Effects Of Opioids Research Articles

Pharmacological pain and sedation interventions for the prevention of intraventricular hemorrhage in preterm infants on assisted ventilation - an overview of systematic reviews.

Pharmacological pain and sedation interventions for the prevention of intraventricular hemorrhage in preterm infants on assisted ventilation - an overview of systematic reviews.

Interaction between benzodiazepines and prescription opioids on incidence of hard braking events in older drivers.

Polypharmacy use among older adults is of increasing concern for driving safety. This study assesses the individual and joint effects of benzodiazepines and prescription opioids on the incidence of hard braking events in older drivers. Data for this study came from the Longitudinal Research on Aging Drivers project-a multisite, prospective cohort study of 2990 drivers aged 65-79 years at enrollment (2015-2017). Adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (defined as maneuvers with deceleration rates ≥0.4 g and commonly known as near-crashes) were estimated through multivariable negative binominal modeling. Of the 2929 drivers studied, 167(5.7%) were taking benzodiazepines, 163 (5.6%) prescription opioids, and 23 (0.8%) both drugs at baseline. The incidence rates of hard braking events per 1000 miles driven were 1.14 (95% CI 1.10-1.18) for drivers using neither benzodiazepines nor prescription opioids, 1.25 (95% CI 1.07-1.43) for those using benzodiazepines only, 1.55 (95% CI 1.35-1.76) for those using prescription opioids only, and 1.63 (95% CI 1.11-2.16) for those using both medications. Multivariable modeling revealed that the use of prescription opioids was associated with a 19% increased risk of hard braking events (aIRR 1.19, 95% CI 1.03-1.36). There existed a positive interaction between the two drugs on the additive scale but not on the multiplicative scale. Concurrent use of benzodiazepines and prescription opioids by older drivers appears to affect driving safety through increased incidence of hard braking events.

Beyond the Syndemic of Opioid Use Disorders and HIV: The Impact of Opioids on Viral Reservoirs.

People with HIV are more likely to have opioid use disorder and to be prescribed opioids for chronic pain than the general population; however, the effects of opioids on the immune system and HIV persistence have not been fully elucidated. Opioids may affect HIV reservoirs during their establishment, maintenance, and reactivation by enhancing HIV infectivity and replication due to upregulation of co-receptors and impairment of innate antiviral responses. Opioids may also modulate immune cell functioning and microbial translocation and can reverse viral latency. In this review, we summarize the current findings for and against the modulating effects of opioids on HIV cellular and anatomical reservoirs, highlighting the current limitations that affect in vitro, ex vivo, and in vivo studies in the field. We propose further research targets and potential strategies to approach this topic.

Cebranopadol for the Treatment of Chronic Pain.

Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Efficacy and safety of an extended-release sebacoyl dinalbuphine ester for laparoscopic cholecystectomy: A randomized controlled trial.

A long-acting κreceptor agonist parenteral analgesic may theoretically improve acute pain and reduce incidence of chronic postsurgical pain (CPSP) after laparoscopic cholecystectomy with minimal drug-related side effects of the traditional μreceptor opioids. Eighty adult patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive single intramuscular injection of an extended-release sebacoyl dinalbuphine ester (SDE, Naldebain 150 mg; n = 40) or placebo (n = 40) after anesthesia induction. Standard multimodal analgesia (MMA) was administered for postoperative pain control. The primary endpoint was pain intensity within 7 days after surgery. The secondary endpoints were incidence CPSP at 3 months and adverse reactions up to 7 days after surgery. The highest visual analogue scale (VAS) and area under the curve of VAS 0 to 48 hours after operation were not different between the two groups and a similar proportion of patients requested rescue parenteral analgesics. Average pain intensities were also not different at 72 hours and 7 days after surgery. Incidence of CPSP was 22.5% and 13.1% in patients who received placebo and SDE treatment, respectively (P = .379). Significantly higher incidence of drug-related adverse events, including dizziness, nausea and injection site reactions, were recorded in the SDE group. A single dose of extended-release analgesic SDE given intraoperatively did not provide sufficient add-on effect for acute and chronic pain management after laparoscopic cholecystectomies in patients who received standard postoperative MMA. Intramuscular injection of 150 mg SDE in patients with average body mass causes adverse events that could have been overlooked. More clinical studies are warranted to determine the target populations who may benefit from SDE injections for improvement of acute and chronic postsurgical pain management.

Neonatal opioid toxicity: opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression.

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratoryrhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported.

An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression.

The opioid overdose crisis primarily driven by potent synthetic opioids resulted in more than 500,000 deaths in the US over the last 20 years. Though naloxone, a short-acting medication, remains the primary treatment option for temporarily reversing opioid overdose effects, alternative countermeasures are needed. Monoclonal antibodies present a versatile therapeutic opportunity that can be tailored to synthetic opioids and help prevent post-treatment renarcotization. The ultrapotent analog carfentanil is especially concerning due to its unique pharmacological properties. With this in mind, we generated a fully human antibody through a drug-specific B cell sorting strategy with a combination of carfentanil and fentanyl probes. The resulting pan-specific antibody was further optimized through scFv phage display, producing C10-S66K. This monoclonal antibody displays high affinity to carfentanil, fentanyl, and other analogs and reversed carfentanil-induced respiratory depression. Additionally, X-ray crystal structures with carfentanil and fentanyl bound provided structural insight into key drug:antibody interactions.

Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users.

Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans. In these studies, we sought to test the magnitude of opioid antagonism effects on neural response to monetary rewards in two groups: light drinkers (for the naltrexone study) and heavy drinkers (for the nalmefene study). We conducted double-blind, randomized, crossover pilot studies of reward activation in the brain following acute administration of opioid antagonist and placebo in 11 light and 9 heavy alcohol users. We used a monetary incentive delay task during functional MRI. We found a main effect of cue type on BOLD activation in the nucleus accumbens, demonstrating a neural reward response. The effect of opioid antagonism, relative to placebo, was small and nonsignificant for reward activation in the accumbens for both light and heavy alcohol users. Based on the results of two pilot studies, opioid antagonist medications do not appear to decrease neural activation to monetary rewards in the nucleus accumbens relative to placebo.

Investigation of the Effects of Opioids on Microglial Nitrite and Nitric Oxide Synthase (iNOS) Production and Phagocytosis during Inflammation.

This study aimed to investigate how opioids affect phagocytosis and microglial nitrite and nitric oxide synthase (iNOS) production during inflammation. Opioids are a group of chemicals that are naturally found in the opium poppy plant and exert a variety of effects on the brain, including pain alleviation in some cases. They are commonly used in surgery and perioperative analgesia. However, research on the impact of opioids on microglial inflammatory factor production and phagocytosis is limited. This study was designed to investigate the effects of opioids on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) generation. Moreover, the influence of opioids on the engulfment of C8-B4 microglial cells after stimulation with LPS was also examined. C8-B4 mouse microglial cells were exposed to various concentrations of opioids after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Nitrite production was assayed. The iNOS and Cox-2 were determined by Western blotting, and fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia cultivating with opioids after being activated by LPS. After LPS and IFN-γ stimulation, microglia produced lower amounts of nitric oxide (NO) production with buprenorphine, salvinorin A, and naloxone (P<0.05). When combined with naloxone, no significant differences were found than buprenorphine. It was observed that buprenorphine and salvinorin A could suppress iNOS expression activated by LPS and IFN-γ. Phagocytosis was greatly increased after LPS stimulation, and a significant increase was observed after adding salvinorin A. Buprenorphine and salvinorin A were found to reduce NO production and iNOS induction in microglial cells activated by LPS and IFN-γ. Salvinorin A promoted the phagocytosis of microglia cells treated by LPS.

Efficacy of intravenous dexmedetomidine-lignocaine infusion compared to morphine for intraoperative haemodynamic stability in modified radical mastectomy: A randomised controlled trial.

In recent times, non-opioid analgesic-based anaesthesia has been gaining popularity as it can achieve the goals of hypnosis, amnesia, and haemodynamic stability while avoiding opioid side effects. Our study compares the efficacy of opioid-free anaesthesia and opioid-based general anaesthesia regarding intraoperative haemodynamic stability, anaesthetic requirements, awareness, and recovery profile. After receiving ethical approval and registering the trial, we conducted this randomised, single-blinded study on American Society of Anesthesiologists (ASA) physical status I and II patients who were aged 18-65 and were scheduled for modified radical mastectomy under general anaesthesia. Patients were randomised into two groups of 60 each. Group DL received IV dexmedetomidine 1 μg/kg loading over 10 min, 10 min before induction and 0.5 μg/kg/h infusion after that along with IV lignocaine 1.5 mg/kg at bolus followed by 1.5 mg/kg/h infusion. Group MN received IV morphine 0.15 mg/kg. Standard monitoring and general anaesthesia protocol were followed. Intraoperative haemodynamics, anaesthetic requirement, extubation time, and recovery profile were monitored. Data were analysed using Stata version 14 software, and statistical tests (Chi-squared test for qualitative variables, unpaired t-test and Mann-Whitney U test for quantitative variables) were performed. Both groups had comparable haemodynamic stability (P > 0.05). Group DL had a significantly lower propofol requirement for induction and maintenance (P < 0.001). Ramsay sedation score (P = 0.002) and extubation time (P = 0.029) were significantly higher in Group MN. The recovery profile was favourable in Group DL, with there being lower postoperative complications. Dexmedetomidine and lignocaine IV infusion demonstrated stable intraoperative haemodynamic stability, lower anaesthetic requirement, and better recovery profile than morphine without significant complications.

Utility of Ultrasound-Guided Erector Spinae Plane Blocks for Postoperative Pain Management Following Thoracolumbar Spinal Fusion Surgery.

The primary objective of this study is to determine if ultrasound-guided erector spinae plane blocks (ESPB) prior to thoracolumbar spinal fusion reduces opioid consumption in the first 24 hours postoperatively. Secondary objectives include ESPB effects on administration of opioids, utilization of intravenous patient-controlled analgesia (IV-PCA), pain scores, length of stay, and opioid related side effects. A retrospective cohort analysis was performed on consecutive, adult patients undergoing primary thoracolumbar fusion procedures. Demographic and baseline characteristics including diagnoses of chronic pain, anxiety, depression, and preoperative use of opioids were collected. Surgical data included surgical levels, opioid administration, and duration. Postoperative data included pain scores, opioid consumption, IV-PCA duration, opioid-related side effects, ESPB-related complications, and length of stay (LOS). Statistical analysis was performed using chi-squared and t-test analyses, multivariable analysis, and covariate adjustment with propensity score. A total of 118 consecutive primary thoracolumbar fusions were identified between October 2019 and December 2021 (70 ESPB, 48 no-block [NB]). There were no significant demographic or surgical differences between groups. Median surgical time (262.50 mins vs 332.50 mins, p = 0.04), median intraoperative opioid consumption (8.11 OME vs 1.73 OME, p = 0.01), and median LOS (152.00 hrs vs 128.50 hrs, p = 0.01) were significantly reduced in the ESPB group. Using multivariable covariate adjustment with propensity score analysis only intraoperative opioid administration was found to be significantly less in the ESPB cohort. ESPB for thoracolumbar fusion can be performed safely in index cases. There was a reduction of intraoperative opioid administration in the ESPB group, however the care team was not blinded to the intervention. Extensive thoracolumbar spinal fusion surgery may require a different approach to regional anesthesia to be similarly effective as ESPB in isolated lumbar surgeries.

The Role of circTmeff-1 in Morphine Addiction Memory of Mice.

In addition to the essential pharmacological effects of opioids, situational cues associated with drug addiction memory are key triggers for drug seeking. CircRNAs, an emerging hotspot regulator in crown genetics, play an important role in central nervous system-related diseases. However, the internal mediating mechanism of circRNAs in the field of drug reward and addiction memory remains unknown. Here, we trained mice on a conditional place preference (CPP) model and collected nucleus accumbens (NAc) tissues from day 1 (T0) and day 8 (T1) for high-throughput RNA sequencing. QRT-PCR analysis revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell, suggesting that it plays a role in addiction memory formation. Meanwhile, the down-regulation of circTmeff-1 by adeno-associated viruses in the NAc core or shell could inhibit the morphine CPP scores. Subsequently, the GO and KEGG analyses indicated that circTmeff-1 might regulate the addiction memory via the MAPK and AMPK pathways. These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory formation.

Perioperative truncal peripheral nerve blocks for bariatric surgery: an opioid reduction strategy.

Bariatric surgical patients are vulnerable to cardiopulmonary depressant effects of opioids. The enhanced recovery after surgery (ERAS) protocol to improve postoperative morbidity recommends regional anesthesia for postoperative pain management. However, there is limited evidence that peripheral nerve blocks (PNB) have added benefit. Study the effect of PNB on postoperative pain and opioid use following bariatric surgery. Academic medical center, United States. We conducted a cohort study of patients who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. A total of 44 patients received the control ERAS protocol with preoperative oral extended-release morphine sulfate (MS), while 45 patients underwent a PNB with either intrathecal morphine (IM) or oral MS per local ERAS protocol. The PNB group either underwent preoperative bilateral T7 paravertebral (PVT) PNBs (27 patients) with IM or postoperative transversus abdominis plane (TAP) PNBs (18 patients) with oral MS. The primary outcome compared total opioid consumption between the ERAS control group and the PNB group up to 48 hours postoperatively. Secondary outcomes included comparison by block type and postoperative pain scores. PVT or TAP PNB patients had a reduction in mean postoperative oral morphine equivalent (OME) requirements compared with the ERAS protocol cohort at 24 hours (93.9 versus 42.8 mg), P < .0001; at 48 hours (72.6 versus 40.5 mg); and in pain scores at 24 hours (5.64/10 versus 4.46/10), P = .02. OME and pain scores were higher in the SG cohort. Addition of truncal PNB to standard ERAS protocol for bariatric surgical patients reduces postoperative total opioid consumption.

Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.

Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a μ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain. To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor. Retrospective cohort study. A total of 274 patients were enrolled, who started a tapentadol extended-release tablet, methadone tablet, hydromorphone extended-release tablet, oxycodone extended-release tablet, or transdermal fentanyl patch for cancer pain due to spinal metastasis in Japan from January 1, 2013 to October 31, 2021. The primary endpoint, the difference in the numerical rating scale (NRS) scores before and seven days after each opioid administration, was compared among the five groups. In patients with numbness, a decrease of the NRS score on day seven compared with before starting each opioid was significantly higher in the tapentadol group than those in the hydromorphone, oxycodone, and fentanyl groups and comparable to that in the methadone group. In patients without numbness, no significant differences were observed in decreases of the NRS scores on day seven among the five groups. Tapentadol and methadone may be more effective than hydromorphone, oxycodone, and fentanyl for cancer pain due to spinal metastasis with numbness.

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients' quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal-glial-immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain.

Аssessment of pain intensity: tools and their clinical using

Pain is an accompanied problem for many pathologic conditions and diseases. Such sensations disappear gradually when related to acute pathology or trauma. However, pain can became chronic and acquire traits of self-sustained disease. In practice, many characteristics can be useful for estimation of pain sensation, and the goal of this paper is to analyze of modern methods for intensity pain assessment in adults and children, of interpretation of pain estimation, and of possible algorithm for next steps. In majority cases, pain intensity is changing parameter. Therefore, pain assessment is performed in some standard points of time. For a quantitative assessment of pain, a scale is proposed to help the patient, relative to the extreme points of which a pointer can be placed indicating the relative severity of his sensations. For such purpose visual analog scale, numeric rating scale, and verbal numeric scale can be used. The Wong-Baker Faces Pain Rating Scale, the FLACC scale, the CRIES pain scale can be exploited in small children. In this population the CHEOPS scale, the OPS scale, and the COMFORT scale were recommended to apply after surgery. The final step of interpretation implies that quantitative data converts to ratings. The last ones form to basis of WHO analgesic ladder that is exploited for drugs selection to treat pain, in particular in patients with cancer pain or postoperative pain. From this approach, moderate and severe pain recommends to administer full opioid agonists. However, today there is a good alternative in the form of selective mu1-receptots agonist, which has lower risk of side opioid effects. Thus, in this time, there is some progress in pain management. This progress, in our opinion, is due to improved analysis of the condition of patients suffering from moderate and severe pain, and the emergence of new opioid agonists with high selectivity for the mu1 subclass of opioid receptors.

Opioid-induced bowel dysfunction: a literature review

Opioid therapy plays a crucial role in the management of acute and chronic pain, with opioids being widely prescribed worldwide. However, alongside the analgesic benefits, the use of opioids is associated with a range of adverse effects, including opioid-induced bowel dysfunction. Opioid-induced bowel dysfunction refers to a constellation of gastrointestinal symptoms caused by the effects of opioids on the gastrointestinal tract. These symptoms primarily manifest as constipation, but can also include abdominal pain, bloating, nausea, and vomiting. Opioid-induced bowel dysfunction poses a significant clinical challenge, as it can severely affect patients' quality of life. Non-pharmacological approaches alone are rarely sufficient to counteract the adverse effects of opioid therapy. The primary pharmacological agents used in opioid-induced bowel dysfunction management are laxatives, which should be chosen according to individual patient needs. Patients with poorly controlled symptoms can benefit from new pharmacological approaches, particularly peripheral mu-opioid receptor antagonists. By better understanding the underlying mechanisms, clinical manifestations, diagnostic criteria, and management strategies, healthcare professionals can optimize patient care, minimize complications, and improve patients' overall well-being.

In utero effects of opioids on fetal growth

Background Studies indicate antenatal opioid use is associated with birth size deficits, as evidenced by reductions in birth weight and head circumference. However, there remains a limited understanding of how early this growth restriction occurs, and what specific parameters are affected. This novel study evaluated global and specific growth deficits associated with prenatal opioid exposure between 18–22 weeks’ gestation as assessed during anatomy ultrasounds. Methods Pregnant women who completed an anatomy ultrasound were identified via electronic medical records from a large academic obstetric practice. The study group used opioids, with tobacco and/or marijuana use permitted (n = 41). The control group could have used tobacco and/or marijuana, but not opioids (n = 308). Neither group had alcohol or other drug exposure. Records were reviewed for medical history and ultrasound size parameters, coded as percentiles for gestational age. Results Demographics and medical histories were compared with several significant differences noted. After controlling for these differences, significant (p < 0.05) growth deficits were identified in opioid-exposed fetuses. Specifically, reductions >10 percentile points were observed in head circumference, biparietal diameter, and humerus length for opioid-exposed fetuses compared to controls. Additionally, intrauterine growth restriction (IUGR) was diagnosed five times more often. Femur length was significantly reduced in opioid-exposed fetuses prior to adjustment for confounding (p = .016), but this reduction was not significant (p = .072) after controlling for background differences. Estimated fetal weight (p = .274) and abdominal circumference (p = .633) were not significantly different between exposure groups. Conclusion Fetal opioid exposure predicted various bone growth deficits during routine anatomy ultrasound, indicating the effects of opioid exposure on size deficits may be evident as early as 18–22 weeks’ gestation. These findings may also suggest that in utero opioid exposure negatively impacts bone growth specifically rather than weight or fat/muscle mass. Additional studies with larger sample sizes may also reveal significantly reduced femur length, further supporting a negative impact on bone growth. Future studies evaluating bone health and immune function in children after antenatal opioid exposure may help clarify this specific effect of opioids on bone development.

Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review.

Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approvalby the FDA, tianeptine has been distributed online and at small retail locations. The term "gas station drugs" refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as "Zaza" and "Tianna Red." It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances.

Attrition of methylnaltrexone treatment-emergent adverse events in patients with chronic noncancer pain and opioid-induced constipation: a post hoc pooled analysis of two clinical trials.

Background: Opioids prescribed for the management of chronic noncancer pain are associated with nausea, vomiting, and constipation. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, has demonstrated robust efficacy and was well-tolerated in treating opioid-induced constipation without affecting central analgesia. Our objective was to assess changes in the frequency of treatment-emergent adverse events (TEAEs) after the first or second dose of methylnaltrexone or placebo. Methods: This post hoc analysis pooled data from two randomized, placebo-controlled clinical trials assessing methylnaltrexone for opioid-induced constipation in the outpatient setting. Patients received subcutaneous methylnaltrexone (12 mg once daily or 12 mg once every other day), oral methylnaltrexone (150, 300, or 450 mg daily), or placebo. TEAEs, opioid withdrawal symptoms, pain intensity, and rescue-free bowel movements (RFBMs) within 4 hours of the first dose (i.e., RFBM responders) were assessed. Associations between TEAE frequencies and RFBM response were also evaluated. Results: The analysis included 1263 adult patients with chronic noncancer pain. TEAE rates declined from treatment day 1 to 2 (methylnaltrexone: 16.2%-5.3%; placebo: 6.6%-5.4%). Among methylnaltrexone-treated patients, significantly greater proportions of RFBM responders versus nonresponders reported gastrointestinal TEAEs on day 1. No associations between RFBM response and the frequency of TEAEs were observed in the placebo group. No meaningful changes in opioid withdrawal symptoms or pain intensity were observed. Conclusions: Early-onset TEAEs following methylnaltrexone treatment, particularly gastrointestinal TEAEs, are at least partially due to laxation. Methylnaltrexone treatment effectively relieves opioid-induced constipation without affecting the central analgesic effects of opioids.