Indian Journal of Pharmacology最新文献

Introduction: Patients with tuberculosis (TB) may have depression as a comorbidity, which may be associated with poor treatment outcomes. Increased production of pro-inflammatory cytokines activating enzyme indoleamine 2,3-dioxygenase (IDO) has been reported in TB. We studied the association of IDO activity and comorbid depression in TB patients.

Materials and methods: Newly diagnosed, treatment-naïve TB patients were evaluated for symptoms of depression using the Patient Health Questionnaire (PHQ)-9 scale. A PHQ-9 score of ≥5 was taken as an indicator for depression. Patients were further categorized into two groups based on their PHQ-9 scores, Group-I with a PHQ-9 score of <5 and Group-II with a PHQ-9 score ≥5. The serum kynurenine (KYN) and tryptophan (TRP) levels were determined using liquid chromatography-mass spectrometry (LC-MS) and the KYN/TRP ratio was taken as a measure for IDO activity.

Results: A total of 106 TB patients and 106 healthy controls were enrolled in this study. Over 73.5% of TB patients had PHQ-9 scores of above 5 with an average score of 7.09 ± 2.83, a significant difference (P < 0.05) as compared to the average PHQ-9 scores of healthy controls (2.93 ± 1.20). Group-II TB patients had lower serum TRP 539.55 ± 194.31 ng/mL versus 1109.45 ± 186.04 ng/mL (P < 0.01) in Group-I; higher serum KYN 425.81 ± 65.51 ng/mL versus 250.06 ± 40.28 ng/mL (P < 0.01) and higher K/T ratio 0.906 ± 0.56 versus 0.251 ± 0.052 (P < 0.01). There was a significant linear correlation between PHQ-9 and serum KYN (r: 0.969; P: <0.01; R2: 0.909); serum TRP (r: 0.841; P: <0.01; R2: 0.745); and KYN/TRP ratio (r: 0.745; P < 0.01; R2: 0.618).

Conclusion: These findings suggest that in TB patients, induction of IDO activity may be relevant to the development of comorbid depression.

Objective: Our study investigated the impact of various cardiovascular drug on the cardiac physiology of zebrafish embryos and validated these findings in mice.

Background: Cardiotoxicity has significantly contributed to the high drug attrition rate over the last two decades, underscoring the cardiac risk assessment in drug discovery and development. Although regulatory authority's guidelines specified the cell-based assays for the safety assessment of drugs, the current requirements fall short due to a lack of in vivo biology. The use of zebrafish experimental system has surged in developmental and pathophysiological investigation due to their striking resemblance to mammals. Hence, we used the zebrafish model system for cardiovascular drug studies and validated it in the mice model.

Materials and methods: The zebrafish embryos of 72 hours post-fertilization (hpf) were exposed to different CVS drug and, recorded their heart rate, and further validated in mice.

Results: We observed that exposure to amlodipine (a calcium channel blocker), atenolol (a class II antiarrhythmic), and amiodarone (a class III antiarrhythmic) led to dose-dependent reductions in heart rate in zebrafish embryos, with effects varying based on drug concentration and mechanism of action. Specifically, amiodarone treatment resulted in a dose-dependent decrease in heart rate (0.001-100 μM) and atrioventricular block starting at a 10 μM concentration. Each class of cardiovascular drug demonstrated unique cardiac effects in zebrafish embryos, reflecting similar patterns in mice treated with these drugs.

Conclusions: Our findings highlight the zebrafish model's utility for early-phase cardiac risk assessment in drug discovery due to its high throughput capabilities and other beneficial features.

Abstract: Hydrocortisone and pheniramine are frequently administered drugs for the management of severe allergic or anaphylactic reactions. However, there is hardly any literature that shows the association between the use of these drugs for the management of anaphylactic reactions that can induce serious adverse effect. We present a peculiar case of loss of consciousness following concurrent administration of intravenous pheniramine (Avil) and hydrocortisone (primacort) for the management of another drug-induced adverse reaction characterized by urticaria and pruritis that erupted succeeding intake of a fluoroquinolone group of the drug (ofloxacin). Loss of consciousness associated with pheniramine is a serious adverse drug reaction and its association was found out to be "probable/likely" according to the WHO-UMC Causality Assessment Scale. Such reactions, although rare, can be serious requiring immediate hospitalization and warrant vigilance.

Background: Hesperidin and ascorbic acid (AA) enhance cellular antioxidant defense systems by neutralizing the free radicals which formed during oxidative stress that could offer protective effects against drug-induced liver injury. Hence, this study aims to investigate the effect of hesperidin, AA and their combination against antitubercular drug (ATDs)- induced hepatotoxicity in Wistar albino rats.

Materials and methods: The rats were divided into six groups of 6 animals each. Isoniazid (H), Rifampicin (R), and pyrazinamide (Z) (27, 54, 135 mg/kg.b.wt) were co-administration for 50 days to induce hepatotoxicity. Hesperidin 200 mg/kg and AA 100 mg/kg p.o were administered 1 h before ATDs administration. At the end of the study, blood and liver tissues were collected and subjected to biochemical and histopathological examination. Biochemical parameters, serum marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, Gamma glutamyltransferase, and lactate dehydrogenase), lipid peroxidation (LPO), antioxidant enzymes (superoxide dismutase, catalase, GSH, glutathione peroxidase, GR, Vitamin C, and Vitamin E), lipid profile, membrane bound ATPase, and histological changes of liver were assessed.

Results: Our results revealed that HRZ-induced hepatotoxicity was evident by significant (P < 0.001) elevation in level of urea, creatinine, bilirubin, liver marker enzymes, lipid profile (P < 0.01), and LPO (P < 0.001) along with significant decline in the level of total protein, albumin (P > 0.05), ATPase (P < 0.001), and antioxidant enzymes (P < 0.001). Treatment with HDN and AA significantly reduced the changes induced by HRZ. However, compared to individual treatment, combined treatment with HDN and AA significantly (P < 0.001) ameliorated all the changes induced by ATDs and improved the hepatic architecture to near normal.

Conclusion: The combination of HDN and AA demonstrated a synergistic therapeutic effect against HRZ-induced liver injury; hence, this combination represents a potential novel strategy for the management of anti-TB drug-induced liver damage.

Abstract: Neuropsychiatric disorders are widespread and serious and have a detrimental effect on the patient's physical and mental health. The aim of the present study was to find the protective effect of Rubus ellipticus in epilepsy by maximal electroshock seizure, pentylenetetrazol, and related depressive behavior by Forced Swim Test and Tail Suspension Test. The animals were given ethanol extract of R. ellipticus (EERE) (100, 200, or 400 mg/kg) doses for 10 days. On every 5th day, seizure monitoring was performed (day 5 and day 10), followed by depressive behavior monitoring by evaluating immobility time. It was revealed that EERE treatment caused antidepressive-like behavior as a comorbid antiepileptogenic effect. This study will provide compelling evidence to support further clinical trials to grow this medicinal plant in the management of epileptogenic and associated debilitating behavioral comorbidities.

Objectives: The analysis of prescriptions plays a crucial role in promoting rational drug use, minimizing medication errors, and enabling effective antimicrobial surveillance. Manual analyzing is time-consuming, expensive, and error-prone. This study aimed to evaluate prescribing patterns and antimicrobial surveillance using a novel digital analytical platform in a tertiary care hospital.

Methodology: A descriptive observational study was conducted in a tertiary care hospital, in India, between June and August 2024. Prescription data were collected from outpatient departments (general medicine, surgery, pediatrics, pulmonology, and orthopedics) and analyzed using the VaidyaRx digital analytic platform. World Health Organization Core Prescribing Indicators were applied to assess prescribing trends, generic drug usage, antibiotic prescribing patterns, fixed-dose combination (FDC), and adherence to the National List of Essential Medicines (NLEM). Data were analyzed using MS Excel and VaidyaRx.

Results: Mean patient age was 35.8 ± 19.2 years, with pediatrics (21.8%), adult (73.3%), and geriatric (4.9%). The average drugs per prescription were 3.2, and generic prescriptions were 37.5%. Antibiotics were prescribed in 24.9% of prescriptions, highest in surgery (46.9%), with ofloxacin + ornidazole and amoxicillin + potassium clavulanate being the most common. NLEM drug use was 36.7%, with more FDCs from non-NLEM (40.9%) than NLEM (8.3%) drugs. Only 64.5% of prescriptions mentioned dosage, raising concerns about completeness.

Conclusions: Using the VaidyaRx digital platform, real-time prescription analysis was possible which helped in enhancing medication safety and antimicrobial stewardship. Suitable interventions are needed to reduce polypharmacy, increase generic prescribing, ensure rational antibiotic use, and improve prescribing practices.