Opioid-based micro and nanoparticulate formulations: alternative approach on pain management

Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids.     

Opioid-induced or pain relief-reduced symptoms in advanced cancer patients?

BACKGROUND: While opioids in increasing doses may produce adverse effects, the same adverse effects may be associated with poor pain control. Moreover, in the clinical setting symptomatic treatment and illness may balance the outcome of opioid titration. Some adverse effects may tend to disappear continuing the treatment in a long-term period. AIMS: The aim of this study was to monitor the effects of a rapid opioid titration combined with symptomatic treatment in patients with poor relief and to monitor these changes in the following period of 20 days. METHODS: A consecutive sample of 35 patients admitted to an acute Pain Relief and Palliative Care Unit were titrated with opioids, according to a department policy, allowing administration of parenteral opioids to assist opioid titration with oral or transdermal opioids. RESULTS: Thirty-three patients were followed up for the period of the study. Pain was adequately controlled and doses were opioid doses were stable after a mean of 40 h. Opioid escalation index (OEI) was extremely high initially, and then progressively declined at the following study intervals. Weakness and nausea and vomiting did not change, as well as confusion and appetite. Drowsiness, constipation and dry mouth significantly increased and then did not change, although a significant decrease in drowsiness was subsequently observed. Well-being improved some weeks after opioid stabilization. In multivariate analysis, drowsiness and dry mouth were correlated to opioid doses. CONCLUSION: The effects reported were often due to multiple causes. A rapid decrease in pain intensity induced by rapid opioid titration does not produce changes in weakness, nausea and vomiting, appetite. While constipation appears the most relevant problem, resistant to common symptomatic treatment, drowsiness initially produced by acute opioid dose increase and the achievement of pain relief, tends to spontaneously decrease, probably as the result of late tolerance. Improved well-being may be the late positive effect of pain relief, also influenced by the setting of home care.     

Neuraxial anesthesia and postoperative opioid administration for cesarean delivery in patients with placenta accreta spectrum disorder: a retrospective cohort study

BackgroundThere is no consensus on optimal anesthetic and analgesic management of patients presenting for cesarean delivery with suspected placenta accreta spectrum disorder. Neuraxial anesthesia is preferred for uncomplicated procedures, but general anesthesia may be indicated for those at risk of hemorrhage and hysterectomy. We compared the effect of anesthesia techniques on postoperative maternal opioid administration and neonatal respiratory distress.MethodsA single-center retrospective study from 2016 to 2019 using electronic records to identify singleton pregnancies with a high index of suspicion of placenta accreta spectrum disorder. Patients were categorized by the anesthetic technique they received: general, neuraxial, or neuraxial with conversion to general anesthesia following delivery. Postoperative maternal opioid administration (oral morphine in mg equivalents) and risk of neonatal respiratory distress were compared using linear mixed models.ResultsThirty-nine records were analyzed. Mean-adjusted oral morphine mg equivalents were 192 for patients receiving general anesthesia vs. 90 for neuraxial anesthesia only (P=0.009) and 104 for neuraxial with conversion to general anesthesia (P=0.052). Neonates delivered under general anesthesia had a 3.5 times relative risk (95% CI 1.3 to 9.8, P=0.017) of respiratory distress compared with those exposed to neuraxial anesthesia alone.ConclusionPatients receiving general anesthesia alone were administered more opioids than those undergoing neuraxial anesthesia or neuraxial with conversion to general anesthesia. This finding was maintained when accounting for whether or not the patient underwent hysterectomy. Deciding on anesthetic management requires consideration of patient comorbidities, severity of placenta accreta spectrum pathology, and surgical requirements.     

Tibia fractures and NSAIDs. Does it make a difference? A multicenter retrospective study

PurposeThe purpose of this study was to compare healing time for diaphyseal tibia fractures (OTA/AO 42 A, B, C) treated with intramedullary nailing (IMN) in one geographic cohort using nonsteroidal anti-inflammatory drugs (NSAIDs) for post-operative pain control to that of another geographic cohort using opioid medications. The groups represent differing cultural approaches to post-operative pain control. We hypothesized there would be no difference in healing time.MethodsTibia fractures presenting at two level I trauma centers located in different countries between January 1, 2010 and December 31, 2017 were retrospectively screened for enrollment. Fractures classified as OTA/AO 42 A, B, or C that were treated with IMN and had radiographic follow up to union were included. At hospital discharge, one cohort (n = 190) was prescribed NSAIDs and the other (n = 182) was prescribed opioids for pain control. Each analgesic method represented the standard of care for that location. Fracture union was defined as cortical bridging in at least 3 out of 4 cortices on AP and lateral radiographs. The primary outcome was healing time on radiographic evaluation.ResultsThere was no statistically significant difference in healing time between the opioid and NSAID groups: 185 vs 180.5 days respectively (p = 0.64). Both groups had similar mean age. Student t-tests were run to compare rates of tobacco use, diabetes mellitus (DM), open fractures, and polytrauma between the two groups. The opioid cohort had statistically significant higher rates of tobacco use, DM, and polytrauma. The NSAID cohort, however, had a larger number of open fractures.ConclusionThe difference in healing time between the NSAID and opioid groups was not statistically significant. The deleterious effect of NSAID use on fracture healing has been debated for decades. Numerous animal studies have supported this theory; however, high quality clinical studies in humans have not provided convincing evidence to substantiate this negative effect. Our study suggests that NSAIDs may be used safely and effectively in the acute phase of fracture healing without significantly increasing the risk of delayed union or nonunion. Prospective randomized studies are necessary to rule out the negative effect of NSAIDS on bone healing.     

A content review of online naloxone Continuing Education courses for pharmacists in states with standing orders

Background

Many community pharmacists are uncomfortable educating patients about naloxone, an opioid reversal agent.

Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems

Background

Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.

Opioids in neuropathic pain: clues from animal studies.

For many years the clinical consensus was that opioids were ineffective in neuropathic pain. However this view is changing and here we discuss the mechanisms of opioid analgesia in terms of the changes that can occur in preclinical models of nerve injury. We argue that opioid mechanisms can be perturbed by neuropathy but in most cases these negative influences can be overcome by dose-escalation.     

Assessment and management of pain in the terminally ill

Regular assessment for the presence of pain and response to pain management strategies should be high priority in terminally ill patients. Pain management interventions are most effective when treatments are individualized based on the various physical and nonphysical components of pain at the end of life, and patients and family are educated and involved in the decision making. Opioids remain the cornerstone of pain management, and adjuvant analgesics and nonpharmacologic options are usually considered after relative stabilization of pain. This article describes the various issues that are pertinent to the assessment and treatment of pain in terminally ill patients.