Pharmacological Concepts Research Articles

Evaluating the quality of multiple-choice question pilot database: A global educator-created tool for concept-based pharmacology learning.

The Core Concepts of Pharmacology (CCP) initiative is developing educational resources to transform pharmacology education into a concept-based approach. This study evaluated the quality of global educator-created MCQs in generating items for the pharmacology concept inventory (PCI) instrument and developed as a resource for learning pharmacology fundamental concepts. A panel of 22 global pharmacology experts recruited from the CCP initiative research team participated in the MCQ pilot database design and evaluation. The quality analysis framework of the MCQs in the pilot database included four assessment tools: item writing guidelines (IWGs), Bloom's taxonomy, the CCP, and the MCQ design format. A two-phase evaluation process was involved, including inter-rater agreement on item quality, followed by resolving conflicts that occurred in quality assessment. The chi-square (χ2) test of independence and Cramer's V correlation tests were utilized to measure the relationship among quality assessment attributes. About 200 MCQs were gathered and 98% underwent expert evaluation. Nearly 80% addressed one or more CCP, with 52% designed using a context-dependent format. However, only 40% addressed higher levels of Bloom's cognitive domain and 10% adhered to all IWGs. A strong positive correlation was observed between the context-based item format and its effectiveness in assessing the higher cognitive domain, the main CCP and improved IWGs adherence. Context-based item construction can assess the higher cognitive skills and fundamental pharmacology concepts, showing potential for rigorous PCI development. The pilot database will store items to create the PCI, aiding the development of a concept-based pharmacology curriculum.

Extrapolating Lessons from Targeted Protein Degradation to Other Proximity-Inducing Drugs.

Targeted protein degradation (TPD) is an emerging pharmacologic strategy. It relies on small-molecule "degraders" that induce proximity of a component of an E3 ubiquitin ligase complex and a target protein to induce target ubiquitination and subsequent proteasomal degradation. Essentially, degraders thus expand the function of E3 ligases, allowing them to degrade proteins they would not recognize in the absence of the small molecule. Over the past decade, insights gained from identifying, designing, and characterizing various degraders have significantly enhanced our understanding of TPD mechanisms, precipitating in rational degrader discovery strategies. In this Account, I aim to explore how these insights can be extrapolated to anticipate both opportunities and challenges of utilizing the overarching concept of proximity-inducing pharmacology to manipulate other cellular circuits for the dissection of biological mechanisms and for therapeutic purposes.

Clinical Pharmacological Reconciliation, Review, and Feedback in Elderly Care: A Transformative Approach

Abstract The care of the aged becomes a critical priority in the ever-changing field of healthcare, requiring a specialized, and sensitive approach. This population is at the intersection of medical innovation and ethical care, as they are susceptible to the compounding effects of various drugs and complex health issues. In this regard, the Clinical Pharmacological Reconciliation, Review, and Feedback methodology is a trailblazing approach that seeks to improve and optimize care for the aged by applying the concepts of clinical pharmacology. This review explores few facets of this transformative approach.

Assessment of self-perceived knowledge of key clinical pharmacology concepts and educational needs among European Paediatric Intensive Care Units: an ESPNIC survey

BackgroundKnowledge of clinical pharmacology concepts is essential to improve patients’ outcomes. Scarce data is available on the utilisation of these concepts in the paediatric intensive care unit (PICU). We aimed to investigate the self-perceived knowledge of clinical pharmacology concepts, educational needs and identify priorities for pharmacological research across European PICUs.MethodsFrom July to November 2022 an online survey was distributed to evaluate i) the self-reported knowledge, and ii) application of key pharmacology concepts in clinical practice (using a likert scale from 1 = never apply to 10 = always apply); iii) need for additional education on them; and iv) key areas for future pharmacological research. The survey was distributed to European Society of Paediatric and Neonatal Intensive Care (ESPNIC) members and other European national PICUs societies members.ResultsTwo-hundred-thirty-seven responses from 149 PICUs were collected. 54% of PICUs reported to have a clinical pharmacologist available for consultation during drug prescription and 65% of them regularly contact them during the prescribing process. Among clinical pharmacology concepts the parameter with the highest self-reported knowledge was half-life (99%) and the lowest were pharmacodynamics and volume-of-distribution (92%). The reported median application of these concepts in clinical practice ranged between 5/10 and 7/10. Most of the respondents reported the need for additional education on specific pharmacology concepts. Reported priorities for drug research mostly involved analgesics/sedatives (87%), antimicrobials (86%), and cardiovascular medications (55%).ConclusionsSelf-reported knowledge on clinical pharmacology concepts seems good, but self-perceived clinical application may improve and most of the respondents report a need for additional education. These findings call for concerted multidisciplinary efforts to streamline education and guidelines to fill this gap.

How does pharmacological and toxicological knowledge evolve? A case study on hydrogen cyanide in German pharmacology and toxicology textbooks from 1878 to 2020

Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison hydrogen cyanide in sixteen German-language pharmacology and toxicology textbooks from 1878 to 2020. The categories of structure, molecular mechanism of action, occurrence, effects, resorption, areas of application, lethal dose, acute symptoms of intoxication, treatment of hydrogen cyanide poisoning, and recommended therapeutic preparations were evaluated. The knowledge on the structure, lethal dosage, and occurrence of hydrogen cyanide has remained constant. In contrast, knowledge on molecular mechanism of action and recommended preparations of the poison has changed dramatically. Until 1944, the binding of hydrogen cyanide to hemoglobin was considered the mechanism of action, whereas from 1951 onwards, the interaction of hydrogen cyanide with the Fe3+ of cytochrome oxidase was described. The number of preparations containing hydrogen cyanide decreased into obsolescence until 1951. The areas of application of hydrogen cyanide also show a change, as from 1919 onwards, mainly industrial areas of application of the poison are described instead of medical ones, and from 1951 onwards, criminalistic areas of application are also mentioned. Thus, pharmacological and toxicological knowledge develops non-linearly, molecular mechanism and uses being the most dynamic areas, whereas the knowledge about hydrogen cyanide’s chemical structure, lethal dose, and occurrence remained constant. Older pharmacology and toxicology textbooks were better than newer ones at discussing changes in scientific concepts. Pharmacology and toxicology textbooks also mostly failed to discuss the misuse of hydrogen cyanide (Zyklon B) during the Nazi regime, missing an important opportunity to showcase the ethical responsibility of pharmacology and toxicology. Thus, future pharmacology and toxicology textbooks should improve on discussing the development of pharmacological and toxicological concepts and the ethical responsibility of the discipline.

Identifying and Exploring the Cognitive Nature of Threshold Concepts in Pharmacology to Improve Medical Students’ Learning

Phenomenon: Pharmacology is a fundamental healthcare discipline, but it can be difficult and counterintuitive for learners to learn. Navigation toward understanding pharmacology can be troublesome, but once the threshold to comprehension is crossed, learners can experience a transformative shift in their ways of thinking and practicing. We conducted an in-depth examination of threshold concepts within pharmacology, aiming to identify and prioritize their learning to improve the medical curriculum and enhance medical treatment and patient safety. Approach: We carried out a consensus generation process using the Nominal Group Technique (NGT) to identify potential threshold concepts in pharmacology. Participant groups of pharmacology experts and medical students considered, identified, reviewed, and ranked potential pharmacology threshold concepts within their own group. Then, using a logical, step-by-step approach, we combined the final ranked data from these multiple NGT sessions. We further analyzed these data using an abductive analysis approach; data were coded, categorized, reorganized, and conceptually mapped after critical evaluation. Conceptual themes were established corresponding to different phases of cognitive schema development. Findings: Six comprehensive conceptual themes were identified: Drug Mechanism of Action; Pharmacotherapeutics; Pharmacokinetics; Drug Receptor Interactions; Drug Terminology and Nomenclature; and Signaling Pathways. These concepts align with many of the key attributes of threshold concepts (e.g., troublesome, integrative and transformative). The cognitive schematic themes generated were (i) acquisition-troublesome; (ii) acquisition-transformative; (iii) automation-troublesome; (iv) automation-transformative. Insights: Transformative learning involves different stages of cognitive schema evolution, including acquisition, elaboration, and automation, and is influenced by both the inherent challenges of the concepts and limitations of human cognition. The high interactivity of these troublesome concepts challenge schema acquisition and automation. Troublesome concepts underpinning procedures or skills, while not easily explained by cognitive rules, can lead to slow, awkward, error-prone performance, creating additional barriers for practice. Integrating concepts into a coherent structure leads to the irreversible assimilation of knowledge and the transferability of both knowledge and skills, influencing learners’ epistemological transitions and ontological transformations at theoretical and professional levels. Further work on designing instructional models around assisting and automating schemas around identified troublesome knowledge, while addressing the impact of cognitive load, has the potential to promote transformational learning.

On heritage pharmacology: Rethinking ‘heritage pathologies’ as tropes of care

This article develops the concept of heritage pharmacology as an encompassing critical framework in order to radically recast the interactions and efficacies of heritage as a particularly potent pharmacology of care. I critically engage with Stiegler's philosophic reflections On Pharmacology, which builds on Derrida's work and recasts pharmacology – a term usually reserved for that branch of the biomedical sciences dealing with drugs and their interactions and efficacies – in order to draw out the ‘curative-toxic’ dimensions at play in wider care tropes. By placing core concepts and practices of heritage and pharmacology in critical dialogue, my aim as heritage critic is to gain mutual insights into ‘care’, as that which links together the two domains of heritage and health, as otherwise distinct discourses, concepts, technics, and practices. My specific intervention rethinks the crucial role of ‘heritage pathologies’ and the underpinning memory-work at play within these tropes while grounding these in a case study of Jerusalem Syndrome (JS). I argue that it is the dynamic of heritage pathologies, best crystallized in JS debates, that invests us in the wider Stieglerian quest/ion of ‘pharmacology’, as a concern with ‘what makes life worth living’. Such quests ultimately take this article into the realpolitik of Palestine.

Application and Quality of Model-Based Meta-Analysis in Pharmaceutical Research: A Systematic Cross-Sectional Analysis and Practical Considerations.

Model-based meta-analysis (MBMA) can be used in assisting drug development and optimizing treatment in clinical practice, potentially reducing costs and accelerating drug approval. We aimed to assess the application and quality of MBMA studies. We searched multiple databases to identify MBMA in pharmaceutical research. Eligible MBMA should incorporate pharmacological concepts to construct mathematical models and quantitatively examine and/or predict drug effects. Relevant information was summarized to provide an overview of the application of MBMA. We used AMSTAR-2 and PRISMA 2020 checklists to evaluate the methodological and reporting quality of included MBMA, respectively. A total of 143 MBMA studies were identified. MBMA was increasingly used over time for one or more areas: drug discovery and translational research (n = 8, 5.6%), drug development decision making (n = 42, 29.4%), optimization of clinical trial design (n = 46, 32.2%), medication in special populations (n = 15, 10.5%), and rationality and safety of drug use (n = 71, 49.7%). The included MBMA covered 17 disease areas, with the top three being nervous system diseases (n = 19, 13.2%), endocrine/nutritional/metabolic diseases (n = 17, 11.8%), and neoplasms (n = 16, 11.1%). Of these MBMA studies, 138 (96.5%) were rated as very low quality. The average rate of compliance with PRISMA was only 51.4%. Our findings suggested that MBMA was mainly used to evaluate the efficacy and safety of drugs, with a focus on chronic diseases. The methodological and reporting quality of MBMA should be further improved. Given AMSTAR-2 and PRISMA checklists were not specifically designed for MBMA, adapted assessment checklists for MBMA should be warranted.

Insights into drug development with quantitative systems pharmacology: A prospective case study of uncovering hyperkalemia risk in diabetic nephropathy with virtual clinical trials

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.

Drug Speed Dating: A Novel Approach to Reinforce Pharmacology Concepts.

Drug Speed Dating: A Novel Approach to Reinforce Pharmacology Concepts.

TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine

The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with “herb-compound-target-pathway” and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub (https://github.com/yangpluszhu/tcmnpas), and the project is freely available at http://54.223.75.62:3838/.

An evaluation of knowledge and perception of pharmacology in undergraduate oral hygiene students and recent graduates at a single higher institution in Pretoria.

Pharmacology is an increasingly important area of study for oral hygienists,as it provides the scientific basis for safe and effective oral healthcare. However, a lack of fundamental understanding of the discipline among clinical graduates can present significant challenges. Oral hygienists require pharmacological training to meet the requirements of their scope of practice. Pharmacology knowledge assists with the diagnosis and treatment of oral conditionsand forms the foundation for further clinical competency development. The knowledge and perceptions of pharmacology for pharmacy, nursing and medical students have been well documented; however, little information is present for Bachelor of Oral Hygiene (BOH) students. This paper sets out to evaluate BOH students' and recent graduates' knowledge and perceptions of pharmacology at a single higher institution in Pretoria to identify possible gaps and weaknesses. A cross-sectional study design was used to collect data using an online questionnaire. The English-language questionnaire consisted of the self-reported perceptions and knowledge and actual knowledge of pharmacology of undergraduate BOH students and recent graduates. The questionnaire consisted of multiple choice questions, true or false questions and Likert scale questions. Ethics was obtained from the institution's Research Ethics Committee (REC 350/2021). Overall, the participants perceived the pharmacology module positively and understood its importance. Concerns were raised about insufficient time for studying and that assessments were more aligned to gaining factual knowledge than the development of problem-solving skills. Students rated their knowledge between 57.24% and 69.44%, with BOH III students and graduates having a statistically significant greater self-rated knowledge of antivirals, antifungals and common agents used to treat oral conditions in comparison with BOH I and BOH II students. Overall, BOH students and graduates' actual knowledge was between 45.24% and 66.84%. Although not statistically significant, the total self-rated knowledge of BOH III students and recent graduates tended to be higher than their actual knowledge. Knowledge deficits were evident with some pharmacological concepts across the various BOH groups, such as pharmacokinetics, pain, drugs altering dental treatment I: central nervous system drugs, drugs altering dental treatment II: respiratory and endocrine drugs, drugs altering dental treatment III: cardiovascular drugs, drug-drug interactions and common agents used to treat oral conditions. Self-rated knowledge deficiencies were noted by students and recent graduates for certain pharmacological concepts and were supported by the measurement of their actual knowledge. Further investigation into knowledge deficiencies is needed to guide curriculum review to further strengthen oral hygienists' pharmacological competencies and ensure alignment to their scope of practice.

Standardization and preliminary characterization of an ayurvedic stress-relieving head massage oil of Nardostachys jatamansi DC

BackgroundJatamansi/Nardostachys jatamansi (NJ) is an important aromatic shrub widely used by Ayurvedic practitioners for centuries due to its usefulness in intellect-enhancing (Medhya), strengthening (Balya), and skin disorders. Several classical dosage forms like hot or cold infusion, decoction, distillate, powders, etc. have been mentioned for NJ. Clinical trials of Jatamansi Oil (JO) as a head massage conducted by clinicians and therapists have shown encouraging results in de-stressing/stress management of cancer patients through head anointing treatment. ObjectiveSuch effective proprietary formulation needs assessment of its characteristics using modern analytical technologies to comprehend the Ayurvedic concept of dermal pharmacology. Materials and methodsTriplicate batches of JO were prepared by evaporating its decoction in sesame oil (SO). Basic physicochemical analysis of the raw material, in-process samples, and finished products was carried out to develop a monograph. Further, raw SO and finished product JO were subjected to TLC, and extracted in hexane and dichloromethane separately for Gas Chromatography-Mass Spectrometry (GC-MS) analysis to profile several bioactive molecules from NJ in the final product, JO. ResultsStandard Operating Procedure was developed and a basic monograph was prepared for JO. GC-MS analysis revealed several phytocompounds dissolved/dispersed in SO after processing, while 18 additional distinct peaks were observed in JO as compared to SO. ConclusionThis preliminary analysis supports the Ayurvedic concept of lipid-based formulations. The plausible phytocompounds anticipated based on retention times can be further quantified and studied for their probable action as anointing treatment. A detailed experimental strategy for understanding the phytochemical changes during the entire process needs to be planned and performed.

The Effect of Bingo Games and Board Games Applied to Nursing Students in Pharmacology Lessons On Lesson Motivation

Objective: This study examined the effects of bingo games and board games on the motivation of nursing students in pharmacology courses.Materials and Methods: A quasi-experimental study with a post-test only design was conducted with 72 nursing students at a state university in Türkiye between March and April 2023. The study participants were allocated to two groups, each with 36 students, using a random assignment procedure. Group A was the bingo game group, and group B was the board game group. All topics related to the pharmacology course were taught to both groups by the same instructor one day a week during the semester. After the lesson, the students in group A played a bingo game that was modified to include pharmacology concepts, while the students in group B played a board game that was also modified to include pharmacology concepts. After the game, all groups filled out the "Information Form" and " Instructional Materials Motivation Scale". Results: The mean Instructional Materials Motivation Scale total score was 132.91 ± 20.06 for the bingo group. The mean Instructional Materials Motivation Scale score was 124.80 ± 20.54 for the table game group. The mean scores of the Instructional Materials Motivation Scale total and sub-dimensions were not significantly different between the bingo game and board game groups (p > 0.05). Conclusion: The study found that there was no significant difference in the motivation levels of nursing students who used bingo or board games as reinforcement in pharmacology lessons.

Learner’s perspectives and outcomes of peer role play as a teaching learning method for prescription communication skills in second year medical students at a tertiary teaching hospital in India

Background: Medical education in India is experiencing a positive shift from traditional curriculum to competency-based medical education. Among the different initiatives, inclusion of role-play with specific aim of improving prescription communication skills in the current curriculum, could lead to beneficial patient- response outcomes. This study aims to evaluate the undergraduate medical student’s perspectives on implementing role-play for learning about prescription communication. Methods: This was a cross-sectional observational study conducted in the department of pharmacology involving second-year medical students of Vydehi institute of medical science and research centre participating for a month-long duration. An internally validated questionnaire was used to assess students’ perspectives on role-play in prescription communication. The outcome was evaluated based on students’ performance in prescription writing and appropriate communication before and after the role-play session. The data obtained was analysed using the SPSS software. Results: The mean score for the overall benefit of role play for prescription communication for all responding participants (n=163) was 4.2 out of 5. In this study, 89.4% of students agreed that role-play in prescription communication should be an essential aspect of their training in the curriculum and is worth taking this additional effort. 84.6% of students found that, the sessions helped to understand and share the pharmacology concepts better. Mean pre and post role play prescription writing assessment scores in students was 7.59 and 9.01 out of 10 respectively. Conclusions: Role-play was well received by the students as a low-cost innovative teaching methodology for better understanding of Pharmacology concepts as mandated by the CBME curriculum. It helps in understanding the importance of teamwork and error-free prescription communication for future clinical practice. Overall, following appropriate demonstration, use of role-play showed significant improvement in student performance in prescription communication.

Applying Pharmacology Concepts Outside the Classroom.

Applying Pharmacology Concepts Outside the Classroom.

Developing an international concept-based curriculum for pharmacology education: The promise of core concepts and concept inventories.

Over recent years, studies have shown that science and health profession graduates demonstrate gaps in their fundamental pharmacology knowledge and ability to apply pharmacology concepts in practice. This article reviews the current challenges faced by pharmacology educators, including the exponential growth in discipline knowledge and competition for curricular time. We then argue that pharmacology education should focus on essential concepts that enable students to develop beyond 'know' towards 'know how to'. A concept-based approach will help educators prioritize and benchmark their pharmacology curriculum, facilitate integration of pharmacology with other disciplines in the curriculum, create alignment between universities and improve application of pharmacology knowledge to professional contexts such as safe prescribing practices. To achieve this, core concepts first need to be identified and unpacked, and methods for teaching and assessment using concept inventories developed. The International Society for Basic and Clinical Pharmacology Education Section (IUPHAR-Ed) Core Concepts of Pharmacology (CCP) initiative involves over 300 educators from the global pharmacology community. CCP has identified and defined the core concepts of pharmacology, together with key underpinning sub-concepts. To realize these benefits, pharmacology educators must develop methods to teach and assess core concepts. Work to develop concept inventories is ongoing, including identifying student misconceptions of the core concepts and creating a bank of multiple-choice questions to assess student understanding. Future work aims to develop and validate materials and methods to help educators embed core concepts within curricula. Potential strategies that educators can use to overcome factors that inhibit adoption of core concepts are presented.

Case-based lectures - An innovative methodology of teaching-learning: A study to evaluate its impact on students

Background: Case-based learning (CBL) is a part of competency-based medical education and is an innovative methodology that starts with a well-structured case-based problem and compels students to approach its diagnosis and treatment by correlating theory and practice. It is a newer approach to making a medical competent professional doctor. Aims and Objectives: This study was conducted among 2nd-year undergraduates to promote case-based lectures and to analyze the effectiveness of CBL and the perception of students toward CBL in comparison with traditional lectures. Materials and Methods: A total of 160 students who enrolled in the study were randomized into two Batches A and B. Batch A was exposed to a case-based session on anti-parkinsonism drugs and Batch B was delivered the same lecture in a conventional pattern. At the end of the lecture, students of both batches were asked to attempt a post-test and to fill out a feedback questionnaire. Post-test scores of both the test groups were compared using the Mann–Whitney U-test. The perception of students was analyzed using the feedback questionnaire. Results: The performance of students who attended case-based lectures was better than those who attended conventional lectures. A statistically significant and better performance of Batch A was observed in critical thinking-based questionnaires as compared to Batch B. Feedback on students’ perception shows that CBL enhanced their interest and motivation for learning, and improved their critical thinking and analytical skills. Conclusion: Positive results of the study indicate that CBL should be implemented in the teaching concepts of pharmacology. A combination of both conventional lectures and CBL can serve as an effective educational tool. Certain challenges associated with the implementation of CBL should be addressed properly.

Impact of blunder lecture on deep learning of pharmacology concepts by cognitive conflict strategy: A new standard in teaching

Background: Small group discussion (SGD) is an established teaching-learning tools in medical colleges to impart a better understanding of the topics. Blunder lecture (BL) is an innovative approach to teaching and learning, placing students at the center and encouraging collaborative, peer-assisted learning. Aims and Objectives: The objectives of the study were to assess the combined effect of BL and SGDs on multiple-choice questions (MCQs) score in pharmacology by comparing the MCQs score after the traditional SGDs approach and after a combined session of BL and SGDs. Materials and Methods: One hundred and two Phase II MBBS students participated in an educational interventional study in the Department of Pharmacology. Two sessions were conducted: First, SGD only; second, integrated BL and SGD on previously covered pharmacology topics in didactic lectures. Twenty deliberate mistakes (blunders) were incorporated in BL that span the hierarchy of bloom’s taxonomy’s cognitive domain. Theory and MCQs tests were performed after each session to assess the impact on scores. Results: There was a statistically significant difference between the means of MCQs test scores of SGD alone and combined SGD + BL session (P < 0.05) after data analysis using a paired t-test. The mean difference of theory test scores of SGD alone and combined SGD + BL session was not statistically significant except cardiovascular system BL session. Conclusion: Combined session of BL and SGD was found to be an effective supplementing method in enhancing MCQs score that can be utilised to support undergraduate students’ learning.

The β-Blocker Carvedilol and Related Aryloxypropanolamines Promote ERK1/2 Phosphorylation in HEK293 Cells with K A Values Distinct From Their Equilibrium Dissociation Constants as β 2-Adrenoceptor Antagonists: Evidence for Functional Affinity.

The determination of affinity by using functional assays is important in drug discovery because it provides a more relevant estimate of the strength of interaction of a ligand to its cognate receptor than radioligand binding. However, empirical evidence for so-called, "functional affinity" is limited. Herein, we determined whether the affinity of carvedilol, a β-adrenoceptor antagonist used to treat heart failure that also promotes extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, differed between these two pharmacological activities. Four structurally related β-adrenoceptor antagonists (alprenolol, carazolol, pindolol, propranolol) that also activated ERK1/2 were included as comparators to enhance our understanding of how these drugs work in the clinical setting. In HEK293 cells stably expressing the human β 2-adrenoceptor carvedilol and related aryloxypropanolamines were partial agonists of ERK1/2 phosphorylation with potencies ([A]50s) that were lower than their equilibrium dissociation constants (K Bs) as β 2-adrenoceptor antagonists. As the [A]50 of a partial agonist is a good approximation of its K B, then these data indicated that the affinities of carvedilol and related ligands for these two activities were distinct. Moreover, there was a significant negative rank order correlation between the [A]50 of each ligand to activate ERK1/2 and their intrinsic activities (i.e., as intrinsic activity for ERK1/2 phosphorylation increased, so did affinity). Genome editing revealed that the transducer that coupled the β 2-adrenoceptor to ERK1/2 phosphorylation in response to carvedilol and other β 2-adrenoceptor antagonists was Gαs. Collectively, these data support the concept of "functional affinity" and indicate that the ability of the β 2-adrenoceptor to recruit Gαs may influence the affinity of the activating ligand. SIGNIFICANCE STATEMENT: In HEK293 cells overexpressing the human β2-adrenoceptor carvedilol and four related aryloxypropanolamines behaved as β2-adrenoceptor antagonists and partial agonists of ERK1/2 phosphorylation with rank orders of affinity that were distinct. These data imply that carvedilol and other β-blockers can stabilize the β2-adrenoceptor in different affinity conformations that are revealed when functionally distinct responses are measured. This is the basis for the pharmacological concept of "functional affinity."