-
Annals of Palliative Medicine Mar 2024Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important...
BACKGROUND
Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant.
CASE DESCRIPTION
The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems.
CONCLUSIONS
The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.
Topics: Male; Humans; Aged; Antiemetics; Aprepitant; Analgesics, Opioid; Oxycodone; Cytochrome P-450 CYP3A; Morpholines; Antineoplastic Agents; Drug Interactions; Prostatic Neoplasms; Pain; Respiratory Insufficiency; Kidney Diseases
PubMed: 38584476
DOI: 10.21037/apm-23-581 -
BMC Geriatrics Apr 2024Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex...
BACKGROUND
Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.
METHODS
This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.
RESULTS
The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.
CONCLUSIONS
Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.
Topics: Humans; Aged; United States; Analgesics, Opioid; Tramadol; Oxycodone; Arthroplasty, Replacement, Knee; Hydrocodone; Retrospective Studies; Arthroplasty, Replacement, Hip; Medicare
PubMed: 38580920
DOI: 10.1186/s12877-024-04933-2 -
JACS Au Mar 2024Opioids collectively cause over 80,000 deaths in the United States annually. The ability to rapidly identify these compounds in seized drug samples on-site will be...
Opioids collectively cause over 80,000 deaths in the United States annually. The ability to rapidly identify these compounds in seized drug samples on-site will be essential for curtailing trafficking and distribution. Chemical reagent-based tests are fast and simple but also notorious for giving false results due to poor specificity, whereas portable Raman spectrometers have excellent selectivity but often face interference challenges with impure drug samples. In this work, we develop on-site sensors for morphine and structurally related opioid compounds based on in vitro-selected oligonucleotide affinity reagents known as aptamers. We employ a parallel-and-serial selection strategy to isolate aptamers that recognize heroin, morphine, codeine, hydrocodone, and hydromorphone, along with a toggle-selection approach to isolate aptamers that bind oxycodone and oxymorphone. We then utilize a new high-throughput sequencing-based approach to examine aptamer growth patterns over the course of selection and a high-throughput exonuclease-based screening assay to identify optimal aptamer candidates. Finally, we use two high-performance aptamers with of ∼1 μM to develop colorimetric dye-displacement assays that can specifically detect opioids like heroin and oxycodone at concentrations as low as 0.5 μM with a linear range of 0-16 μM. Importantly, our assays can detect opioids in complex chemical matrices, including pharmaceutical tablets and drug mixtures; in contrast, the conventional Marquis test completely fails in this context. These aptamer-based colorimetric assays enable the naked-eye identification of specific opioids within seconds and will play an important role in combatting opioid abuse.
PubMed: 38559723
DOI: 10.1021/jacsau.3c00801 -
Pain Research & Management 2024Patients undergoing breast surgery are at risk of severe postoperative pain. Several opioid-sparing strategies exist to alleviate this condition. Regional anesthesia has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients undergoing breast surgery are at risk of severe postoperative pain. Several opioid-sparing strategies exist to alleviate this condition. Regional anesthesia has long been a part of perioperative pain management for these patients.
AIM
This randomized study examined the benefits of interpectoral and pectoserratus plane block (IPP/PSP), also known as pectoralis nerve plain block, compared with advanced local anesthetic infiltration.
METHODS
We analyzed 57 patients undergoing partial mastectomy with sentinel node dissection. They received either an ultrasound-guided IPP/PSP block performed preoperatively by an anesthetist or local anesthetic infiltration performed by the surgeon before and during the surgery.
RESULTS
Pain measured with the numerical rating scale (NRS) indicated no statistically significant difference between the groups (IPP/PSP 1.67 vs. infiltration 1.97; value 0.578). Intraoperative use of fentanyl was significantly lower in the IPP/PSP group (0.18 mg vs 0.21 mg; value 0.041). There was no statistically significant difference in the length of stay in the PACU (166 min vs 175 min; value 0.51). There were no differences in reported postoperative nausea and vomiting (PONV) between the groups. The difference in postoperative use of oxycodone in the PACU ( value 0.7) and the use of oxycodone within 24 hours postoperatively ( value 0.87) was not statistically significant.
CONCLUSIONS
Our study showed decreased intraoperative opioid use in the IPP/PSP group and no difference in postoperative pain scores up to 24 hours. Both groups reported low postoperative pain scores. This trial is registered with NCT04824599.
Topics: Humans; Female; Anesthetics, Local; Analgesics, Opioid; Mastectomy, Segmental; Oxycodone; Prospective Studies; Breast Neoplasms; Mastectomy; Pain, Postoperative
PubMed: 38550709
DOI: 10.1155/2024/9989997 -
Frontiers in Psychiatry 2024
PubMed: 38544850
DOI: 10.3389/fpsyt.2024.1382894 -
Pathophysiology : the Official Journal... Mar 2024Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related...
Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone administration in young female rats is associated with neurodegeneration in the brain. Males and females are susceptible to neurodegenerative diseases via differing mechanisms. To investigate whether opioid exposure affects males and females differently, we treated young mice with chronic morphine. We observed that females had stronger antinociceptive responses to acute morphine and showed a delayed development of tolerance. Males had a higher basal Bax level in the brain that correlated with a higher number of apoptotic cells. Morphine increased Bax levels in both males and females without affecting the numbers of apoptotic cells. Morphine increased activated caspase 3 in axons and increased the MBP level in plasma only in females, suggesting a demyelination process. Our data suggest that males are protected from demyelination by having a higher basal BDNF level. Altogether, our results suggest that males and females have different molecular signaling underlying their patterns in the development of morphine tolerance and drug-induced neuronal degeneration.
PubMed: 38535622
DOI: 10.3390/pathophysiology31010012 -
Drug Design, Development and Therapy 2024Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of...
PURPOSE
Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids.
METHODS
Mixtures of oxycodone (1mg.mL) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150.
RESULTS
IV oxycodone (1 mg.mL) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested.
CONCLUSION
According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.
Topics: Humans; Child; Oxycodone; Infusions, Intravenous; Potassium Chloride; Vancomycin; Glucose
PubMed: 38533429
DOI: 10.2147/DDDT.S444581 -
Pharmacy (Basel, Switzerland) Mar 2024Opioid prescribing and dispensing from emergency departments is a noteworthy issue given widespread opioid misuse and diversion in many countries, contributing both...
Opioid prescribing and dispensing from emergency departments is a noteworthy issue given widespread opioid misuse and diversion in many countries, contributing both physical and economic harm to the population. High patient numbers and the stochastic nature of acute emergency presentations to emergency departments (EDs) introduce challenges for prescribers who are considering opioid stewardship principles. This study investigated the effect of changes to electronic prescribing software on prescriptions with an auto-populated quantity of oxycodone immediate release (IR) from an Australian tertiary emergency department following the implementation of national recommendations for reduced pack sizes. A retrospective review of oxycodone IR prescriptions over two six-month periods between 2019 and 2021 was undertaken, either side of a software adjustment to reduce the default quantities of tablets prescribed from 20 to 10. Patient demographic details were collected, and prescriber years of practice calculated for inclusion in linear mixed effects regression modelling. A reduction in the median number of tablets prescribed per prescription following the software changes (13.5 to 10.0, < 0.001) with little change in the underlying characteristics of the patient or prescriber populations was observed, as well as an 11.65% reduction in the total number of tablets prescribed. The prescriber's years of practice, patient age and patient sex were found to influence increased prescription sizes. Reduced quantity of oxycodone tablets prescribed was achieved by alteration of prescribing software prefill parameters, providing further evidence to support systems-based policy interventions to influence health care providers behaviour and to act as a forcing function for prescribers to consider opioid stewardship principles.
PubMed: 38525724
DOI: 10.3390/pharmacy12020044 -
Clinical and Translational Science Mar 2024PF614, a trypsin-activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs)... (Randomized Controlled Trial)
Randomized Controlled Trial
PF614, a trypsin-activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two-part design including a multi-ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses. In part B, 60 subjects randomized in a four-way crossover to evaluate BE, received PF614 100 mg and OxyContin 40 mg in fasted and fed (high-fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid-related adverse effects; repeat doses were provided on days 1-5. In part A, PF614 was well-tolerated following twice daily doses of up to 200 mg for 5 days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100 mg PF614 or 40 mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single-ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone-blocked conditions.
Topics: Humans; Administration, Oral; Analgesics, Opioid; Cross-Over Studies; Healthy Volunteers; Naltrexone; Oxycodone; Prodrugs; Therapeutic Equivalency
PubMed: 38511523
DOI: 10.1111/cts.13765 -
BMJ Paediatrics Open Mar 2024Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy....
BACKGROUND
Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy. Effective pain management after SDR is essential for early rehabilitation. This study aimed to describe the anaesthetic and early pain management, pain and adverse events in children following SDR.
METHODS
This was a retrospective cohort study. Participants were all children who underwent SDR at a single Australian tertiary hospital between 2010 and 2020. Electronic medical records of all children identified were reviewed. Data collected included demographic and clinical data (pain scores, key clinical outcomes, adverse events and side effects) and medications used during anaesthesia and postoperative recovery.
RESULTS
22 children (n=8, 36% female) had SDR. The mean (SD) age at surgery was 6 years and 6 months (1 year and 4 months). Common intraoperative medications used were remifentanil (100%), ketamine (95%), paracetamol (91%) and sevoflurane (86%). Postoperatively, all children were prescribed opioid nurse-controlled analgesia (morphine, 36%; fentanyl, 36%; and oxycodone, 18%) and concomitant ketamine infusion. Opioid doses were maximal on the day after surgery. The mean (SD) daily average pain score (Wong-Baker FACES scale) on the day after surgery was 1.4 (0.9), decreasing to 1.0 (0.5) on postoperative day 6 (POD6). Children first attended the physiotherapy gym on median day 7 (POD8, range 7-8). Most children experienced mild side effects or adverse events that were managed conservatively. Common side effects included constipation (n=19), nausea and vomiting (n=18), and pruritus (n=14). No patient required return to theatre, ICU admission or prolonged inpatient stay.
CONCLUSIONS
Most children achieve good pain management following SDR with opioid and ketamine infusions. Adverse events, while common, are typically mild and managed with medication or therapy. This information can be used as a baseline to improve postoperative care and to support families' understanding of SDR before surgery.
Topics: Child; Humans; Female; Male; Rhizotomy; Pain Management; Analgesics, Opioid; Retrospective Studies; Ketamine; Australia; Pain, Postoperative
PubMed: 38490692
DOI: 10.1136/bmjpo-2023-002381