scholarly journals Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use

2019 ◽  
Vol 8 (7) ◽  
pp. 989 ◽  
Author(s):  
Joshua Brown ◽  
Almut Winterstein
Keyword(s):  
Drug Interactions ◽  
Sleep Disturbances ◽  
Adverse Drug Events ◽  
Alternative Therapy ◽  
Consumer Products ◽  
Medical Cannabis ◽  
Biological Targets ◽  
Safety Issues ◽  
Treatment Regimens ◽  
Potential Safety

Cannabidiol (CBD) is ubiquitous in state-based medical cannabis programs and consumer products for complementary health or recreational use. CBD has intrinsic pharmacologic effects and associated adverse drug events (ADEs) along with the potential for pharmacokinetic and pharmacodynamic drug–drug interactions (DDIs). Given CBD use among patients with complex conditions and treatment regimens, as well as its expanded consumer use, awareness of potential safety issues with CBD is needed. Prescribing information for federally approved products containing CBD were reviewed. Data on ADEs and DDIs were extracted and summarized. Nearly one-half of CBD users experienced ADEs, which displayed a general dose-response relationship. Common ADEs include transaminase elevations, sedation, sleep disturbances, infection, and anemia. Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19) and excretion (e.g., P-glycoprotein), the potential for DDIs with commonly used medication is high. General clinical recommendations of reducing substrate doses, monitoring for ADEs, and finding alternative therapy should be considered, especially in medically complex patients. CBD is implicated as both a victim and perpetrator of DDIs and has its own ADE profile. These effects should be considered in the risk-benefit assessment of CBD therapy and patients and consumers made aware of potential safety issues with CBD use.

scholarly journals Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions

2020 ◽  
Vol 9 (4) ◽  
pp. 919 ◽  
Author(s):  
Joshua D. Brown
Keyword(s):  
Drug Interactions ◽  
Adverse Drug Events ◽  
Alternative Therapy ◽  
Medical Marijuana ◽  
Racial Groups ◽  
Metabolizing Enzymes ◽  
Potential Risks ◽  
Neurological Effects ◽  
Medical Marijuana Use ◽  
Future Work

Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.

Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19

2020 ◽  
Vol 21 (6) ◽  
pp. 427-435 ◽  
Author(s):  
Cheng Cui ◽  
Siqi Tu ◽  
Valerie Sia Jie En ◽  
Xiaobei Li ◽  
Xueting Yao ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Clinical Efficacy ◽  
Relevant Literature ◽  
The United States ◽  
Efficacy And Safety ◽  
Open Label ◽  
Infected People ◽  
Treatment Regimens ◽  
Therapeutic Drugs

Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information. Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate. Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
Yong Zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

2020 ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
yong zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background: Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP) method was the strongest. Conclusion: The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.

scholarly journals Fine-grained lineage for safer notebook interactions

2021 ◽  
Vol 14 (6) ◽  
pp. 1093-1101
Author(s):  
Stephen Macke ◽  
Hongpu Gong ◽  
Doris Jung-Lin Lee ◽  
Andrew Head ◽  
Doris Xin ◽  
...  
Keyword(s):  
Static Analysis ◽  
Intermediate State ◽  
Data Science ◽  
Safety Issues ◽  
Fine Grained ◽  
Potential Safety

Computational notebooks have emerged as the platform of choice for data science and analytical workflows, enabling rapid iteration and exploration. By keeping intermediate program state in memory and segmenting units of execution into so-called "cells", notebooks allow users to enjoy particularly tight feedback. However, as cells are added, removed, reordered, and rerun, this hidden intermediate state accumulates, making execution behavior difficult to reason about, and leading to errors and lack of reproducibility. We present nbsafety, a custom Jupyter kernel that uses runtime tracing and static analysis to automatically manage lineage associated with cell execution and global notebook state. nbsafety detects and prevents errors that users make during unaided notebook interactions, all while preserving the flexibility of existing notebook semantics. We evaluate nbsafety's ability to prevent erroneous interactions by replaying and analyzing 666 real notebook sessions. Of these, nbsafety identified 117 sessions with potential safety errors, and in the remaining 549 sessions, the cells that nbsafety identified as resolving safety issues were more than 7X more likely to be selected by users for re-execution compared to a random baseline, even though the users were not using nbsafety and were therefore not influenced by its suggestions.

Perspectives for Potential Therapies for SARS-CoV-2

2021 ◽  
Vol 6 (4) ◽  
pp. 1-24
Author(s):  
Preeti Suman Saxena ◽  
Kirti Singh ◽  
Poonam Jangir ◽  
Manish Nath Tripathi ◽  
Vimal Singh ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Current Treatment ◽  
Third Wave ◽  
Biological Targets ◽  
Treatment Regimens ◽  
Current Review ◽  
Corona Virus ◽  
Current Treatment Strategy ◽  
Ongoing Development ◽  
Corona Viruses

The current pandemic, novel corona virus 19 disease (COVID-19), has created havoc across the world. Now a third wave is possible, and we have already crossed two waves. The current review article presents recent reports about the COVID-19, the ways of treatments, and prevention. In view of the potential threats of a pandemic, various scientists have been trying to understand the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To add further information to support the ongoing current research and development against SARS-CoV-2, the authors have provided the basics of pathophysiology, possible targets, and current treatment strategy for corona viruses. The current review highlights the antiviral strategies involving small molecules and different biological targets involved in corona virus infection and replication. The information included in this article provides a strong intellectual foundation for the ongoing development of therapeutic agents and vaccines.

Disaster Prevention Strategies: A Study on Underground Commercial Street

2016 ◽  
Vol 41 (3) ◽  
pp. 38-43
Author(s):  
Qin Yan ◽  
Yin Pan
Keyword(s):  
Open Space ◽  
Underground Space ◽  
Disaster Prevention ◽  
Prevention Strategies ◽  
Air Defense ◽  
Safety Issues ◽  
Potential Safety ◽  
Evacuation Routes ◽  
The City ◽  
Commercial Street

Planning for underground spaces has become an effective way to use central areas in cities given the steady economic growth in China. The development of underground spaces in mountainous cities has satisfied the needs of the diversification of the city commercial areas and pedestrian movement. Safety issues exist because these underground spaces were originally used for civil air defense. This study was based on the underground commercial street in Chongqing, which is a typical mountainous city. Based on the results of combined fieldwork and survey, this paper summarized current safety issues, which include the not-fully-open exit, the imbalanced exit location, blocked evacuation routes, and the poor awareness of the potential safety issues. This paper proposed a framework of the safety factors for the underground space and synopsized prevention strategies that are specific to potential disasters in the underground environment. The framework comprises ensuring that the exits are fully open, the underground corridors are kept unblocked, the open space on the street is increased for disaster prevention, and equipment security is maintained and managed. At last, This paper summarized disaster prevention strategies, which include ensuring unimpeded exits, balancing the locations of the exits, avoiding blocks, increasing the disaster prevention square area in the underground space, maintaining and managing the security of the equipment.

Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit

2020 ◽  
Vol 30 (6) ◽  
Author(s):  
Junaidi Khotib ◽  
Henny Utami Setiawan ◽  
Ahmad Dzulfikri Nurhan ◽  
Erreza Rahadiansyah ◽  
Chrismawan Ardianto ◽  
...  
Keyword(s):  
Side Effects ◽  
Drug Interactions ◽  
Adverse Drug Events ◽  
Laboratory Data ◽  
Age Distribution ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Drug Related Problems ◽  
Pain Reliever ◽  
Pain Medications

AbstractBackgroundOsteoarthritis (OA) is a chronic degenerative joint disease, characterized by physiological disorders, such as cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation, which results in pain. Several studies have reported problems with the use of pain medications in OA, such as the use of a combination of many drugs and their long-term use. Therefore, this study was designed to evaluate the use of pain medications in OA patients. The study focused on the analysis of effectiveness and drug related problems (DRPs) with the category of drug interactions and adverse drug events (ADEs) in knee OA patients in Orthopedic and Traumatology Clinic, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia.MethodsThe study used a retrospective approach through tracking and recording of the medical data from the period of 1st January to 30th June, 2018. The potential of drug interactions was determined by analyzing data based on literature. The actual side effects of the drug were identified based on the patient’s medical record through clinical data, laboratory data, and therapeutic data received by the patient. The study involved 143 subjects who met the inclusion criteria of 871 visits to the hospital.ResultsThe results showed that women as much as 80.42% with an age distribution of at most 46–65 years are the most affected by OA cases. The predominant history of illness and comorbidities in OA patients was hypertension in 58.74% of patients. The use of analgesic meloxicam had a percentage of 26.06%, sodium diclofenac 20.21%, mefenamic acid 4.36% and paracetamol 4.25%. The effectiveness of the use of pain reliever was characterized by a decrease in VAS in each patient at the beginning and at the end of the study, where a decrease in pain intensity occurred in 79.72% of patients who received pain medications. Based on drug interactions, we were able to identify pharmacodynamic interactions of 43 events (4.94%) and onine events of pharmacokinetic interactions (1.03%), with a minor severity of 7 events (0.80%),44 moderate events (5.05%), and one major event (0.11%). Mostly identified side effects of the drugs were those due to the use of non-steroid anti inflammatory drugs, which occurred in 42 events (4.82%).ConclusionsIt can be concluded that OA therapy with a number of pain relievers shows an adequate therapeutic response with some side effects and interactions both pharmacokinetically and pharmacodynamically.

Generic Issues Program Overview and Update

2008 ◽  
Author(s):  
Jack W. Foster ◽  
John V. Kauffman
Keyword(s):  
Effective Means ◽  
Cost Effective ◽  
Nuclear Regulatory Commission ◽  
The United States ◽  
The Body ◽  
Safety Issues ◽  
Potential Safety ◽  
Construction Operation ◽  
Regulatory Commission ◽  
Available Information

The United States Nuclear Regulatory Commission (NRC) has a Generic Issues Program (GIP) to address Generic Issues (GI). A GI is defined as “a regulatory matter involving the design, construction, operation, or decommissioning of several, or a class of, NRC licensees or certificate holders that is not sufficiently addressed by existing rules, guidance, or programs.” This rather legalistic definition has several practical corollaries: First, a GI must involve safety. Second, the issue must involve at least two plants, or it would be a plant-specific issue rather than a GI. Third, the potential safety question must not be covered by existing regulations and guidance (compliance). Thus, the effect of a GI is to potentially change the body of regulations and associated guidance (e.g., regulatory guides). The GIP was started in 1976, thus it is a relatively mature program. There have been approximately 850 issues processed by the program to date. More importantly, even after 30 years, new GIs continue to be proposed. The entire set of Generic Issues (GIs) is updated annually in NUREG-0933, “A Prioritization of Generic Safety Issues.” GIs tend to involve complex questions of safety and regulation. The efficient and effective means of addressing these issues is very important for regulatory effectiveness. If an issue proves to pose a genuine, significant safety question, then swift, effective, enforceable, and cost-effective action needs to be taken. Conversely, if an issue is of little safety significance, the issue should be dismissed in an expeditious manner, avoiding unnecessary expenditure of resources and regulatory burden or uncertainty. This paper provides an overview of the 5-stage program, from identification through the regulatory assessment stage. The paper also includes a discussion of the program’s seven criteria, sources of proposed GIs, recent improvements, publicly available information, historical performance, and status of current GIs.

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