Indian Journal of Pharmacology最新文献

Abstract: For a robust Pharmacovigilance system in a country, training of healthcare professionals is of utmost importance. The training is the integral part of continual improvement in any quality management system. The present article describes the different training modules and experience from the Pharmacovigilance Programme of India (PvPI) and emphasizes that if training and education elements with special reference to pharmacovigilance are implemented for all concerned stakeholders in a healthcare system, the efficiency of deliverables will be improved and objectives of the organization can easily be achieved. The PvPI has been putting its best efforts to train healthcare professionals in pharmacovigilance and it has achieved new heights in establishing best practices for the other countries to follow for the development of pharmacovigilance system in their respective countries or regions. The aim of this article is to suggest how capacity building in a pharmacovigilance system can help low- and middle-income countries in area of pharmacovigilance. The authors tried to conceptualize the process and implementation of the training program under PvPI.

Abstract: Ensuring the safety and quality of drugs is a crucial component for the development of any pharmaceutical industry. This requires stringent regulation in the process of drug manufacturing and marketing. A Drug Master File (DMF) serves as a comprehensive document containing information about the quality, safety, and manufacturing procedure/facility of a drug or drug substance. Many countries with highly regulated markets use the DMF system extensively to protect their intellectual property rights while providing accurate and detailed information about their products to regulatory bodies. In India, the regulatory body, the Central Drug Standard Control Organization, does not currently mandate the submission of a DMF. However, adopting a DMF system may have immense benefits to regulatory bodies, pharmaceutical industries, as well as to patients. This review aims to provide a comprehensive overview of DMF and highlight the significance of its adoption in India.

Objectives: The development and progression of chronic heart failure (CHF), hypertrophy, and remodeling strongly correlate with myocardial inflammation and oxidative stress. S-adenosylmethionine (SAMe), available as a dietary supplement, exerts anti-inflammatory and antioxidant effects. Previous reports show that by regulating angiogenesis and fibrosis, S-adenosyl-L-methionine improves ventricular remodeling. The study objectives were to investigate the cardioprotective effect of SAMe in isoproterenol (ISO)-induced CHF and explore the anti-inflammatory and antioxidant properties of SAMe in this model.

Methodology: After animal ethics permission, CHF was induced using ISO of 10 mg/kg for 14 consecutive days in 24 Wistar rats. There were four groups of six rats in each group: Sham Control, Disease Control (DC), ISO + SAMe 100 mg, and ISO + SAMe 200 mg. The variables assessed were heart to body weight ratio (HW/BW mg/g), bio-distribution of Flourine 18-Fluorodeoxyglucose (18F-FDG) in heart tissue, tumor necrosis factor-α (TNF-α) and glutathione (GSH) levels in heart tissue, histopathology, and positron emission tomography imaging.

Results: SAMe in ISO-induced CHF animals showed a significant decrease in the HW/BW compared to DC group (P < 0.001). 18F-FDG uptake was significantly reduced by SAMe in CHF-induced rats compared to DC rats for both doses (P < 0.001). SAMe showed significantly better values of both TNF-α and GSH than the DC group in both doses (P < 0.001). SAMe in both doses showed multifocal necrosis with scarring and minimal inflammatory cells.

Conclusion: SAMe exerts a cardioprotective effect on ISO-induced CHF in rats because of its antioxidant and anti-inflammatory properties.

Background: Sansevieria trifasciata, common name, mother-in-law's tongue, is a member of the Agavaceae family. We undertook this study to evaluate the cytotoxicity of S. trifasciata leaf extract against two cancer cell lines as well as its antibacterial activities against six bacterial strains.

Materials and methods: The investigated cell lines include primary colon epithelial (PCE) cells and human colorectal cancer cells; the studied bacterial strains are Staphylococcus aureus, Proteus vulgaris, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Using the agar well-diffusion method, various doses (5, 10, and 20 mg/mL) of plant extracts (ethanol and petroleum ether) were evaluated against each kind of bacterial strain. The minimal inhibitory doses were found using the two-fold serial dilution approach, with a range of 0.156-5 mg/mL.

Results: Comparing extracts of S. trifasciata leaves to tetracycline (0.05 mg/mL), a common antibiotic, revealed a wide range of antibacterial activity. P. vulgaris and S. aureus were the most sensitive bacterial strains to ethanol and petroleum ether extracts, respectively. The MTT test was employed to ascertain the viable cell count of PCE cells and HCT-116. When various ethanol extract concentrations (7.8, 15.63, 31.25, 62.5, 125, 250, 500, and 1000 μg/mL) were tested against the cell lines, HCT-116's IC50, values were lower as compared to PCE. The IC50 values for HCT-116 and PCE cells ranged from 10.0 to 14.07 μg/mL and 92.9-216.9 μg/mL, respectively.

Conclusions: Ethanolic extract of S. trifasciata showed promising antibacterial and anticancer properties.

Background: To study the pharmacokinetic interaction of cephalosporin antibiotic ceftriaxone (CFT) with raw undiluted Ocimum sanctum L. leaf juice in chronic staphylococcal mastitis in caprine.

Materials and methods: Chronic inflammation of the udder was evoked in goats by Staphylococcus aureus (J638) intracisternal inoculation 2000 cfu for 30 days into the left udder. Animals of Group I were given one single dose of CFT at 20 mg/kg i.v. Group II animals were given one single dose of CFT at 20 mg/kg i.v, and contemporary extracted fresh leaf juice of O. sanctum L. given at 5 ml/kg orally for 7 consecutive days.

Results: O. sanctum L. at 5 ml/kg oral had synergistic herb-drug pharmacokinetic interaction with CFT antibiotic (i.v.) and increased its bioavailability. It prolonged its rate of elimination (β) and enhanced the volume of distribution (Vdarea) and mean residence time in the body. Bioavailability and persistence of the antibiotic CFT and its metabolite ceftizoxime were increased in the milk from the udder.

Conclusion: Administration of O. sanctum L. at 5 ml/kg oral with intravenous CFT at 20 mg/kg may be advocated for effective treatment of S. aureus inflammation of the udder in caprine.

OBJECTIVE: 

The objective is to determine the efficacy and safety of paracetamol in preterm babies with hemodynamically significant patent ductus arteriosus (hsPDA).

BACKGROUND: 

In preterm babies, patent ductus arteriosus, when hemodynamically significant, causes considerable morbidity and mortality and also affects 20% of very low birth weight infants. Medical therapy is the mainstay of treatment. Currently used drug cyclooxygenase inhibitor has multiple serious adverse effects, including gastrointestinal perforation, bleeding, and renal failure. Hence, an alternative drug like paracetamol has been proposed for the treatment of hsPDA for fewer side effects. Hence, we used paracetamol in our neonatal intensive care unit in preterm neonates with hsPDA.

METHODS: 

A total of 14 preterm babies diagnosed to have hsPDA on clinical and echocardiographic evaluation in neonatal ICU on days 3–14 of life during 13 months were included. Birth weight was between 1000 g and 1650 g and gestation was between 28 weeks and 33 weeks. Paracetamol in a dose of 15 mg/kg/dose every six hourly given to all the included babies for 3 days and re-evaluated echocardiographically after 3 days of treatment.

RESULTS: 

In 12 (86%) out of 14 cases, PDA was closed, whereas in 2 (14%) hemodynamic closure with insignificant residual flow was achieved. Paracetamol was effective in 100% of cases. No adverse event was observed during treatment.

CONCLUSIONS: 

Paracetamol is a very safe and efficacious drug for treating hemodynamically significant patent ductus arteriosus in premature babies.

P-glycoprotein acts as a protective barrier against xenobiotics and cellular toxicants in the human body while playing an important role in drug transportation in many organs. Overexpression of p-glycoprotein can lead to a decrease in the absorption of many drugs. After screening, 33 phytochemicals from 25 spices were selected for docking with p-glycoprotein to detect some naturally occurring p-glycoprotein inhibitors to modulate multidrug resistance. Absorption, distribution, metabolism, excretion, and toxicity prediction and drug-like properties of those ligands were investigated from pkCSM, Molinspiration, and SwissADME software, followed by molecular docking study and molecular dynamic simulation on BIOVIA Discovery Studio. These 33 phytochemicals met the criteria of p-glycoprotein inhibitor as much as the reference drug verapamil. Pandamarilactone-31 showed the highest binding affinity for p-glycoprotein, acting as the lead p-glycoprotein inhibitor, followed by α-D-fructofuranoside methyl, sesamolinol, and nigellidine.

Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier’s disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy.

The combination of local anesthetic drugs with epinephrine has conventionally been contraindicated in acral regions due to concerns of potential necrosis caused by compromised blood flow. However, this belief has been challenged since 2001, when studies demonstrated the safety and effectiveness of the combination. This review aims to analyze reported cases of acral area necrosis following the use of local anesthesia with epinephrine since 2001. A thorough search was conducted on PubMed and Google Scholar using specific keywords to identify articles reporting acral area necrosis caused using local anesthesia and epinephrine. Our search yielded eight publications describing a total of 13 cases of ischemic events in acral areas. These cases involved finger necrosis (five cases), scrotal skin necrosis (two cases), and eyelid necrosis (six cases), following the injection of a combination of epinephrine and lignocaine. The majority of affected patients were female who underwent surgical intervention and reconstruction. The use of epinephrine in local anesthesia offers significant advantages and is generally safe for acral areas. However, the risk of necrosis cannot be entirely eliminated, particularly in patients with compromised vascular function. Adhering to proper guidelines and selecting suitable patients can help mitigate the risk. Phentolamine serves as a potential rescue agent if vascular compromise occurs. Precautionary measures must be taken when using this combination in high-risk patients.