Relapse to drug taking is a major factor contributing to the low success rate of opioid addiction treatment programmes. Recently, studies have revealed a buprenorphine/naltrexone combination had successfully increased the treatment retention rate (compared to naltrexone alone) among heroin addicts (with history of cocaine abuse) who had undergone detoxification. However, buprenorphine and naltrexone could not be administered as a single formulation due to their different bioavailability, which could create compliance issues. Therefore, in this project, we aimed to synthesise a series of ligands each having the pharmacological profile of the buprenorphine/naltrexone combination (partial agonist (ORL-1 receptors), antagonist (u- and x-opioid receptors)). Based on the group's previous work, this profile can be achieved within the orvinols series. Compound BU127, a buprenorphine analogue with phenyl substituent (C20) is very close to the desired profile. Therefore, in order to optimize BU127's profile, we designed and synthesised a series of aromatic analogues, including analogues with a small group attached to the aromatic system to increase the ORL-1 receptor efficacy, while retaining the low efficacy / antagonist activity at the u-opioid receptor and antagonist activity at x-opioid receptor. However, [35S]GTPyS screening has shown a sudden increase of x-opioid receptor efficacy with these modifications. The related compound BU10119, having a Cv-methyl, met the desired profile at all targeted receptors in the [35S]GTPyS screen. A few analogues were selected for further evaluation in functional assays in the isolated tissue preparations (rat vas deferens (for the ORL-1 and u-opioid receptors) and mouse vas deferens (for the K-opioid receptor)) to estimate their binding affinity (Ks) and potency (pA2) of the compounds relative to buprenorphine, using Schild analysis and Schild equation. Of the analogues synthesised, only compounds BU127 and BU1 0119 have met the desired profile at the targeted receptors (competitive reversible at the ORL-1 and u-opioid receptors) and having binding affinity at each receptor similar to buprenorphine (ORL-1, ~- and K-opioid receptors). Based on these results, at this point, the optimum features of buprenorphine analogues in order to achieve the targeted profiles are having a small group at Cy and a 6-membered aromatic substituent at C . 20 Without any substituent group attached to the aromatic ring.

Behavioral Modification and Relapse Rates in Opioid-Dependent Pregnant Women Managed with Subutex by Tammy Minor MSN, Walden University, 2009 BSN, Marshall University, 1986 Project Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Nursing Practice Walden University March 2016 Opioid dependency affects not only the individual who is dependent on opioids but negatively impactsalso the family unit, the community, and society as a whole. Opioid use in the prenatal period can have devastating effects on both the mother and the fetus. The purpose of this paper is to perform a secondary analysis of the effectiveness of behavioral modification in reducing relapse rates and improving compliance of treatment regimen in opioid- dependent pregnant women who were being managed in a FamilyCare Health Center in West Virginia. The transtheoretical model was used as a framework to determine participants' behavioral readiness to change. The Stetler model was used to evaluate outcomes and goal achievement. The sample consisted of 43 pregnant opioid-dependent women who had participated in the Subutex-assisted program at 3 Family Care Health Centers in West Virginia. Descriptive statistics and regressive analysis were used to analyze relapse data at weeks 2, 6, and 10. A secondary analysis was conducted to determine if behavioral modification contributed to a reduction in relapse rates and improved compliance with the treatment regimen using ANOVA and MANOVA. The results of ANOVA and MANOVA tests showed that behavioral modification has a potential to influence a reduction in relapse rates in the target population. The information obtained from this analysis can be used to influence social change by assisting healthcare providers in revising or modifying existing programs; this information can also and inform the help to design of future programs that effectively meet the needs of this target population .

Syftet med studien var att undersöka hur olika professionella yrkesverksamma inom missbruksvården upplever LARO behandling. Vi valde att rikta in oss på förändringsproccesen som kan tillkomma för klienter när man genomför en LARO behandling samt vad som hindrar eller möjliggör förändring för klienter som har/haft LARO behandling. Därav riktade vi in oss på vilket sätt de olika professionella yrkesverksama inom missbruksvården tycker att LARO är en del i en förändringsprocess. Studien grundar sig i en hermenutistiskt utgångspunkt där semistrukterade intervjuer genomfördes med sex olika professionella yrkersverksamma som arbetar inom missbruksvården i södra Sverige. Den teorietiska utgångspunkten som denna studien innehar är James Prochaska och Carlo Di Clementes, Stages of change. Studiens resultat visar att de professionella yrkerverksamma i missbruksvården upplever att LARO är en behandlingsmetod som funkar när den är kontrollerat och när andra inkopplande insatser samarbetar tillsammans runt omkring klienten. Det som sedan vårt resultat påvisade var det faktum att möjligheterna till förändring uppstår genom motivation, vilja och resurser. Denna behandlingsmetod skapar möjligheter till att förbättra klienters livskvalite samt att förändringen utav det befintliga beteendet bidrar till att man utvecklar egenskaper som hjälpen en i sin förändringsprocess.

Made available in DSpace on 2016-01-26T18:55:29Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 268100 bytes, checksum: 6241b0a17b0be139b2c12e6e32575a6d (MD5) Previous issue date: 2009-08-31 / This double-blind study compared the cardiorespiratory, analgesic, sedative and neuroendocrine effects of different doses of tramadol administered intravenously (iv) in bitches, submitted to ovariohisterectomy. The animals were randomly assigned to three groups of 08 animals each, and treated with doses of tramadol in1mg kg-1 (GT1), 2mg kg-1 (GT2) and 4mg kg-1 (GT4). The pre-anesthetic medication administered was acepromazine (0.05 mg kg-1 iv), the anesthetic induction was performed with propofol (4mg kg-1 iv), and subsequent maintenance with general inhalatory anesthesia with isoflurane. The tramadol was administered 5 minutes after general inalatory anesthesia in all groups. Heart rate, respiratory rate, rectal temperature, systolic blood pressure, degree of analgesia and sedation, serum cortisol concentration and adverse effects were measured. In relation to analgesia degee there was not difference between the groups, excepted in the 3rd h after surgery, when GT4 group had lower pain scores than other groups. In the cardiorespiratory, mild alterations were observed, without difference between the groups. Sedation degree was not different between the groups, with lower scores until the 3rd h after to the end of surgery. The serum cortisol did not differ between the groups, although an increase was observed in the trans-operative period until the 3rd h after to the end of surgery. Vomit was observed in 50% of the dogs. It was concluded that the different doses of tramadol promoted satisfactory analgesia, with mild sedative and cardiorespiratory effects in bitches submitted to ovariohisterectomy. / Esse estudo duplo cego comparou os efeitos cardiorrespiratório, analgésico, sedativo e neuroendócrino de diferentes doses de tramadol administrado via intravenosa (iv) em cadelas, submetidas a ovariossalpingohisterectomia (OSH). Os animais foram distribuídos aleatoriamente em três grupos de 8 animais cada, sendo tratados com tramadol nas doses de 1mg kg-1 (GT1), 2mg kg-1 (GT2) e 4mg kg-1 (GT4). Na medicação pré-anestésica foi administrada acepromazina (0,05mg kg-1 iv), a indução anestésica foi realizada com propofol (4mg kg-1 iv), com posterior manutenção em anestesia geral inalatória, com isoflurano. O tramadol foi administrado 5 minutos após a estabilização da anestesia geral inalatória em todos os grupos. Foram mensurados: frequência cardíaca (FC), frequência respiratória (f), temperatura retal (T), pressão arterial sistólica (PAS), grau de analgesia, grau de sedação, concentração sérica de cortisol e efeitos adversos. Com relação ao escore de dor, não houve diferença entre grupos, com exceção da 3ª h pós-cirúrgica em que o GT4 apresentou escores inferiores em relação aos demais grupos. Na avaliação cardiorrespiratória mínimas alterações foram observadas, sem diferença entre os grupos. O cortisol não variou entre os grupos, porém foi observado aumento no período trans-operatório e às 3h após término da cirurgia. O grau de sedação não variou entre os grupos, com escores mais baixos até a 3ª h de avaliação pós-cirúrgica. Vômito foi observado em 50% dos animais do GT4. Conclui-se que as doses de tramadol empregadas nesse estudo induziram efeito analgésico adequado, com discreto efeito sedativo e mínimas alterações cardiorrespiratórias em cadelas submetidas à OSH.

Made available in DSpace on 2016-07-18T17:53:06Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 268100 bytes, checksum: 6241b0a17b0be139b2c12e6e32575a6d (MD5) Previous issue date: 2009-08-31 / This double-blind study compared the cardiorespiratory, analgesic, sedative and neuroendocrine effects of different doses of tramadol administered intravenously (iv) in bitches, submitted to ovariohisterectomy. The animals were randomly assigned to three groups of 08 animals each, and treated with doses of tramadol in1mg kg-1 (GT1), 2mg kg-1 (GT2) and 4mg kg-1 (GT4). The pre-anesthetic medication administered was acepromazine (0.05 mg kg-1 iv), the anesthetic induction was performed with propofol (4mg kg-1 iv), and subsequent maintenance with general inhalatory anesthesia with isoflurane. The tramadol was administered 5 minutes after general inalatory anesthesia in all groups. Heart rate, respiratory rate, rectal temperature, systolic blood pressure, degree of analgesia and sedation, serum cortisol concentration and adverse effects were measured. In relation to analgesia degee there was not difference between the groups, excepted in the 3rd h after surgery, when GT4 group had lower pain scores than other groups. In the cardiorespiratory, mild alterations were observed, without difference between the groups. Sedation degree was not different between the groups, with lower scores until the 3rd h after to the end of surgery. The serum cortisol did not differ between the groups, although an increase was observed in the trans-operative period until the 3rd h after to the end of surgery. Vomit was observed in 50% of the dogs. It was concluded that the different doses of tramadol promoted satisfactory analgesia, with mild sedative and cardiorespiratory effects in bitches submitted to ovariohisterectomy. / Esse estudo duplo cego comparou os efeitos cardiorrespiratório, analgésico, sedativo e neuroendócrino de diferentes doses de tramadol administrado via intravenosa (iv) em cadelas, submetidas a ovariossalpingohisterectomia (OSH). Os animais foram distribuídos aleatoriamente em três grupos de 8 animais cada, sendo tratados com tramadol nas doses de 1mg kg-1 (GT1), 2mg kg-1 (GT2) e 4mg kg-1 (GT4). Na medicação pré-anestésica foi administrada acepromazina (0,05mg kg-1 iv), a indução anestésica foi realizada com propofol (4mg kg-1 iv), com posterior manutenção em anestesia geral inalatória, com isoflurano. O tramadol foi administrado 5 minutos após a estabilização da anestesia geral inalatória em todos os grupos. Foram mensurados: frequência cardíaca (FC), frequência respiratória (f), temperatura retal (T), pressão arterial sistólica (PAS), grau de analgesia, grau de sedação, concentração sérica de cortisol e efeitos adversos. Com relação ao escore de dor, não houve diferença entre grupos, com exceção da 3ª h pós-cirúrgica em que o GT4 apresentou escores inferiores em relação aos demais grupos. Na avaliação cardiorrespiratória mínimas alterações foram observadas, sem diferença entre os grupos. O cortisol não variou entre os grupos, porém foi observado aumento no período trans-operatório e às 3h após término da cirurgia. O grau de sedação não variou entre os grupos, com escores mais baixos até a 3ª h de avaliação pós-cirúrgica. Vômito foi observado em 50% dos animais do GT4. Conclui-se que as doses de tramadol empregadas nesse estudo induziram efeito analgésico adequado, com discreto efeito sedativo e mínimas alterações cardiorrespiratórias em cadelas submetidas à OSH.

Bakgrund: Smärta är en komplex, individuell och subjektiv upplevelse och kan således inte jämföras mellan olika individer. I sjuksköterskans arbetsuppgifter ingår bland annat att lindra lidande och behandla alla människor med respekt. För patienter med smärta och samtidigt opioidberoende kan smärtlindringen skapa utmaningar för sjuksköterskan men även för patienten där kommunikation är en faktor för optimal omvårdnad. Syfte: Syftet med studien var att undersöka sjuksköterskans och den opioidberoende patientens erfarenheter vid smärtlindring.Metod: En litteraturstudie med kvalitativ design utfördes med hjälp av tolv vetenskapliga artiklar.Resultat: Sjuksköterskan upplevde patientgruppen som ”svår” på grund av rädslan av att upprätthålla patientens beroende. Delade uppfattningar kring behandlingssmålen skapade konflikter mellan sjuksköterskan och patienten. Sjuksköterskorna önskade mer utbildning för att lättare kunna behandla patientgruppen. Stödet av kollegor gav en ökad trygghet för sjuksköterskorna i omvårdnadsarbetet. Det framkom att patienterna ofta upplevde frustration på grund av förutfattade meningar hos sjuksköterskorna samt att de upplevde sig bli olikt behandlade. Ömsesidig respekt och vikten av kommunikation ökade förtroendeskapandet. Konklusion: Det saknas rätt utbildning för sjuksköterskor att ge korrekt omvårdnad till patientgruppen. Förutfattade meningar påverkar hur sjuksköterskan bemöter patienten. Att ta hjälp av sina kollegor och arbeta i team ger en säkrare omvårdnad och att skapa ett partnerskap med patienten bidrar till ökat förtroende. Patienterna önskar att bli bemötta med respekt där sjuksköterskan ser bortom beroendet. Nyckelord: Erfarenheter, opioidberoende, sjuksköterska, smärta, smärtlindring, stigmatisering. / Background: Pain is a complex, subjective and individual experience and can therefore not be compared between patients. One of the duties for the nurse is to relieve pain and to show respect. Patients with pain and coexisting opioid-dependency creates challenges concerning pain relief for the nurse but also the patient where communication is a factor for optimal care.Aim: The aim of the literature review is to examine pain relief and opioid-dependency from the nurse and patient perspective.Method: A literature review with a qualitative design using twelve articles.Result: The nurse experienced the patient group as “difficult” because of the fear in maintaining the patient addiction. Different opinions regarding treatment goals created conflicts between the patient and the nurse. Education was something that the nurses wished for in order to more easily treat the patient group. The support from colleagues gave an increased feeling of safety for the nurses in the caring work. Other findings were that the patients often experienced frustration and felt mistreated due to prejudices from the nurses. Mutual respect and the importance of communication helped creating trust.Conclusion: The nurses experienced a lack of education regarding the patient group. Prejudices was determined to how the nurses trust and treat the patient. Teamwork helps to optimize care and the aim of building trust nurses need to create a partnership with the patient. The patients wish to be treated with respect and that the nurses look beyond the addiction.Keywords: Experiences, nurse, opioid dependency, pain, pain relief, stigma.