International Journal of Basic & Clinical Pharmacology
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Oncogenic challenge of bromocriptine and L-arginine versus conventional antidiabetics on diethyl nitrosamine-induced liver tumorigenesis in diabetic rats: focus on AMPK activation
Get PDFBackground: Diabetes mellitus (DM) is associated with a spectrum of cancers where the metabolic antecedents, consequences, and therapy might affect cancer risk. The association between hepatocellular carcinoma (HCC) and DM had been confirmed. Approaches to HCC prevention focus on the molecular regulators of the disease process defined as the inflammation-fibrosis-cancer axis. The AMP-activated protein kinase (AMPK) is an interesting metabolic tumor suppressor and a promising target for cancer prevention and therapy. This study aimed to investigate the effects of bromocriptine mesylate and L-arginine on hepatic carcinogenesis on a rat model of hepatic neoplasia induced by diethyl nitrosamine (DENA) and promoted by type-2 DM in contrast to the conventional antidiabetics.Methods: One hundred male Wistar rats were randomly assigned into two sets; control set (normal, HCC, DM, and combined HCC/DM) and treated set where rats received one of the following drugs for another 5 weeks: insulin glargine, glimepiride, metformin, pioglitazone, bromocriptine mesylate, or L-arginine. Bodyweight changes, blood glucose level, liver functions tests, serum C-peptide and alpha-fetoprotein (AFP), and hepatic activated AMPK were assessed beside the hepatic histopathological changes.Results: Equivalent to metformin, bromocriptine and L-arginine treatment significantly reduced AFP, despite their minor glycemic control. L-arginine induced AMPK activation, yet less than metformin. Histopathologic examination revealed a reduction in hepatic intra-lobular chronic inflammatory cell infiltration, steatosis and necrosis by metformin, bromocriptine, and L-arginine. Hepatic necro-inflammatory changes were most prominent in insulin-treated rats.Conclusions: L-arginine and bromocriptine mesylate prevent early neoplastic changes almost equivalent to metformin at least partially via hepatic AMPK activation
Diclofenac predisposes benign prostate hyperplasia in fat feed albino rats
Get PDFBackground: An attempt to establish the possible cause(s) of benign prostate hyperplasia (BPH) in fat feed albino rats treated with diclofenac (DCF)-potassium (K) was performed to ascertain its likely translational relationship in humans.Methods: Thirty-five male wistar albino rats of 24 weeks old were divided into five groups of 7 animals each were used. Group 1; the normal control (NC) was injected subcutaneously with the vehicle (olive oil) only and served normal diet. Group 2; standard group treated with testosterone propionate in olive oil (3 mg/kg b. wt.). Groups 3, 4, and 5 were fed with the standard feed mixed with animal fat (sourced from roasted meat/condiments in aluminium foils) in 20, 40 and 80% portions, then treated with DCF-K in solution as low (2 mg/kg b. wt.), mid (4 mg/kg b. wt.), and high (6 mg/kg b. wt.) doses, respectively. The blood samples collected were analysed for prostate specific antigen (PSA), hematological parameters, kidney and liver function.Results: Group 3 showed the highest PSA elevation (p<0.05) when compared to the control and the untreated group. There was a significant elevation (p<0.05) in WBC levels compared to all other groups. PCV, MCV, NEUT, MONO and EOSIN levels increased significantly (p<0.05) across all groups. Significant (p<0.05) increase was observed in liver and kidney parameters compared to the untreated groups. Significant (p<0.05) elevation in total cholesterol and LDL-C levels across the groups was observed. The DCF-K treated groups showed increase in several parameters compared to the untreated groups.Conclusions: It was obvious that fatty diet and use of DCF-K contributed to the observed hepatotoxicity, nephrotoxicity, hence predisposed tissue damage and inflammation which conjunctly elevated PSA
Comparative analysis of medical pharmacology books based on competency based undergraduate curriculum followed by MBBS student in Rani Durgavati Medical College, Banda
Get PDFBackground: National Medical Commission (NMC) has implemented competency based undergraduate curriculum for training of new M.B.B.S. students. As per these curriculum authors of Medical Pharmacology books also changed their book content to fulfill the subject requirement.Methods: A systematic comparison of books carried out in department of pharmacology Rani Durgawati Medical College, Banda, Uttar Pradesh. There was comparison of 5 books of medical pharmacology of Indian author belongs to edition after 2019. The books included were Essentials of Medical Pharmacology (Jaypee Publication, 8th Edition, 2021), Medical Pharmacology (CBS Publishers And Distributors Pvt Ltd, 7th Edition, 2021), Pharmacology and Pharmacotherepeutics (Elsvier Publication, 26th Edition, 2021), Pharmacology for MBBS (Avichal Publication Company, 2nd edition, 2021) and Pharmacology for Medical Graduates (Elsvier Publication, 4th Edition, 2020). All the books were examined for the competencies described in the pharmacology syllabus. The table was prepared for the availability of topics according to the competencies of different section of syllabus. The chapter/page numbers mentioned in competency table were looked upon for the respective competencies and presence or absence of the topic was noted down.Results: All the books mainly covered competency given in the knowledge section of the syllabus. Few competencies in skill and communication sections were also covered in the text books.Conclusions: When all the five books were evaluated according to pharmacology competency in syllabus, none of the books covered whole pharmacology syllabus. This may be because authors considered the competency topics in skill and communication section as a part of practical or because many practical books or manuals are available in the market which covered topics in these sections
Rational use and cost variation analysis of antifungal drugs available in the Indian market: a pharmacoeconomic study
Get PDFBackground: Fungal infections are the 4th most common skin disease affecting 984 million people. Fungal infections are mostly associated with the use of broad-spectrum antibiotics, corticosteroids, anticancer/immunosuppressant drugs, indwelling catheters and implants, and the emergence of AIDS. The aim of this study was to analyze the rational use, cost ratio, and percentage cost variations in different brands of the commonly prescribed antifungal drugs available in the Indian market.Method: The maximum and minimum price of each brand of the drugs given in Indian rupees (INR) was noted by using ‘Drug Today’ (January to April 2021, volume II). The cost range, cost ratio, and the percentage cost variation for individual drug brands were calculated. The cost of tablets/capsule/injection was calculated and the cost ratio and percentage cost variation of various brands was compared.Results: After calculation of cost ratio and percentage cost variation for each brand of antifungal agents, tab Itraconazole 100 mg had a maximum percentage cost variation of 733.33% and a cost ratio of 8.33 while tab Griseofulvin 250 mg had a minimum percentage cost variation of 16.98% and cost ratio of 1.16.Conclusions: The present study shows there was a wide variation in the cost of the different brands of antifungal drugs manufactured by pharmaceutical companies which increases the economic burden. The clinicians prescribing these drugs should be aware of rational use and cost variation to reduce cost of drug therapy and improve patient compliance.
Ascorbic acid attenuates ethanol induced apoptotic and oxidative response by blocking the Bax, Bcl2 and Caspase signaling pathways
Get PDFBackground: Research evidence has demonstrated that oxidative stress plays important etiological role in pathogenesis of alcoholic liver disease. The agents having antioxidant property plays a promising therapeutic intervention in ALD. In our present study we investigate the effect of ascorbic acid on ethanol induced liver injury and molecular mechanism of ethanol induced apoptosis.Methods: Wistar albino rats were randomly divided into 4 groups with 6 animals in each group control, ethanol treatment 40% (2ml/100gm), ethanol+ascorbic acid 100mg/kg b.w. intra-gastric gavage, ethanol+silymarin 100mg/kg b.w. intra-gastric gavage for 21 days. Statistical analysis was carried out using one-way ANOVA followed by Tukey multiple comparision test.Results: Ethanol induced hepatotoxicity is evidenced by increased level of liver marker enzymes (AST, ALT, ALP and LDH) and lipid peroxidation whereas the level of antioxidants (SOD, CAT, GSH, VIT C and E) was significantly decreased. Our results are further supported by histopathological examination which shows drastic changes in liver architecture. Hepatic Bax, Bcl-2, Caspase 3 and Caspase 9 proteins expressions were altered. On contrary treatment with ascorbic acid ameliorated the changes induced by ethanol and improved liver architecture. Conclusions: Ascorbic acid as an antioxidant protect the liver from ethanol induced oxidative damage and apoptosis.
Physical comorbidity and its impact on symptom profile of depression in Indian setting 2 (COSPO-DEP-2 study)
Get PDFBackground: The objective of the study was to determine the symptom profile and prevalence of comorbidities and to understand the prescription patterns of antidepressants among depression patients in India.Methods: The real-world, retrospective, observational COSPO-DEP-2 study was conducted at various centres across India between April 2021 and March 2022.Results: Data of 7288 patients with depression was analyzed. The mean (SD) age of the patients was 45.1 (11.9) years. Majority of the patients were males (54.2%) and literate (92.7%); 53.1% were unemployed; 14.5% were unmarried and other 8.8% patients were divorced or separated. Almost equal proportion of patients were from urban and rural areas. A family history of psychiatric disorder was present in 14.9% patients. More than half (57.3%) of the patients presented with first episode of depression. Mild depression was present in 38.87% patients, moderate depression in 38.06% patients and severe depression in 23.07% patients. Diabetes was the most common comorbid condition (31.5%) followed by hypertension (26.6%), migraine (24.6%), and chronic pain (16.6%). Majority (54%) of patients were prescribed combination of pharmacotherapy with psychotherapy. The most commonly prescribed drug for depression management was escitalopram (57.5%) followed by benzodiazepines (38.7%). Escitalopram was also the most commonly prescribed drug in patients with depression having comorbidities.Conclusions: Depression is common among both genders and more commonly seen among unemployed people and in those with family history of depression. The commonly reported comorbidities include diabetes, hypertension, migraine and chronic pain. Escitalopram is the most commonly used agent followed by benzodiazepines among patients of depression with or without comorbidities
Carbetocin: a therapy advance for prevention of postpartum haemorrhage
Get PDFPostpartum haemorrhage (PPH) is the major cause of maternal death. To prevent PPH, the routine administration of a uterus-contracting (‘uterotonic’) agent is a standard practice across the world. Oxytocin is the standard uterotonic agent recommended for this purpose, and is recommended for all women giving birth. Oxytocin is problematic as it requires cold storage and transport, and in low-resource settings, the cold chain is not commonly available. Heat-stable carbetocin is a promising alternative to oxytocin. Because of its heat stability, it can overcome the persistent problems with oxytocin quality as it does not require cold chain for storage and transport. Considering the totality of the evidence, it appears to have some additional desirable effects compared with oxytocin and a very favourable side effect profile similar to oxytocin. With a standardized dosing of single injection recommendation, it can address the variations in dosing regimen as is with oxytocin. Carbetocin has been added to the World Health Organization (WHO) essential medicines list of uterotonics for the prevention of excessive bleeding after childbirth, we might see a new standard of care in coming months for prevention of uterine atony
Analysis of individual case safety reports of spontaneous reporting in adverse drug reaction monitoring centre at a tertiary care hospital
Get PDFBackground: In developing countries like India, the increased economic burden in healthcare system is due to adverse drug reactions (ADRs) related hospitalizations which in turn are related to polypharmacy associated with increased potential of ADRs. World Health Organization (WHO) started the program for international drug monitoring (WHO PIDM) in the year 1968. India is one of the member countries under WHO PIDM using the Vigibase for analysis of individual case safety reports (ICSRs). Aim of the study was to analyse the ICSRs by spontaneous reporting at ADR monitoring centre.Methods: The present study was focused on analyzing the ICSRs of spontaneous reporting using Vigiflow data from the ADR monitoring centre (AMC), Madras Medical College, Chennai.Results: A total of 541 ICSRs from the period between July 2017 and June 2018 were analysed. Among 541 ICSRs, 814 ADRs were analysed and found that the majority of the ADRs belonged to SOC of gastrointestinal disorders and the most of the ADRs were implicated by antimicrobial agents followed by non-steroidal anti-inflammatory drugs (NSAIDs). Among all the ICSRs, majority of the ADRs occurred in males (n=292) and the maximum number of ADRs were in the age group of 45-60 years (n=197). Of the 541 ICSRs, 313 were found to be of “serious” category and majority of the ICSRs outcome was found to be “recovered” (n=262). The causality assessment of the ICSRs were anlysed and found that the maximum number of ICSRs were under “probable” category as per WHO-UMC scale.Conclusions: Robust pharmacovigilance activities plays important role in minimizing the ADRs for better patient safety
Inmazeb: new hope for Zaire Ebola virus disease
Get PDFEbola virus disease first appeared in 1976 in Zaire (now democratic republic of Congo). Since then virus outbreaks occurred periodically in African countries. The cases notified in March 2014 in west Africa was largest outbreak till now. In 2020 there is ongoing outbreak of Zaire Ebola virus in democratic republic of Congo. Ebola virus is single stranded RNA virus which causes viral hemorrhagic fever in humans presenting as high fever, chills, loss of appetite, myalgia, headache. Till now there was no specific treatment, symptomatic treatment methods including infusion of electrolyte and/or antibiotics were mainly used. In October 2020 FDA approved the first treatment for Zaire Ebola virus disease in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. The treatment is called Inmazeb, combination of three recombinant human IgG1κ monoclonal antibodies (Atoltivimab, Maftivimab, and Odesivimab-ebgn) each targeting the Zaire ebolavirus glycoprotein.
Randomized double blind comparative study on efficacy and safety of oral oxaceprol 200 mg versus oral diclofenac 50 mg in patients with moderate osteoarthritis
Get PDFBackground: Osteoarthritis of knee is the most common form of arthritis globally, approximately 250 million people are suffering from osteoarthritis of the knee alone throughout the world. It is a chronic joint disease leading to cause cartilage degradation that involves synovial Inflammation, Subchondral bone remodelling, and Formation of osteophyte pathologically, which leads to cause pain, joint destruction and difficulty in walking. Aim of the current study was to compare the safety and efficacy of oxaceprol 200 mg versus diclofenac 50 mg in patients with moderate osteoarthritis and to determine cost-effectiveness between these two drugsMethods: this is a randomized controlled study, in our study total of 94 patients were screened, of which 85 patients met inclusion & exclusion criteria. In this, 78 members gave written informed consent, they were randomly assigned by double-blind fashion into two treatment groups (oxaceprol and diclofenac). Results were analyzed by applying paired and unpaired student t-test by using SPSS softwareResults: In our study, both oxaceprol and diclofenac were extremely significant in reducing joint pain and joint stiffness and improving physical activity, but when comparing with one another oxaceprol group showed better results in improving physical activityConclusions: From our study, it is concluded that oxaceprol is equally efficacious as diclofenac in reducing knee pain, joint stiffness but more efficacious than diclofenac in improving physical activity of patients by enhancing bone remodelling