右美托咪定临床应用的研究进展

α2肾上腺受体分布于机体各组织,关于右美托咪定的临床应用及其与机体α2肾上腺受关系的研究不能仅局限于其镇静和镇痛作用方面。除此以外,右美托咪定在临床其他方面也有许多值得注意的作用。右美托咪定具有器官保护、酒精戒断症状治疗以及对恐惧记忆形成的抑制作用等,该文对相关的研究进展予以综述。     

二陈汤对吗啡依赖小鼠位置偏爱效应的影响

目的：探讨二陈汤对吗啡诱导的小鼠条件性位置偏爱（CPP）的影响。方法：连续给予小鼠吗啡（9 mg/kg,sc,7 d）,使小鼠产生显著的条件性位置偏爱效应。将小鼠随机分为正常对照组、吗啡组、二陈汤低剂量、中剂量、高剂量五组,正常对照组注射等体积生理盐水,吗啡组注射吗啡,二陈汤组注射吗啡,同时给予三种不同剂量的二陈汤灌胃,并且检测对小鼠的奖赏效应或厌恶效应。结果：吗啡组小鼠在伴药箱中停留的时间明显延长,二陈汤可抑制吗啡引起的小鼠位置偏爱的形成。结论：二陈汤能在一定程度上抑制吗啡诱导的小鼠条件性位置偏爱效应。     

The role of “Integrated Pulmonary Index” monitoring during morphine-based intravenous patient-controlled analgesia administration following supratentorial craniotomies: a prospective,randomized, double-blind controlled study

Objective: Morphine is commonly used in post-operative analgesia, but opioid-related respiratory depression causes a general reluctance for its use. The “Integrated Pulmonary Index” is a tool calculated from non-invasively obtained respiratory and hemodynamic parameters. The aim of this prospective, randomized, double blind, and placebo-controlled study is to determine a more safe and effective dose for morphine in patient-controlled analgesia following supratentorial craniotomy using the “Integrated Pulmonary Index”.

Methods: This study included 60 patients (ASA I, II, and III). All patients used iv PCA for 24?h following supratentorial craniotomy. The PCA was set to administer a bolus dose of 1?mg morphine in Group 1 and 0.5?mg morphine in Group 2. The PCA contained placebo in Group 3 and patients received dexketoprofen 50?mg iv after awakening, repeated every 8?h. The IPI and NRS scores, total morphine consumption, and morphine related side-effects were recorded at 10?min, 1, 2, 6, 12, and 24?h post-operatively. The lowest IPI score, count of apnea, and desaturation events were recorded during the study period.

Results: The IPI scores were similar among the groups. Although a statistically significant difference was not observed among the groups the lowest IPI scores were observed in Group 1; apnea and desaturation counts were also higher in Group 1. Statistically significant differences were not observed among the groups in terms of pain scores, but were lower in Groups 1 and 2 compared to Group 3.

Conclusion: Patient controlled analgesia with 0.5?mg morphine may be safe and effective for pain management following supratentorial craniotomies. Integrated pulmonary index can be used for detecting opioid-induced respiratory depression.

Clinical Trials registration number: NCT02929147.     

Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules

ABSTRACT

Objective: To demonstrate the efficacy and tolerability of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN) for the treatment of chronic, moderate-to-severe, non-malignant pain in a community-based outpatient population not satisfactorily relieved with their current therapies.

Design: Phase IV, prospective, randomized, open-label, blinded endpoint.

Participants: Adults (N = 1428) with chronic, moderate-to-severe, non-malignant pain with visual numeric scale scores ≥ 4 (0 = no pain; 10 = worst pain).

Interventions: Patients were randomized to P‐ERMS once daily in am or pm for a 4‐week treatment period. Dose increases were allowed; however, switching to twice-daily dosing was reserved until week 2.

Main outcome measures: Improvement from baseline in pain and sleep scales (0–10) (after weeks 2 and 4), quality of life (physical and mental component summary scores of the SF-36v2 Health Survey) (week 4), and patient (weeks 2 and 4) and clinician (week 4) assessments of current therapy (–4 to +4). Patient satisfaction was assessed again 1 month after the study.

Results: Approximately 70% of patients completed the study, with 2.4% (n = 34) discontinuing due to lack of efficacy, and 9.6% (n = 136) discontinuing due to an adverse event. Improvements were seen in pain and sleep scores, physical and mental component scores of the SF-36v2, and patient and clinician global assessment scores (?p < 0.0001, all assessments). Patients attained similar results regardless of am vs. pm dosing. More than half (55.4%) of patients were maintained on once-daily therapy, with the remainder on a twice-daily regimen, in accordance with the prescribing information. Most adverse events (71.6%) were mild to moderate in severity, the most common being constipation (11.6%) and nausea (9.2%). One‐month follow-up indicated continued satisfaction with P‐ERMS vs. previous medication (?p < 0.0001).

Conclusions: P‐ERMS was efficacious and well tolerated in patients with chronic, moderate-to-severe, non-malignant pain when used once or twice daily.     

Management of emergent psychiatric symptoms during smoking cessation

ABSTRACT

Background: Tobacco smoking is a major risk factor for cardiovascular disease, respiratory disease and cancer and, for current smokers, smoking cessation is one of the most effective therapeutic interventions for reducing the risk of all-cause morbidity and mortality. However, smoking cessation causes nicotine withdrawal syndrome, a condition with symptoms that overlap those of major depression and anxiety disorders.

Scope: The objective of this review was to examine the evidence that smoking cessation may be associated with new onset of psychiatric illness, particularly in individuals with no history of psychiatric disease, and to provide recommendations for the management of emergent psychiatric symptoms in smokers attempting cessation. Relevant articles were obtained from a MEDLINE search (articles indexed up to, and including, October 2008, with no historical date limit), and citation review of selected primary and review articles.

Findings: There is evidence that smoking cessation can result in new onset of major depressive disorder, even in individuals with no history of depression. It has also been suggested that nicotine may be used as a form of self-medication for depression, and that smoking cessation can reveal a previously undiagnosed condition. There is little evidence of an association between smoking cessation and increased risk for other types of psychiatric illness. The management of emergent psychiatric symptoms in smokers attempting abstinence is discussed.

Conclusion: The overall health benefits of quitting smoking undoubtedly outweigh any potential side-effects associated with nicotine withdrawal. However, a well-managed quit attempt must plan for the emergence of nicotine withdrawal, monitor for symptoms of depression and psychiatric disease, and manage these conditions appropriately should they present.     

Behavioral,biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

Background

Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF₁) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking.

Methods

We review the biology of CRF₁ systems, the activity of CRF₁ receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF₁ receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF₁ receptor pharmacotherapy for alcohol dependence.

Results

The evidence suggests that brain penetrant-CRF₁ receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF₁ receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation.

Conclusions

Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF₁ receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence.     

Anxiety and depressive symptoms and affective patterns of tobacco withdrawal

Background

The complex concordance and discordance across and within anxiety and depressive symptoms complicates understanding of the relation between emotional symptoms and manifestations of tobacco withdrawal. The goal of this study was to parse the broad variation in anxiety and depressive symptoms into conceptually discrete components and explore their relative predictive influence on affective patterns of acute tobacco withdrawal.

Methods

We employed a within-participant experimentally manipulated tobacco abstinence design involving: (i) a baseline visit at which past-week depression and anxiety symptoms were assessed and (ii) two counterbalanced experimental visits—one after ad lib smoking and one after 16-h of tobacco abstinence—at which state affect was assessed. Participants were community-dwelling adults (N = 187) smoking 10+ cig/day for at least two years without an active mood disorder.

Results

Anxiety-related general distress symptoms (e.g., tension, nervousness) predicted greater abstinence-induced increases in various negative affective states but not changes in positive affect (βs .17–.33). Depression-related general distress symptoms (e.g., sadness, worthlessness) predicted greater abstinence-induced increases in acute depressed affect only (βs .24–.25). Anhedonic symptoms (e.g., diminished interest, lack of pleasure) predicted larger abstinence-induced decreases in acute positive affect only (βs .17–.20). Anxious Arousal symptoms (e.g., shakiness, heart racing) predicted larger abstinence-induced increases in fatigue and depressive affect (βs .15–.24).

Conclusion

Different components of anxiety and depressive symptoms are associated with unique affective patterns of acute tobacco withdrawal. These results provide insight into the affective mechanisms underlying tobacco dependence and could inform smoking cessation treatment approaches tailored to individuals with emotional distress.     

The prevalence of cigarette smoking in an acute inpatient physical medicine and rehabilitation population

The purpose of this study was to determine the prevalence of cigarette smoking among patients before and after discharge from an acute inpatient physical medicine and rehabilitation unit and. to assess smokers’ interest in and desire for smoking cessation. A consecutive sample of inpatients (n = 233) admitted over a 5‐month period to a regional rehabilitation inpatient center for acute rehabilitation treatment was surveyed for their smoking patterns. Ten percent of patients admitted to rehabilitation were active smokers prior to their hospitalization. In spite of reporting high motivation to stop smoking, half were not interested in participating in a smoking cessation program if one were offered to them. Following discharge from inpatient rehabilitation, 54% of a small sample of patients who could be contacted had resumed smoking (all within 4 weeks of being home). Given the prevalence of smoking in this population and its adverse consequences on health and quality of life, we suggest that rehabilitation professionals actively address this health problem during the patient's hospitalization.     

Rapid transition from methadone to buprenorphine using naltrexone-induced withdrawal: A case report

Background: Patients taking methadone for opioid use disorder may desire transition to buprenorphine for a number of reasons. However, the current recommended approach for this transition generally takes weeks to months as an outpatient, causing considerable discomfort to the patient and a heightened risk of relapse during the transition period. Case: We describe the case of a patient on methadone maintenance who was rapidly transitioned to buprenorphine because of her desire to not return to her methadone clinic. In order to rapidly transition the patient from methadone to buprenorphine, naltrexone was administered to precipitate acute opioid withdrawal, which was followed soon after by buprenorphine induction. Discussion: Rapid transition from methadone maintenance to buprenorphine can be accomplished in inpatients by precipitating acute withdrawal with naltrexone, providing an effective alternative for patients who cannot tolerate the typical protracted methadone taper required prior to buprenorphine induction as an outpatient.     

Craving in Alcohol-Dependent Patients After Detoxification Is Related to Glutamatergic Dysfunction in the Nucleus Accumbens and the Anterior Cingulate Cortex

The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.