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Surgery Nov 2023Excessive opioid prescribing has resulted in opioid diversion and misuse. In July 2018, Michigan's Public Act 251 established a state-wide policy limiting opioid...
BACKGROUND
Excessive opioid prescribing has resulted in opioid diversion and misuse. In July 2018, Michigan's Public Act 251 established a state-wide policy limiting opioid prescriptions for acute pain to a 7-day supply. Traumatic injury increases the risk for new persistent opioid use, yet the impact of prescribing policy in trauma patients remains unknown. To determine the relationship between policy enactment and prescribing in trauma patients, we compared oral morphine equivalents prescribed at discharge before and after implementation of Public Act 251.
METHODS
In this cross-sectional study, adult patients who received any oral opioids at discharge from a Level 1 trauma center between January 1, 2016, and June 30, 2021, were identified. The exposure was patients admitted starting July 1, 2018. Inpatient oral morphine equivalents per day 48 hours before discharge and discharge prescription oral morphine equivalents per day were calculated. Student's t test and an interrupted time series analysis were performed to compare mean oral morphine equivalents per day pre- and post-policy. Multivariable risk adjustment accounted for patient/injury factors and inpatient oral morphine equivalent use.
RESULTS
A total of 3,748 patients were included in the study (pre-policy n = 1,685; post-policy n = 2,063). Implementation of the prescribing policy was associated with a significant decrease in mean discharge oral morphine equivalents per day (34.8 ± 49.5 vs 16.7 ± 32.3, P < .001). After risk adjustment, post-policy discharge prescriptions differed by -19.2 oral morphine equivalents per day (95% CI -21.7 to -16.8, P < .001). The proportion of patients obtaining a refill prescription 30 days post-discharge did not increase after implementation (0.38 ± 0.48 vs 0.37 ± 0.48, P = .7).
CONCLUSION
Discharge prescription amounts for opioids in trauma patients decreased by approximately one-half after the implementation of opioid prescribing policies, and there was no compensatory increase in subsequent refill prescriptions. Future work is needed to evaluate the effect of these policies on the adequacy of pain management and functional recovery after injury.
Topics: Adult; Humans; Analgesics, Opioid; Cross-Sectional Studies; Aftercare; Pain, Postoperative; Patient Discharge; Practice Patterns, Physicians'; Morphine
PubMed: 37709648
DOI: 10.1016/j.surg.2023.08.006 -
Indian Journal of Pharmacology 2023
Topics: Ketamine; Morphine; Analgesics, Opioid
PubMed: 38174540
DOI: 10.4103/ijp.ijp_230_23 -
Progress in Neuro-psychopharmacology &... Jan 2024Few pharmacological treatments are available for substance use disorders (SUDs). Neuroplastic changes induced by increased activity of metalloproteinase (MMP) enzymes in...
Few pharmacological treatments are available for substance use disorders (SUDs). Neuroplastic changes induced by increased activity of metalloproteinase (MMP) enzymes in the brain are among the several molecular processes that may play a role in drug addiction. Doxycycline, a widely used tetracycline that crosses the blood-brain barrier, inhibits MMPs and has been investigated as a potential treatment for brain disorders. However, the effects of doxycycline on rewarding properties of drugs of abuse remain not investigated. Here, we tested the effects of low doses of doxycycline on the rewarding effects of morphine and cocaine in conditioned place preference (CPP) and locomotor sensitization in mice. Acute doxycycline (10 mg/kg) attenuated the cocaine-induced CPP and hyperlocomotion. Repeated doxycycline (10 mg/kg) blocked hyperlocomotion and attenuated the locomotor sensitization induced by cocaine. It also decreased the rewarding effects in the CPP induced by morphine and cocaine. Our results suggest that doxycycline could be repurposed for treating SUDs.
Topics: Mice; Animals; Morphine; Cocaine; Doxycycline; Substance-Related Disorders; Reward
PubMed: 37793480
DOI: 10.1016/j.pnpbp.2023.110870 -
The International Journal of... Jul 2023Evidence has accumulated demonstrating the existence of opioid receptor heteromers, and recent data suggest that targeting these heteromers could reduce opioid side...
BACKGROUND
Evidence has accumulated demonstrating the existence of opioid receptor heteromers, and recent data suggest that targeting these heteromers could reduce opioid side effects while retaining therapeutic effects. Indeed, CYM51010 characterized as a MOR (mu opioid receptor)/DOR (delta opioid receptor) heteromer-preferring agonist promoted antinociception comparable with morphine but with less tolerance. In the perspective of developing these new classes of pharmacological agents, data on their putative side effects are mandatory.
METHODS
Therefore, in this study, we investigated the effects of CYM51010 in different models related to drug addiction in mice, including behavioral sensitization, conditioned place preference and withdrawal.
RESULTS
We found that, like morphine, CYM51010 promoted acute locomotor activity as well as psychomotor sensitization and rewarding effect. However, it induced less physical dependence than morphine. We also investigated the ability of CYM51010 to modulate some morphine-induced behavior. Whereas CYM51010 was unable to block morphine-induced physical dependence, it blocked reinstatement of an extinguished morphine induced-conditioned place preference.
CONCLUSIONS
Altogether, our results reveal that targeting MOR-DOR heteromers could represent a promising strategy to block morphine reward.
Topics: Mice; Animals; Morphine; Receptors, Opioid, delta; Receptors, Opioid, mu; Analgesics, Opioid; Reward
PubMed: 37343217
DOI: 10.1093/ijnp/pyad032 -
Scientific Reports Dec 2023Although pain and sepsis are comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ...
Although pain and sepsis are comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ damage caused by sepsis remain inconclusive. Here, we tested the hypothesis that morphine, the gold standard narcotic analgesic, modifies behavioral and hippocampal structural defects induced by sepsis in male rats. Sepsis was induced with cecal ligation and puncture (CLP) and behavioral studies were undertaken 24 h later in septic and/or morphine-treated animals. The induction of sepsis or exposure to morphine (7 mg/kg) elicited similar: (i) falls in systolic blood pressure, (ii) alterations in spatial memory and learning tested by the Morris water maze, and (iii) depression of exploratory behavior measured by the new object recognition test. These hemodynamic and cognitive defects were significantly exaggerated in septic rats treated with morphine compared with individual interventions. Similar patterns of amplified inflammatory (IL-1β) and histopathological signs of hippocampal damage were noted in morphine-treated septic rats. Additionally, the presence of intact opioid receptors is mandatory for the induction of behavioral and hemodynamic effects of morphine because no such effects were observed when the receptors were blocked by naloxone. That said, our findings suggest that morphine provokes sepsis manifestations of inflammation and interrelated hemodynamic, behavioral, and hippocampal deficits.
Topics: Rats; Male; Animals; Morphine; Hippocampus; Analgesics, Opioid; Sepsis; Pain
PubMed: 38052832
DOI: 10.1038/s41598-023-46427-y -
Experimental Animals Aug 2023Chicken embryos (CE) are an experimental model used as an important life science research tool worldwide, and then, adequate anesthetic protocols must be adopted to...
Chicken embryos (CE) are an experimental model used as an important life science research tool worldwide, and then, adequate anesthetic protocols must be adopted to avoid the unjustifiable suffering of animals. Thus, our objective was to evaluate different anesthetic protocols in CEs using an easy inoculation route, the shell membrane (SM). We adopted the heart rate by pulse and the CE movements as a parameter of pain by assessing the vase in the chorioallantoic membrane (CAM) through the shell by a sensor of a multiparametric monitor. CEs were distributed into the following groups: (i) association of ketamine (5 mg/CE), midazolam (0.05 mg/CE) and morphine (0.15 mg/CE); (ii) ketamine (5 mg/CE) and xylazine (0.125 mg/CE); (iii) xylazine (0.0125 mg/CE) and morphine (0.15 mg/CE). The stress method used to test the anesthetic potential of the drugs was high temperature stimulation, keeping the CEs 10 cm from the fire of a Bussen nozzle for 30 s. In this experimental model, associations between different drugs decreased the pulse and the movement, indicating possible sedation. After treatment, the CE's submitted to the stress method had the heart rate and movements kept low in the groups ketamine-midazolam-morphine and ketamine-xylazine, while the non-drug-treated group increased heart rate. In a group treated with xylazine-morphine, the heart rate did not decrease, but the movement decreased after the stimulus. As the best results were the combinations of ketamine-midazolam-morphine and ketamine-xylazine, we recommend these associations for use in embryos in the final third of embryonic development in experimental protocols and euthanasia.
Topics: Chick Embryo; Animals; Midazolam; Ketamine; Xylazine; Chickens; Anesthesia; Anesthetics; Morphine Derivatives
PubMed: 36642540
DOI: 10.1538/expanim.22-0133 -
The Journal of Surgical Research Nov 2023Some surgeons have raised concerns regarding the sympathectomy-like effect of epidural anesthesia during lower limb microvascular reconstruction. The combined... (Review)
Review
INTRODUCTION
Some surgeons have raised concerns regarding the sympathectomy-like effect of epidural anesthesia during lower limb microvascular reconstruction. The combined spinal-epidural (CSE) anesthetic technique incorporates several benefits of spinal and epidural techniques in a single approach. The aim of this study was to analyze the postoperative outcomes of patients undergoing soft-tissue reconstruction of the lower limb by implementing the CSE anesthesia approach.
METHODS
We reviewed medical records from patients who underwent lower limb reconstructive procedures under CSE anesthesia with free tissue transfer from January 2017 to December 2020. We evaluated the postoperative outcomes.
RESULTS
Thirty-eight patients underwent microvascular reconstructive procedures of the lower extremity over the study period. The average age and BMI were 38.4-year and 28 kg/m. All patients only had one postoperative rescue dose with epidural anesthesia. The most common type of flap used was the anterolateral thigh flap (53%). The average splinting time and length of stay (LoS) were 8.4 days and 18.4 days, respectively. Donor-site complications included wound dehiscence (3%) and surgical site infection (3%). Recipient-site complications included partial flap loss (8%) and total flap loss (10%). No pro re nata morphine analgesia was used. Tramadol and/or ketoprofen were administered for postoperative analgesia. The average time to start physiotherapy and to resume daily activities were 10 days and 29 days, respectively.
CONCLUSIONS
The CSE anesthesia for microvascular reconstruction of the lower limb demonstrated a similar success rate compared to historical records. CSE provided adequate pain management and none of the patients required postoperative monitoring in the ICU.
Topics: Humans; Anesthesia, Epidural; Anesthesia, Spinal; Surgical Flaps; Thigh; Morphine; Lower Extremity
PubMed: 37562232
DOI: 10.1016/j.jss.2023.07.026 -
Advanced Emergency Nursing JournalThe emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last... (Review)
Review
The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.
Topics: Humans; Analgesics, Opioid; Emergency Service, Hospital; Fentanyl; Hydromorphone; Morphine
PubMed: 37885077
DOI: 10.1097/TME.0000000000000480 -
Pharmacology Research & Perspectives Aug 2023Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The...
Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.
Topics: Animals; Rats; Receptors, Opioid; Serotonin; Oxycodone; Morphine; Analgesics, Opioid; Naloxone; Pain
PubMed: 37488088
DOI: 10.1002/prp2.1119 -
Addiction Biology May 2024Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact...
Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.
Topics: Animals; Substance Withdrawal Syndrome; Reward; Motivation; Male; Goals; Morphine; Rats; Morphine Dependence; Narcotics; Conditioning, Operant
PubMed: 38706098
DOI: 10.1111/adb.13393