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Morphine
Kinds of Morphine Terms modified by Morphine Selected AbstractsEFFECTS OF MORPHINE ON METHOTREXATE DISPOSITION IN MICECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2004Yuai Li SUMMARY 1.,Morphine has been shown to slow the renal excretion of other drugs. The present study in mice evaluated the effects of morphine on the disposition of methotrexate (MTX), an antimetabolite eliminated by the kidneys. 2.,Mice were injected with morphine (20 mg/kg) or saline s.c. After 30 min, 20,80 mg/kg MTX was injected i.v. Blood and urine samples were assayed for MTX by HPLC. 3.,Morphine reduced plasma clearance (CL) of MTX from 0.147 ± 0.015 to 0.061 ± 0.009 mL/min per g bodyweight (P < 0.01). The area under the plasma concentration,time curve (AUC0,,) was raised by morphine from 151 ± 18 to 369 ± 36 µg·mL per min (P < 0.01). Without morphine administration, 22,27% of an MTX dose was excreted into the urine in 30 min. The corresponding fractions excreted into the urine after morphine were reduced to 15,18% (P < 0.01). 4.,Plasma levels of MTX administered intravenously to mice are elevated by the concomitant administration of morphine, which reduces renal elimination of MTX. [source] A survey on two years of medication regulation in horse races in IranEQUINE VETERINARY JOURNAL, Issue 2 2010S. LOTFOLLAHZADEH Summary Reasons for performing study: The present survey evaluated the use of prohibited substances cases in the first 2 years of medication regulation in horseracing in Iran so that the impact of these regulations on the level of positive cases over the period could be assessed. Objectives: To determine the prevalence of positive tests for prohibited substances in horse races during 2 years of a drugs testing programme in Iran. Methods: A total of 656 horses that were winners or second in races were tested during the 2 year study. In the first year 354 horses (209 males and 145 females) and in the second year 302 horses (155 males and 147 females) were tested. In the 2 years, 306 were found to be positive. Urine samples were taken from candidate horses and sent to the Central Doping Laboratory. Blood samples were taken from those horses where a urine sample could not be taken within one hour. Detection and measurement of prohibited substances were carried out by ELISA, GC and HPLC using standard methods. Results: Thirty-two percent of males were positive for prohibited substances, which was not significantly different from the percentage of females (25.5%). In the second year, of the 302 horses tested for prohibited substances, 33.5% of males were positive, again similar to females (33.3%). Almost 83% of horses tested positive for prohibited substances once in the first year, 15% tested positive twice and 2% tested positive 3 times. In the second year 78% tested positive once, 15% tested positive twice and 7% tested positive 3 times. Morphine was the most used prohibited substance and was detected 42 times during the survey, followed by caffeine and phenylbutazone. Morphine was also the most used drug in combination with other drugs in both years. Conclusions: Morphine and caffeine were the most popular prohibited substances found in the measurements. As these substances were found in the environment and food stuffs, their presence in the samples may be due to unintentional feeding of contaminated materials (bread, hay and chocolate). [source] Morphine modulation of temporomandibular joint-responsive units in superficial laminae at the spinomedullary junction in female rats depends on estrogen statusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2008A. Tashiro Abstract The influence of analgesic agents on neurons activated by stimulation of the temporomandibular joint (TMJ) region is not well defined. The spinomedullary junction [trigeminal subnucleus caudalis (Vc)/C1,2] is a major site of termination for TMJ sensory afferents. To determine whether estrogen status influences opioid-induced modulation of TMJ units, the classical opioid analgesic, morphine, was given to ovariectomized (OvX) rats and OvX rats treated for 2 days with low-dose (LE2) or high-dose (HE2) 17,-estradiol-3-benzoate. Under thiopental anesthesia, TMJ units in superficial and deep laminae at the Vc/C1,2 junction were activated by injection of ATP (1 mm) directly into the joint space. In superficial laminae, morphine inhibited evoked activity in units from OvX and LE2 rats in a dose-related and naloxone-reversible manner, whereas units from HE2 rats were not inhibited. By contrast, in deep laminae, morphine reduced TMJ-evoked unit activity similarly in all groups. Morphine reduced the background activity of units in superficial and deep laminae and resting arterial pressure similarly in all groups. Morphine applied to the dorsal surface of the Vc/C1,2 junction inhibited all units independently of E2 treatment. Quantitative polymerase chain reaction and immunoblots revealed a similar level of expression for ,-opioid receptors at the Vc/C1,2 junction in LE2 and HE2 rats. These results indicated that estrogen status differentially affected morphine modulation of TMJ unit activity in superficial, but not deep, laminae at the Vc/C1,2 junction in female rats. The site(s) for estrogen influence on morphine-induced modulation of TMJ unit activity was probably outside the medullary dorsal horn. [source] Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine toleranceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Kazuaki Yokoyama Abstract Morphine is the drug of choice to treat intractable pain, although prolonged administration often causes undesirable side-effects including analgesic tolerance. It is speculated that voltage-dependent Ca2+ channels (VDCCs) play a key role in morphine analgesia and tolerance. To examine the subtype specificity of VDCCs in these processes, we analysed mice lacking N-type (Cav2.2) or R-type (Cav2.3) VDCCs. Systemic morphine administration or exposure to warm water swim-stress, known to induce endogenous opioid release, resulted in greater analgesia in Cav2.3,/, mice than in controls. Moreover, Cav2.3,/, mice showed resistance to morphine tolerance. In contrast, Cav2.2,/, mice showed similar levels of analgesia and tolerance to control mice. Intracerebroventricular (i.c.v.) but not intrathecal (i.t.) administration of morphine reproduced the result of systemic morphine in Cav2.3,/, mice. Furthermore, i.c.v. administration of an R-type channel blocker potentiated morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca2+ current could lead to high-efficiency opioid therapy without tolerance. [source] Morphine withdrawal-induced abnormalities in the VTA: confocal laser scanning microscopyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Saturnino Spiga No abstract is available for this article. [source] Fracture risk associated with the use of morphine and opiatesJOURNAL OF INTERNAL MEDICINE, Issue 1 2006P. VESTERGAARD Abstract. Objectives., To study the effect of morphine and opiates on fracture risk. Design., Case,control study. Setting., Nationwide register-based study. Subjects., Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Main outcome measure., Fracture. Results., Morphine (1.47, 95% CI 1.37,1.58), fentanyl (2.23, 95% CI 1.89,2.64), methadone (1.39, 95% CI 1.05,1.83), oxycodone (1.36, 95% CI 1.08,1.69), nicomorphine (1.57, 95% CI 1.38,1.78), ketobemidone (1.07, 95% CI 1.02,1.13), tramadol (1.54, 95% CI 1.49,1.58) and codeine (1.16, 95% CI 1.12,1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79,0.95), pethidine (0.98, 95% CI 0.89,1.08), dextropropoxiphene (1.02, 95% CI 0.90,1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88,1.01). Conclusions., An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness. [source] Role of Src in ligand-specific regulation of ,-opioid receptor desensitization and internalizationJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Min-Hua Hong Abstract The opioid receptors are a member of G protein-coupled receptors that mediate physiological effects of endogenous opioid peptides and structurally distinct opioid alkaloids. Although it is well characterized that there is differential receptor desensitization and internalization properties following activation by distinct agonists, the underlying mechanisms remain elusive. We investigated the signaling events of ,-opioid receptor (,OR) initiated by two ligands, DPDPE and TIPP. We found that although both ligands inhibited adenylyl cyclase (AC) and activated ERK1/2, only DPDPE induced desensitization and internalization of the ,OR. We further found that DPDPE, instead of TIPP, could activate GRK2 by phosphorylating the non-receptor tyrosine kinase Src and translocating it to membrane receptors. Activation of GRK2 led to the phosphorylation of serine residues in the C-terminal tail, which facilitates ,-arrestin1/2 membrane translocation. Meanwhile, we also found that DPDPE promoted ,-arrestin1 dephosphorylation in a Src-dependent manner. Thus, DPDPE appears to strengthen ,-arrestin function by dual regulations: promoting ,-arrestin recruitment and increasing ,-arrestin dephosphorylation at the plasma membrane in a Src-dependent manner. All effects initiated by DPDPE could be abolished or suppressed by PP2, an inhibitor of Src. Morphine, which has been previously shown to be unable to desensitize or internalize ,OR, also behaved as TIPP in failure to utilize Src to regulate ,OR signaling. These findings point to the existence of agonist-specific utilization of Src to regulate ,OR signaling and reveal the molecular events by which Src modulates ,OR responsiveness. [source] Morphine and HIV-Tat increase microglial-free radical production and oxidative stress: possible role in cytokine regulationJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Jadwiga Turchan-Cholewo Abstract Opiate abuse alters the progression of human immunodeficiency virus and may increase the risk of neuroAIDS. As neuroAIDS is associated with altered microglial reactivity, the combined effects of human immunodeficiency virus-Tat and morphine were determined in cultured microglia. Specifically, experiments determined the effects of Tat and morphine on microglial-free radical production and oxidative stress, and on cytokine release. Data show that combined Tat and morphine cause early and synergistic increases in reactive oxygen species, with concomitant increases in protein oxidation. Furthermore, combined Tat and morphine, but not Tat or morphine alone, cause reversible decreases in proteasome activity. The effects of morphine on free radical production and oxidative stress are prevented by pre-treatment with naloxone, illustrating the important role of opioid receptor activation in these phenomena. While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-, and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1). Finally, experiments using the reversible proteasome inhibitor MG115 show that temporary, non-cytotoxic decreases in proteasome activity increase protein oxidation and decrease tumor necrosis factor-,, interleukin-6, and MCP-1 release from microglia. Taken together, these data suggest that oxidative stress and proteasome inhibition may be involved in the immunomodulatory properties of opioid receptor activation in microglia. [source] Morphine activates Arc expression in the mouse striatum and in mouse neuroblastoma Neuro2A MOR1A cells expressing ,-opioid receptorsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Barbara Zió, kowska Abstract Activity-regulated cytoskeleton-associated protein (Arc) is an effector immediate early gene product implicated in long-term potentiation and other forms of neuroplasticity. Earlier studies demonstrated Arc induction in discrete brain regions by several psychoactive substances, including drugs of abuse. In the present experiments, the influence of morphine on Arc expression was assessed by quantitative reverse transcription real-time PCR and Western blotting in vivo in the mouse striatum/nucleus accumbens and, in vitro, in the mouse Neuro2A MOR1A cell line, expressing ,-opioid receptor. An acute administration of morphine produced a marked increase in Arc mRNA and protein level in the mouse striatum/nucleus accumbens complex. After prolonged opiate treatment, tolerance to the stimulatory effect of morphine on Arc expression developed. No changes in the striatal Arc mRNA levels were observed during spontaneous or opioid antagonist-precipitated morphine withdrawal. In Neuro2A MOR1A cells, acute, but not prolonged, morphine treatment elevated Arc mRNA level by activation of ,-opioid receptor. This was accompanied by a corresponding increase in Arc protein level. Inhibition experiments revealed that morphine induced Arc expression in Neuro2A MOR1A cells via intracellular signaling pathways involving mitogen-activated protein (MAP) kinases and protein kinase C. These results lend further support to the notion that stimulation of opioid receptors may exert an activating influence on some intracellular pathways and leads to induction of immediate early genes. They also demonstrate that Arc is induced in the brain in vivo after morphine administration and thus may play a role in neuroadaptations produced by the drug. © 2005 Wiley-Liss, Inc. [source] Three-cycle fentanyl patch system significantly improves pain control in gynecologic cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2006Chiharu Kanamori Abstract Pain affects many cancer patients, and in advanced stages of the disease it can significantly affect the quality of their lives. Morphine has long been the ,gold standard' for the treatment of cancer pain. However, its side-effects, particularly sedation and cognitive impairment at high doses, have encouraged the use of ,opioid rotation'. The transdermal fentanyl patch has advantages over oral morphine, with reduced side-effects and increased convenience in practical usage. The side-effects were reduced in patients who changed to the fentanyl patch, but rescue analgesia was often needed because of the decrease of fentanyl release from the patch, especially on the patch replacement day. We have developed a three-cycle fentanyl patch system that provided an appropriate pain control, and this system should be considered for pain relief in cancer patients. [source] Morphine or its withdrawal affects plasma malondialdehyde, vitamin E levels and absence or presence of abstinence signs in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2009Professor Arnaldo Pinelli Abstract Objectives Various experimental observations show that morphine treatment generates reactive oxygen species, and that its discontinuation leads to signs of withdrawal. We therefore investigated plasma malondialdehyde and vitamin E levels under both conditions to verify the occurrence of any alterations in oxidative metabolism, and whether these are associated with behavioural changes. Methods We investigated the effects of morphine or morphine plus naloxone on plasma malondialdehyde, vitamin E levels and withdrawal signs such as jumping, wet dog shakes and faecal excretion in rats. Furthermore, isopropylnoradrenaline was injected in rabbits to verify its effects on plasma malondialdehyde levels. Key findings Morphine treatment increased free malondialdehyde and decreased vitamin E levels. The elevation in malondialdehyde levels were exacerbated by the abrupt removal of morphine by naloxone, which also led to the appearance of withdrawal signs. The increased malondialdehyde values can be attributed to the interactions of reactive oxygen species with unsaturated fatty acids, and the lowered levels of vitamin E to its interactions with reactive oxygen species. Conclusions A connection seems to exist between altered peroxide status and withdrawal signs in abstinent animals. [source] Microinjection of morphine into thalamic nucleus submedius depresses bee venom-induced inflammatory pain in the ratJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Jie Feng Previous studies have provided evidence of the existence of a pain modulatory feedback pathway consisting of thalamic nucleus submedius (Sm),ventrolateral orbital cortex-periaqueductal grey pathway, which is activated during acute pain and leads to depression of transmission of nociceptive information in the spinal dorsal horn. The aim of this study was to test the hypothesis that morphine microinjection into the Sm decreased spontaneous pain and bilateral thermal hyperalgesia, as well as ipsilateral mechanical allodynia, induced by subcutaneous injections of bee venom into the rat hind paw. Morphine (1.0, 2.5 or 5.0 m,g in 0.5 ,L) injected into the Sm, contralateral to the bee venominjected paw, depressed spontaneous nociceptive behaviour in a dose-dependent manner. Furthermore, morphine significantly decreased bilateral thermal hyperalgesia and ipsilateral mechanical allodynia 2 h after bee venom injection. These morphine-induced effects were antagonized by 1.0 ,g naloxone (an opioid antagonist) microinjected into the Sm 5 min before morphine administration. The results provided further support for the important role of the Sm and Sm-opioid receptors in inhibiting nociceptive behaviour and indicated for the first time that Sm opioid receptors were also effective in inhibiting the hypersensitivity provoked by bee venom-induced inflammation. [source] Morphine, opioids, and the feline pulmonary vascular bedACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008A. D. KAYE Background: Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects. Methods: This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of l - N5 -(1-iminoethyl) ornithine hydrochloride (l -NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H1 -receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. Results: In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of l -NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine. Conclusion: The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways. [source] CREB Gene Transcription Factors: Role in Molecular Mechanisms of Alcohol and Drug AddictionALCOHOLISM, Issue 2 2005Subhash C. Pandey This article presents the proceedings of a symposium presented at the meeting of the Research Society on Alcoholism, held in Vancouver, British Columbia, Canada, in June 2004. The organizers and chairpersons were Subhash C. Pandey and Fulton Crews. The presentations were (1) Ethanol Modulation of CREB: Role in Dependence and Withdrawal, by Fulton Crews; (2) Effects of D1 Dopamine Receptor Activation During Withdrawal From Chronic Morphine: Enhanced CREB Activation and Decreased Conditioned Place Aversion, by Elena H. Chartoff; (3) CREB-Haplodeficient Mice: Role in Anxiety and Alcohol-Drinking Behaviors, by Subhash C. Pandey; and (4) A Role for CREB in Stress and Drug Addiction, by Julie A. Blendy. [source] Effect of Naloxone on Appetitive and Consummatory Phases of Ethanol Self-AdministrationALCOHOLISM, Issue 7 2001Amanda L. Sharpe Background : The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. Methods: Intraperitoneal injections of naloxone (0.3,10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. Results: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. Conclusions: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior. [source] The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2008P. NETZER Summary Background, Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. Aim, To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. Methods, Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. Results, Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. Conclusions, Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects. [source] Morphine-6-glucuronide: Actions and mechanismsMEDICINAL RESEARCH REVIEWS, Issue 5 2005Gavin J. Kilpatrick Abstract Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the µ-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the µ-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the µ-opioid receptor, (3) M6G has a lower affinity for the ,-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether µ-opioid receptors in these brain areas differ in either their regulation or pharmacology. © 2005 Wiley Periodicals, Inc. Med Res Rev [source] The Use of Implanted Programmable Infusion Pumps in the Management of Nonmalignant, Chronic Low-Back PainNEUROMODULATION, Issue 4 2007Peter Staats MD ABSTRACT Objectives., To assess the mode-of-use of implanted programmable infusion pumps in patients with nonmalignant, chronic low-back pain. Materials and Methods., Charts from 101 consecutive eligible patients were analyzed retrospectively. Data were extracted relating to patient demographics, pump mode of infusion and flow rate, and medications used. Results., Morphine was the agent most frequently used and most patients received one medication at each visit. At the last visit, 94.1% of patients were receiving constant-flow treatment; 90.1% had received such treatment for , six months and 68.3% throughout the entire analysis period. For patients attaining constant-flow treatment, mean time from implantation to start of such treatment was 2.7 months. Discussion., The results suggest that many patients with nonmalignant low-back pain could be implanted with a constant-flow pump when their programmable device needs replacing or, in some cases, at the start of intrathecal treatment. This would reduce costs and the requirement for surgery. [source] Chemical Stability of Ziconotide-Clonidine Hydrochloride Admixtures With and Without Morphine Sulfate During Simulated Intrathecal AdministrationNEUROMODULATION, Issue 2007David Shields PhD ABSTRACT Objective., To determine the stability of ziconotide,clonidine hydrochloride admixtures with and without morphine sulfate during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods., Admixtures of ziconotide (25 µg/mL) and clonidine hydrochloride (2 mg/mL) with and without morphine sulfate (35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°. Pumps were sampled immediately after filling and at four additional time points over the course of 28 (ziconotide,clonidine hydrochloride admixture) or 20 (ziconotide,clonidine hydrochloride,morphine sulfate admixture) days. Drug concentrations were determined using high-performance liquid chromatography. Results., Ziconotide concentration exceeded 97% of initial at all time points when combined with clonidine alone; statistical evaluation indicated that both ziconotide and clonidine concentrations would remain above 90% of initial for more than 60 days. When compounded with both clonidine and morphine, ziconotide and clonidine concentrations declined; statistical evaluation indicated that the ziconotide concentration was 70% of initial after 20 days, and that clonidine would remain 90% stable for 42 days. Morphine was stable in the presence of ziconotide and clonidine. Conclusions., A ziconotide-clonidine admixture was 90% stable for 60 days (extrapolated), and a ziconotide-clonidine-morphine admixture was 70% stable for 20 days. [source] Interpreting Urine Drug Tests: Prevalence of Morphine Metabolism to Hydromorphone in Chronic Pain Patients Treated with MorphinePAIN MEDICINE, Issue 7 2008Ajay D. Wasan MD ABSTRACT Objective., Pain medicine practitioners frequently use urine drug testing (UDT) to monitor adherence to opioid therapy. It can be difficult to interpret a result as normal or abnormal in relation to which opioid compounds are expected to be found in the urine. We investigated whether hydromorphone may be a metabolite of morphine normally appearing in UDT of patients prescribed morphine. Design., This is a retrospective case-control study of urine toxicology results in pain patients taking only morphine. Inclusion criteria included urine results positive for morphine only (controls) or morphine and hydromorphone (cases). Demographic and medical history variables, and any history of aberrant drug behavior were recorded and related to the presence or absence of hydromorphone in the urine. Results., Hydromorphone was present in 21 of 32 cases (66%), none of whom had a history of aberrant drug behavior. Positive cases occurred more frequently in women, in those taking higher daily doses of morphine, and in those with higher urine morphine concentrations (P < 0.05). Only morphine urine concentration was a significant predictor of the hydromorphone metabolite in a logistic regression model (P < 0.05). Conclusions., Hydromorphone is likely a minor metabolite of morphine, normally appearing in the UDT of patients taking morphine. This finding assists in determining whether a UDT result is normal or abnormal, and subsequently whether a patient is compliant with opioid therapy. This observation should be confirmed by a prospective study in a controlled environment. Variables such as gender, morphine dose, morphine urine concentration, and genetic determinants of morphine metabolism should be investigated further. [source] Synergistic Interactions Between a KCNQ Channel Opener and an Opioid: Flupirtine and Morphine in Rat Pain Models Including Neuropathic PainPAIN MEDICINE, Issue 7 2007C Goodchild Purpose of the study:, Flupirtine is an established clinical analgesic for mild to moderate musculoskeletal pain states. It has recently been shown to be a KCNQ 2,3 potassium channel opener. These experiments were performed to see if this property could be useful in treating more severe pain states characterised by central sensitisation with the drug either given alone or in combination with morphine. Methods:, Experiments were performed in rats in an observer blinded fashion with vehicle controls. Non sedating doses of flupirtine, morphine and combinations containing both drugs were defined using the rotarod technique. Dose response relationships were determined for non sedating doses of both drugs given alone and together in combination in causing antinociception in three nociception paradigms: electrical pain; carrageenan paw inflammation; streptozotocin-induced diabetic neuropathy. Results:, Flupirtine and morphine when given alone caused slight to moderate antinociception in all three paradigms. Flupirtine also caused significant increases in morphine antinociception in all three models. In carrageenan paw inflammation complete reversal of carrageenan-induced hyperalgesia was caused by 10 mg/kg flupirtine in combination with 0.4 mg/kg morphine. These doses of the two drugs were ineffective when given alone but the combination caused complete antinociception in this model of inflammatory pain. In the diabetic neuropathy model (see figure) morphine 3.2 mg/kg given alone caused significant antinociception but the size of that response was significantly less than that caused by a lower dose of morphine (1.6 mg/kg shown to be ineffective when it was given alone) given in combination with flupirtine 10 mg/kg (p < 0.001; one way ANOVA). Conclusions:, Flupirtine should be investigated as an adjunct analgesic with opioids for the management of patients with severe pain states involving central sensitization. [source] Toward Evidence-Based Prescribing at End of Life: A Comparative Analysis of Sustained-Release Morphine, Oxycodone, and Transdermal Fentanyl, with Pain, Constipation, and Caregiver Interaction Outcomes in Hospice PatientsPAIN MEDICINE, Issue 4 2006BCPS, Douglas J. Weschules PharmD ABSTRACT Objective., The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. Patients and Settings., This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. Design., We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Results., Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. Conclusion., There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved. [source] Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)PAIN PRACTICE, Issue 4 2008Joseph Pergolizzi MD ,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source] Use of premedication for intubation in tertiary neonatal units in the United KingdomPEDIATRIC ANESTHESIA, Issue 7 2009RAJIV CHAUDHARY MBBS MRCPCH Summary Background:, Endotracheal intubation and laryngoscopy are frequently performed procedures in neonatal intensive care. These procedures represent profoundly painful stimuli and have been associated with laryngospasm, bronchospasm, hemodynamic changes, raised intracranial pressure and an increased risk of intracranial hemorrhage. These adverse changes can cause significant neonatal morbidity but may be attenuated by the use of suitable premedication. Aims:, To evaluate current practices for premedication use prior to elective intubation in UK tertiary neonatal units. Methods:, Telephone questionnaire survey of all 50 tertiary neonatal units in the UK. Results:, Ninety percent of units report the routine use of sedation prior to intubation and 82% of units routinely use a muscle relaxant. Morphine was the most commonly used sedative and suxamethonium was the most commonly used muscle relaxant. Approximately half of the units also used atropine during intubation. Seventy seven percent of units had a written policy for premedication. Ten percent of the units did not routinely use any sedatives or muscle relaxants for elective intubation. Conclusions:, In comparison with data from a 1998 survey, our study demonstrated an increase in the number of units that have adopted a written policy for premedication use, and in the number routinely using premedication drugs for elective intubation. There remains little consensus as to which drugs should be used and in what dose. [source] The efficacy of morphine and Entonox analgesia during chest drain removal in childrenPEDIATRIC ANESTHESIA, Issue 3 2006ELIZABETH BRUCE BSc(HONS) MSc RSCN RGN Summary Background:, Morphine is commonly used for chest drain removal pain, although a few studies in adults suggest that inhalation agents may be effective for this procedure. Little is known about chest drain removal pain and its management in children. Methods:, Three separate studies were carried out at a large tertiary pediatric hospital to examine the characteristics and management of chest drain removal pain in children. Study 1 examined the prevalence and clinical characteristics of pain and analgesic practices in 135 nonventilated children aged 1 week to 18 years having chest drains removed. Study 2 was an observation study to determine the efficacy and safety of self-administered Entonox (50% nitrous oxide and oxygen) for chest drain removal pain in 30 children aged 7,18 years. Study 3 was a pilot randomized controlled trial comparing intravenous morphine and continuous flow Entonox for chest drain removal pain in 14 children aged 3.5 months to 2.75 years. Results:, In study 1, the prevalence of moderate to severe pain during chest drain removal was 76%. Morphine was commonly given preprocedure, but the dose varied considerably. In study 2, children experienced a significant increase in pain during the procedure compared with preprocedure pain at rest, despite receiving Entonox, morphine and/or diclofenac. However, procedure pain was no worse than preprocedure pain during movement or deep breathing. A few minor side effects occurred, which resolved spontaneously. In study 3, no differences were found in pain between the two treatment groups. Children experienced moderate to severe pain during the procedure, despite receiving Entonox or morphine. Conclusions:, Morphine or Entonox alone are unlikely to provide adequate analgesia for chest drain removal pain in children. More research is needed to determine the most effective interventions for this procedure. [source] Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphinePEDIATRIC ANESTHESIA, Issue 3 2003Thomas Engelhardt MD SummaryBackground: Pain control for paediatric patients undergoing tonsillectomy remains problematic. Tramadol is reported to be an effective analgesic and to have a side-effect profile similar to morphine, but is currently not licensed for paediatric use in the UK. Methods: We conducted a prospective, double-blind, randomized controlled trial in children who were scheduled for elective tonsillectomy or adenotonsillectomy at the Royal Aberdeen Children Hospital. Following local ethics committee approval and after obtaining a drug exemption certificate from the Medicines Licensing Agency for an unlicensed drug, we recruited 20 patients each into morphine (0.1 mg·kg,1), tramadol (1 mg·kg,1) and tramadol (2 mg·kg,1) groups. These drugs were given as a single injection following induction of anaesthesia. In addition, all patients received diclofenac (1 mg·kg,1) rectally. The postoperative pain scores, analgesic requirements, sedation scores, signs of respiratory depression and nausea and vomiting, as well as antiemetic requirements, were noted at 4-h intervals until discharge. Results: There were no statistically significant differences in age, weight, type of operation or induction of anaesthesia, 4-h sedation and pain scores and further analgesic requirements. There were no episodes of respiratory depression. Morphine was associated with a significantly higher incidence of vomiting following discharge to the wards (75% versus 40%, P=0.03) compared with both tramadol groups. Conclusions: Tramadol has similar analgesic properties, when compared with morphine. The various pharmaceutical presentations and the availability as a noncontrolled substance may make it a useful addition to paediatric anaesthesia if it becomes licensed for paediatric anaesthesia in the UK. [source] Tropisetron reduces postoperative vomiting in children undergoing tonsillectomyPEDIATRIC ANESTHESIA, Issue 1 2000Anette B. Jensen MS Summary In this patient, parent and investigator blinded, randomized, placebo-controlled study, children undergoing tonsillectomy (mean age 6.4 years) received either intravenous placebo (n=36) or tropisetron 0.2 mg·kg,1 up to 5 mg (n=35) at induction of anaesthesia with halothane, nitrous oxide and oxygen. Morphine and paracetamol were given in theatre for postoperative pain. Episodes of vomiting were recorded during the first 24 h after surgery. Intravenous tropisetron was significantly (P<0.001, chi-squared) more effective than placebo in controlling the incidence and frequency of emesis during the first 24 h: vomiting was reduced from 89% to 46% and the mean number of vomits from 4.6 to 2.4. Minor side-effects occurred equally in both the placebo and active groups. Intravenous tropisetron is an effective and safe antiemetic for reducing postoperative vomiting in children undergoing tonsillectomy or adenotonsillectomy. [source] Effect of crocin on the morphine-induced antinociception in the formalin test in ratsPHYTOTHERAPY RESEARCH, Issue 3 2010Esmaeal Tamaddonfard Abstract In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra-plantar (i.pl.) injection of formalin (50,,L, 1%), and the time spent licking and biting of the injected paw was measured for 1,h. Formalin induced a marked biphasic (first phase: 0,5,min and second phase: 15,45,min) pain response. Morphine (1,mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2,mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2,mg/kg) significantly (p < 0.05) prevented morphine (1,mg/kg)-induced antinociception. Crocin at doses of 50, 100 and 200,mg/kg significantly (p < 0.05) attenuated pain. Crocin (100,mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1,mg/kg, s.c.)-induced antinociception. Naloxone (2,mg/kg) did not reverse the suppressive effect of crocin (100,mg/kg) on pain. Crocin at a dose of 400,mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone-sensitive mechanism produced analgesia. Crocin produced a dose-dependent antinociceptive effect. In addition, crocin increased morphine-induced antinociception, but naloxone did not change the antinociceptive effect of crocin. Copyright © 2009 John Wiley & Sons, Ltd. [source] Gas chromatography/negative-ion chemical ionisation mass spectrometry for the quantitative analysis of morphine in human plasma using pentafluorobenzyl carbonate derivativesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2002H. J. Leis A sensitive and specific method for the quantitative determination of morphine in human plasma is presented. Morphine was extracted from plasma by solid phase extraction on C18 and converted to its pentafluorobenzyl carbonate trimethylsilyl derivative. The derivatives were analysed without further purification. Using gas chromatography/negative ion chemical ionisation mass spectrometry, a useful diagnostic fragment ion at m/z 356 is obtained at high relative abundance. Deuterated morphine was used as internal standard. Calibration graphs were linear within the range 1.25 to 320,nmol/L. Intra-day precision was 3.82% (15,nmol/L), 2.85% (75,nmol/L) and 4.13% (225,nmol/L), inter-day variability was found to be 1.77% (15,nmol/L), 4.95% (75,nmol/L) and 9.88% (225,nmol/L). Inter-day accuracy showed deviations of 2.18% (15,nmol/L), ,0.72% (75,nmol/L) and ,0.13% (225,nmol/L). The method is rugged and robust and has been applied to the batch analysis of morphine during pharmacokinetic profiling of the drug. Copyright © 2002 John Wiley & Sons, Ltd. [source] Antinociceptive effect of a ruthenium complex in miceAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2008M. P. Cristiano Summary 1,The ruthenium complexes are important tools in inorganic chemistry. Different biological properties are found in the presence of distinct coordinate ligands, which offer a variety of potential clinical and pharmacological uses. 2,The aim of this work was to evaluate the antinociceptive and behavioural effects of the ruthenium complex, trans -[RuCl2(i-dinic)4]Cl, in mice. 3,The potential analgesic activity was tested using the formalin and hot plate tests and the behavioural effect was evaluated using the rotarod and spontaneous locomotor tests. The complex was administered at concentrations of 1.3, 4.5 and 18.0 ,mol kg,1 i.p. Morphine (6.0 mg kg,1, i.p.) and diclofenac sodium (20.0 mg kg,1, i.p.) were used as reference drugs. 4,The compound had no sedative activity on motor ataxia in the behavioural and analgesic tests. No significant effect was observed in the first phase of the formalin test, however, an effect was observed in the second phase. 5,The complex studied was probably more powerful than the reference drugs as an antinociceptive agent, as this mechanism also involved the nitric oxide (NO) pathway. From this perspective, further experimental studies will be useful to understand the effect of these compounds on NO and the relationship between prostaglandin and NO biosynthesis. [source] | ||||||||||||||||||||||||||||||||||||||||