Adverse Drug Responses Research Articles

Evaluation of Drug and Herbal Medicinal Promotions on Social Media During the COVID-19 Pandemic in Relation to World Health Organization Ethical Criteria and South African Health Products Regulatory Authority Guidelines in South Africa: Cross-Sectional Content Analysis.

Consideration of ethics in the promotion of medications is essential to safeguard the health of consumers, particularly during health crises. The World Health Organization (WHO) and the South African Health Products Regulatory Authority (SAHPRA) have established stringent standards to ensure the integrity of pharmaceutical promotions and safeguard public health, including advertisements on the internet and social media platforms. However, the dynamic nature of online advertising poses challenges for monitoring and enforcing ethical standards. The study aimed (1) to examine the COVID-19 drug and medicinal promotions across online platforms and social media from 2020 to 2022 in South Africa and (2) to ensure that drug promotions adhere to ethical guidelines outlined by the WHO and SAPHRA. A cross-sectional content analysis was conducted to assess drug and medicinal advertisements across various internet and social media platforms. A systematic approach was used to identify and analyze promotional content, focusing on adherence to ethical guidelines outlined by WHO and SAPHRA. Data were collected and analyzed to determine the extent of compliance and identify any potential violations or areas for improvement. A total of 14 online drug advertisements were included in this analysis. Our findings show that most of the drugs advertised did not meet the regulations and guidelines provided by WHO and SAHPRA. There were omissions about active ingredients, proprietary names, adverse drug responses, precautions, and overdosage and adverse drug reactions. Traditional medicines were not fully consistent with the approved WHO ethical criteria data sheet. Our analysis highlights the critical importance of ensuring compliance with ethical guidelines in drug promotions on the internet and social media platforms. There is a need for continued vigilance and enforcement efforts to uphold ethical standards and protect the health of the public. Ongoing monitoring and collaboration between national drug regulatory agencies, pharmaceutical companies, and online platforms will be essential for promoting responsible advertising. In addition, safety monitoring and pharmacovigilance systems for herbal medicinal products are yet to be established.

Heparin-Induced Thrombocytopenia

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

APF2: an improved ensemble method for pharmacogenomic variant effect prediction

Lack of efficacy or adverse drug response are common phenomena in pharmacological therapy causing considerable morbidity and mortality. It is estimated that 20–30% of this variability in drug response stems from variations in genes encoding drug targets or factors involved in drug disposition. Leveraging such pharmacogenomic information for the preemptive identification of patients who would benefit from dose adjustments or alternative medications thus constitutes an important frontier of precision medicine. Computational methods can be used to predict the functional effects of variant of unknown significance. However, their performance on pharmacogenomic variant data has been lackluster. To overcome this limitation, we previously developed an ensemble classifier, termed APF, specifically designed for pharmacogenomic variant prediction. Here, we aimed to further improve predictions by leveraging recent key advances in the prediction of protein folding based on deep neural networks. Benchmarking of 28 variant effect predictors on 530 pharmacogenetic missense variants revealed that structural predictions using AlphaMissense were most specific, whereas APF exhibited the most balanced performance. We then developed a new tool, APF2, by optimizing algorithm parametrization of the top performing algorithms for pharmacogenomic variations and aggregating their predictions into a unified ensemble score. Importantly, APF2 provides quantitative variant effect estimates that correlate well with experimental results (R2 = 0.91, p = 0.003) and predicts the functional impact of pharmacogenomic variants with higher accuracy than previous methods, particularly for clinically relevant variations with actionable pharmacogenomic guidelines. We furthermore demonstrate better performance (92% accuracy) on an independent test set of 146 variants across 61 pharmacogenes not used for model training or validation. Application of APF2 to population-scale sequencing data from over 800,000 individuals revealed drastic ethnogeographic differences with important implications for pharmacotherapy. We thus think that APF2 holds the potential to improve the translation of genetic information into pharmacogenetic recommendations, thereby facilitating the use of Next-Generation Sequencing data for stratified medicine.

Efficacy of pregabalin, amitriptyline, and gabapentin for neuropathic pain

Neuropathic pain largely influences the well-being of patients. Anticonvulsant and antidepressant medications, such as Pregabalin, Gabapentin, and Amitriptyline, are routinely prescribed as initial treatments for neuropathic pain. The study sample has a total of 270 patients who meet the inclusion criteria and are further distributed into three equally sized groups (A, B, and C). Group A was administered with Gabapentine 300mg, Group B with Pregabalin 75 mg, and Amitriptyline 10 mg to Group C. The occurrence of any adverse drug response was documented using the ADR reporting form, while the pain of the patient's post-medication was recorded using a numerical pain rating scale (NPRS). The comparison of the NPRS scores of all three groups "by using ANOVA test" both at baseline and after 15 days reveal that the differences between the three groups are statistically insignificant (p > 0.089). However, after one month of continuous use, the difference becomes slightly significant (I.e., p = 0.003). Gabapentin, pregabalin, and amitriptyline demonstrate similar effectiveness in alleviating neuropathic (NeP) pain. The study concludes that gabapentin is superior to both pregabalin and amitriptyline with fewer adverse effects, leading to improved patient adherence for long-term use.

Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial.

Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC24/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have showed that intermittent infusion of vancomycin (IIV) may not achieve the desired levels, continous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity. This study aimed to compare the serum concentrations, AUC24, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population. This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC24 between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated. Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC24 ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC24 (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups. This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.

Analysis of Favipiravir Adverse Drug Reactions during COVID-19 Pandemic: A Retrospective Study Based on Iraqi Pharmacovigilance Center Database

The “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” was the reason behind the recent pandemic “COVID-19” that started from Wuhan, china, and rapidly spread to many regions of the world. Research in Drug repurposing processes to treat this novel coronavirus involved many medications, one of the most discussed is Favipiravir. The objective of the current work was aimed towards Examining the cause, severity, preventability, predictability, and outcome of favipiravir-associated adverse events that had been reported in Iraq. In terms of adverse drug responses, "Gastrointestinal disorders" accounted for the majority (57.4%), followed by "Cardiac disorders" (35.2%), and "Investigations" (abnormal lab test results) (13%). The causality of these reactions Is majorly “Possible” (62%). Severity level 1 (40.9%) and 2 (41.8%). Ninety-nine percent of the ADRs are expected. The majority of the ADRs are non-Preventable (76.3%). The main outcome is Recovered / Resolved (44.5%). About (50%) of the ADRs were serious.

A harmonisation approach to traditional Chinese medicine registration in Asian countries

The traditional Chinese medicine (TCM) industry is critical to not only for public health but also for economic growth. According to the European Union (EU) directives, under the EU framework for (traditional) herbal medicinal products, herbal medicines with long history of use can be registered in EU. However, there is a condition in this directive in which only those that have at least 10–15 years in the EU market are accepted for registration and/or marketing authorization. In author opinion, the condition of 10–15 years of use in EU countries set within the EU regulatory framework is with consideration of the genetic differences which can result in variation in adverse drug responses among different world populations. With this concept in mind, it is reasonable to project the principal of the EU directive to the Asian countries where TCM is originated. Countries like China, Singapore, Japan and South Korea that have well established drug registration framework are in best position in executing the best practice and facilitate harmonization of registration for TCM within the region. Furthermore, the registration process itself allows more safety and efficacy data to be collected systemically before and after product registration/marketing authorization. These are valuable information for future drug development. The therapeutic value of TCM is limitless, it has been left out in the EU regulatory framework, and the opportunity for it to be expanded and carried forward in modern medicines is shadowed by the limited number of TCM that are qualified to be registered under the EU regulatory framework. An early establishment of a harmonized risk-based registration process for TCM in Asian countries is important. This will strengthen the database to substantiate the history of safe use and further preserving and expanding the therapeutic values of TCM within and beyond the Asian region.

Improving cognitive function with intermittent dose escalation of curcumin extract in chemotherapy-induced cognitive impairment patients: a randomized controlled trial

Chemotherapy-induced cognitive impairment (CICI) is an impairment of memory, learning power, concentration, reasoning, executive function, attention, and visuospatial during and after chemotherapy exposures. No proven safe and effective therapeutic regimen are available to improve cognitive function in CICI patients. To evaluate the safety and effectiveness of curcumin extract to improve cognitive function in CICI patients. This study was a double-blind randomized controlled trial clinical trial in patients with cervical carcinoma who underwent a carboplatin-paclitaxel chemotherapy regimen from March to October 2021 at single center hospital. Subjects divided into two groups that received curcumin and placebo caplets by dose escalation method from 240 to 400 mg intermittently (14 days on and 7 days off) between chemotherapy cycles. Cognitive function was evaluated pre- and post-therapy using the AFI questionnaire, Stroop test, and MoCA-Ina. A total of 78 subjects were equally divided into the treatment and control groups. The percentage of drop-out, mortality, and adverse drug response were relatively comparable between each treatment arm. The group of subjects receiving curcumin extract experienced clinically and statistically significant improvements in cognitive function based on the Stroop test (∆ median 8.57 vs. 2.46; Z − 4.503 vs. − 1.762; p < 0.0001 vs. 0.078) and MoCA- Ina (∆ mean 1.53 vs. 0.72; Z − 2.99 vs. − 2.05; p < 0.003 vs. 0.04) versus placebo in between-group and between-subject analyses, respectively. Administration of curcumin extract with intermittent dose escalation regimen proved to be safe and able to improve cognitive function of CICI patients clinically and statistically significant.

Assessment of antitubercular treatment induced adverse drug reactions data at a tertiary care hospital

Background: Standard anti-tuberculosis (TB) treatment is highly effective, but managing adverse drug responses is a major challenge that can negatively affect treatment compliance and outcomes of an anti-tubercular treatment (ATT) regimen. Hence, monitoring of these adverse drug reactions (ADRs) is very essential wherein the drug-causing ADR can be detected and an appropriate therapeutic regimen can be given to the patient. Aims and Objectives: To assess the ATT-induced ADRs in Individual Case Safety Reports (ICSRs), to find the incidence and prevalence of ADRs due to ATT, and to analyze the causality assessment of the ADRs due to ATT. Materials and Methods: A retrospective observational study was carried out using spontaneous ICSRs data from the ADR monitoring centre at Madras Medical College, Chennai. A suspected adverse drug reaction reporting form (sADR reporting form) provided by the Pharmacovigilance Programme of India was used to collect the data of an ICSR. Results: A total of 93 ICSRs were assessed during the study period. The majority of the ADRs occurred in males (n = 55), and the maximum number of ADRs were found in the age group of 18–44 years (n = 46). The majority of the ICSRs were categorized as “serious” (n = 60), of which the maximum number of ADRs belonged to the “hospitalization/prolonged hospital stay” category (n = 45). Most of the suspected ATT drugs involved in implicating ADRs were found to be fixed-dose combination pills of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol (n = 71). Most of the ADRs were “skin and subcutaneous disorders” (n = 51) of the system organ class. The outcome of the ADRs was assessed and found that the majority of them were in the “recovering” (n = 54) category, and the majority of the ICSRs were found to be “probable” (n = 67). Conclusion: An effective implementation of a Pharmacovigilance system with early detection and management of ADRs is needed to overcome the nonadherence to TB therapy.

Time to major adverse drug reactions and its predictors among children on antiretroviral treatment at northwest Amhara selected public hospitals northwest; Ethiopia, 2023.

Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia. This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023. A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance. The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person-months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74-19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21-0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26-9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23-0.52)] were predictors of major adverse drug reactions. The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions.

Amlodipine-induced pedal edema with bilateral lower limb cellulitis: A case report

Amlodipine stands as a third-generation 1,4 Dihydropyridine (DHP) Calcium Antagonist, showcasing remarkable selectivity for vascular smooth muscle. It exhibits minimal impact on heart rate, without inducing negative inotropic or electrophysiological alterations. Amlodipine recommended for Atherosclerosis, Hypertension, and Stable Angina management, this Case Report delves into a prevalent adverse event associated with its use: Pedal Edema. In comparison to other Antihypertensive Medications, Amlodipine displays a heightened incidence of Pedal Edema. This case report details the situation of a 65-year-old male patient who is dealing with Hypertension. Over a span of 4 years, the patient had been on oral Amlodipine 5 mg, which led to the development of Pedal Edema. The symptoms saw resolution upon cessation of the medication, followed by a switch to an alternative Antihypertensive regimen. This study deepens our comprehension of Amlodipine's effects and facilitates early identification and mitigation of major adverse drug responses among patients.

The Critical Role of Pharmacists in the Clinical Delivery of Pharmacogenetics in the U.S.

Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice.

The Effect of a Pharmacist-Intervention Program on Clinical Outcomes in Diabetes Mellitus Patients

Background: Clinical pharmacists are skilled in identifying patient medication-related problems such as adverse drug responses and non-adherence. Pharmacists participate in diabetes management teams and offer direct patient treatment using several practice models in different ambulatory practice settings. The objective is to evaluate the effect of a pharmacist-intervention program on clinical outcomes in diabetes mellitus patients. Materials and methods: The cohort consisted of diabetes patients attending multi-speciality care hospitals. Eligible patients were randomly assigned in a 1:1 ratio to the intervention and control groups. Each patient in the intervention group was counselled by the research pharmacist. The measure of diabetes self-management was assessed using the Summary of Diabetes Self –Care activities (SDSCA) questionnaire. Results: 150 patients out of this population met the inclusion criteria. The study succeeded in proving the effect of pharmacist-led patient education in the improvement of the quality of life and clinical parameters of diabetes. The pronounced differences in the SDSCA scores of the test group and control group signify the impact of interventions and the consistency of the scale as well. Conclusion: The effect of pharmacist-led interventions on diabetic treatment outcomes was evaluated. The results recommend the need for extensive pharmacist-led intervention programs in metabolic disorder management.

Guardians of Safety: The Crucial Role of Pharmacists in Reducing Adverse Drug Reactions

Adverse drug responses, often known as ADRs, are a major cause for concern in contemporary medical treatment. These reactions are a major contributor to the morbidity and mortality rates of patients, as well as the rising expenditures of medical care. Because of their considerable understanding in drug management, patient education, and pharmacovigilance techniques, chemists are in a position to limit these risks in a way that is not possible with any other member of the healthcare team. The purpose of this research is to investigate the significant contribution that chemists play in the reduction of adverse drug reactions (ADRs), focussing on the impact that they have through patients' education, comprehensive medication therapy management (MTM), and active engagement in pharmacovigilance. The research also tackles difficulties such as excessive workloads and barriers to adverse drug reaction (ADR) reporting, and it proposes solutions to enhance the effectiveness of chemists in reducing adverse drug reactions (ADR). This review highlights the crucial role that chemists play in protecting the health of patients and enhancing the safety of medications by putting an emphasis on technical breakthroughs, constant professional growth, and collaboration across disciplines.

Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities.

Older adults have a higher prevalence of chronic obstructive pulmonary disease (COPD), which will likely increase substantially in the coming decades owing to aging populations and increased long-term exposure to risk factors for this disease. COPD in older adults is characterized by low-grade chronic systemic inflammation, known as inflamm-aging. It contributes substantially to age-associated pulmonary changes that are clinically expressed by reduced lung function, poor health status, and limitations in activities of daily living. In addition, inflamm-aging has been associated with the onset of many comorbidities commonly encountered in COPD. Furthermore, physiologic changes that are often seen with aging can influence the optimal treatment of older patients with COPD. Therefore, variables such as pharmacokinetics, pharmacodynamics, polypharmacy, comorbidities, adverse drug responses, drug interactions, method of administration, and social and economic issues that impact nutrition and adherence to therapy must be carefully evaluated when prescribing medication to these patients because each of them alone or together may affect the outcome of treatment. Current COPD medications focus mainly on alleviating COPD-related symptoms, so alternative treatment approaches that target the disease progression are being investigated. Considering the importance of inflamm-aging, new anti-inflammatory molecules are being evaluated, focusing on inhibiting the recruitment and activation of inflammatory cells, blocking mediators of inflammation thought to be important in the recruitment or activation of these inflammatory cells or released by these cells. Potential therapies that may slow the aging processes by acting on cellular senescence, blocking the processes that cause it (senostatics), eliminating senescent cells (senolytics), or targeting the ongoing oxidative stress seen with aging need to be evaluated.

Adverse Drug Reaction Reporting in Geriatric Oncology in India: An Understudied Topic that Needs Attention

AbstractIn the elderly, polypharmacy is a common problem, and drug interactions and adverse drug reactions (ADR) have been linked to considerable harm in several population-based studies. However, when compared with other medical disciplines, studies with elderly cancer patients are lacking in oncology and India in particular. Additionally, intake of multiple drugs and, at times, potentially inappropriate medications (PIMs) are also common in older cancer patients. Physiologically, the body's metabolic functions are reduced in the elderly, resulting in altered medication pharmacokinetics and pharmacodynamic characteristics. There is also a high risk of aging-related disorders, and an increase in pharmaceutical use. Because cancer can affect the physiological milieu, patients are more likely to experience negative drug responses, drug–disease interactions, and drug–drug interactions, thereby making the elderly more vulnerable to the ill effects. Considering this, there is a need for greater knowledge and measures that try to lessen exposure to and the risks connected to drug combinations that might be detrimental. As the geriatric population grows, the need to address medical issues among aging cancer patients becomes more pressing, particularly in India. As far as the authors are aware, there is no review that addresses the drug–drug interactions and adverse drug responses brought on by polypharmacy in older cancer patients. It is expected that this endeavor will help the fraternity and the patients, and will serve as a valuable academic material for the health care students.

Review on Concept of Pharmacovigilance

In order for clinical practise, public health efforts, and effective drug regulatory systems to function effectively, pharmacovigilance—the term used to describe the processes for recording and analysing adverse drug reactions—must be implemented. A high level of skill is required to grasp pharmacovigilance in order to swiftly identify pharmacological dangers and to defend the product against an unjustified withdrawal. The volume of data handled has increased as a result of the reporting of number of the adverse drug reactions (ADRs). The present global network of pharmacovigilance centres, which is supervised by the Uppsala Monitoring Center, would be strengthened by an independent review procedure. This would consider disputed and important pharmaceutical safety problems that might have a detrimental effect on public health across international borders. Recently, the main goal of pharmacovigilance has been to identify previously unrecognised or poorly understood adverse drug reactions. Clinical research must include pharmacovigilance, which is becoming more and more popular in many countries. To improve drug safety and monitoring, pharmacovigilance faces significant obstacles at the turn of the millennium. Currently, a number of pharmacovigilance centres are engaged in this global effort to monitor the safety of pharmaceuticals. We'll discuss medication safety, the role of worldwide pharmacovigilance centres, the benefits and downsides of pharmacovigilance, and how the healthcare sector can employ it in the future in this review. (4) Pharmacovigilance encourages the correct and safe use of drugs. Adverse drug responses (ADRs) must be reported spontaneously, and this is a crucial part of pharmacovigilance. ADRs are, nonetheless, considerably underreported. In developing nations, adverse medication responses are now a significant issue. Understanding pharmacovigilance could serve as the foundation for actions meant to increase reporting rates and lower ADRs. (1).

Comparitive Study of Pharmacovigilance System in India and USA

A system of pharmacovigilance is a field of pharmacological sciences that deals with the Adverse Events Reaction reporting produced by medical devices and or drugs. One of the possible public health problems is an adverse event, which needs ongoing recording, assessment, and surveillance. Drug regulations have improved and got stronger since the 1937 sulphanilamide tragedy and the1960 thalidomide disaster. As such response, a Pharmacovigilance System was developed, which is capable of receiving, diagnosing, evaluating, monitoring, and mitigating harmful effects of medical products. The Central Drug Standard Control Organization-CDSCO regulates India's pharmacovigilance system, whereas the United States Food and Drug Administration-USFDA regulates the US pharmacovigilance system. In India, the pharmacovigilance programme monitors adverse drug responses. India has a Pharmacovigilance Program in place to track adverse drug reactions. The United States likewise has strict laws in place to strengthen Food &amp; Drug Administration (FDA) pharmacovigilance requirements. (WHO) -World Health Organization established an International Monitoring System in collaboration with (UMC) Uppsala Monitoring Centre.

Design and Optimization of 1H-1,2,3-Triazole-4-carboxamides as Novel, Potent, and Selective Inverse Agonists and Antagonists of PXR.

The pregnane X receptor (PXR) is a key regulator of drug metabolism. Many drugs bind to and activate PXR, causing adverse drug responses. This suggests that PXR inhibitors have therapeutic value, but potent PXR inhibitors have so far been lacking. Herein, we report the structural optimization of a series of 1H-1,2,3-triazole-4-carboxamides compounds that led to the discovery of compound 85 as a selective and the most potent inverse agonist and antagonist of PXR, with low nanomolar IC50 values for binding and cellular activity. Importantly, compound 89, a close analog of 85, is a selective and pure antagonist with low nanomolar IC50 values for binding and cellular activity. This study has provided novel, selective, and most potent PXR inhibitors (a dual inverse agonist/antagonist and a pure antagonist) for use in basic research and future clinical studies and also shed light on how to reduce the binding affinity of a compound to PXR.

COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics.

This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12 billion vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amid an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discussion of the effects of viral infections on placental amino acid transport and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infections and vaccine technologies on drug metabolism and disposition, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness. SIGNIFICANCE STATEMENT: Altered pharmacokinetics of small molecule and complex molecule drugs and fetal brain distribution of amino acids following SARS-CoV-2 infection or immunization are possible. The proposed mechanisms involve decreased liver cytochrome P450 metabolism of small molecules, enhanced innate immune system metabolism of complex molecules, and altered placental and fetal blood-brain barrier amino acid transport, respectively. Future research is needed to understand the effects of these interactions on adverse drug responses, drug and vaccine safety, and effectiveness and fetal neurodevelopment.