A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients

Opioid drugs are used to manage moderate to severe pain in mammals and avian species. In dosing opioids for a particular species, it is optimal to use dosing regimens based on pharmacokinetics or pharmacodynamics studies conducted in the same species as variability in the physiology among different species may result in differences in drug pharmacokinetics and pharmacodynamics. Unfortunately, dosing regimens are typically extrapolated from closely related avian species or even mammals, which is unideal. Therefore, this critical review aims to collate and evaluate the dosing regimens of selected opioids: tramadol, hydromorphone, buprenorphine, butorphanol, and fentanyl, in avian species and its related safety, efficacy and pharmacokinetic data. Our review found specific dosing regimens not described in the Exotic Animal Formulary for tramadol used in Indian Peafowl (Pavo cristatus), Muscovy Duck (Cairina moschata) and Hispaniolan Parrot (Amazona ventralis); hydromorphone used in Orange-winged Parrot (Amazona amazonica); buprenorphine used in Cockatiel (Nymphicus hollandicus), American Kestrel (Falco sparverius) and Grey Parrot (Psittacus erithacus); and butorphanol used in Hispaniolan Parrot (Amazona ventralis), Broiler Chicken and Indian Peafowl (Pavo cristatus). Cockatiel appeared to not experience analgesic effects for hydromorphone and buprenorphine, and American Kestrel exhibited sex-dependent responses to opioids. The selected opioids were observed to be generally safe, with adverse effects being dose-dependent.

Are Opioids Overprescribed to Pediatric Neurosurgery Patients? A Prospective Study on Prescribing Practices and Patient Use

Background and Hypothesis: The opioid crisis continues to worsen in the United States with opioid overdose deaths reaching record highs in 2020. While a large body of literature exists surrounding the risks of opioids in adults, opioids also pose unique risks to pediatric patients, including accidental ingestion, nonmedical use, and acute cerebellitis causing death. Opioid medications prescribed in the medical setting are often an unwitting source of excess opioids, with half of pediatric overdoses in those under 2 years of age. Although legislative efforts have significantly limited opioid prescribing, recent studies suggest these medications may still be overprescribed. We hypothesized opioid medications are overprescribed to pediatric neurosurgery patients upon hospital discharge. Methods: Pediatric patients undergoing neurosurgical procedures at Riley Hospital for Children were identified prospectively. Surgery type, length of stay, and inpatient use of opioid medications were collected. Patients prescribed an opioid medication upon hospital discharge were contacted 7 days after discharge and asked to report the number of doses of opioid medication used. Results: Thirty patients were successfully contacted 7 days after hospital discharge. Patients underwent a variety of cranial and spinal procedures and the mean length of hospital stay was 3.9 days. An average of 24.9 doses of opioid medication were prescribed at hospital discharge, while an average of 3.8 doses were used by patients in the 7 days following hospital discharge. Twelve patients (40%) had used zero doses of the prescribed opioid medication at 7-day follow-up. Conclusions: Pediatric neurosurgery patients used only 15.3% of prescribed opioids in 7 days after hospital discharge. This creates an excess of leftover opioid medication that may increase the risk of accidental ingestion and misuse. The present study highlights the need for educational initiatives for providers to minimize excess opioids prescribed and for parents to safely dispose of leftover opioid medication.

Exploring Knowledge, Beliefs, and Attitudes of Older Adults About Prescription Opioids

Over the past two decades, opioids have been considered important and acceptable in the treatment of pain for older adults, especially for chronic health conditions. Despite the fact that older adults are prescribed opioid medications at high rates, there is little research examining older adults’ knowledge, beliefs, and attitudes about opioid medications. The purpose of this study was to explore the knowledge, beliefs, and attitudes surrounding prescription opioid medications of community living older adults in a southeast area of the United States. A cross-sectional, descriptive, anonymous survey design of participants aged 55 or over was used. Study participants (N=119) reported bias in their attitudes and beliefs about the use and misuse of prescription opioid medications. Multiple regression analyses revealed that gender, age, work, marital status, and education level all had significant results in explaining variance in the statistical models. Even though study participants demonstrated high levels of education and understanding of the potential of addiction to opiates, there were a number of misconceptions revealed about prescription pain medications. This urges the necessity of increased awareness via further research, presentations, and creative discourse to assist in the understanding of precursors of addiction and ways to deal with pain that do not automatically rely on prescription opioid medicines. Implications include outreach to a larger and more diverse sample to address knowledge, beliefs, and attitudes surrounding prescription opioid medications of community living older adults.

Intravenous patient-controlled analgesia plus psychoeducational intervention for acute postoperative pain in patients with pulmonary nodules after thoracoscopic surgery: a retrospective cohort study

Background The association of psychological factors with postoperative pain has been well documented. The incorporation of psychoeducational intervention into a standard analgesia protocol seems to be an attractive approach for the management of acute postoperative pain. Our study aimed to evaluate the impact of psychoeducational intervention on acute postoperative pain in pulmonary nodule (PN) patients treated with thoracoscopic surgery. Methods In this study, 76 PN patients treated with thoracoscopic surgery and intravenous patient-controlled analgesia (IV-PCA) plus psychoeducational evaluation and intervention were selected as the psychoeducational intervention group (PG). Another 76 PN patients receiving IV-PCA without psychoeducational intervention after thoracoscopic surgery, treated as the control group (CG), were identified from the hospital database and matched pairwise with PG patients according to age, sex, preoperative body mass index (BMI), opioid medications used for IV-PCA and the educational attainment of patients. Results The most common psychological disorders were anxiety and interpersonal sensitivity, which were recorded from 82.9% (63/76) and 63.2% (48/76) of PG patients. The numerical rating scale (NRS) pain scores of the PG patients were significantly lower than those of the CG patients at 2 and 24 h after surgery (P < 0.001). Total opioid consumption for acute postoperative pain in the PG was 52.1 mg of morphine equivalent, which was significantly lower than that (67.8 mg) in the CG (P = 0.038). PG patients had a significantly lower incidence of rescue analgesia than CG patients (28.9% vs. 44.7%, P = 0.044). Nausea/vomiting was the most common side effect of opioid medications, recorded for 3 (3.9%) PG patients and 10 (13.2%) CG patients (P = 0.042). In addition, no significant difference was observed between PG and CG patients in terms of grade 2 or higher postoperative complications (10.5% vs. 17.1%, P = 0.240). Conclusions Psychoeducational intervention for PN patients treated with thoracoscopic surgery resulted in reduced acute postoperative pain, less opioid consumption and fewer opioid-related side effects.

Sickle Cell Disease Bias: An Early Opportunity for Intervention?

Background: Sickle cell disease (SCD) is a genetic condition leading to multi-organ dysfunction and chronic pain, with 1 out of 13 African Americans having the trait. Despite its prevalence and debilitating symptoms, SCD remains a disease with limited therapeutic interventions and decreased life expectancy. There is a clinical bias to undertreat the pain of patients with SCD with opioid medications, despite their effectiveness (Zempsky 2009). Early education about SCD may lead to improvements in provider perceptions and disease management. Methods: An anonymous survey was sent to first-year medical students at an academic institution prior to their hematology course. Data was collected about demographics, prior exposure to SCD, perceptions about opioid use disorder (OUD) in SCD, and baseline knowledge of management. Identical questions were asked for cancer-related pain. The survey was sent again after the completion of the hematology course to assess whether the curriculum was effective at characterizing misperceptions about patients with SCD. Results: Fifty-five medical students answered the survey prior to the course. Students were 38% male and 62% female. Seventy-five percent of students (N=41) had never encountered a patient with SCD. Forty percent (N=22) answered that OUD in patients with SCD is more likely, 60% as likely (N=33), and 0% less likely than the general population. Seventy-one percent (N=39) believed opiates should play a minor role, 5% (N=3) a major role, and 24% (N=13) said opioids should be avoided when managing SCD-related pain. After course completion, 35 students who had completed the survey prior to the course responded, 29% male and 71% female. Fifty-four percent (N=19) answered that OUD in patients with SCD is more likely, 43% (N=15) as likely, and 3% (N=1) less likely than the general population. Seventy-one percent (N=25) thought opiates should play a minor role, 9% (N=3) a major role, and 20% (N=7) said they should be avoided when managed SCD-related pain. Conclusion: After course completion, a higher percentage of medical students thought that OUD was more frequent in patients with SCD than the general population, with a similarly high percentage determining that opioid medications should play a minor role or be avoided in SCD. Opioid medications are an important part of treatment for SCD, especially for acute vaso-occlusive pain. Patients with SCD are no more likely to have OUD than the general population and have a lower rate of OUD than other patients with chronic pain conditions (Solomon 2008). This pilot study highlights that there is an opportunity to intervene in misperceptions of patients with SCD in early medical school education. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Investigating the Use of a Serious Game to Improve Opioid Safety Awareness Among Adolescents: A Quantitative Study (Preprint)

BACKGROUND The misuse of opioid medications among adolescents is a serious problem in the United States. Serious games (SGs) are a novel way to promote safe and responsible management of opioid medications among adolescents, thereby reducing the number of adolescent opioid misuse cases reported annually. OBJECTIVE This study aimed to examine the effect of the SG MedSMA℞T: Adventures in PharmaCity on adolescents’ opioid safety knowledge, awareness, behavioral intent, and self-efficacy. METHODS A nationally representative sample of adolescents age 12 to 18 years old were recruited online through Qualtrics panels from October to November 2020. Data collection consisted of a pre-game survey, 30 minutes of gameplay, and a post-game survey. The pre- and post-game survey included 66 items examining participants’ baseline opioid knowledge, safety, and use, and demographic information. The post-game survey had 25 additional questions regarding the MedSMA℞T game. Gameplay scenarios included five levels intended to mimic adolescents’ daily life while educating players about appropriate opioid storage and disposable practices, negative consequences of sharing opioid medications, and use of Narcan®. Survey questions were divided into 10 categories to represent key concepts and summarized into concept scores. Differences in concept scores were described by overall mean (SD) when stratified by gender, race, school, grade, and age. Differences of change in concept score were analyzed using Kruskal-Wallis and correlation tests. RESULTS A total of 117 responses were analyzed. Results showed significant improvement on all concept scores except for Narcan® knowledge (mean change = -0.04, SD = 0.29, p = 0.600) and safe storage (mean change = 0.03, SD = 0.20, p = 0.088). Female participants had greater improvement than males for safe disposal (female mean (SD) = 0.12 (0.25), male = 0.04 (0.17), p = 0.050). Male participants had higher improvement than females for misuse behavior (female mean (SD) = 0.05 (0.28) male = 0.14 (0.27), p = 0.043). Perceived knowledge for participants who were non-white or Hispanic had higher improvement than non-Hispanic white participants (non-white mean (SD) = 1.10 (1.06), white = 0.75 (0.91), p = 0.026). Older grades were associated with greater improvement in opioid knowledge (correlation coefficient -0.23 (95% CI -0.40 to -0.05), p = 0.012). There were 28 (23.9%) participants who played all 5 levels of the game and had better improvement in opioid use self-efficacy. CONCLUSIONS Findings suggest MedSMA℞T: Adventures in PharmaCity can be used as an effective tool to educate adolescents on the safe and responsible use of prescribed opioid medications. Future testing of the effectiveness of this SG should involve a randomized control trial. Additionally, the feasibility of implementing and disseminating MedSMA℞T: Adventures in PharmaCity in schools and healthcare settings, such as adolescent health or primary care clinics, emergency departments, and pharmacies, should be investigated.

Patterns, trends and determinants of medical opioid utilization in Canada 2005–2020: characterizing an era of intensive rise and fall

Background Into the 21st century, the conflation of high rates of chronic pain, systemic gaps in treatment availability and access, and the arrival of potent new opioid medications (e.g., slow-release oxycodone) facilitated strong increases in medical opioid dispensing in Canada. These persisted until post-2010 alongside rising opioid-related adverse (e.g., morbidity/mortality) outcomes. We examine patterns, trends and determinants of opioid dispensing in Canada, and specifically its 10 provinces, for the years 2005–2020. Methods Raw data on prescription opioid dispensing were obtained from a large national community-based pharmacy database (IQVIA/Compuscript), converted into Defined-Daily-Doses/1,000 population/day for ‘strong’ and ‘weak’ opioid categories per standard methods. Dispensing by opioid category and formulations by province/year was assessed descriptively; regression analysis was applied to examine possible segmentation of over-time strong opioid dispensing. Results All provinces reported starkly increasing strong opioid dispensing peaking 2011–2016, and subsequent marked declines. About half reported lower strong opioid dispensing in 2020 compared to 2005, with continuous inter-provincial differences of > 100 %; weak opioids also declined post-2011/12. Segmented regression suggests breakpoints for strong opioids in 2011/12 and 2015/16, coinciding with main interventions (e.g., selective opioid delisting, new prescribing guidelines) towards more restrictive opioid utilization control. Conclusions We characterized an era of marked rise and fall, while featuring stark inter-provincial heterogeneity in opioid dispensing in Canada. While little evidence for improvements in pain care outcomes exists, the starkly inverting opioid utilization have been associated with extensive population-level harms (e.g., misuse, morbidity, mortality) over-time. This national case study raises fundamental questions for opioid-related health policy and practice.