Introduction: Pain is commonly experienced by patients with cancer, particularly those with advanced disease. Alleviating pain is an important goal of cancer treatment. Opioids are the cornerstone of the analgesic treatment.
Areas covered: Pharmacology, characteristics, and use of opioids in clinical practice are presented.
Expert opinion: Although the use of opioids is largely accepted as a fundamental step for controlling cancer pain, existing data supporting this statement are poor. All opioids provide analgesia and are effective in controlling cancer pain. New drugs have been developed and experience is accumulating among clinicians. Despite these drugs having different pharmacokinetic and chemical properties, there is no proof that one opioid is better than another one. Thus, the optimum benefit depends on the experience of the users. Clinicians should weight evidence, clinical experience, patient preferences, and treatment costs when choosing the optimal treatment for an individual patient with cancer pain. New opioids with specific receptor activities are under investigation. 相似文献
Introduction: Cancer pain is one of the most important symptoms of malignant disease, which has a major impact on the quality of life of cancer patients. Therefore, it needs to be treated appropriately after a careful assessment of the types and causes of pain.
Areas covered: The mainstay of cancer pain management is systemic pharmacotherapy. This is, in principle, still based on the WHO guidelines initially published in 1986. Although these have been validated, they are not evidence-based. The principles are a stepladder approach using non-opioids, weak and then strong opioids. In addition, adjuvants can be added at any step to address specific situations such as bone or neuropathic pain. Patients, even if they are on long-acting opioids, need to be provided with immediate-release opioids for breakthrough pain. In case of inefficacy or severe adverse effects of one opioid, rotation to another opioid is recommended.
Expert opinion: There is a major need for more and better randomized controlled trials in the setting of cancer pain as the lack of evidence is hampering the improvement of current treatment guidelines. 相似文献
Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10–15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician''s armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients. 相似文献
Context: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value.
Aim: To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature.
Methods: We made a systematic search of EMBASE 1980–2016 using the search terms (“bile/” OR “exp drug bile level/concentration/”) AND “drug blood level/concentration/”, PubMed 1975–2017 for (“bile[tw]” OR “biliary[tw]”) AND (“concentration[tw]” OR “concentrations[tw]” OR “level[tw]” OR “levels[tw]”) AND “post-mortem[tw]” and also MEDLINE 1990–2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs.
Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058–0.32) for dextromoramide to 520 (range 0.62–43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes.
Limitations: The data were difficult to find. Medline does not explicitly index the term “drug bile concentration”. It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile.
Conclusions: For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection. 相似文献
Objective: There is a need to identify safe and effective opioid-sparing multimodal alternative treatment strategies and approaches, including topical analgesics, for opioid-experienced chronic pain patients to mitigate the risk of addiction, misuse, and abuse of opioids.
Methods: This subset analysis from a prospective, observational study evaluated changes in opioid use, other concurrent medication use, and pain severity and interference in opioid-experienced patients (OEP) treated with topical analgesics for chronic pain with measures obtained at baseline and 3- and 6- month follow-up.
Results: The 3-month opioid-experienced patient (3-month OEP) group included 121 patients who completed baseline and 3-month follow-up assessments; 27 opioid-experienced patients completed baseline and 6-month follow-up assessments (6-month OEP). Demographic characteristics, and mean pain severity and interference scores were similar between groups at baseline. After treatment with topical analgesics, 49% of patients in the 3-month and 56% of patients in the 6-month group reported they had completely discontinued use of opioids. In addition, 31% of patients at the 3-month assessment and 30% at the 6-month assessment reported that they were no longer taking any pain medication. Other concurrent medications decreased by 65% after 3 months, and 74% after 6 months. There were statistically significant decreases from baseline in pain severity and interference scores within the 3- (CI:0.7–1.4, 1.4–2.2) and 6-month (CI:0.7–2.4 (severity); CI:1.2–3.5 (interference)) OEP groups.
Conclusions: Opioid use and other concurrent medications decreased among opioid-experienced chronic pain patients after 3- and 6- months of treatment with topical analgesics. Pain severity and interference scores also decreased. The topical analgesics were reported to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings. 相似文献
Morphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine.
Methods
This single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy adult subjects compared the relative bioavailability of morphine ARER 100 mg to that of ER morphine 100 mg in the fasted condition. At 12 and 1.5 hours before dosing and 12 hours after dosing, all subjects received a 50-mg oral naltrexone tablet to minimize opioid-related side effects. Pharmacokinetic parameters including the AUC0–t, AUC0–∞, and Cmax of morphine and its metabolite morphine-6-glucuronide (M6G) were determined at various times up to 48 hours postdose. The bioequivalence of morphine ARER and ER morphine was determined using an ANOVA of the least-squares mean values of morphine and M6G bioavailability.
Findings
Forty-nine subjects completed the study. Both morphine ARER and ER morphine exhibited peak plasma morphine and M6G concentrations of ～30 ng/mL and ～200 ng/mL, respectively, at 3 hours postdose. The 90% CIs of the ln-transformed values of morphine AUC0–t, AUC0–∞, and Cmax were within the 80% to 125% range for bioequivalence. M6G values also indicated bioequivalence of morphine ARER and ER morphine. The most common adverse events were nausea and somnolence.
Implications
These data show that, in these subjects, morphine ARER was bioequivalent to ER morphine, a treatment for pain with well-established efficacy and safety profiles. 相似文献
Substance use and misuse is prevalent in emergency department (ED) populations. While the prevalence of substance use and misuse is reported, sex-specific trends in ED populations have not been documented. We set out to determine the sex-specific prevalence of ED patient substance use during this current epidemic.
Methods
A retrospective electronic data abstraction tool, developed for quality-improvement purposes, was used to assess ED visits in 3 hospitals in northeastern Pennsylvania. All patients with ED diagnosis codes for substance use F10.000 through F 19.999 (excluding F17 codes for nicotine) were abstracted for network ED visits at all 3 hospitals. Data points included ED clinical enrollment site, primary substance used, sex, date of ED visit, disposition (including left without being seen, left against medical advice, discharged, admitted, and treatment in rehabilitation) for 18 months (January 1, 2016 through July 31, 2017). The categorical parameters of sex, clinical enrollment site, diagnosis, date of ED visit, and disposition status were summarized as a proportion of the subject group. Time series analysis was used to assess trends in substance use and misuse visits by patient sex.
Findings
A total of 10,511 patients presented to the EDs during the study time period with a final diagnosis of a substance use?related reason and were included in the analysis. The mean age for these patients was 43.6 (SD 16.4) years, and the majority was male (65.6%, n = 6900). The most common substance in the final diagnosis for the ED visit was alcohol (54.3%; 95% CI, 53.3–55.2), followed by opioids (19.2%; 95% CI, 18.4–19.9) and cannabis (14.4%; 95% CI, 13.7–15.0). Females tended to be younger than males (42.4 years vs 44.3 years; P < 0.001), and were more likely to be discharged after the ED visit than males (36.1% vs 32.3%; P < 0.001). When exploring differences in age by sex and substance, males with a final diagnosis including alcohol- and cannabis-related issues were older than females, whereas females diagnosed with opioid-related reasons were older than males (41.3 vs 38.9 years; P < 0.001).
Implications
There are sex-specific differences in prevalence of patients presenting with substance use in the ED setting. 相似文献
Pain is one of the most common reasons patients present to the emergency department (ED). Emergency physicians should be aware of the numerous opioid and nonopioid alternatives available for the treatment of pain.
Objectives
To provide expert consensus guidelines for the safe and effective treatment of acute pain in the ED.
Methods
Multiple independent literature searches using PubMed were performed regarding treatment of acute pain. A multidisciplinary panel of experts in Pharmacology and Emergency Medicine reviewed and discussed the literature to develop consensus guidelines.
Recommendations
The guidelines provide resources for the safe use of opioids in the ED as well as pharmacological and nonpharmacological alternatives to opioid analgesia. Care should be tailored to the patient based on their specific acute painful condition and underlying risk factors and comorbidities.
Conclusions
Analgesia in the ED should be provided in the most safe and judicious manner, with the goals of relieving acute pain while decreasing the risk of complications and opioid dependence. 相似文献
There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.
Objectives
To compare characteristics of patients with unscheduled vs. scheduled outpatient palliative care clinic visits.
Methods
Medical records of 183 unscheduled cancer new outpatients and 104 unscheduled follow-up (FU) patients were compared with random samples of 361 and 314 scheduled new patients and FU patients, respectively. We gathered data on demographics, symptoms, daily opioid usage, and performance status.
Results
Compared with scheduled new patients, unscheduled new patients had worse Edmonton Symptom Assessment Scale subscores for pain (P < 0.001), fatigue (P = 0.002), nausea (P = 0.016), depression (P = 0.003), anxiety (P = 0.038), drowsiness (P = 0.002), sleep (P < 0.001), and overall feeling of well-being (P = 0.001); had a higher morphine equivalent daily dose of opioids (median of 45 mg for unscheduled vs. 30 mg for scheduled; P < 0.001); and were more likely to be from outside the greater Houston area (P < 0.001). Most unscheduled and scheduled new and FU visits were for uncontrolled physical symptoms. Unscheduled FU patients, compared with scheduled FU patients, had worse Edmonton Symptom Assessment Scale subscores for pain (P < 0.001), fatigue (P < 0.001), depression (P = 0.002), anxiety (P = 0.004), drowsiness (P = 0.010), appetite (P = 0.023), sleep (P = 0.022), overall feeling of well-being (P < 0.001), and higher morphine equivalent daily dose of opioid (median of 58 mg for unscheduled FU visits vs. 40 mg for scheduled FU visits; P = 0.054).
Conclusion
Unscheduled new FU patients have higher levels of physical and psychosocial distress and higher opioid intake. Outpatient palliative care centers should consider providing opportunities for walk-in visits for timely management and close monitoring of such patients. 相似文献
