Clinical pharmacology and pharmacogenomics for implementation of personalized medicine.

With the aim of integrating clinical pharmacology with pharmacogenomics and providing a platform to gather clinicians, academicians, diagnostic laboratory personnel and scientists from related domains, the International Conference on Clinical Pharmacology and Pharmacogenomics 2023 (ICCPP 2023) was jointly organized by the Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India and the CANSEARCH research platform in Pediatric Oncology and Hematology, University of Geneva, Geneva, Switzerland. The conference was held on 31 August and 1 September 2023, as a continued Indo-Swiss scientific exchange event series. In this report we describe the proceedings of this conference for the benefit of peers who could not attend the conference but are interested in knowing about the scientific program in detail.

Effect of resveratrol and combination of resveratrol and donepezil on the expression of microglial cells and astrocytes in Wistar albino rats of colchicine-induced Alzheimer's disease.

Aim: The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model. Methods: The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively. Results: AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS (p < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group (p < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups (p < 0.001). Conclusion: RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.

Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.

Pediatric cancer treatment has evolved significantly in recent decades. The implementation of risk stratification strategies and the selection of evidence-based chemotherapy combinations have improved survival outcomes. However, there is large interindividual variability in terms of chemotherapy-related toxicities and, sometimes, the response among this population. This variability is partly attributed to the functional variability of drug-metabolizing enzymes (DME) and drug transporters (DTS) involved in the process of absorption, distribution, metabolism and excretion (ADME). The DTS, being ubiquitous, affects drug disposition across membranes and has relevance in determining chemotherapy response in pediatric cancer patients. Among the factors affecting DTS function, ontogeny or maturation is important in the pediatric population. In this narrative review, we describe the role of drug uptake/efflux transporters in defining pediatric chemotherapy-treatment-related toxicities and responses. Developmental differences in DTS and the consequent implications are also briefly discussed for the most commonly used chemotherapeutic drugs in the pediatric population.

Levetiracetam exposure during prenatal and postnatal period induces cognitive decline in rat offsprings, not completely prevented by Bacopa monnieri.

OBJECTIVES: Levetiracetam (LEV) is an antiepileptic recommended during pregnancy. Bacopa monneri is a medicinal herb used in Ayurveda for improvement of cognition. Data on effects of LEV and Bacopa on cognition is inadequate. The study evaluated the cognitive effects of LEV on rat offspring of dams exposed to LEV and whether pretreatment with Bacopa monnieri, inhibits the potential cognitive decline by LEV. METHODS: Pregnant rats were allocated into four groups of three rats each. Groups 1, 2, 3 and 4 received 2% gum acacia, LEV 270 mg/kg, LEV 270 mg/kg + Bacopa 100 mg/kg and LEV 270 mg/kg + Bacopa 200 mg/kg respectively during pregnancy and lactation. Three pups from all dams were chosen at random and exposed to passive avoidance, Hebb-Williams and Morris water maze tests to check for their cognition and relevant histopathology was done. RESULTS: In the passive avoidance model groups 3 and 4, showed an increase in escape latency compared with group 2, demonstrating an improved learning (p=0.05). In Hebb-Williams maze, the time taken to reach reward chamber by group 2 increased compared to group 1, p=0.006, showing cognitive decline. Neuronal count in hippocampus and prefrontal cortex decreased significantly in group 2, which improved in group 3 & 4 however there was distortion of architecture in group 4. CONCLUSIONS: LEV exposure in intrauterine and neonatal period induced cognitive decline in rat offsprings and Bacopa 100 mg/kg prevented LEV induced cognitive decline. However safety of exposure to Bacopa during the gestation period has to be evaluated.

Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database.

Tocilizumab (TCZ) is used to treat rheumatoid arthritis and other systemic inflammatory disorders. There is some evidence suggesting the occurrence of pancreatitis following TCZ use. We aimed to determine the reporting of pancreatitis following TCZ use in comparison with other drugs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse event reports submitted to FAERS during 2013-2019. A reporting odds ratio (ROR) with the lower bound 95% confidence interval (CI) > 1 and a lower limit of a two-sided 95% interval of information component (IC025) more than zero was considered significant. Following deduplication, 3,383,910 adverse event reports were available; 144 (0.004%) reports were of pancreatic adverse events associated with TCZ use, and 15,907 (0.47%) associated with other drugs. Of the 144 cases, 74 (51.39%) received concomitant medications with pancreatotoxic potential. The likelihood of reporting of pancreatic events, compared with any other adverse event, with TCZ use was 1.32 times higher than that with other drugs. The lower bound of the 95% CI of the ROR and IC remained above the criteria of significance throughout the study period, except 2013. The findings suggest disproportionately high reporting of pancreatitis in patients receiving TCZ as compared with other drugs. This marginally high reporting is not likely to be of immediate clinical concern and needs to be interpreted cautiously.

Liver injury associated with drug intake during pregnancy.

Drug use during pregnancy is not common. Drug-induced liver injury (DILI) is a potential complication that is rare but can adversely affect both the mother and the fetus. Although many drugs can directly cause hepatotoxicity, idiosyncratic liver injury is common in pregnancy. Underreporting of adverse drug reactions, lack of adequate literature regarding drug safety in pregnancy, and the inherent difficulty in diagnosing DILI during pregnancy make the management of this condition challenging. This review attempts to describe the existing literature regarding DILI in pregnancy, which is mainly in the form of case reports; several studies have looked at the safety of antithyroid drugs, antiretroviral drugs, and paracetamol, which have an indication for use in pregnancy; the relevant data from these studies with regard to DILI has been presented. In addition, the review describes the diagnosis of DILI, grading the disease severity, assessment of causality linking the drug to the adverse event, regulatory guidelines for evaluating the potential of drugs to cause liver injury, efforts to ensure better participation of women in clinical trials and studies in pregnant women population in particular, and the challenges involved in generating adequate research evidence. The establishment of DILI registries in various countries is an encouraging development; however, there is a need for promoting active, spontaneous reporting of adverse events during pregnancy to ensure rapid generation of evidence regarding the safety of a drug in pregnant women.

Approaches to learning and academic performance in pharmacology among second-year undergraduate medical students / Abordagens de aprendizagem e desempenho acadêmico em farmacologia entre estudantes de medicina do segundo ano

AIMS: To determine the learning approach of second-year undergraduate medical students and whether a surface or deep approach to learning had any correlation with the pharmacology sessional and university examination marks obtained. METHODS: A cross-sectional study was conducted among second-year medical students in their fifth semester. To determine the students' learning approach, whether superficial or deep, we used the Revised Two Factor Study Process Questionnaire (R-SPQ-2F), which contains 20 items in the form of a five-point Likert scale and is suitable for use in higher education settings. Cronbach's alpha was calculated using the scores obtained from a sample of 20 students to determine the internal consistency. To determine the relationship between the learning approach and examination scores, the average of the individual sessional examination marks and the university examination scores obtained by the students were calculated. RESULTS: Of the 170 students who participated in the study, 87 (51.2%) were females. The Cronbach's alpha value was considered acceptable for both surface and deep approach. While the academic performance was significantly better in females (U=2571.5; p=0.001), no difference was seen in the learning approach based on gender. Fifty (29.4%) students had a higher score for the surface approach. This group had lower examination scores compared with those with equal scores for surface and deep approach or higher scores for the deep approach. A weak negative correlation was seen between the examination marks and surface approach (τb=-0.167; p=0.002). When analyzed based on gender, the correlation was statistically significant only in females (τb=-0.173; p=0.02). CONCLUSIONS: A weak negative correlation was seen between the examination marks and surface approach to learning. Although statistically significant, the actual difference between the groups was of a small magnitude. Hence, whether promoting deep learning approach improves academic performance in terms of marks obtained in the examination needs to be confirmed by further studies.

OBJETIVOS: Investigar a abordagem de aprendizagem de estudantes de medicina do segundo ano de graduação e se uma abordagem superficial ou profunda teve alguma correlação com as notas obtidas na disciplina de farmacologia e nos exames universitários. MÉTODOS: Um estudo transversal foi conduzido entre estudantes do segundo ano de medicina em seu quinto semestre. Para determinar a abordagem de aprendizagem dos alunos, como superficial ou profunda, usamos o questionário Revised Two Factor Study Process Questionnaire (R-SPQ-2F), que contém 20 itens em forma de uma escala Likert de cinco pontos, sendo o seu uso adequado para ambientes de ensino superior. O alfa de Cronbach foi calculado usando as pontuações obtidas de uma amostra de 20 alunos para determinar a consistência interna. Para determinar a relação entre a abordagem de aprendizagem e as pontuações do exame, calculou-se a média das notas dos exames individuais e as pontuações dos exames universitários obtidas pelos alunos. RESULTADOS: Dos 170 alunos que participaram do estudo, 87 (51,2%) eram do gênero feminino. O alpha de Cronbach foi considerado bom tanto para a abordagem superficial quanto profunda. Enquanto o desempenho acadêmico foi significativamente melhor em mulheres (U=2571,5; p=0,001), nenhuma diferença baseada no gênero foi observada na abordagem de aprendizagem. Cinquenta (29,4%) estudantes tiveram uma pontuação mais alta para a abordagem superficial. Esse grupo teve escores de exame mais baixos em comparação com aqueles com escores iguais para abordagem superficial e profunda ou escores mais altos para a abordagem profunda. Uma fraca correlação negativa foi observada entre as notas do exame e a abordagem superficial (τb=-0,167; p=0,002). Quando analisada com base no gênero, encontrou-se uma correlação de magnitude fraca e negativa apenas no gênero feminino (τb=-0,173; p=0,02). CONCLUSÕES: Uma fraca correlação negativa foi observada entre as notas do exame e a abordagem superficial para a aprendizagem. Embora estatisticamente significativa, a diferença real entre os grupos foi de pequena magnitude. Portanto, se a promoção de uma abordagem de aprendizagem profunda melhora o desempenho acadêmico em termos de notas obtidas no exame, isso precisa ser confirmado por outros estudos.

Health Literacy Status and Understanding of the Prescription Instructions in Diabetic Patients.

This study aimed to assess the health literacy (HL) of patients having diabetes mellitus, their understanding of prescription instructions (PI), and the correlation between HL and understanding of PI. A cross-sectional survey was conducted in 263 adult diabetic patients who were assessed for their understanding of route of intake of the prescribed medication(s), frequency of intake, number of medication(s) to be consumed each time, indication for the medication(s), and the relation of drug intake with food. The HL of the patients was assessed by using Rapid Estimate of Adult Literacy in Medicine, a screening test comprising of 66 health-related words. The number of correctly pronounced words was used to assign a grade-equivalent reading level. There was a significant difference in the understanding of PI in patients with low and high HL levels. A significant difference was observed between the mean total score for interpreting PI in patients with 7 or fewer years of education compared with the other groups with a higher educational status (P < 0.001). To conclude, diabetic patients with low HL level will have difficulty in understanding PI. Hence, an alternative comprehensive strategy needs to be adopted in clinical practice in these patients to provide them the instructions to take medications properly.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

Effect of vanillin on lipid profile in a model of hyperlipidemia, a preliminary study.

To evaluate the effect of vanillin on the lipid profile of high fat diet induced hyperlipidemia in rats, the hyperlipidemia was induced by feeding cholesterol-rich high fat diet for 45 days in wistar rats of either sex. The reduction in the triglycerides and VLDL-C was significant at 200 & 400 mg/kg dose of vanillin compared to atorvastatin group. Reduction in total cholesterol was significant at 200 and 400 mg/kg doses compared to hyperlipidemic control. The results demonstrate that vanillin at a dose of 200 and 400 mg/kg body weight lowers the serum triglyceride, VLDL-C and total cholesterol level significantly in high fat diet induced hyperlipidemic rats. However there was no significant effect on the lipid profile at 100 mg/kg dose. There were no statistically significant changes in the HDL-C and LDL-C levels at any of the given doses.