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The Journal of Pharmacology and... Nov 2023Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings, including both chronic... (Review)
Review
Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings, including both chronic and disease-related pain. Not only do opioids have narrow therapeutic indexes and are extensively used, but they have the potential to cause severe toxicity. Opioids are the classical pain treatment for patients who suffer from moderate to severe pain. More importantly, opioids are often prescribed in combination with multiple other drugs, especially in patient populations who typically are prescribed a large drug regimen. This review focuses on the current knowledge of common opioid drug-drug interactions (DDIs), focusing specifically on hydrocodone, oxycodone, and morphine DDIs. The DDIs covered in this review include pharmacokinetic DDI arising from enzyme inhibition or induction, primarily due to inhibition of cytochrome p450 enzymes (CYPs). However, opioids such as morphine are metabolized by uridine-5'-diphosphoglucuronosyltransferases (UGTs), principally UGT2B7, and glucuronidation is another important pathway for opioid-drug interactions. This review also covers several pharmacodynamic DDI studies as well as the basics of CYP and UGT metabolism, including detailed opioid metabolism and the potential involvement of metabolizing enzyme gene variation in DDI. Based upon the current literature, further studies are needed to fully investigate and describe the DDI potential with opioids in pain and related disease settings to improve clinical outcomes for patients. SIGNIFICANCE STATEMENT: A review of the literature focusing on drug-drug interactions involving opioids is important because they can be toxic and potentially lethal, occurring through pharmacodynamic interactions as well as pharmacokinetic interactions occurring through inhibition or induction of drug metabolism.
Topics: Humans; Analgesics, Opioid; Oxycodone; Hydrocodone; Pain; Drug Interactions; Morphine; Cytochrome P-450 Enzyme System
PubMed: 37679047
DOI: 10.1124/jpet.123.001651 -
Drugs in R&D Dec 2023Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government... (Review)
Review
Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government regulations create barriers to its use. This narrative review is intended to facilitate buprenorphine use-including non-traditional initiation methods-by providers ranging from primary care providers to addiction specialists. This article briefly discusses the opioid epidemic and the diagnosis and treatment of opioid use disorder (OUD). We then describe the basic and complex pharmacologic properties of buprenorphine, linking these properties to their clinical implications. We guide readers through the process of initiating buprenorphine in patients using full agonist opioids. As there is no single recommended approach for buprenorphine initiation, we discuss the details, advantages, and disadvantages of the standard, low-dose, bridging-strategy, and naloxone-facilitated initiation techniques. We consider the pharmacology of, and evidence base for, buprenorphine in the treatment of pain, in both OUD and non-OUD patients. Throughout, we address the use of buprenorphine in children and adolescent patients, and we finish with considerations related to the settings of pregnancy and breastfeeding.
Topics: Pregnancy; Female; Adolescent; Child; Humans; Buprenorphine; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Analgesics, Opioid
PubMed: 37938531
DOI: 10.1007/s40268-023-00443-5 -
Clinical Pharmacokinetics Apr 2024Naloxone is a World Health Organization (WHO)-listed essential medicine and is the first choice for treating the respiratory depression of opioids, also by lay-people... (Review)
Review
Naloxone is a World Health Organization (WHO)-listed essential medicine and is the first choice for treating the respiratory depression of opioids, also by lay-people witnessing an opioid overdose. Naloxone acts by competitive displacement of opioid agonists at the μ-opioid receptor (MOR). Its effect depends on pharmacological characteristics of the opioid agonist, such as dissociation rate from the MOR receptor and constitution of the victim. Aim of treatment is a balancing act between restoration of respiration (not consciousness) and avoidance of withdrawal, achieved by titration to response after initial doses of 0.4-2 mg. Naloxone is rapidly eliminated [half-life (t) 60-120 min] due to high clearance. Metabolites are inactive. Major routes for administration are intravenous, intramuscular, and intranasal, the latter primarily for take-home naloxone. Nasal bioavailability is about 50%. Nasal uptake [mean time to maximum concentration (T) 15-30 min] is likely slower than intramuscular, as reversal of respiration lag behind intramuscular naloxone in overdose victims. The intraindividual, interindividual and between-study variability in pharmacokinetics in volunteers are large. Variability in the target population is unknown. The duration of action of 1 mg intravenous (IV) is 2 h, possibly longer by intramuscular and intranasal administration. Initial parenteral doses of 0.4-0.8 mg are usually sufficient to restore breathing after heroin overdose. Fentanyl overdoses likely require higher doses of naloxone. Controlled clinical trials are feasible in opioid overdose but are absent in cohorts with synthetic opioids. Modeling studies provide valuable insight in pharmacotherapy but cannot replace clinical trials. Laypeople should always have access to at least two dose kits for their interim intervention.
Topics: Humans; Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Half-Life; Naloxone; Narcotic Antagonists
PubMed: 38485851
DOI: 10.1007/s40262-024-01355-6 -
International Journal of Molecular... Mar 2024Breast cancer is the second leading contributor to the age-standardized mortality rate, for both sexes and all ages worldwide. In Europe and the United States, it is the... (Review)
Review
Breast cancer is the second leading contributor to the age-standardized mortality rate, for both sexes and all ages worldwide. In Europe and the United States, it is the second leading cause of mortality, with an incidence rate of about 2.6 million cases per year. Noscapine, a well-known alkaloid used as a cough suppressant, demonstrated anti-tumor effects by triggering apoptosis in various cancer cell lines and has the potential to become another ally against breast, ovarian, colon, and gastric cancer, among other types of malignancy. Apoptosis plays a crucial role in the treatment of cancer. Noscapine affected , , , , and gene and protein expression in the MCF-7 and MDA-MB-231 cell lines. Gene expression was higher in tumor than in normal tissue, including the BAX expression levels in lung, ovary, endometrium, colon, stomach, and glioblastoma patients; BCL2L1 expression in endometrium, colon, and stomach patients; CASP8 gene expression levels in lung, endometrium, colon, stomach, and glioblastoma patients; RELA in colon, stomach, and glioblastoma patients; and NFKBIA in glioblastoma patients. It can be concluded that noscapine affected genes and proteins related to apoptosis in cancer cell lines and several types of cancer patients.
Topics: Female; Humans; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Glioblastoma; Noscapine
PubMed: 38542508
DOI: 10.3390/ijms25063536 -
Pain Medicine (Malden, Mass.) Nov 2023At low doses, naltrexone (LDN) has been shown to modulate inflammation through the interruption of microglial cell activation within the central nervous system. One of... (Review)
Review
BACKGROUND
At low doses, naltrexone (LDN) has been shown to modulate inflammation through the interruption of microglial cell activation within the central nervous system. One of the most likely contributors to centralized pain is changes in microglial cell processing. Therefore, it has been postulated that LDN can be used to manage patients with pain resulting from central sensitization due to this relationship. This scoping review aims to synthesize the relevant study data for LDN as a novel treatment strategy for various centralized pain conditions.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, and Google Scholar, guided by the Scale for Assessment of Narrative Review Articles (SANRA) criteria.
RESULTS
Forty-seven studies related to centralized pain conditions were identified. Many of the studies were case reports/series and narrative reviews, but a few randomized control trials have been conducted. Overall, the body of evidence revealed improvement in patient-reported pain severity and in outcomes related to hyperalgesia, physical function, quality of life, and sleep. Variability in dosing paradigms and the time to patient response was present in the reviewed studies.
CONCLUSIONS
Evidence synthesized for this scoping review supports the ongoing use of LDN for the treatment of refractory pain in various centralized chronic pain conditions. Upon review of the currently available published studies, it is apparent that further high-quality, well-powered randomized control trials need to be conducted to establish efficacy, standardization for dosing, and response times. In summary, LDN continues to offer promising results in the management of pain and other distressing symptoms in patients with chronic centralized pain conditions.
Topics: Humans; Naltrexone; Chronic Pain; Quality of Life; Chronic Disease; Inflammation
PubMed: 37302106
DOI: 10.1093/pm/pnad074 -
Biomedicine & Pharmacotherapy =... Nov 2023Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, is one of the herb components of many Chinese Traditional Medicine prescriptions such as... (Review)
Review
Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo, their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations.
PubMed: 37729733
DOI: 10.1016/j.biopha.2023.115511 -
JAMA Network Open Sep 2023Buprenorphine treatment for opioid use disorder (OUD) has more than doubled since 2009. However, current US Food and Drug Administration buprenorphine dosing guidelines...
IMPORTANCE
Buprenorphine treatment for opioid use disorder (OUD) has more than doubled since 2009. However, current US Food and Drug Administration buprenorphine dosing guidelines are based on studies among people using heroin, prior to the emergence of fentanyl in the illicit drug supply.
OBJECTIVE
To estimate the association between buprenorphine dose and time to treatment discontinuation during a period of widespread fentanyl availability.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used statewide Rhode Island Prescription Drug Monitoring Program data. Participants were Rhode Island residents initiating buprenorphine treatment for OUD between October 1, 2016, and September 30, 2020. Data analysis was performed from December 9, 2022, to August 10, 2023.
EXPOSURE
Daily dose of buprenorphine (16 mg and 24 mg) defined starting on the day of initiation based on total quantity and days' supply dispensed. Patients were censored on any dose change.
MAIN OUTCOMES AND MEASURES
Buprenorphine treatment discontinuation in the 180 days following initiation, defined as a gap in treatment of more than 27 days based on prescription fill dates and days' supply. Kaplan-Meier and Cox regression survival analyses were conducted to estimate the association between buprenorphine dose and time to treatment discontinuation, controlling for potential informative censoring and measured potential confounders.
RESULTS
Among 6499 patients initiating buprenorphine treatment for OUD, most were aged 25 to 44 years (57%; n = 3682), were male (61%; n = 3950), and had private (47%; n = 3025) or Medicaid (33%; n = 2153) insurance. More than half of patients were prescribed a daily dose of interest at initiation (16 mg: 50%; n = 3264; 24 mg: 10%; n = 668). In Kaplan-Meier analyses, 58% of patients discontinued buprenorphine treatment within 180 days (16 mg: 59% vs 24 mg: 53%; log-rank test P = .005). In Cox regression analyses, patients prescribed a dose of 16 mg had a greater risk of treatment discontinuation than those prescribed 24 mg (adjusted hazard ratio, 1.20; 95% CI, 1.06-1.37).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients initiating buprenorphine treatment from 2016 to 2020, patients prescribed a 24 mg dose of buprenorphine remained in treatment longer than those prescribed 16 mg. The value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.
Topics: United States; Humans; Male; Female; Buprenorphine; Cohort Studies; Retrospective Studies; Opioid-Related Disorders; Fentanyl
PubMed: 37721749
DOI: 10.1001/jamanetworkopen.2023.34540 -
Indian Journal of Pharmacology 2023
Topics: Ketamine; Morphine; Analgesics, Opioid
PubMed: 38174540
DOI: 10.4103/ijp.ijp_230_23 -
Revista Espanola de Sanidad... 2023To evaluate the effectiveness of opioid maintenance programs in treating opioid dependence in Spanish prisons. (Review)
Review
OBJECTIVES
To evaluate the effectiveness of opioid maintenance programs in treating opioid dependence in Spanish prisons.
MATERIAL AND METHOD
A narrative bibliographic review was carried out on the following databases: PubMed; Cochrane; IBECS; LILACS; HealthCare. All clinical trials were chosen as a preference, along with systematic review articles and some articles that were considered relevant for their content. The time period was limited to between January 2011 and November 2021. The languages chosen were English, Spanish and Catalan. Repeated articles and those that were not related to the objectives were rejected. The search criteria were: "methadone AND prisons"; "opiate substitution treatment AND prisons"; "methadone AND buprenorphine"; "methadone OR buprenorphine"; "prisons AND Methadone AND buprenorphine".
RESULTS
20 articles were selected out of 647 items consulted after applying the corresponding filters and after discarding duplicates.
DISCUSSION
There was a slightly greater effectiveness of buprenorphine versus methadone. The high prevalence of the program was highlighted, as well as the variety of adverse effects of methadone. Usefulness with regard to inmates' behavior showed a range of opinions. The possibility of new treatment alternatives with better pharmacological control is mentioned.
Topics: Humans; Analgesics, Opioid; Buprenorphine; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prisons
PubMed: 38289166
DOI: 10.18176/resp.00077 -
Anesthesiology Jul 2023Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities remain poorly understood. This study tested the hypothesis that IV morphine and hydromorphone differ in onset, magnitude, duration, and variability of analgesic and ventilatory effects.
METHODS
The authors conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-h IV infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1 to 2 weeks apart. The authors measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discrete preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired carbon dioxide, and respiratory rate for 12 h after dosing.
RESULTS
For morphine and hydromorphone, respectively, maximum miosis was less (3.9 [3.4 to 4.2] vs. 4.6 mm [4.0 to 5.0], P < 0.001; median and 25 to 75% quantiles) and occurred later (3.1 ± 0.9 vs. 2.3 ± 0.7 h after infusion start, P < 0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs. 50 ± 2°C, P < 0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P < 0.001); maximum end-expired CO2 was 47 (45 to 50) and 48 mmHg (46 to 51; P = 0.007) and occurred later (5.5 ± 2.8 vs. 3.0 ± 1.5 h after infusion start, P < 0.001); and respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P < 0.001), and occurred at similar times. The area under the temperature tolerance-time curve was less for morphine (1.8 [0.0 to 4.4]) than hydromorphone (5.4°C-h [1.6 to 12.1] P < 0.001). Interindividual variability in clinical effects did not differ between opioids.
CONCLUSIONS
For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.
Topics: Humans; Hydromorphone; Morphine; Analgesics, Opioid; Cross-Over Studies; Healthy Volunteers; Pain; Drug-Related Side Effects and Adverse Reactions; Respiratory Insufficiency; Miosis; Pain, Postoperative; Double-Blind Method
PubMed: 37014986
DOI: 10.1097/ALN.0000000000004567