients receiving methadone alone as the baseline before they were randomized to coadminister either 200 mg voriconazole twice daily (BID) (400-mg BID loading doses on the first day) (n = 16) or matching placebo (n = 7) for the next 5 days. Pharmacokinetic samples for methadone and voriconazole were collected on the last day of voriconazole dosing. The safety data were collected throughout the study. Voriconazole increased the steady-state exposure of pharmacologically active enantiomer (R)-methadone: the mean area under the concentration-time curve from 0 to 24 h (AUC0-24) was increased by 47.2% (90% confidence intervals [CI]: 37.7%, 57.4%), and the mean peak concentration (Cmax) was increased by 30.7% (90% CI: 22.2%, 39.8%). The magnitude of increase in (S)-methadone exposure was greater than that of (R)-methadone: the AUC0-24 was increased by 103.4% (90% CI: 85.0%, 123.6%), and the Cmax was increased by 65.4% (90% CI: 52.6%, 79.2%). Methadone appeared to have no effect on the steady-state voriconazole pharmacokinetics compared to the historical data for voriconazole alone. Methadone patients receiving voriconazole showed no signs or symptoms of significant opioid withdrawal or overdose. Coadministration of 200 mg voriconazole BID with methadone was generally safe and well tolerated. Nevertheless, caution should be exercised when voriconazole is coadministered with methadone due to the increase in (R)-methadone exposure, which in turn may require a dose reduction of methadone. PMID

  10. ¹H NMR-based metabonomic analysis of brain in rats of morphine dependence and withdrawal intervention.

    PubMed

    Hu, Zhengtao; Deng, Yi; Hu, Chunyan; Deng, Pengchi; Bu, Qian; Yan, Guangyan; Zhou, Jiaqing; Shao, Xue; Zhao, Jinxuan; Li, Yan; Zhu, Ruiming; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo

    2012-05-16

    Metabolic consequences of morphine dependence and withdrawal intervention have not been well explored. In the present study, the metabolic changes in brain hippocampus, nucleus accumbens (NAc), prefrontal cortex (PFC) and striatum of rats with morphine dependence and withdrawal intervention were explored by using ¹H nuclear magnetic resonance coupled with principal component analysis, partial least squares and orthogonal signal correction analysis. We found that the concentrations of neurotransmitters including glutamate, glutamine and gamma-aminobutyric acid changed differentially in hippocampus, NAc, PFC and striatum after repeated morphine treatment. Significant changes were also found in a number of cerebral metabolites including N-acetyl aspartate (NAA), lactic acid, creatine, myo-inositol and taurine. These findings indicate the profound disturbances of energy metabolism, amino acid metabolism and neurotransmitters caused by chronic morphine treatment. Interestingly, morphine-induced changes in lactic acid, creatine and NAA were clearly reversed by intervention of methadone or clonidine. Our study provides a comprehensive understanding of the metabolic alteration associated with morphine addiction and withdrawal therapy, which may help to develop new pharmacotherapies. PMID:22391120

  11. Methadone Maintenance as Law and Order

    ERIC Educational Resources Information Center

    Heyman, Florence

    1972-01-01

    Argues that substitution of methadone for heroin would not rehabilitate the drug addict, but it may be used as a method of tranquilizing a potentially troublesome ghetto and poor white population. (RJ)

  12. Managing acute withdrawal syndrome on patients with heroin and morphine addiction by acupuncture therapy.

    PubMed

    Lu, Po-kuang; Lu, Gabriel P; Lu, Dominic P; Lu, D P; Lu, Winston I

    2004-01-01

    Though there are articles and case reports about using acupuncture to detoxify and to break the narcotic addiction, few articles describe in the West about using acupuncture therapy to treat the emergence of acute withdrawal symptom due to heroin, opium, or morphine. Most often the method of treatment are using the methadone or benzodiazepine and phenoziazine drugs this article describes many years of clinical experience with non-drug approach to treat the acute withdrawal symptoms with acupuncture therapy. Unlike the drug approach, which usually has side effects, there is no adverse effect with acupuncture therapy. PMID:15807100

  13. Manifest and Latent Components in Methadone Maintenance: The Methadone Maintenance Game

    ERIC Educational Resources Information Center

    King, Charles H.

    1975-01-01

    This paper discusses various difficulties which arise when the staff of a methadone maintenance clinic must come to grips with the manifest and latent issues in service delivery. A solution is suggested which involves severing the tie between methadone and the behaviors which are reinforced by its use. (Author)

  14. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    PubMed Central

    Webster, Lynn R; Rolleri, Robert L; Pixton, Glenn C; Sommerville, Kenneth W

    2012-01-01

    Background Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users. Methods Forty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h), peak disliking, and effect at 0.5 hours post-dose (E0.5h). Other endpoints included take drug again assessment, overall drug liking, and pupillometry. Results There were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons), suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing) were consistent with the expected vasocutaneous effects of niacin. No serious adverse events were reported. Conclusion Oxycodone HCl-niacin tablets may, in a dose-dependent manner, decrease the potential for oral abuse of oxycodone without unexpected adverse events or clinically

  15. CYP2D6 Genotype Dependent Oxycodone Metabolism in Postoperative Patients

    PubMed Central

    Stamer, Ulrike M.; Zhang, Lan; Book, Malte; Lehmann, Lutz E.; Stuber, Frank; Musshoff, Frank

    2013-01-01

    Background The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Methods Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Results Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12th hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. Conclusions In this postoperative setting, the number of

  16. Methadone

    MedlinePlus

    ... fluvoxamine (Luvox); medications for glaucoma, irritable bowel disease, Parkinson's disease, ulcers, and urinary problems; certain medications for ... naltrexone (ReVia, Vivitrol, in Embeda); pentazocine (Talwin); phenobarbital; phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate, in ...

  17. (1) H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus monkeys with morphine treatment and withdrawal intervention.

    PubMed

    Deng, Yi; Bu, Qian; Hu, Zhengtao; Deng, Pengchi; Yan, Guangyan; Duan, Jiachuan; Hu, Chunyan; Zhou, Jiaqing; Shao, Xue; Zhao, Jinxuan; Li, Yan; Zhu, Ruiming; Zhao, Yinglan; Cen, Xiaobo

    2012-11-01

    Comprehensive cerebral metabolites involved in morphine dependence have not been well explored. To gain a better understanding of morphine dependence and withdrawal therapy in a model highly related to humans, metabolic changes in brain hippocampus and prefrontal cortex (PFC) of rhesus monkeys were measured by (1) H-nuclear magnetic resonance spectroscopy, coupled with partial least squares and orthogonal signal correction analysis. The results showed that concentrations of myoinositol (M-Ins) and taurine were significantly reduced, whereas lactic acid was increased in hippocampus and PFC of morphine-dependent monkeys. Phosphocholine and creatine increased in PFC but decreased in hippocampus after chronic treatment of morphine. Moreover, N-acetyl aspartate (NAA), γ-aminobutyric acid, glutamate, glutathione, methionine, and homocysteic acid also changed in these brain regions. These results suggest that chronic morphine exposure causes profound disturbances of neurotransmitters, membrane, and energy metabolism in the brain. Notably, morphine-induced dysregulations in NAA, creatine, lactic acid, taurine, M-Ins, and phosphocholine were clearly reversed after intervention with methadone or clonidine. Our study highlights the potential of metabolic profiling to enhance our understanding of metabolite alteration and neurobiological actions associated with morphine addiction and withdrawal therapy in primates. PMID:22847893

  18. Methadone toxicity in a poisoning referral center

    PubMed Central

    Taheri, Fatemeh; Yaraghi, Ahmad; Sabzghabaee, Ali Mohammad; Moudi, Maryam; Eizadi-Mood, Nastaran; Gheshlaghi, Farzad; Farajzadegan, Ziba

    2013-01-01

    Objective: Methadone poisoning can occur accidentally or intentionally for suicide or homicide purposes. The aim of this study was to evaluate the epidemiological and clinical manifestations of Methadone poisoning. Methods: A descriptive analytical study was performed from 2010 to 2012 in the poisoning emergency and clinical toxicology departments of Noor hospital affiliated with Isfahan University of Medical Sciences (Isfahan, Iran). All patients with Methadone poisoning within this period of time were investigated. Different variables were recorded in a checklist. Findings: A total of 385 patients were studied. About 85.7% had ingested only Methadone and 14.3% had ingested other medications with Methadone. Mean ± standard deviation of the age was 32.1 ± 15 years (range: 1-90). Most of the patients were male (76.4%). Nearly 40% of the patients were narcotic addicts, 25.5% were addicts under surveillance of Methadone maintenance therapy centers and 34.5% were non-addicts. Intentional poisoning was observed in most of the patients (57.7%). Most of the patients had a low level of consciousness on admission (58.2%). Respiratory depression and hypotension was observed in 35.6% and 12.7% of the cases as the most common symptoms. Regarding vital signs, there was a significant difference in respiratory rate on admission among different evaluated groups (P = 0.02). Length of hospital stay was 18.79 ± 0.72 h (range: 4-240 h, median: 15 h). About 57 patients (25.8%) from the intentionally poisoned patients and 19 patients (12.3%) from the unintentionally poisoned patients had a history of psychiatric disorder (P = 0.001). Most of the patients survived without complications. Conclusion: Addiction, age, gender, attempt to suicide and a history of psychiatric disorder were of the most important factors effective in Methadone poisoning, which should be considered in the public training and prevention of poisoning. PMID:24991620

  19. "Influence of methadone on clopidogrel in addicts on methadone maintenance therapy" Drug interaction between methadone and clopidogrel

    PubMed Central

    Fallah, Ferigol; Hamidikenari, Abolhasan; Sajadi, Seyed Navid; Sajadi, Seyed Rohollah; Shiran, Mohammadreza

    2016-01-01

    Background: Clopidogrel is a prodrug that converts in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. It seems that methadone as CYP2C19 inhibitor affects ticlopidine activity in vivo. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics. Methods: We conducted a case–control study in 10 subjects. The cases (5 subjects) in our study were addicts who were receiving methadone maintenance treatment (MMT) for preventing opium withdrawal symptoms. The control group were opiate users before starting MMT. In both groups, the patients received clopidogrel (75mg/day) for 5 days. On the 6th day, the subjects returned to the clinic, blood samples were taken up to 12 hours following clopidogrel dosing in case and control groups. Plasma concentration of clopidogrel was measured by GC-MAS. Noncompartmental pharmacokinetic analysis was performed using Microsoft Excel software to estimate PK parameters. Results: In this study, methadone decreased clopidogrel clearance by 25% and increased the AUC0-inf nearly 1.3 fold during the coadministration of clopidogrel as an antiplatelet drug. Conclusion: A significant decrease in the clearance of clopidogrel during the coadministration of methadone consistent with a decrease in clopidogrel conversion to its active metabolite and this may decrease its efficacy and may have life-threatening consequences for the patients undergoing clopidogerel maintenance therapy. PMID:27386066

  20. Contributing factors to methadone-related deaths in Ontario.

    PubMed

    Albion, Caroline; Shkrum, Michael; Cairns, James

    2010-12-01

    To identify factors contributing to methadone-related deaths in Ontario in 2004, demographic factors, methadone blood levels, evidence of concurrent drug use, the source of methadone (prescribed or illicit), and its contribution in exacerbating preexistent disease were studied to identify users at risk for methadone toxicity and death. This retrospective study reviewed postmortem data, autopsy reports, police reports, hospital data, and postmortem toxicological analyses available in the Ontario Chief Coroner's Information System. There were 54 cases with methadone detected in postmortem blood samples. Of total, 9 cases were not included in the study because of incomplete documentation. About 11 deaths were due to methadone toxicity alone; 25 deaths were due to combined methadone and other drug toxicity (notably cocaine and alcohol); 7 deaths were due to the exacerbation of a preexisting disease by methadone; 1 death was due to disease alone, and 1 death was due to trauma sustained in a motor vehicle collision. A significant number of methadone-related deaths were due to illicit methadone ingestion, which exceeded the opioid tolerance level. The source of methadone in these cases was unknown. Drug addicts, unaware of the hazard of consuming other illicit or prescription drugs concurrently, are at risk. This study demonstrated that methadone toxicity is enhanced by underlying disease, especially in individuals with underlying cardiac and pulmonary pathology. PMID:20081524

  1. Going Through the Changes: Methadone in New York City

    ERIC Educational Resources Information Center

    Agar, Michael

    1977-01-01

    Methadone has been defined as an agent to draw addicts out of the street life into "straight" society. However, the complementary perspective of the streets sees methadone as a new, widely available drug to be integrated into a subculture previously dominated by heroin. This article discusses the adaptation to methadone and its implications. (NQ)

  2. Work Adjustment of the Methadone-Maintained Corporate Employee

    ERIC Educational Resources Information Center

    Yankowitz, Robert; Randell, Joan

    1977-01-01

    The work adjustment of 26 methadone-maintained corporate employees was evaluated. Results indicated: (a) relative to their nonmethadone-maintained coworkers, the methadone-maintained employees had comparable job performance and superior punctuality and attendance; and (b) the methadone-maintained skilled laborers were satisfied with their…

  3. Comparison of oxycodone and fentanyl for postoperative patient-controlled analgesia after laparoscopic gynecological surgery

    PubMed Central

    Park, Joong-Ho; Lee, Chiu; Shin, Youngmin; Ban, Jong-Seouk; Lee, Ji-Hyang

    2015-01-01

    Background Opioids are widely used in boluses and patient-controlled analgesia (PCA) for postoperative pain control. In this study, we compared the effects of oxycodone and fentanyl on postoperative pain in patients with intravenous patient-controlled analgesia (IV-PCA) after laparoscopic gynecological surgery. Methods Seventy-four patients undergoing elective total laparoscopic hysterectomy or laparoscopic myomectomy were randomly assigned to the administration of either fentanyl or oxycodone using IV-PCA (potency ratio 1 : 60). The cumulative dose administered in the patient-controlled mode during the initial 48 hours after the operation was measured. Patients were also assessed for postoperative pain severity, adverse effects, and patient satisfaction. Results No significant differences were observed in patient satisfaction with the analgesia during the postoperative period. Patients in the oxycodone group experienced significantly more dizziness compared to the fentanyl group. Patients in the oxycodone group showed significantly lower consumption of opioid in the patient-controlled mode (10.1 ± 8.5 ml vs. 16.6 ± 12.0 ml, P = 0.013). Conclusions Our data suggest that oxycodone and fentanyl demonstrated similar effects, and therefore oxycodone may be a good alternative to fentanyl in postoperative pain management. Further studies in various clinical settings will be needed to determine the adequate potency ratio. PMID:25844134

  4. Characterization of (+/-)-methadone uptake by rat lung.

    PubMed Central

    Chi, C H; Dixit, B N

    1977-01-01

    1. By use of a sensitive and specific fluorescence assay procedure it was shown that after subcutaneous administration to rats, (+/-)-methadone was concentrated in the lung. Lung to serum ratios ranging from 25 to 60 were obtained indicating that the rat lung tissue was capable of extracting (+/-)-methadone against a concentration gradient. 2. This phenomenon was investigated in vitro with rat lung slices incubated in Krebs-Ringer phosphate buffer (pH 7.4). The uptake was expressed in terms of tissue to medium concentration ratios (T/M ratio). 3. The principal observations were: (i) Studies on the time-course of the uptake showed that the T/M ratios of (+/-)-methadone increased rapidly during the first 60 min of incubation and then more slowly, with a plateau occurring at 180 min; (ii) The T/M ratio of (+/-)-methadone progressively increased from 9.5 to 17 as the pH of the incubation medium was varied from 6.2 to 7.5; (iii) When the concentration of (+/-)-methadone in the incubation medium was varied from 0.005 to 0.5 mM, the T/M ratio decreased rapidly suggesting self-saturation of the transport process. Beyond the medium concentration of 0.5 mM, the T/M ratio declined very slowly. 4. These results suggested that at low concentrations, (+/-)-methadone was transported predominantly by a self-saturable process while at higher concentrations it was transported by a process of simple diffusion. 5. At low concentrations (0.01 mM) the uptake of (+)-methadone was higher than that of (-)-isomer indicating stereo-specificity of the uptake process. The uptake of (+/-)-methadone at low concentration (0.01 mM) was significantly inhibited by low temperature, lack of O2, lack of glucose, lack of Na+ in the incubation medium, and by exposure of the tissue to high temperature (approximately 100 degrees C). The uptake was also inhibited by relatively high concentration of iodoacetate (1.0 mM) and of naloxone (1.0 mM). 6. Kinetic analysis of data showed that the diffusion constant

  5. Profile of Clients Attending a Methadone Clinic

    PubMed Central

    JACOB, Sabrina Anne; MOHAMMED, Fauziah; HASSALI, Mohamed Azmi Ahmad

    2015-01-01

    Background: Client characteristics provide useful information for designing programs that target individuals with risk factors for substance use and for determining client retention. Therefore, this study examined the profiles of clients attending a methadone clinic. Methods: A cross-sectional analysis of clients of a methadone clinic was conducted through a survey to obtain a profile of methadone clients. Results: Of the 51 patients who responded (response rate: 66.2%), the mean (SD) age at which they started substance use was 19.8 (5.1) years. Friends were cited as the most regular source of drugs (82.4%), and heroin was the most commonly used drug (98%). Daily substance use was reported by 72.5% of the respondents; 23.5% admitted to having stolen money to purchase drugs; 92.2% tried quitting substance use on their own and 98% stated that the main reason for registering at the clinic was that they wanted to stop their drug dependence. Approximately 60% of clients were receiving methadone doses of less than 60 mg/day. Conclusion: Heroin is still the most popular drug of abuse and most clients still receive methadone doses below the recommended level, despite evidence of poor patient retention rates associated with these low doses. PMID:25892951

  6. [Fatal methadone poisoning of a child].

    PubMed

    Klupp, N; Risser, D; Stichenwirth, M; Hönigschnabl, S; Stimpfl, T; Bauer, G

    2000-04-21

    The substance methadone is used for substitution therapy since the 1960s in the U.S. Mainly because of the endemic spread of HIV-1 infections among intravenous drug abusers methadone was made legally available through medical prescription in Austria in 1987. Legal authorities today also allow the patient to take home the necessary daily consumption for weekends or public holidays. The drug is distributed as a watery solution in tiny bottles, which are fitted with an ordinary screw cap. This kind of distribution may, however, have fatal consequences. This is demonstrated in the following case of accidental poisoning of an infant: A two-year-old girl whose parents were both participating in the substitution scheme was found dead in her bed in Vienna in 1997. Forensic autopsy revealed a methadone concentration in the liver tissue of 640 ng/g. The criminal investigation determined that the girl had opened a bottle of methadone solution and subsequently had taken the drug. Considering the circumstances of this accident, from the medical point of view safety devices for the screw caps of the methadone bottles should be required by law, in order to avoid future accidental poisoning. PMID:10849943

  7. The Adverse Events of Oxycodone in Cancer-Related Pain

    PubMed Central

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-01-01

    Abstract The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69–1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72–1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70–1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38–1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81–1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58–1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44–1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07–1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25–0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted. PMID:27082588

  8. Body Composition Changes Associated With Methadone Treatment

    PubMed Central

    Sadek, Gamal E.; Chiu, Simon; Cernovsky, Zack Z.

    2016-01-01

    Background: Methadone is associated with a statistically significant increase in BMI in the first 2 years of treatment. Objectives: To evaluate the changes of body composition (bone mass, % fat, % muscle mass, % water, and basal metabolic rate) related to this increase. Patients and Methods: Changes in body composition were monitored, via bioelectrical impedance, in 29 patients in methadone treatment for opiate dependency (age 18 to 44, mean = 29.3, SD = 7.0, 13 men, 16 women). Results: Within one year from admission to treatment, a statistically significant (t-tests, P < 0.05) increase was noted in their body mass index (BMI), % of body fat, average body mass, and average basal metabolic rate, and relative decrease in their % of muscle mass and % of bone mass. Neither absolute bone mass nor muscle mass changed significantly. Conclusions: Physicians involved in care of methadone patients should recommend dietary and lifestyle changes to improve their overall health. PMID:27162765

  9. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  10. Methadone, Cocaine, Opiates and Metabolite Disposition in Umbilical Cord and Correlations to Maternal Methadone Dose and Neonatal Outcomes

    PubMed Central

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2011-01-01

    Objectives To explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure. Methods Subjects, 19 opioid-dependent pregnant women from two clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment, and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared to those in placenta and meconium, and urine specimens collected throughout gestation. Results Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the 3rd trimester and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine and opiate positive specimens than umbilical cord. Conclusion Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion. PMID:21743375

  11. Employment Patterns of Methadone Maintenance Clients

    ERIC Educational Resources Information Center

    Bloch, Harriet I.; And Others

    1977-01-01

    Analysis of employment patterns of methadone maintenance clients had indicated that the majority were not employed at time of program admission. At time of evaluation, 70 percent of the sample were employed; 88 percent of these clients had previous work histories and brought marketable skills with them. (Author)

  12. Methadone Maintenance: The Addict's Family Recreated.

    ERIC Educational Resources Information Center

    Schwartzman, John; Bokos, Peter

    1979-01-01

    A study of four methadone clinics, the addicts treated at these clinics, and their families, reveals basic dissonances in treatment ideology and professional-paraprofessional relationships which, combined with the addict's particular mode of functioning, make significant change in his behavior improbable. (Author)

  13. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2013-01-01

    Background There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Methods Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5 mg alprazolam, 10mg oxycodone, and 0.5 mg alprazolam combined with 10mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Results Oxycodone by itself increased drug liking and “take again” ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. Conclusions In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. PMID:22365897

  14. Opioids for cancer breakthrough pain: a pilot study reporting patient assessment of time to meaningful pain relief.

    PubMed

    Zeppetella, Giovambattista

    2008-05-01

    Breakthrough pain is a common and distinct component of cancer pain that is usually managed with normal release opioids (also known as rescue medication) either before or soon after its onset. A prospective survey of hospice inpatients with breakthrough pain was undertaken to characterize their pain and then compare the time to onset of pain relief of their rescue medication. Patients presented with, on average, 1.7 different types of breakthrough pains (range, 1-4). The average number of breakthrough pains was four per day (range, 1-8), and the average duration of breakthrough pain was 35 minutes (range, 15-60); most occurred suddenly and unpredictably. Patients used morphine, oxycodone, hydromorphone, methadone, or oral transmucosal fentanyl citrate as rescue medication and the average time to meaningful pain relief following their administration was 31 minutes (range, 5-75). No difference was found between morphine, oxycodone, and hydromorphone. Methadone appeared to work faster than morphine (P<0.01) but no faster than oxycodone or hydromorphone, whereas oral transmucosal fentanyl citrate worked faster than morphine, oxycodone, hydromorphone, and methadone (P<0.001). PMID:18258412

  15. Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

    PubMed

    Meini, Milo; Moncini, Marco; Daini, Laura; Giarratana, Tania; Scaramelli, Daniela; Chericoni, Silvio; Stefanelli, Fabio; Rucci, Paola

    2015-08-01

    This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage. PMID:25891369

  16. Profile of extended-release oxycodone/acetaminophen for acute pain

    PubMed Central

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  17. Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases.

    PubMed

    Cone, Edward J; Fant, Reginald V; Rohay, Jeffrey M; Caplan, Yale H; Ballina, Mayra; Reder, Robert F; Spyker, Daniel; Haddox, J David

    2003-03-01

    An oxycodone postmortem database was created from 1243 solicited cases from Medical Examiner and Coroner (ME/C) offices in 23 states in the United States over the period from August 27, 1999, through January 17, 2002. The request for cases was specific to only those cases in which the ME/C opined that the death involved oxycodone. Each case was evaluated to determine the role of oxycodone and the specific drug product OxyContin tablets in the death. Oxycodone identification was based on toxicology testing, and OxyContin identification was based on evidence found at the scene, credible witness reports, or identification of tablets in gastrointestinal contents. A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology. Of the 1243 cases, 79 cases were incomplete and could not be evaluated. There were an additional 150 cases submitted in which oxycodone was not identified by the originating ME/C. Of the remaining 1014 cases, 919 (90.6%) were related to drug abuse, whereas 95 (9.4%) cases were categorized as not involving drug abuse. Only 30 (3.3%) of the drug abuse cases involved oxycodone as the single reported chemical entity; of these, 12 cases had OxyContin identified as a source of oxycodone. Of the 919 drug abuse cases, the vast majority (N = 889, 96.7%) were multiple drug abuse deaths in which there was at least one other plausible contributory drug in addition to oxycodone. The most prevalent drug combinations were oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. Using the DAWN definitions, drug abuse cases were further categorized as drug-induced or drug-related. A total of 851 (92.6%) cases met the criteria for classification as being drug-induced, and the remaining 68 (7.4%) cases were categorized as drug-related. Cause

  18. Methadone for Fun Sake… Kidneys Are at Stake!!!

    PubMed

    Chaudhari, Sameer; Wankhedkar, Kashmira; Popis-Matejak, Beata; Baumstein, Donald

    2016-01-01

    Acute renal failure from rhabdomyolysis is a well-established clinical entity; however, rhabdomyolysis exclusively caused by the ingestion of methadone requiring hemodialysis is very uncommon. With a similar mechanism to opiates, methadone can cause rhabdomyolysis and further consequences. Given the increasing use of methadone as a therapy for opiate dependence, clinicians prescribing this medication should be aware of this life-threatening complication. PMID:25782567

  19. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions.

    PubMed

    Barrett, D A; Barker, D P; Rutter, N; Pawula, M; Shaw, P N

    1996-06-01

    1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 micrograms kg-1 or 200 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2. Following both the 50 micrograms kg-1 or 200 micrograms kg-1 loading doses the mean steady-state plasma concentration (+/- s.d.) of morphine, M3G and M6G were 86 +/- 52 ng ml-1, 703 +/- 400 ng ml-1 and 48 +/- 28 ng ml-1 respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min-1 kg-1. 3. M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min-1 kg-1. 4. M3G metabolite clearance was 0.46 +/- 0.60 ml min-1 kg-1, the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg-1. M6G metabolite clearance was 0.71 +/- 0.36 ml min-1 kg-1, the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg-1. 5. No significant effect of the loading dose (50 micrograms kg-1 or 200 micrograms kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  20. Methadone as a chemical weapon: two fatal cases involving babies.

    PubMed

    Kintz, Pascal; Villain, Marion; Dumestre-Toulet, Véronique; Capolaghi, Bernard; Cirimele, Vincent

    2005-12-01

    Methadone is largely used for the substitution management of opiate-dependent individuals but can also be easily found on the black market. The first cases involving repetitive sedation linked to the use of methadone and subsequent death of 2 babies are reported. At the autopsy, no particular morphologic changes were noted except for pulmonary and visceral congestion. There was no evidence of violence, and the pathologist in both cases found no needle marks. Toxicological analyses, as achieved by GC/MS, demonstrated both recent and repetitive methadone exposure. In case 1, a 14-month-old girl was found dead at home. Blood concentrations were 1071 and 148 ng/mL for methadone and EDDP, respectively. Hair (6 cm) tested positive at 1.91 and 0.82 ng/mg for methadone and EDDP, respectively. In case 2, a 5-month-old girl was taken to hospital in a pediatric unit for coma. Antemortem blood analysis demonstrated methadone exposure (142 ng/mL), and the baby was declared dead 12 days after admission. Hair analysis (5 cm) by segmentation was positive for methadone in the range 1.0 (root) to 21.3 ng/mg (end). The death of the babies was attributed to accidental asphyxia ina situation where methadone was considered as a chemical weapon. The mothers, who were the perpetrators in both cases, did not deny the use of methadone as a sedative drug. PMID:16404812

  1. Methadone-related deaths. A ten year overview.

    PubMed

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Groppi, Angelo

    2015-12-01

    Over the last 10 years we have registered in our district (about 500,000 inhabitants) 36 cases of fatal methadone poisoning, involving both patients on treatment and naive subjects: this is a significant increase of deaths due to methadone use, misuse or abuse compared with previous years. Twenty-four patients (66.7%) were on methadone maintenance programs for heroin detoxification, while 12 (33.3%) were taking the drug without a medical prescription. The average blood concentration of methadone in patients undergoing a maintenance program was 1.06 mg/L (0.21-3.37 mg/L), against 0.79 mg/L (0.2-3.15 mg/L) in those taking the non-prescribed drug. Since 111 heroin-related deaths were recorded in our district in the same period, the fact that there appear to be many methadone deaths (about a third of heroin-related deaths) cannot be overlooked. The aim of this work is to understand the possible reasons for such a large number of methadone-related deaths. On this subject, we have noticed that risks associated with methadone intake are often underestimated by clinicians prescribing the drug: sometimes methadone is prescribed without taking into account patient's tolerance to opiates, and a large number of subjects enrolled in methadone maintenance programs in Italy, have also been given take-home doses, thus increasing the risk of abuse and diversion. PMID:26360592

  2. Better retention of Malaysian opiate dependents treated with high dose methadone in methadone maintenance therapy

    PubMed Central

    2010-01-01

    Background Methadone is a synthetic opiate mu receptor agonist that is widely used to substitute for illicit opiates in the management of opiate dependence. It helps prevent opiate users from injecting and sharing needles which are vehicles for the spread of HIV and other blood borne viruses. This study has the objective of determining the utility of daily methadone dose to predict retention rates and re-injecting behaviour among opiate dependents. Methods Subjects comprised opiate dependent individuals who met study criteria. They took methadone based on the Malaysian guidelines and were monitored according to the study protocols. At six months, data was collected for analyses. The sensitivity and specificity daily methadone doses to predict retention rates and re-injecting behaviour were evaluated. Results Sixty-four patients volunteered to participate but only 35 (54.69%) remained active and 29 (45.31%) were inactive at 6 months of treatment. Higher doses were significantly correlated with retention rate (p < 0.0001) and re-injecting behaviour (p < 0.001). Of those retained, 80.0% were on 80 mg or more methadone per day doses with 20.0% on receiving 40 mg -79 mg. Conclusions We concluded that a daily dose of at least 40 mg was required to retain patients in treatment and to prevent re-injecting behaviour. A dose of at least 80 mg per day was associated with best results. PMID:21167035

  3. Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment.

    PubMed

    Perez de Los Cobos, Jose; Trujols, Joan; Siñol, Núria; Duran-Sindreu, Santiago; Batlle, Francesca

    2016-04-01

    Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone. PMID:26825608

  4. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    PubMed

    Koek, Wouter; Gerak, Lisa R; France, Charles P

    2015-08-01

    In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks. PMID:26061355

  5. Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier transport and antinociceptive effect.

    PubMed

    Nakazawa, Yusuke; Okura, Takashi; Shimomura, Keita; Terasaki, Tetsuya; Deguchi, Yoshiharu

    2010-01-01

    To examine possible blood-brain barrier (BBB) transport interactions between oxycodone and adjuvant analgesics, we firstly screened various candidates in vitro using [(3)H]pyrilamine, a substrate of the oxycodone transporter, as a probe drug. The uptake of [(3)H]pyrilamine by conditionally immortalized rat brain capillary endothelial cells (TR-BBB13) was inhibited by antidepressants (amitriptyline, imipramine, clomipramine, amoxapine, and fluvoxamine), antiarrhythmics (mexiletine, lidocaine, and flecainide), and ketamine. On the other hand, antiepileptics (carbamazepine, phenytoin, and clonazepam) and corticosteroids (dexamethasone and prednisolone) did not inhibit [(3)H]pyrilamine uptake, with the exception of sodium valproate. The uptake of oxycodone was significantly inhibited in a concentration-dependent manner by amitriptyline, fluvoxamine and mexiletine with K(i) values of 13, 65, and 44 microM, respectively. These K(i) values are 5-300 times greater than the human therapeutic plasma concentrations. Finally, we evaluated in vivo interaction between oxycodone and amitriptyline in mice. Antinociceptive effects of oxycodone were increased by coadministration of amitriptyline. The oxycodone concentrations in plasma and brain were not changed by coadministration of amitriptyline. Overall, the results suggest that several adjuvant analgesics may interact with the BBB transport of oxycodone at relatively high concentrations. However, it is unlikely that there would be any significant interaction at therapeutically or pharmacologically relevant concentrations. PMID:19499573

  6. Pharmacotherapy in the Treatment of Addiction: Methadone

    PubMed Central

    Kreek, Mary Jeanne; Borg, Lisa; Ducat, Elizabeth; Ray, Brenda

    2010-01-01

    Methadone maintenance treatment is the most widely available pharmacotherapy for opioid addiction and has been shown over a period of 40 years to be an effective and safe treatment. While women comprise approximately 40% of clients currently being treated in MMT programs, comparatively little research geared specifically toward this group has been published. This article begins with an overview of neurobiological studies on opioid addiction, including a discussion of gender differences, followed by a review of the pharmacology of methadone The authors then examine the particular needs and differences of women being treated in MMTs, including co-dependence with other substances, women’s health issues and psychosocial needs unique to this population. In conclusion, research shows that women have different substance abuse treatment needs in comparison to their male counterparts. One New York City MMT program that has attempted to address these differences is highlighted. PMID:20407977

  7. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  8. Interim Methadone Treatment: Impact on Arrests

    PubMed Central

    Schwartz, Robert P.; Jaffe, Jerome H.; O’Grady, Kevin E.; Kinlock, Timothy W.; Gordon, Michael S.; Kelly, Sharon M.; Wilson, Monique E.; Ahmed, Ashraf

    2009-01-01

    AIMS This study examines the frequency and severity of arrest charges among heroin addicts randomly assigned to either interim methadone maintenance (IM) or to remain on a waiting list for methadone treatment. It was hypothesized that IM participants would have a: 1) lower number of arrests at 6 and 12 months and 2) lower mean crime severity scores at 6 and 12 months post-baseline. METHODS Available official arrest data were obtained for all 319 study participants for a period of 2 years before and after study enrollment. Crime severity ratings of charges were made using an established measure of crime severity. FINDINGS Participants randomly assigned to IM as compared to those on a waiting list had a significant reduction in number of arrests at 6 but not at 12 months from study enrollment. There were no significant differences in whether participants were arrested for a more severe crime but frequency of severe crime was relatively low in both groups. Additional post hoc analyses based on whether participants were in methadone treatment at 4 and 10 months after original random assignment to treatment condition revealed that those participants not in treatment at these follow-up assessment points were significantly more likely to be arrested and to have a higher mean crime severity rating at 12 and 24 months post-baseline assessment. CONCLUSIONS IM as compared to the waiting list condition, had a significant reduction in number of officially- recorded arrests from baseline to 6 months post-baseline. Those who were enrolled in methadone treatment at the 4 and 10 month follow-up assessment, regardless of initial assignment, had fewer arrests at 12 and 24 months post-baseline. PMID:19443133

  9. Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

    PubMed Central

    2012-01-01

    Background Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community. Methods The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined. Results 128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP. Conclusions The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of

  10. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    ERIC Educational Resources Information Center

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  11. Comparison of the pharmacokinetics of oxycodone administered in three Percocet formulations.

    PubMed

    Gammaitoni, Arnold R; Davis, Matthew W

    2002-02-01

    This randomized, open-label, three-period crossover study compared the single-dose pharmacokinetics of three dose levels of oxycodone in combination with acetaminophen (5 mg/325 mg, 7.5 mg/500 mg, or 10 mg/650 mg) in healthy volunteers. Serial 24-hour blood samples were collectedfrom 23 fasting subjects after drug administration. The individual dose levels were evaluated on 3 different days, which were separated by washout periods of at least 7 days, in each subject. Oxycodone AUC(0-t), AUC(0-infinity), and Cmax were dose dependent, whereas tma and t(1/2) were not. The most frequently reported adverse events were dizziness, nausea, headache, pruritus, and vomiting. Most adverse events were mild, and all were self-limiting. Only dizziness occurred in a dose-related manner. Increasing dose levels of oxycodone/acetaminophen provides proportional increases in oxycodone Cmax and AUC. Adverse events were predictable based on the opioid pharmacologic actions of this agent. PMID:11831542

  12. Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014.

    PubMed

    Jones, Christopher M; Baldwin, Grant T; Manocchio, Teresa; White, Jessica O; Mack, Karin A

    2016-01-01

    Use of the prescription opioid methadone for treatment of pain, as opposed to treatment of opioid use disorder (e.g., addiction), has been identified as a contributor to the U.S. opioid overdose epidemic. Although methadone accounted for only 2% of opioid prescriptions in 2009 (1), it was involved in approximately 30% of overdose deaths. Beginning with 2006 warnings from the Food and Drug Administration (FDA), efforts to reduce methadone use for pain have accelerated (2,3). The Office of the Assistant Secretary for Planning and Evaluation of the U.S. Department of Health and Human Services and CDC analyzed methadone distribution, reports of diversion (the transfer of legally manufactured methadone into illegal markets), and overdose deaths during 2002-2014. On average, the rate of grams of methadone distributed increased 25.1% per year during 2002-2006 and declined 3.2% per year during 2006-2013. Methadone-involved overdose deaths increased 22.1% per year during 2002-2006 and then declined 6.5% per year during 2006-2014. During 2002-2006, rates of methadone diversion increased 24.3% per year; during 2006-2009, the rate increased at a slower rate, and after 2009, the rate declined 12.8% per year through 2014. Across sex, most age groups, racial/ethnic populations, and U.S. Census regions, the methadone overdose death rate peaked during 2005-2007 and declined in subsequent years. There was no change among persons aged ≥65 years, and among persons aged 55-64 years the methadone overdose death rate continued to increase through 2014. Additional clinical and public health policy changes are needed to reduce harm associated with methadone use for pain, especially among persons aged ≥55 years. PMID:27387857

  13. Prenatal oxycodone exposure impairs spatial learning and/or memory in rats.

    PubMed

    Davis, Chris P; Franklin, La'tonya M; Johnson, Gabriel S; Schrott, Lisa M

    2010-09-01

    Recent changes in demographic patterns of drug use have resulted in the increased non-medical use of prescription opiates. These users are younger and more likely to be female, which has the potential for increasing rates of in utero exposure. Therefore, we developed a rat model that simulates a prescription opiate-dependent woman who becomes pregnant. Adult female Sprague-Dawley rats were treated for 30 days via oral gavage with ascending doses of oxycodone HCl up to a final dose of 15mg/kg/day, which was maintained during breeding and gestation. Controls were treated with water. The adult male offspring of these treated dams were tested on the radial arm maze, the Morris water maze (with a short and a long intertrial interval), and a spatial T-maze. Prenatal oxycodone exposure led to a deficit in the radial arm maze characterized by a greater number of reference memory errors, especially in the beginning of testing. In contrast, in the T-maze, prenatal oxycodone-exposed rats learned the task as well as well as the prenatal water controls. However, they had a modest deficit in retention of the task when assessed 5 days after acquisition training ended. For the Morris water maze, the intertrial interval affected the pattern of learning. While there was no deficit when the training had a short intertrial interval, when there was a long intertrial interval, prenatal oxycodone-exposed rats had poorer acquisition. The spatial learning deficit was characterized by and increased latency to find and a greater distance traveled to the platform in the prenatal oxycodone-exposed rats. These data were corroborated by analysis of the behavioral search strategy, which showed a decreased use of spatial strategies and an increase in non-spatial strategies, especially wall-hugging, in prenatal oxycodone-exposed rats as compared to prenatal water control rats on day 2 of acquisition. These results indicate that prenatal oxycodone exposure consistently impairs learning and memory in

  14. Human Methadone Self-Administration and the Generalized Matching Law

    ERIC Educational Resources Information Center

    Spiga, Ralph; Maxwell, R. Stockton; Meisch, Richard A.; Grabowski, John

    2005-01-01

    The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited…

  15. Factors Associated with Illegal Drug Use among Older Methadone Clients

    ERIC Educational Resources Information Center

    Rosen, Daniel

    2004-01-01

    Purpose. The overall aims of this study are to describe the life stressors of, exposure to illegal drug use of, and illegal drug use by older methadone clients. Design and Methods. The current study focuses on a sub-sample of the larger administrative data of a methadone clinic that is limited to African American and White clients over the age of…

  16. Behavioral Treatments During Outpatient Methadone Maintenance: A Controlled Evaluation.

    ERIC Educational Resources Information Center

    Bigelow, George; And Others

    The Treatment Evaluation Project was established to evaluate the feasibility of using behavioral treatment in conjunction with methadone maintenance to improve the effectiveness of methadone treatment. Over 100 outpatients were accepted into treatment and randomly assigned to one of four behavioral treatment modalities in addition to the usual…

  17. Methadone Diversion: Experiences and Issues. Services Research Monograph Series.

    ERIC Educational Resources Information Center

    Inciardi, James A.

    This report is a description of the phenomenon of methadone diversion as it exists now and places it in the context of prior research in this area. The intent here is to clarify issues around methadone diversion and to provide guidance to treatment administrators and program planners regarding efforts they can initiate to monitor this significant…

  18. Multimodality Approach to Methadone Treatment of Narcotic Addicts

    ERIC Educational Resources Information Center

    Brill, Leon; Chambers, Carl D.

    1971-01-01

    This multimodality approach is geared primarily to the goal of abstinence. For addicts who cannot achieve this goal, methadone maintenance is suggested as the next step. The modalities described range from low-dose maintenance for clinic outpatients to intensive rehabilitation in a methadone maintenance residential center facility. (Author)

  19. Implosive Therapy Treatment of Heroin Addicts during Methadone Detoxification.

    ERIC Educational Resources Information Center

    Hirt, Michael; Greenfield, Heywood

    1979-01-01

    Examined effectiveness of implosive therapy with heroin addicts during detoxification from methadone. Treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a six-week period. The implosive therapy group were the only ones to significantly reduce their methadone level during treatment and follow-up.…

  20. Decreasing Methadone Dose Via Anxiety Reduction: A Treatment Manual.

    ERIC Educational Resources Information Center

    Kushner, Marlene; And Others

    This manual describes a Relaxation-Information Presentation program based on the clinical observation that anxiety is a serious barrier to detoxification for many methadone clients, and on experimental evidence indicating that expectations may play a greater role in the discomfort experienced during detoxification than the actual methadone dose.…

  1. Development and validation of a solid-phase extraction gas chromatography–mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat

    PubMed Central

    Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick

    2009-01-01

    A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5–1000 ng/patch) and methadone (10–1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000–10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N=5) and between-run (N=20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576

  2. Development and validation of a solid-phase extraction gas chromatography-mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat.

    PubMed

    Brunet, Bertrand R; Barnes, Allan J; Scheidweiler, Karl B; Mura, Patrick; Huestis, Marilyn A

    2008-09-01

    A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5-1000 ng/patch) and methadone (10-1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within +/-20% of the target concentrations. Extended calibration curves (1000-10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N = 5) and between-run (N = 20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were +/-11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576

  3. Prenatal Methadone Exposure, Meconium Biomarker Concentrations and Neonatal Abstinence Syndrome

    PubMed Central

    Gray, Teresa R.; Choo, Robin E.; Concheiro, Marta; Williams, Erica; Elko, Andrea; Jansson, Lauren M.; Jones, Hendrée E.; Huestis, Marilyn A.

    2010-01-01

    Aims Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Design Prospective clinical study Setting An urban drug treatment facility treating pregnant and post-partum women and their children Participants Forty-nine opioid-dependent pregnant women received 30–110 mg methadone daily. Measurements Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. Findings There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid, cocaine and tobacco biomarkers also were found in 36.7, 38.7 and 81.1% of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Conclusions Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as three months, rather than the currently accepted six months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period. PMID:20854338

  4. Simultaneous determination of opiates, methadone, buprenorphine and metabolites in human urine by superficially porous liquid chromatography tandem mass spectrometry.

    PubMed

    Lin, Huei-Ru; Chen, Chin-Lun; Huang, Chieh-Liang; Chen, Shao-Tsu; Lua, Ahai-Chuang

    2013-04-15

    For monitoring compliance of methadone or buprenorphine maintenance patient, a method for the simultaneous determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, opiates (morphine, codeine, 6-monoacetylmorphine) in urine by superficially porous liquid chromatography tandem mass spectrometry was developed and validated. After enzyme digestion and liquid-liquid extraction, reverse-phase separation was achieved in 5.2 min and quantification was performed by multiple reaction monitoring. Chromatographic separation was performed at 40 °C on a reversed phase Poroshell column with gradient elution. The mobile phase consisted of water and methanol, each containing 0.1% formic acid, at a flow rate of 0.32 mL/min. Intra-day and inter-day precision were less than 12.1% and accuracy was between -9.8% and 13.7%. Extraction efficiencies were more than 68%. Although ion suppression was detected, deuterated internal standards compensated for these effects. Carryover was minimal, less than 0.20%. All analytes were stable at room temperature for 16 h, 4 °C for 72 h, and after three freeze-thaw cycles. The assay also fulfilled compound identification criteria in accordance with the European Commission Decision 2002/657/EC. We analyzed 62 urine samples from patients received maintenance therapy and found that 54.8% of the patient samples tested were detected for morphine, codeine, or 6-monoacetylmorphine. This method provides a reliable and simultaneous quantification of opiates, maintenance drugs, and their metabolites in urine samples. It facilitates the routine monitoring in individuals prescribed the drug to ensure compliance and help therapeutic process. PMID:23507455

  5. [Driving fitness/driving capacity of patients treated with methadone].

    PubMed

    Hauri-Bionda, R; Bär, W; Friedrich-Koch, A

    1998-10-10

    To answer the question whether or not therapeutic methadone doses significantly reduce traffic-related performance of drivers on medically supervised methadone programmes, 34 methadone substitution patients, all of them volunteers, were subjected to a test series: the focus of the study was a psychophysical test battery consisting of 10 individual performance tests to assess essential functions with regard to driving ability, such as concentration, attention, reaction capability, memory, perception and sensorimotor coordination. In evaluating the results of the psychophysical tests, multiple drug use and subjective methadone influence at the time of the examination were taken into consideration but current methadone blood level was neglected. The results were compared to those of a control group. The methadone group (n = 34) consisted of 25 men and 9 women aged between 18 and 38. At the time of the study, the majority of the test persons (29) were on low dosage methadone maintenance (up to 60 mg/day). In the urine samples of approximately 2/3 of the test persons, evidence was found for multiple drug use together with other psychotropic substances, the most frequent (14) being cannabis metabolites. Referring to their driving practices, a mere 4 out of 29 drivers had not committed any driving offences. A comparison of the psychophysical performance of the whole methadone group (n = 34) with a control group demonstrated that the methadone substitution patients achieved rather lower results in almost all variables. These performance deficits were particularly conspicuous in sustained attention, sensorimotor coordination and reaction capability. 12 "methadone only" participants, i.e. methadone probands without any additional consumption of psychotropic substances showed-partly considerably-better performance than the methadone group as a whole and also achieved normal results in relation to the test norm. Nevertheless, once again, results tended to be of lower level in

  6. Comparison of the analgesic effect of patient-controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery.

    PubMed

    Jung, Kyeo-Woon; Kang, Hyeon-Wook; Park, Chan-Hye; Choi, Byung-Hyun; Bang, Ji-Yeon; Lee, Soo-Han; Lee, Eun-Kyung; Choi, Byung-Moon; Noh, Gyu-Jeong

    2016-08-01

    Oxycodone is a μ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery. PMID:27128496

  7. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

    PubMed Central

    Samer, CF; Daali, Y; Wagner, M; Hopfgartner, G; Eap, CB; Rebsamen, MC; Rossier, MF; Hochstrasser, D; Dayer, P; Desmeules, JA

    2010-01-01

    Background and purpose: There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored. Experimental approach: A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg−1 and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session. Key results: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and Cmax (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone Cmax was 62% and 75% lower in PM than EM and UM. Noroxymorphone Cmax reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone Cmax by 40% and 80%, and increased noroxycodone AUC∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. Conclusions and implications: Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. PMID:20590587

  8. Attenuation of Withdrawal Signs, Blood Cortisol, and Glucose Level with Various Dosage Regimens of Morphine after Precipitated Withdrawal Syndrome in Mice.

    PubMed

    Motaghinejad, Majid; Sadeghi-Hashjin, Goudarz; Koohi, Mohammad Kazem; Karimian, Seyed Morteza

    2016-01-01

    Morphine withdrawal usually results in unsuccessful outcomes. Despite partial benefits from alternative substances such as methadone, its use may not lead to the desired result due to the lack of mental tranquility during the withdrawal period. In this study, by means of an animal model, morphine itself was used to manage morphine dependence. Forty mice were divided into 5 groups, in which 4 groups became dependent by increasing daily doses of morphine for 7 days (15-45 mg/kg). Afterwards, the animals received morphine for 14 days by either of the following regimens: Once daily 45 mg/kg (positive controls)Increasing the interval (each time 6 hours longer than the previous interval)Irregular interval in every 36, 12 and 24 hours until the 21(th) day12, 24, 36 hours decreasing doses (each time 2.5 mg/kg less than the former dosage). Negative controls received saline solution only. On day 22, total withdrawal index (TWI) was determined by injecting 3 mg/kg of naloxone. Thereafter, blood samples were taken for the measurement of cortisol and glucose levels. TWI significantly decreased in all test groups in comparison with the positive control animals (P<0.001). Cortisol levels significantly decreased when either the dosage or the administration frequencies were decreased on a regular and gradual basis (P<0.005). Blood glucose levels significantly decreased in animals that received decreasing doses of morphine (P<0.005). This study suggests that no other measures may be required in clinical practice except for changing the dosage regimen of morphine for the cessation of self-administration. PMID:26722146

  9. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

    PubMed Central

    BARRETT, D. A.; BARKER, D. P.; RUTTER, N.; PAWULA, M.; SHAW, P. N.

    1996-01-01

    1The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants(24–41 weeks gestation) who were given a loading dose of 50 μg kg−1 or 200 μg kg−1 of diamorphine followed by an intravenous infusion of 15 μg kg−1 h−1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2Following both the 50 μg kg−1 or 200 μg kg−1 loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52 ng ml−1, 703±400 ng ml−1 and 48±28 ng ml−1 respectively and morphine clearance was found to be 4.6±3.2 ml min−1 kg−1. 3M3G formation clearance was estimated to be 2.5±1.8 ml min−1 kg−1, and the formation clearance of M6G was estimated to be 0.46±0.32 ml min−1 kg−1. 4M3G metabolite clearance was 0.46±0.60 ml min−1 kg−1, the elimination half-life was 11.1±11.3 h and the volume of distribution was 0.55±1.13 l kg−1. M6G metabolite clearance was 0.71±0.36 ml min−1 kg−1, the elimination half-life was 18.2±13.6 h and the volume of distribution was 1.03±0.88 l kg−1. 5No significant effect of the loading dose (50 μg kg−1 or 200 μg kg−1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  10. Effects of cold pressor pain on the abuse liability of intranasal oxycodone in male and female prescription opioid abusers

    PubMed Central

    Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.

    2012-01-01

    Background Approximately 1.9 million persons in the U.S. have prescription opioid use disorders often with concomitant bodily pain, but systematic data on the impact of pain on abuse liability of opioids is lacking. The purpose of this study was to determine whether pain alters the intranasal abuse liability of oxycodone, a commonly prescribed and abused analgesic, in males and females. Methods Sporadic prescription opioid abusers (10 females, 10 males) participated in this mixed (between and within-subject), randomized inpatient study. Experimental sessions (n=6) tested intranasal placebo, oxycodone 15 or 30 mg/70 kg during cold pressor testing (CPT) and a warm water control. Observer- and subject-rated drug effect measures, analgesia, physiologic and cognitive effects were assessed. Results The CPT significantly increased blood pressure, heart rate, pain, stress, and “opiate desire” compared to the no-pain control but did not alter opioid liking, high or street value. Intranasal oxycodone produced effects within 10 minutes, significantly decreasing pain and significantly increasing subjective measures of abuse liability (e.g., high). Females had higher ratings of street value, high, and liking for one or both active doses. Conclusions The CPT was a reliably painful and stressful stimulus that did not diminish the abuse liability of intranasal Oxycodone®. Females were more sensitive to oxycodone on several abuse liability measures that warrant further follow-up. Snorting oxycodone rapidly produced psychoactive effects indicative of substantial abuse liability. PMID:22209386

  11. A systematic review of the cardiotoxicity of methadone

    PubMed Central

    Alinejad, Samira; Kazemi, Toba; Zamani, Nasim; Hoffman, Robert S.; Mehrpour, Omid

    2015-01-01

    Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. Methods: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users. PMID:26869865

  12. Methadone dosing, heroin affordability, and the severity of addiction.

    PubMed Central

    Bach, P B; Lantos, J

    1999-01-01

    OBJECTIVES: This study sought to track changes in US heroin prices from 1988 to 1995 and to determine whether changes in the affordability of heroin were associated with changes in the use of heroin by users seeking methadone treatment, as indexed by methadone dose levels. METHODS: Data on the price of heroin were from the Drug Enforcement Administration; data on methadone doses were from surveys conducted in 1988, 1990, and 1995 of 100 methadone maintenance centers. Multivariable models that controlled for time and city effects were used to ascertain whether clinics in cities where heroin was less expensive had patients receiving higher doses of methadone, which would suggest that these patients had relatively higher physiological levels of opiate addiction owing to increased heroin use. RESULTS: The amount of pure heroin contained in a $100 (US) purchase has increased on average 3-fold between 1988 and 1995. The average dose of methadone in clinics was positively associated with the affordability of local heroin (P < .01). CONCLUSIONS: When heroin prices fall, heroin addicts require more methadone (a heroin substitute) to stabilize their addiction--evidence that they are consuming more heroin. PMID:10224975

  13. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    PubMed

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps. PMID:25935159

  14. Psychopathology and Urine Toxicology in Methadone Patients

    PubMed Central

    Sadek, Gamal; Cernovsky, Zack; Chiu, Simon

    2015-01-01

    Several studies reported high rates of psychiatric commorbidity among methadone patients. We examined the relationships of measures of psychopathology to outcomes of screening urine tests for cocaine, opiates, and benzodiazepines in a sample of 56 methadone patients. They also completed the Symptom Check List-90-Revised (SCL-90-R). The highest scales in the SCL-90-R profile of our patients were those indicating somatic discomfort, anger, phobic anxiety, paranoid ideation, and also obsessive-compulsive disorder symptoms (scores above the 39th percentile). The only significant correlations between urine tests and SCL-90-R psychopathology were those involving benzodiazepines: patients with urine tests positive for benzodiazepines had lower social self-confidence (r=0.48), were more obsessive-compulsive (r=0.44), reported a higher level of anger (r=0.41), of phobic tendencies (r=40), of anxiety (r=0.39), and of paranoid tendencies (r=0.38), and also reported more frequent psychotic symptoms (r=0.43). PMID:26266026

  15. Combined administration of oxycodone/naloxone in chronic osteo-articular diseases pain therapy.

    PubMed

    Rosa, Palomba; Federica, Miralto; Annamaria, Vinciguerra; Fabiana, Salvato; Anna, Vaccarella

    2014-04-01

    The aim of this study is the analysis of the beneficial impact of using opioid receptor antagonist associated to opioid analgesic on the quality of life in patients suffering from chronic non-cancer pain. We recruited 60 patients suffering from osteo-articular diseases who were randomized into two groups of treatment. The group A was treated with the association of opioid receptor antagonist and opioid agonist, represented by Oxycodone. The group B was treated with the opioid analgesics Oxycodone, transdermal Fentanil, and Hidromorphone, without the opioid antagonist. The end-points assessed were the duration of titration, the average reached dosage, the duration of the stability of dosage and the opioid-induced constipation (OIC) using the BFI. PMID:24809034

  16. 78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ...The Food and Drug Administration (FDA) has determined that OXYCONTIN (oxycodone hydrochloride) extended-release tablets (10 milligrams (mg), 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, and 160 mg) approved under new drug application (NDA) 20-553 were withdrawn from sale for reasons of safety or effectiveness. The Agency will not accept or approve abbreviated new drug applications (ANDAs) for......

  17. Social influences on morphine sensitization in adolescent females.

    PubMed

    Hofford, Rebecca S; Roberts, Kris W; Wellman, Paul J; Eitan, Shoshana

    2010-08-01

    We recently observed that social interactions influence morphine responsiveness in adolescent males. Given sex-related differences in both social interactions and responses to morphine, the present study examines social influences on morphine sensitization in adolescent female mice. Four experimental groups were examined: (1) morphine-treated mice (twice daily, 10-40 mg/kg, s.c.) housed physically and visually separated from saline-treated mice ('morphine only'), (2) morphine-treated mice housed together with saline-treated mice ('morphine cage-mates (of saline)'), (3) saline-treated mice housed together with morphine-treated mice ('saline cage-mates (of morphine)'), and (4) saline-treated mice housed physically and visually separated from morphine-treated mice ('saline only'). Following the treatment period, mice were tested individually for their locomotor response to 20 mg/kg morphine (s.c.). There were no significant differences in morphine-induced hyper-locomotion between saline only and saline cage-mates (of morphine) female adolescent mice. Notably, morphine only mice exhibited significantly greater morphine sensitization as compared to morphine cage-mates (of saline). Thus, this study demonstrates social influences on morphine sensitization in adolescent females. Drug use during early adolescence is a key predictor of later drug abuse and dependence during adulthood. Thus, understanding the specific vulnerabilities to drug use in this age group may represent a first step in helping develop more effective treatment programs. PMID:20456874

  18. Absorption of morphine from a slow-release emulsion used to induce morphine dependence in rats.

    PubMed

    Salem, A; Hope, W

    1998-10-01

    This study was performed to measure absorption of morphine from the injection site following treatment of rats with slow-release emulsions formulated with morphine hydrochloride and morphine base. Samples of emulsion were collected from the injection site of halothane anesthetized animals at 24 and 48 h following emulsion treatment and concentrations of morphine remaining in the emulsion were analyzed using high-performance liquid chromatography (HPLC). In another group of morphine-treated rats, at times equivalent to collecting samples of emulsion, the intensity of naloxone-precipitated withdrawal behaviors was monitored. Both morphine base- and hydrochloride-containing emulsions induced a high degree of physical dependence in animals treated over 48 h. Release of morphine from emulsions containing morphine base was slower than that from the hydrochloride formulations. In the 24-h morphine base-treated animals, approximately 45% was absorbed from the injection site as opposed to 99% in the 24-h morphine hydrochloride-treated animals. These results suggest that morphine base containing emulsions provide a more sustained exposure to the opioid. PMID:10334632

  19. Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor

    PubMed Central

    Wang, Na; Wang, Yuantao; Pang, Lei; Wang, Jinguo

    2015-01-01

    Objective: To evaluate the efficacy of preemptive intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Methods: Sixty ASA I or II patients undergoing elective laparoscopic resection of ovarian tumor were randomly allocated to one of two groups: Group O (n=30) received intravenous oxycodone (0.1 mg·kg-1) 10 minutes before surgery over 2 minutes, and Group N (n=30) received an equivalent volume of normal saline. All patients received a standardized general anesthesia. MBP and HR at the time of arrival of the operating room (T1), 5 min before pneumoperitoneum (T2), 5 minutes (T3), 10 minutes (T4), and 15 minutes after pneumoperitoneum (T5), and VAS scores at postoperative 2, 4, 8, 12 and 24 hour were recorded. The tramadol consumption and side effects in 24 h after surgery were recorded. Results: VAS pain scores at 2, 4, 8 and 12 hour after operation were significantly lower in Group O (P<0.05). MBP and HR increased significantly due to pneumoperitoneum at T3, T4 and T5, compared with T1 and T2 within Group N, and were higher at T3, T4 and T5 in Group N than at the same time points in Group O. Tramadol consumption was statistically lower in Group O (P=0.0003). Conclusions: Preemptive intravenous oxycodone was an efficient and safe method to reduce intraoperative haemodynamic effect and postoperative pain. PMID:26101479

  20. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  1. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    PubMed Central

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  2. Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: A placebo-controlled, randomized study

    PubMed Central

    Cloutier, C; Taliano, J; O’Mahony, W; Csanadi, M; Cohen, G; Sutton, I; Sinclair, D; Awde, M; Henein, S; Robinson, L; Eisenhoffer, J; Piraino, PS; Harsanyi, Z; Michalko, KJ

    2013-01-01

    BACKGROUND For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD) pain scores measured on a visual analogue scale (48.6±23.1 mm versus 55.9±25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1±0.8 versus 2.4±0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity. PMID:23662289

  3. Use of intramuscular methadone in managing intravenous drug abuse.

    PubMed

    Bezant, Edward Michael

    2014-01-01

    A 30-year-old woman was referred to the Acute Pain Team for their advice on how to manage her current pain, in light of her unique pre-admission medications. On questioning it was discovered that the patient was receiving 50 mg of intramuscular methadone daily, in the community. She was a former intravenous drug user who had been enrolled into a methadone substitution programme for 10 years and had been receiving her methadone intramuscularly for the past 6 years. It had been discovered that her addiction was not solely to opioids but, moreover, to the process of injecting as well. She was diagnosed with obsessive compulsive disorder, with a needle fixation, and started on the intramuscular methadone regimen on which she has maintained abstinence from heroin for 6 years. PMID:25414219

  4. Cocaine abuse sharply reduced in an effective methadone maintenance program.

    PubMed

    Borg, L; Broe, D M; Ho, A; Kreek, M J

    1999-01-01

    A comprehensive study of an urban methadone clinic with supervised urine analyses for illicit drugs was conducted over an 18 month period for a 133 patient cohort as they entered or remained in methadone maintenance for narcotic addiction. Overall retention during the study was 85%, with significantly (p < .05) higher daily methadone doses (mean 67.1 mg +/- 2.1) in those patients still in treatment at the end of the study. Predictably, illicit opioid use was dramatically reduced, to 10% as measured by urine toxicology in the last month of treatment. Moreover, significantly more patients stopped regular cocaine abuse (69%) than started using cocaine (10%, Fisher's exact test, p = .02). Thus, with effective methadone maintenance using adequate dosages, the majority of patients remain in treatment and reduce cocaine abuse as well as illicit opioid use, with implications for public health by reducing the spread of infectious diseases including hepatitis B, C, D and human immunodeficiency virus (HIV-1). PMID:10631964

  5. Are empty methadone bottles empty? An analytic study

    PubMed Central

    2014-01-01

    Background Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. In naïve users or in case of recreational misuse, methadone can be a source of potentially lethal intoxications, resulting in fatal overdoses. A few cases of infantile intoxications have been described in the literature, some of which resulted in death. Nowadays, more than 50,000 bottles are used every day in France, most of which are thrown away in the bin. Relatives at home, especially children, can have access to these empty bottles. This study aims to determine whether the residual quantity of methadone in the bottles is associated with a risk of intoxication for someone who has a low tolerance to opiates, such as a child. Methods The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013. Results The mean residual quantity of methadone left in each bottle after use is 1.9 ± 1.8 mg and 3.3 ± 2.4 mg in the sample of 60 mg bottles. Conclusions There is a potential danger of accidental overdose with empty bottles of methadone syrup, especially for children. To take into account this hazard, several harm reduction strategies can be proposed, such as favouring the taking of the treatment within the delivery centres rather than the ‘take home’ doses, asking methadone users to bring back their used bottles, and raising patients’ awareness of the intoxication risks and the necessary everyday precautions. For stable patients with take home methadone, the use of capsules could be considered. PMID:24990630

  6. THE ACTION OF MORPHINE-LIKE DRUGS ON IMPULSE TRANSMISSION IN MAMMALIAN NERVE FIBRES.

    PubMed

    KOSTERLITZ, H W; WALLIS, D I

    1964-06-01

    Experiments on nerves in situ and on isolated nerves provide no evidence that morphine interferes with impulse transmission in myelinated or nonmyelinated nerve fibres. The concentrations used in experiments on isolated nerves were 10- to 100-times as high as those required to depress transmission at autonomic nerve-effector cell junctions. Examination of the resting membrane potential, the action potential and the positive after-potential, the conduction velocity, the time courses of the recovery of the size of the action potential and of the excitability after a conditioning stimulus, the ability of the axons to sustain repetitive activity and the posttetanic hyperpolarization gave no indication that morphine affects either the mechanisms involved in the initiation of the propagated impulse or those leading to restoration of the resting state after activity. Analgesic drugs, such as pethidine and methadone which have a local anaesthetic action, may cause a reversible decrease in the size of the compound action potential and in the conduction velocity of A-B and C fibres. PMID:14211680

  7. Delay of Morphine Tolerance by Palmitoylethanolamide

    PubMed Central

    Di Cesare Mannelli, Lorenzo; Corti, Francesca; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

    2015-01-01

    In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30 mg kg−1 PEA was subcutaneously daily administered in morphine treated rats (10 mg kg−1 intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-α levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-α immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested. PMID:25874232

  8. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy

    PubMed Central

    Graziani, Manuela; Nisticò, Robert

    2015-01-01

    Gender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain. Method: We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics (PK) and pharmacodynamics (PD) of methadone. Results: None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles and Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT-related cardiac arrhythmias in methadone maintenance subjects. Conclusion: Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women. PMID:26106330

  9. Medication-assisted treatment for opioid addiction: methadone and buprenorphine.

    PubMed

    Saxon, Andrew J; Hser, Yih-Ing; Woody, George; Ling, Walter

    2013-12-01

    Among agents for treatment of opioid addiction, methadone is a full mu-opioid receptor agonist, whereas buprenorphine is a partial agonist. Both are long-acting. Buprenorphine has a superior safety profile. Methadone is formulated for oral administration and buprenorphine for sublingual administration. A subdermal buprenorphine implant with a 6-month duration of action is being considered for approval by the U.S. Food and Drug Administration. Both medications reduce mortality rates and improve other outcomes. Data from a recent randomized controlled comparison of both medications (N = 1269) show better treatment retention with methadone but reduced illicit opioid use early in treatment with buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study completers. In the 30 days prior to treatment entry, 14.4% of the completers randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers randomized to methadone treatment (n = 391) shared needles. The percent sharing needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of the completers randomized to buprenorphine and 8.2% of the completers randomized to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively, reporting multiple partners at Week 24 (p < 0.04). PMID:24436573

  10. Predictors of engagement in vocational counseling for methadone treatment patients.

    PubMed

    Kang, Sung-Yeon; Magura, Stephen; Blankertz, Laura; Madison, Elizabeth; Spinelli, Michael

    2006-01-01

    Employment enhances the outcomes of substance dependency treatment. Unfortunately, although unemployed methadone treatment patients frequently state they are interested in a job, many fail to participate in vocational services when available. Unless patients become engaged, vocational services do not have an opportunity to be effective. This is the first study to explore a broad array of factors that may be associated with differential engagement in vocational services among methadone patients. The study was conducted in two methadone programs in New York City during 2001-2004. Unemployed methadone patients (n = 211) were voluntarily randomly assigned to either of two vocational counseling programs (standard vs. experimental) and followed for 6 months. The sample was 59% male, 75% minority group, aged 45 years on average, and in methadone treatment for 5 years on average. Being engaged in the vocational counseling programs was defined as five or more sessions with the counselor in the first 6 months after study entry. In multivariate analysis, the factors associated with higher engagement in vocational counseling were being non-Hispanic, having more education, a drug injection history, a crack use history, having chronic emotional/mental problems, better work attitudes, and assignment to the experimental vocational program. The results indicate that it is often the most "needy" unemployed methadone patients who become more engaged in vocational counseling. A vocational counseling model which emphasizes assertive outreach and attends to nonvocational clinical issues as well is more likely to engage patients. PMID:16798680

  11. Intrathecal morphine for post-thoracotomy pain.

    PubMed

    Gray, J R; Fromme, G A; Nauss, L A; Wang, J K; Ilstrup, D M

    1986-08-01

    We wished to investigate possible differences in the duration of postoperative analgesia and the incidence of respiratory depression after the intrathecal injection in the lumbar area of 10 micrograms/kg morphine in hypobaric and hyperbaric solution for relief of post-thoracotomy pain. Twenty-nine patients received morphine plus dextrose (hyperbaric) and 21 received morphine in preservative-free normal saline. The duration of analgesia was longer with the morphine in the normal saline group than in the hyperbaric group (P less than 0.04). One patient developed delayed respiratory depression. Our data support the use of morphine in normal saline mixtures for greater duration of analgesia after thoracic operations. PMID:3755305

  12. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  13. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  14. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  15. Slow drug delivery decreased total body clearance and altered bioavailability of immediate- and controlled-release oxycodone formulations.

    PubMed

    Li, Yan; Sun, Duxin; Palmisano, Maria; Zhou, Simon

    2016-02-01

    Oxycodone is a commonly used analgesic with a large body of pharmacokinetic data from various immediate-release or controlled-release formulations, under different administration routes, and in diverse populations. Longer terminal half-lives from extravascular administration as compared to IV administration have been attributed to flip-flop pharmacokinetics with the rate constant of absorption slower than elimination. However, PK parameters from the extravascular studies showed faster absorption than elimination. Sustained release formulations guided by the flip-flop concept produced mixed outcomes in formulation development and clinical studies. This research aims to develop a mechanistic knowledge of oxycodone ADME, and provide a consistent interpretation of diverging results and insight to guide further extended release development and optimize the clinical use of oxycodone. PK data of oxycodone in human studies were collected from literature and digitized. The PK data were analyzed using a new PK model with Weibull function to describe time-varying drug releases/ oral absorption, and elimination dependent upon drug input to the portal vein. The new and traditional PK models were coded in NONMEM. Sensitivity analyses were conducted to address the relationship between rates of drug release/absorption and PK profiles plus terminal half-lives. Traditional PK model could not be applied consistently to describe drug absorption and elimination of oxycodone. Errors were forced on absorption, elimination, or both parameters when IV and PO profiles were fitted separately. The new mechanistic PK model with Weibull function on absorption and slower total body clearance caused by slower absorption adequately describes the complex interplay between oxycodone absorption and elimination in vivo. Terminal phase of oxycodone PK profile was shown to reflect slower total body drug clearance due to slower drug release/absorption from oral formulations. Mechanistic PK models with

  16. Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure.

    PubMed

    Smith, Maree T; Wyse, Bruce D; Edwards, Stephen R; El-Tamimy, Mahmoud; Gaetano, Giacinto; Gavin, Paul

    2015-07-01

    This study was designed to assess the analgesic efficacy and systemic exposure of oxycodone administered topically in a novel tocopheryl phosphate mixture (TPM) gel formulation, to the inflamed hindpaws in a rat model of inflammatory pain. Unilateral hindpaw inflammation was induced in male Sprague-Dawley rats by intraplantar (i.pl.) injection of Freund's complete adjuvant (FCA). Mechanical hyperalgesia and hindpaw inflammation were assessed by measuring paw pressure thresholds and hindpaw volume, respectively, just prior to i.pl. FCA and again 5-6 days later. The analgesic effects of oxycodone administered topically (1 mg in TPM gel) or by i.pl. injection (50 μg), were assessed. Systemic oxycodone exposure was assessed over an 8-h postdosing interval following topical application. Skin permeation of oxycodone from the gel formulation was assessed in vitro using Franz diffusion cells. Oxycodone administered topically or by i.pl. injection produced significant (p < 0.05) analgesia in the inflamed hindpaws. Systemic oxycodone exposure was insignificant after topical dosing. The in vitro cumulative skin permeation of oxycodone was linearly related to the amount applied. Topical TPM/oxycodone gel formulations have the potential to alleviate moderate to severe inflammatory pain conditions with minimal systemic exposure, thereby avoiding central nervous system (CNS)-mediated adverse effects associated with oral administration of opioid analgesics. PMID:25995048

  17. Controlled release formulation of oxycodone in patients with moderate to severe chronic osteoarthritis: a critical review of the literature

    PubMed Central

    Taylor, Robert; Raffa, Robert B; Pergolizzi, Joseph V

    2012-01-01

    Osteoarthritis (OA) is a physically and emotionally debilitating disease that predominantly affects the aging adult population. Current pharmacologic treatment options primarily consist of nonsteroidal anti-inflammatory drugs and/or acetaminophen, but associated side effects, analgesic limitations, especially in the elderly, and the need for around-the-clock analgesia have led physicians to search for alternative analgesics. Opioids have shown effectiveness at mitigating both chronic cancer and noncancer pain, and their ability to be placed into controlled release (CR) formulations suggests that they may prove efficacious for OA patients. One formulation, oxycodone CR, has shown effectiveness in cancer pain patients and in some trials of noncancer low back pain. In this review, the objective was to synthesize the reported findings by researchers in this field and present an up-to-date look at the efficacy, safety, and tolerability of oxycodone CR in OA patients. Public literature databases were searched using specific keywords (eg, oxycodone CR) for studies assessing the efficacy and safety profile of oxycodone CR and its use in patients with OA. A total of eleven articles that matched the criteria were identified, which included three placebo-controlled trials, six comparative trials, one pharmacokinetic study in the elderly, and one long-term safety trial. Analysis of the studies revealed that oxycodone CR is reasonably efficacious, safe, and tolerable when used to manage moderate to severe chronic OA pain, with similar side effects to that of other opioids. PMID:22570559

  18. The combination of mitragynine and morphine prevents the development of morphine tolerance in mice.

    PubMed

    Fakurazi, Sharida; Rahman, Shamima Abdul; Hidayat, Mohamad Taufik; Ithnin, Hairuszah; Moklas, Mohamad Aris Mohd; Arulselvan, Palanisamy

    2013-01-01

    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine. PMID:23292329

  19. Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study

    PubMed Central

    Klepstad, Pål; Hilton, Priscilla; Moen, Jorunn; Kaasa, Stein; Borchgrevink, Petter C; Zahlsen, Kolbjørn; Dale, Ola

    2004-01-01

    Background The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. Methods We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) ×100). Results The patients' median morphine doses were 90 (range; 20–1460) mg/24 h and 135 (range; 30–440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). Conclusion These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine. PMID:15461818

  20. The nature of methadone diversion in England: a Merseyside case study

    PubMed Central

    2012-01-01

    Background Methadone maintenance treatment (MMT) is a key element in treatment for opiate addiction; however concerns about the diversion of methadone remain. More current empirical data on methadone diversion are required. This research investigated the market for diverted methadone in Merseyside, UK, in order to provide a case study which can be transferred to other areas undertaking methadone maintenance treatment on a large scale. Methods Questionnaires were completed (in interview format) with 886 past year users of methadone recruited both in and out of prescribing agencies. Topic areas covered included current prescribing, obtaining and providing methadone, reasons for using illicit methadone and other drug use. Results Large proportions of participants had obtained illicit methadone for use in the past year with smaller proportions doing so in the past month. Proportions of participants buying and being given methadone were similar. Exchange of methadone primarily took place between friends and associates, with 'dealers' rarely involved. Gender, age, whether participant's methadone consumption was supervised and whether the aims of their treatment had been explained to them fully, influenced the extent to which participants were involved in diverting or using diverted methadone. Conclusion Methadone diversion is widespread although drug users generally do not make use of illicit methadone regularly (every month). The degree of altruism involved in the exchange of methadone does not negate the potential role of this action in overdose or the possibility of criminal justice action against individuals. Treatment agencies need to emphasise these risks whilst ensuring that treatment aims are effectively shared with clients to ensure adherence to treatment. PMID:22243982

  1. Morphine-theophylline interaction: antagonism or facilitation?

    PubMed Central

    Brailowsky, S.; Guerrero-Muñoz, F.; Luján, M.; Shkurovich, M.

    1981-01-01

    1 Morphine-theophylline interactions were investigated in both acute and narcotic-dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone-induced contractions in the electrically-stimulated and opiate-dependent isolated ileum of the guinea-pig; naloxone-induced jumps in the mouse; an calcium uptake in synaptosomal preparations. 2 The LD50 of morphine was significantly increased by theophylline. 3 The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone. 4 Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically-stimulated isolated ileum of the guinea-pig. 5 The number of jumps induced by naloxone in morphine-dependent mice was significantly diminished by theophylline. 6 The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline. 7 The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed. PMID:7272590

  2. Effect of morphine on synaptosomal Ca++ uptake.

    PubMed

    Guerrero-Munoz, F; Cerreta, K V; Guerrero, M L; Way, E L

    1979-04-01

    The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence. PMID:571016

  3. Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)

    SciTech Connect

    Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

    1982-05-01

    The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

  4. Abuse-related effects of µ-opioid analgesics in an assay of intracranial self-stimulation in rats: modulation by chronic morphine exposure.

    PubMed

    Altarifi, Ahmad A; Rice, Kenner C; Negus, S Stevens

    2013-09-01

    Intracranial self-stimulation (ICSS) is an operant procedure in which responding is maintained by electrical brain stimulation. Stimulation frequency can be varied rapidly to maintain a wide range of baseline response rates, and drugs' effects can be evaluated simultaneously on both low ICSS rates maintained by low stimulation frequencies and high ICSS rates maintained by high stimulation frequencies. ICSS 'facilitation' indicates drug-induced increases in low ICSS rates and is often considered an abuse-related effect, whereas ICSS 'depression' indicates decreases in high ICSS rates and may indicate abuse-limiting effects. This study examined the roles of µ-agonist efficacy and of previous µ-agonist exposure as determinants of µ-agonist effects on ICSS in rats with electrodes implanted into the medial forebrain bundle. The high-efficacy, intermediate-efficacy, and low-efficacy µ agonists methadone, fentanyl, and nalbuphine were tested during escalating regimens of morphine exposure (vehicle, 3.2, and 18 mg/kg/day). During vehicle treatment, methadone and fentanyl primarily depressed ICSS, whereas nalbuphine produced weak facilitation that was not dose dependent. Chronic morphine produced tolerance to ICSS depression and increased expression of ICSS facilitation. These results suggest that µ-agonist exposure increases the expression of abuse-related ICSS facilitation by µ agonists with a broad range of efficacies at µ receptors. PMID:23881045

  5. Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report

    ERIC Educational Resources Information Center

    Stotts, Angela L.; Masuda, Akihiko; Wilson, Kelly

    2009-01-01

    Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from an MM client who voluntarily participated in an Acceptance and…

  6. Methadone Maintenance: The Experience of Four Programs. The Drug Abuse Council Manuscript Series, No. 1.

    ERIC Educational Resources Information Center

    Danaceau, Paul

    Methadone maintenance is a relatively new method for treating heroin addiction. Controversy and questions remain about the drug itself and its use of methadone. The author was engaged by The Drug Abuse Council to prepare these descriptions of four methadone programs and the accompanying summary. The evolution of these programs is examined, and the…

  7. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    PubMed

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats. PMID:26397757

  8. Retention in methadone and buprenorphine treatment among African Americans

    PubMed Central

    Gryczynski, Jan; Mitchell, Shannon Gwin; Jaffe, Jerome H.; Kelly, Sharon M.; Myers, C. Patrick; O’Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

    2013-01-01

    Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. public sector treatment, but availability of buprenorphine as an alternative medication continues to increase. Drawing data from two community-based clinical trials that were conducted nearly contemporaneously, this study examined retention in methadone vs. buprenorphine treatment over 6 months among urban African Americans receiving treatment in one of four publicly-funded programs (N= 478; 178 methadone; 300 buprenorphine). Adjusting for confounds related to medication selection, survival analysis revealed that buprenorphine patients are at substantially higher risk of dropout compared to methadone patients (HR= 2.43; p< .001). Buprenorphine’s retention disadvantage appears to be concentrated in the earlier phases of treatment (approximately the first 50 days), after which risk of subsequent dropout becomes similar for the two medications. These findings confirm a retention disparity between methadone and buprenorphine in this population, and suggest potential avenues for future research to enhance retention in buprenorphine treatment. PMID:23566446

  9. Priapism Followed by Discontinuation of Methadone: A rare Case Report

    PubMed Central

    Mostafavi, Seyed-Ali; Bidaki, Reza

    2015-01-01

    Objective: Priapism is defined by persistent, painful penile erection which occurs without sexual stimulation. Methadone is used as an analgesic and is also used in detoxification and maintenance protocol for opioid dependence treatment. Here we will report a case of a male with priapism after rapid discontinuation doses of methadone. Case presentation: The case was a young married male who referred to a psychiatry clinic due to long-time spontaneous erections. The patient had no history of mental disorders, trauma or sickle cell anemia. He used to smoke opium for five years and used methadone for four years at a dose of 17 cc daily, which he abruptly discontinued. Then he often experienced spontaneous and painful erections without physical or mental stimulation that caused him shame and embarrassment. Conclusion: In this case, chronology indicates that rapid discontinuation of methadone was possibly responsible for the occurrence of priapism. This may have happened due to a compensatory reaction to methadone side effect of erectile dysfunction, followed by its rapid withdrawal. PMID:26884791

  10. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation. PMID:25660662

  11. A randomized trial of an interim methadone maintenance clinic.

    PubMed Central

    Yancovitz, S R; Des Jarlais, D C; Peyser, N P; Drew, E; Friedmann, P; Trigg, H L; Robinson, J W

    1991-01-01

    BACKGROUND. Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs. METHODS. A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group. RESULTS. There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%). CONCLUSIONS. Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment. PMID:1659236

  12. Intractable restless legs syndrome: role of prolonged-release oxycodone-naloxone.

    PubMed

    de Biase, Stefano; Valente, Mariarosaria; Gigli, Gian Luigi

    2016-01-01

    Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs accompanied by uncomfortable sensations that occur at night or at time of rest. Pharmacological therapy should be limited to patients who suffer from clinically relevant symptoms. Chronic RLS is usually treated with either a dopamine agonist (pramipexole, ropinirole, rotigotine) or an α2δ calcium-channel ligand (gabapentin, gabapentin enacarbil, pregabalin). Augmentation is the main complication of long-term dopaminergic treatment, and frequently requires a reduction of current dopaminergic dose or a switch to non-dopaminergic medications. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a recent Phase III trial, oxycodone-naloxone prolonged release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatments. The adverse-event profile was consistent with the safety profile of opioids. The most frequent adverse events were fatigue, constipation, nausea, headache, hyperhidrosis, somnolence, dry mouth, and pruritus. Adverse events were usually mild or moderate in intensity. No cases of augmentation were reported. Oxycodone-naloxone PR is approved for the second-line symptomatic treatment of adults with severe to very severe idiopathic RLS after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone-naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α2δ ligands are needed. PMID:26966363

  13. The analgesic efficacy of etoricoxib compared with oxycodone/acetaminophen in an acute postoperative pain model: a randomized, double-blind clinical trial.

    PubMed

    Chang, David J; Desjardins, Paul J; King, Thomas R; Erb, Tara; Geba, Gregory P

    2004-09-01

    Our objective in this study was to compare the analgesic effects of etoricoxib and oxycodone/acetaminophen in a postoperative dental pain model. Patients experiencing moderate to severe pain after extraction of two or more third molars were randomized to single doses of etoricoxib 120 mg (n = 100), oxycodone/acetaminophen 10/650 mg (n = 100), or placebo (n = 25). The primary end-point was total pain relief over 6 h. Other end-points included patient global assessment of response to therapy; onset, peak, and duration of effect; and rescue opioid analgesic use. Active treatments were statistically significantly superior to placebo for all efficacy measures. Total pain relief over 6 h for etoricoxib was significantly more than for oxycodone/acetaminophen (P < 0.001). Patient global assessment of response to therapy at 6 and 24 h was superior for etoricoxib. Both drugs achieved rapid onset, although the time was faster for oxycodone/acetaminophen by 5 min. The peak effect was similar for both drugs. Compared with oxycodone/acetaminophen patients, etoricoxib patients experienced a longer analgesic duration, had a smaller percentage requiring rescue opioids during 6 and 24 h, and required less rescue analgesia during 6 and 24 h. Oxycodone/acetaminophen treatment resulted in more frequent adverse events (AEs), drug-related AEs, nausea, and vomiting compared with etoricoxib treatment. In conclusion, etoricoxib 120 mg provided superior overall efficacy compared with oxycodone/acetaminophen 10/650 mg and was associated with significantly fewer AEs. PMID:15333415

  14. Morphine is an arteriolar vasodilator in man

    PubMed Central

    Afshari, Reza; Maxwell, Simon R J; Webb, David J; Bateman, D Nicholas

    2009-01-01

    AIM The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra-arterial morphine in healthy subjects. METHODS Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine-1 and histamine-2 receptor blockade or during a nitric oxide clamp. RESULTS Morphine caused an increase in FBF at doses of 30 µg min−1[3.25 (0.26) ml min−1 100 ml−1][mean (SEM)] doubling at 100 µg min−1 to 5.23 (0.53) ml min−1 100 ml−1. Acute tolerance was not seen to 50 µg min−1 morphine, with increased FBF [3.96 (0.35) ml min−1 100 ml−1] (P = 0.003), throughout the 30-min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P < 0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min−1 100 ml−1 after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min−1 100 ml−1. CONCLUSIONS Intra-arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine-modulated nitric oxide release. Opioid receptor mechanisms need further exploration. PMID:19371311

  15. Coexisting addiction and pain in people receiving methadone for addiction.

    PubMed

    St Marie, Barbara

    2014-04-01

    The aim of this qualitative study was to examine the narratives of people who experience chronic pain (lasting 6 months or more) and were receiving methadone for the treatment of their opiate addiction through a major methadone clinic. This paper featured the pathway of how the participants developed chronic pain and addiction, and their beliefs of how prescription opioids would impact their addiction in the future. Thirty-four participants who experienced chronic pain and received methadone for treatment of opiate addiction were willing to tell the story of their experiences. The findings in three areas are presented: (a) whether participants experienced addiction first or pain first and how their exposures to addictive substances influenced their experiences, (b) the significance of recreational drug use and patterns of abuse behaviors leading to chronic pain, and (c) participants' experiences and beliefs about the potential for abuse of prescription opioid used for treatment of pain. PMID:23858068

  16. Assessment of Cognitive Functions in Methadone Maintenance Patients

    PubMed Central

    Mazhari, Shahrzad; Keshvari, Zeinab; Sabahi, Abdolreza; Mottaghian, Shirin

    2015-01-01

    Background Methadone maintenance has received little scientific attention regarding neurocognitive effects. This study is aimed to assess the neuropsychological performance of methadone maintenance patients (MMP) compared to those healthy controls. Methods Thirty-five MMP and 35 healthy controls, matched for age, gender, education and employment status, examined on a battery of tests aimed at assessing verbal fluency, executive functions, verbal memory, and working memory, using controlled oral word association test (COWAT), trial making test (TMT) Part A and B, Rey auditory verbal learning test (RAVLT), and backward digit span. Findings MMP performed significantly poorly than controls in cognitive domains of verbal fluency, executive function, and verbal memory. MMP did not exhibit impairment in working memory, and TMT Part A compared to controls. Conclusion These results suggest that methadone consumption induces significant cognitive impairment that could compromise drug-treatment outcomes in MMP. PMID:26885347

  17. Coexisting Addiction and Pain in People Receiving Methadone for Addiction

    PubMed Central

    St. Marie, Barbara

    2014-01-01

    The aim of this qualitative study was to examine the narratives of people who experience chronic pain (lasting 6 months or more) and were receiving methadone for the treatment of their opiate addiction through a major methadone clinic. This paper featured the pathway of how the participants developed chronic pain and addiction, and their beliefs of how prescription opioids would impact their addiction in the future. Thirty-four participants who experienced chronic pain and received methadone for treatment of opiate addiction were willing to tell the story of their experiences. The findings in three areas are presented: (a) whether participants experienced addiction first or pain first and how their exposures to addictive substances influenced their experiences, (b) the significance of recreational drug use and patterns of abuse behaviors leading to chronic pain, and (c) participants’ experiences and beliefs about the potential for abuse of prescription opioid used for treatment of pain. PMID:23858068

  18. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry

    PubMed Central

    Concheiro, Marta; Shakleya, Diaa M.

    2013-01-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2–107.7%, extraction efficiency 35.3– 160.9%, and process efficiency 25.5–91.7%. Ion suppression was detected for EME (−63.3%) and EDDP (−60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  19. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry.

    PubMed

    Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A

    2011-04-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2-107.7%, extraction efficiency 35.3-160.9%, and process efficiency 25.5-91.7%. Ion suppression was detected for EME (-63.3%) and EDDP (-60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  20. Using Poison Center Exposure Calls to Predict Methadone Poisoning Deaths

    PubMed Central

    Dasgupta, Nabarun; Davis, Jonathan; Jonsson Funk, Michele; Dart, Richard

    2012-01-01

    Purpose There are more drug overdose deaths in the Untied States than motor vehicle fatalities. Yet the US vital statistics reporting system is of limited value because the data are delayed by four years. Poison centers report data within an hour of the event, but previous studies suggested a small proportion of poisoning deaths are reported to poison centers (PC). In an era of improved electronic surveillance capabilities, exposure calls to PCs may be an alternate indicator of trends in overdose mortality. Methods We used PC call counts for methadone that were reported to the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System in 2006 and 2007. US death certificate data were used to identify deaths due to methadone. Linear regression was used to quantify the relationship of deaths and poison center calls. Results Compared to decedents, poison center callers tended to be younger, more often female, at home and less likely to require medical attention. A strong association was found with PC calls and methadone mortality (b = 0.88, se = 0.42, t = 9.5, df = 1, p<0.0001, R2 = 0.77). These findings were robust to large changes in a sensitivity analysis assessing the impact of underreporting of methadone overdose deaths. Conclusions Our results suggest that calls to poison centers for methadone are correlated with poisoning mortality as identified on death certificates. Calls received by poison centers may be used for timely surveillance of mortality due to methadone. In the midst of the prescription opioid overdose epidemic, electronic surveillance tools that report in real-time are powerful public health tools. PMID:22829925

  1. Methadone: six effects in search of a substance.

    PubMed

    Gomart, Emilie

    2002-02-01

    What is the difference between heroin and methadone? Is this difference one of interpretation, where an 'opiate-like' substance is 'labelled' differently through social processes that arbitrarily describe methadone as 'legal' and 'therapeutic', and heroin as 'illegal' and 'harmful'? To study the nature of this difference, I follow two experiments in the United States and in France of methadone substitution, where medical practices attempt to replace heroin by methadone, and thereby to reduce the user's (illegal) drug use. In these trials, the experimenters ask precisely this question. The question of the nature of the difference between the substance's actions is further illustrated by the comparison between the substitution trials: when the experimenters describe methadone differently in different places and times, do they 'interpret' the drug differently, or is the drug itself different? I show that far too many elements vary from trial to trial to say that the 'interpretation' of the substance is all that varies. In order to explore the variation in detail, then, I draw on works about 'performance', and on the actor-network 'theory of action': what heroin and methadone do, but also also the very way in which they 'pass into action', is what varies in each trial. In the end, this question about difference is a question about action. In each trial, there is not from the start one substance with fixed or vague properties which one can then interpret in various manners. 'Substance' does not contain inherent actions from the start ('properties'). Rather, following the experimenters, it is possible to say that 'effects' are primary and that only at the end of the trial do the experimenters laboriously 'find substance' to effects. PMID:12051261

  2. Morphine

    MedlinePlus

    ... breathing problems or other serious, life-threatening side effects. Tell your doctor if you are taking or plan to take any of the following medications: cimetidine (Tagamet); other narcotic pain medications; medications for anxiety, seizures, depression, mental illness, or nausea; muscle relaxants; ...

  3. Effectiveness of Relapse Prevention Cognitive-Behavioral Model in Opioid-Dependent Patients Participating in the Methadone Maintenance Treatment in Iran

    PubMed Central

    PASHAEI, Tahereh; SHOJAEIZADEH, Davoud; RAHIMI FOROUSHANI, Abbas; GHAZITABATABAE, Mahmoud; MOEENI, Maryam; RAJATI, Fatemeh; M RAZZAGHI, Emran

    2013-01-01

    Background: To evaluate the effectiveness of a relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) in Iran. Methods: The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies (INCAS). Participants were randomized into two groups: educational intervention group (N=46) and control group (N=46). The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instrument. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. Results: While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 (P<0.01). Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 (P<.03), 0.31 (P<.02), and 0.13 (P<.02) respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group Conclusion: Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance. PMID:26056645

  4. Quantitation of methadone enantiomers in humans using stable isotope-labeled (2H3)-, (2H5)-, and (2H8)Methadone

    SciTech Connect

    Nakamura, K.; Hachey, D.L.; Kreek, M.J.; Irving, C.S.; Klein, P.D.

    1982-01-01

    A new technique for simultaneous stereoselective kinetic studies of methadone enantiomers was developed using three deuterium-labeled forms of methadone and GLC-chemical-ionization mass spectrometry. A racemic mixture (1:1) of (R)-(-)-(2H5)methadone (l-form) and (S)-(R)-(2H3)methadone (d-form) was administered orally in place of a single daily dose of unlabeled (+/-)-(2H0)methadone in long-term maintenance patients. Racemic (+/-)-(2H8)methadone was used as an internal standard for the simultaneous quantitation of (2H0)-, (2H3)-, and (2H5)methadone in plasma and urine. A newly developed extraction procedure, using a short, disposable C18 reversed-phase cartridge and improved chemical-ionization procedures employing ammonia gas, resulted in significant reduction of the background impurities contributing to the ions used for isotopic abundance measurements. These improvements enabled the measurement of labeled plasma methadone levels for 120 hr following a single dose. This methodology was applied to the study of methadone kinetics in two patients; in both patients, the analgesically active l-enantiomer of the drug had a longer plasma elimination half-life and a smaller area under the plasma disappearance curve than did the inactive d-form.

  5. Ethnic and genetic factors in methadone pharmacokinetics: A population pharmacokinetic study☆

    PubMed Central

    Bart, Gavin; Lenz, Scott; Straka, Robert J.; Brundage, Richard C.

    2014-01-01

    Background Treatment of opiate use disorders with methadone is complicated by wide interindividual variability in pharmacokinetics. To identify potentially contributing covariates in methadone pharmacokinetics, we used population pharmacokinetic modeling to estimate clearance (CL/F) and volume of distribution (V/F) for each methadone enantiomer in an ethnically diverse methadone maintained population. Methods Plasma levels of the opiate-active R-methadone and opiate-inactive S-methadone were measured in 206 methadone maintained subjects approximately two and twenty-three hours after a daily oral dose of racmethadone. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction (FOCE-I) was used to evaluate methadone CL/F and V/F. The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included ethnicity, gender, weight, BMI, age, methadone dose, and 21 single nucleotide polymorphisms in genes implicated in methadone pharmacokinetics. Results In the final model, for each enantiomer, Hmong ethnicity reduced CL/F by approximately 30% and the rs2032582 (ABCB1 2677G > T/A) GG genotype was associated with a 20% reduction in CL/F. The presence of the rs3745274 minor allele (CYP2B6 515G > T) reduced CL/F by up to 20% for S-methadone only. A smaller effect of age was noted on CL/F for R-methadone. Conclusion This is the first report showing the influence of the rs2032582 and rs3745274 variants on methadone pharmacokinetics rather than simply dose requirements or plasma levels. Population pharmacokinetics is a valuable method for identifying the influences on methadone pharmacokinetic variability. PMID:25456329

  6. Trends in Controlled-Release Oxycodone (Oxycontin[R]) Prescribing among Medicaid Recipients in Kentucky, 1998-2002. Research Note

    ERIC Educational Resources Information Center

    Havens, Jennifer R.; Talbert, Jeffrey C.; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G.

    2006-01-01

    Context: Prescription opioid abuse has emerged as a public health problem, particularly in rural America. Purpose: To examine temporal and geographic trends in rates of controlled-release oxycodone (OxyContin) prescribing for Kentucky Medicaid recipients. Methods: A cross-sectional analysis was completed in which the state was divided into 3…

  7. Pattern of QTc prolongation in Methadone Maintenance Therapy (MMT) subjects receiving different methadone dosages: A prospective cohort study

    PubMed Central

    Mohamad, Nasir; Abdul Jalal, Muhammad Irfan; Hassan, Azlie; Abdulkarim Ibrahim, Muslih; Salehuddin, Roslanuddin; Abu Bakar, Nor Hidayah

    2013-01-01

    Objectives: This study aimed to compare the QTc interval between low and high dose methadone groups and evaluate the pattern of QTc variation. Methods: This is a prospective cohort study conducted from December 2010 till August 2011 at Malaysian University of Science’s Hospital. Forty six subjects, grouped in high dose (>80mg) and low dose (<80mg) oral methadone, were followed-up at 4-weekly for QTc measurements. Relevant demographic and biochemical profiles were taken at intervals with concurrent QTc measurements. Results: No significant QTc differences between methadone dosage groups were found at Week 0 (434ms vs 444ms, p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs 450ms, p = 0.029). However, there were significant associations between the groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044 and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR 2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and 0.017, respectively), but not at week 8. Conclusion: High-dose methadone group is more likely to develop prolonged QTc than low-dose group. However, such effects were inconsistent and occurred even during chronic methadone therapy, mandating judicious QTc and serum methadone monitoring. PMID:24353706

  8. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  9. Effects of morphine on the disposition of ampicillin in mice.

    PubMed Central

    Garty, M; Hurwitz, A

    1985-01-01

    Morphine raised the levels of intravenously administered ampicillin in the plasma of mice. Despite higher ampicillin levels in plasma after administration of morphine, levels of this antibiotic in bile and urine were not elevated. After ligation of the common bile duct, ampicillin levels in plasma were elevated. Morphine caused a further rise in drug levels in plasma of duct-ligated mice. Ampicillin levels in plasma were higher in mice made anephric by prolonged ligation of their external urethras. In such animals, morphine also caused ampicillin levels in plasma to be even higher. These experiments suggest that morphine impairs both renal and hepatobiliary elimination of ampicillin. These effects of morphine were completely reversed by naloxone. In contrast to effects on intravenously administered ampicillin, morphine markedly reduced drug levels in plasma when ampicillin was given by gastric intubation. This resulted from delayed absorption because of retardation of gastric emptying by morphine. PMID:4073871

  10. Comparative Cognitive and Subjective Side Effects of Immediate Release Oxycodone in Healthy Middle Age and Older Adults

    PubMed Central

    Cherrier, M.; Amory, J.; Ersek, M.; Risler, L.; Shen, D.

    2009-01-01

    This study measured the objective and subjective neurocognitive effects of a single 10mg dose of immediate-release oxycodone in healthy, older (>65 years) and middle age (35 – 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed two separate study days and were blind to medication condition (placebo, 10 mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 min post dose (p<0.01) and pupil size, an indication of physiological effects of the medication peaked at approximately 90 to 120 min post dose (p<0.01). Significant declines in simple and sustained attention, working memory and verbal memory were observed at one hour post dose compared to baseline for both age groups with a trend toward return to baseline by five hours post dose. For almost all cognitive measures there were no medication by age interaction effects, which indicates that the two age groups exhibited a similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10 mg dose of immediate release oxycodone are similar to those observed for middle age adults. Perspective Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-age and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults. PMID:19729346

  11. Long-term effects of methadone maintenance treatment with different psychosocial intervention models.

    PubMed

    Wang, Lirong; Wei, Xiaoli; Wang, Xueliang; Li, Jinsong; Li, Hengxin; Jia, Wei

    2014-01-01

    This study evaluated the long-term effects of different psychosocial intervention models in methadone maintenance treatment (MMT) in Xi'an China. Patients from five MMT clinics were divided into three groups receiving MMT only, MMT with counseling psychology (CP) or MMT with contingency management (CM). A five-year follow-up was carried out with daily records of medication, monthly random urine morphine tests, and tests for anti-HIV and anti-HCV every six months. Drug use behavior was recorded six months after initial recruitment using a survey. Adjusted RRs and their 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model or a Cox proportional hazard model. A total of 2662 patients were recruited with 797 in MMT, 985 in MMT with CP, and 880 in MMT with CM. Following six months of treatment, the injection rates of MMT with CP and MMT with CM groups were significantly lower than that of MMT (5.1% and 6.9% vs. 16.3%, x²  =  47.093 and 29.908, respectively; P<0.05). HIV incidences for MMT, MMT with CP and MMT with CM at the five year follow-up were 20.09, 0.00 and 10.02 per ten thousand person-years, respectively. HCV incidences were 18.35, 4.42 and 6.61 per hundred person-years, respectively, demonstrating that CP and CM were protective factors for HCV incidence (RR  =  0.209 and 0.414, with range of 0.146-0.300 and 0.298-0.574, respectively). MMT supplemented with CP or CM can reduce heroin use and related risk behaviors, thereby reducing the incidence of HIV and HCV. PMID:24498406

  12. Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis

    PubMed Central

    Lazzari, Marzia; Greco, Maria Teresa; Marcassa, Claudio; Finocchi, Simona; Caldarulo, Clarissa; Corli, Oscar

    2015-01-01

    Background World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. Methods Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. Results Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60 days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0–20.4 mg/d for OXY and 11.5–22.0 mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30 days and 60 days in OXN recipients (−16, P<0.0001 and −3.5, P=0.02, respectively); BFI worsened in the OXY group. The overall incidence of drug-related adverse events was 28.9% in the OXY group and 8.2% in the OXN group (P<0.01); nausea and vomiting were two to five times less frequent with OXN. Quality of life improved to a significantly greater extent in patients receiving OXN compared to OXY (increase in Short Form-36 physical component score of 7.1 points vs 3.2 points, respectively; P<0.001). Conclusion In patients with chronic cancer pain, OXN provided analgesic effectiveness that is similar to OXY, with early and sustained benefits in tolerability. The relationship between responsiveness to OXN and clinical characteristics is currently being investigated. PMID:26586937

  13. Physician Peer Assessments for Compliance with Methadone Maintenance Treatment Guidelines

    ERIC Educational Resources Information Center

    Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret

    2007-01-01

    Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…

  14. Tandem DART™ MS Methods for Methadone Analysis in Unprocessed Urine.

    PubMed

    Beck, Rachel; Carter, Patrick; Shonsey, Erin; Graves, David

    2016-03-01

    Current methods of methadone analysis in untreated urine are traditionally limited to enzyme immunoassays (EIA) while confirmation techniques require specimen processing (i.e., sample clean-up) before analyzing by gas or liquid chromatography coupled with mass spectrometry (GC-MS or LC-MS-MS). EIA and traditional confirmation techniques can be costly and, at times inefficient. As an alternative approach, we present Direct Analysis in Real Time (DART™) coupled with both time-of-flight and triple quadrupole linear ion trap (Q-TRAP™) mass spectrometers for screening and confirming methadone in untreated urine specimens. These approaches require neither expensive kits nor sample clean-up for analysis. More importantly, the total combined analysis time for both screening and confirmation methods was <5 min per sample; in contrast to the 3-5 day process required by traditional EIA, GC-MS and LC-MS-MS techniques. To examine the fundamental protocol and its applicability for routine drug screening, studies were performed that included limits of detection, precision, selectivity and specificity, sample recovery and stability and method robustness. The methods described in this report were determined to be highly specific and selective; allowing for detection of methadone at 250 ng/mL, consistent with cutoffs for current EIA techniques (300 ng/mL). The results reported here demonstrate the DART™ MS platform provides rapid and selective methadone analysis and the potential for providing savings of both time and resources compared with current analysis procedures. PMID:26590378

  15. Counseling with Methadone Clients: A Review of Recent Research

    ERIC Educational Resources Information Center

    Powers, Robert J.; Powers, Henrietta B.

    1978-01-01

    A review of studies on counseling with methadone clients affirmed the importance of counseling services. Support was found for analytic therapy, T-group therapy, behavioral training, reality therapy, and family therapy. There was evidence of client resistance to group therapy. (Author)

  16. Attitudes of Employers toward Hiring Methadone Maintenance Patients.

    ERIC Educational Resources Information Center

    Pugliese, Anthony

    1978-01-01

    Results of this study indicate that at present employers are not ready to accept methadone maintained patients into their firms. The stigma placed on heroin addicts by employers is a very important issue when the treated patient tries to make it in the employment field. More employer education is needed. (Author)

  17. Cost Analysis of Training and Employment Services in Methadone Treatment.

    ERIC Educational Resources Information Center

    French, Michael T.; And Others

    1994-01-01

    A cost analysis is presented for developing a training and employment (TEP) program at four methadone treatment centers in a quasi-experimental pilot study. Average annual costs for TEP per client were derived. The methodology can be used in other projects to compare standard and TEP-enhanced substance-abuse treatment. (SLD)

  18. Integrating Fieldwork into Employment Counseling for Methadone-Treatment Patients

    ERIC Educational Resources Information Center

    Blankertz, Laura; Spinelli, Michael; Magura, Stephen; Bali, Priti; Madison, Elizabeth M.; Staines, Graham L.; Horowitz, Emily; Guarino, Honoria; Grandy, Audrey; Fong, Chunki; Gomez, Augustin; Dimun, Amy; Friedman, Ellen

    2005-01-01

    An innovative employment counseling model, Customized Employment Supports, was developed for methadone-treatment patients, a population with historically low employment rates. The effectiveness of a key component of the model, "vocational fieldwork," the delivery of services in the community rather than only within the clinic, was assessed through…

  19. Changing Needle Practices in Community Outreach and Methadone Treatment.

    ERIC Educational Resources Information Center

    Wechsberg, Wendee M.; And Others

    1994-01-01

    This pretest/posttest study used two samples of injecting drug users (184 from street outreach and 103 from a methadone program) to assess drug use and human immunodeficiency virus risk practices. The improvement in risk behaviors at posttest suggests that intervention programs were agents of change. (SLD)

  20. Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

    PubMed

    Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G

    2014-04-01

    We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn. PMID:24057890

  1. Pharmacologic Evidence to Support Clinical Decision Making for Peripartum Methadone Treatment

    PubMed Central

    Bogen, D. L.; Perel, J. M.; Helsel, J. C.; Hanusa, B. H.; Romkes, M.; Nukui, T.; Friedman, C. R.; Wisner, K. L.

    2012-01-01

    Rationale Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. Objectives Study goals were to: 1) Characterize changes in methadone dose across childbearing, 2) Determine enantiomer-specific methadone withdrawal kinetics from steady-state during late pregnancy, 3) Assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and 4) Explore relationships between CYP2B6, CYP2C19 and CYP3A4 single nucleotide polymorphisms and maternal dose, plasma concentration and L/D. Methods Methadone dose changes and timed plasma samples were obtained for women on methadone (n=25) followed prospectively from third trimester of pregnancy to three months postpartum. Results Participants were primarily white, Medicaid insured and multiparous. All women increased their dose from first to end of second trimester (mean peak increase=23 mg/day); 71% of women increased from second trimester to delivery (mean peak increase=19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 hours; S-methadone 8.02-18.9 hours) were about half of those reported in non-pregnant populations. In 3 women with weekly 24-hour methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. Conclusions Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery. PMID:22926004

  2. The bioavailability of morphine applied topically to cutaneous ulcers.

    PubMed

    Ribeiro, Maria D C; Joel, Simon P; Zeppetella, Giovambattista

    2004-05-01

    A number of studies have reported the analgesic effect of morphine when applied topically to painful skin ulcers. It has been suggested that morphine may exert a local action, as opioid receptors have been demonstrated on peripheral nerve terminals. In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers. Six hospice inpatients with skin ulcers were given morphine sulfate 10 mg in Intrasite gel topically and morphine sulfate 10 mg subcutaneously over 4 hours, at least 48 hours apart, in randomized order. Morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) were determined in plasma using a specific HPLC method. In five patients morphine and its metabolites were undetectable when applied topically. In one patient (with the largest ulcer), morphine and M6G were detected. The calculated morphine and M6G bioavailability in this patient were 20% and 21%, respectively. M3G was also detected but was below the lower limit of quantitation. When applied topically to ulcers, morphine was not absorbed in the majority of patients, suggesting any analgesic effect would be mediated locally rather than systemically. However, in ulcers with a large surface area, systemic absorption may occur. PMID:15120772

  3. The effect of different durations of morphine exposure on mesencephalic dopaminergic neurons in morphine dependent rats.

    PubMed

    Shi, Weibo; Ma, Chunling; Qi, Qian; Liu, Lizhe; Bi, Haitao; Cong, Bin; Li, Yingmin

    2015-12-01

    Mesencephalic dopaminergic neurons are heavily involved in the development of drug dependence. Thyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, plays an important role in the survival of dopaminergic neurons. Therefore, this study investigated TH changes in dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN), as well as the morphine effects on dopaminergic neurons induced by different durations of morphine dependence. Models of morphine dependence were established in rats, and paraffin-embedded sections, immunohistochemistry and western blotting were used to observe the changes in the expression of TH protein. Fluoro-Jade B staining was used to detect degeneration and necrosis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) detected the apoptosis of mesencephalic dopaminergic nerve cells. Immunohistochemistry and western blotting showed that the number of TH positive cells and the protein levels in the VTA and SN were significantly decreased in the rats with a long period of morphine dependency. With prolonged morphine exposure, the dopaminergic nerve cells in the VTA and SN showed degeneration and necrosis, while apoptotic cells were not observed. The number of VTA and SN dopaminergic nerve cells decreased with increasing periods of morphine dependence, which was most likely attributable to the degeneration and necrosis of nerve cells induced by morphine toxicity. PMID:26386147

  4. Implementing methadone maintenance treatment in prisons in Malaysia

    PubMed Central

    Wickersham, Jeffrey A; Marcus, Ruthanne; Kamarulzaman, Adeeba; Zahari, Muhammad Muhsin

    2013-01-01

    Abstract Problem In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed. Approach After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) – those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners’ release. Local setting Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy. Relevant changes Standard operating procedures were modified to: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners’ release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (> 80 mg) before releasing prisoners. Lessons learnt Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates. PMID:23554524

  5. Reformulation of controlled-release oxycodone and pharmacy dispensing patterns near the US–Canada border

    PubMed Central

    Gomes, Tara; Paterson, J Michael; Juurlink, David N; Dhalla, Irfan A; Mamdani, Muhammad M

    2012-01-01

    Background In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border. Methods We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US–Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength. Results The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit–Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit–Windsor Tunnel between August 2010 and October 2011. Conclusions Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit–Windsor Tunnel reflects specific

  6. Methadone-induced Damage to White Matter Integrity in Methadone Maintenance Patients: A Longitudinal Self-control DTI Study

    PubMed Central

    Li, Wei; Li, Qiang; Wang, Yarong; Zhu, Jia; Ye, Jianjun; Yan, Xuejiao; Li, Yongbin; Chen, Jiajie; Liu, Jierong; Li, Zhe; Wang, Wei; Liu, Yijun

    2016-01-01

    Methadone maintenance treatment (MMT) can induce impairments in brain function and structure, despite its clinical effectiveness. However, the effect of chronic MMT on brain white matter (WM) is not fully known. Thirty-three MMT patients underwent diffusion tensor imaging (DTI) twice – at the start of the study (Scan1) and one year later (Scan2). Tract-based spatial statistics were used to investigate changes in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) between the two scans. The correlations between DTI indices and methadone consumption and neuropsychological status were analysed. We found significantly decreased FA, decreased AD and increased RD in Scan2 in extensive WM regions; overlapping regions were found in the left posterior limb and the retrolenticular part of internal capsule, superior and posterior corona radiata, bilateral external capsule and the right superior longitudinal fasciculus. In addition, the change of FA in the overlapping regions was positively correlated with the accumulated dosage of methadone use, the RD value in Scan2 and non-planning impulsiveness (NPI) measured at follow-up. The results suggest that methadone has damaging effects on WM integrity. The dose-dependent pattern and characteristics of the impairment may suggest new strategies for MMT. PMID:26794650

  7. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials

    PubMed Central

    2010-01-01

    Background Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Methods These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day). Results No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively). Conclusions Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy. Trial registration numbers ClinicalTrials.gov identifier: NCT00412100 and NCT00412152 PMID:20920236

  8. Infrequent Illicit Methadone Use Among Stimulant-Using Patients in Methadone Maintenance Treatment Programs: A National Drug Abuse Treatment Clinical Trials Network Study

    PubMed Central

    Wu, Li-Tzy; Blazer, Dan G.; Stitzer, Maxine L.; Patkar, Ashwin A.; Blaine, Jack D.

    2009-01-01

    We sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use. PMID:18612886

  9. Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report

    PubMed Central

    Stotts, Angela L.; Masuda, Akihiko; Wilson, Kelly

    2010-01-01

    Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from a MM client who voluntarily participated in an Acceptance and Commitment Therapy (ACT) – based methadone detoxification program are presented. The program consisted of a 1-month stabilization and 5-month gradual methadone dose reduction period, combined with weekly individual ACT sessions. Urine samples were collected twice weekly to assess for use of illicit drugs. The participant successfully completed the program and had favorable drug use outcomes during the course of treatment, and at the one-month and one-year follow-ups. Innovative behavior therapies, such as ACT, that focus on acceptance of the inevitable distress associated with opiate withdrawal may improve methadone detoxification outcomes. PMID:20628479

  10. Synthetic substances with morphine-like effect

    PubMed Central

    Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

    1957-01-01

    A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135