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Coverpage
May-June 2021
Volume 53 | Issue 3
Page Nos. 187-251

Online since Tuesday, June 22, 2021

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EDITORIAL  

Antimicrobial resistance: An unseen threat prowling behind the COVID-19 outbreak Highly accessed article p. 187
Vidya Mahalmani, J Kumaravel, Manav Jain, Ajay Prakash, Bikash Medhi
DOI:10.4103/ijp.ijp_430_21  PMID:34169902
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RESEARCH ARTICLES Top

Retrospective pharmacovigilance analysis of nonsteroidal anti-inflammatory drugs-induced chronic kidney disease Highly accessed article p. 192
Vardhipathi Sravana Swathi, Shrishti Saroha, Jai Prakash, Shashi Bhushan
DOI:10.4103/ijp.IJP_704_20  PMID:34169903
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with kidney damage. In India, only a few reports related to the risk of chronic kidney disease (CKD) with NSAIDs are available. The present study highlights the prevalence and pattern of NSAIDs-induced CKD adverse drug reactions in the Indian population. MATERIALS AND METHODS: The individual case safety reports (ICSRs) reported by the National Coordination Centre (NCC)-Pharmacovigilance Program of India to the Uppsala monitoring center Pharmacovigilance database system “VigiLyze” were analyzed by using the preferred term “Chronic Kidney Disease” and “NSAIDs” from July 1, 2011 to September 12, 2019. A total of 28 ICSRs of NSAIDs associated CKD ICSRs were analyzed retrospectively for age, gender, concomitant medication, seriousness, and other criteria. RESULTS: About 82% of CKD cases due to NSAIDs were in the age group of 40–80 years, in which 54% belong to male. About 43% of the patients had CKD due to the use of diclofenac, and almost 96% of the patients had oral dosage forms of NSAIDs. The main indications of NSAIDs in these CKD cases were generalized body pain and joint pain. About 79% case of NSAID-induced CKD were serious, among which 54% led to the hospitalization and further use of NSAIDs discontinued in 86% of CKD cases. CONCLUSION: The present study revealed that prolonged use of NSAIDs in chronic pain conditions was responsible for CKD. To reduce the risk of NSAIDs-induced CKD, health care professionals should take the necessary steps to improve patient safety.
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Nephroprotective effects of ethanolic root extract of Azima tetracantha lam in adenine-induced chronic kidney failure in Wistar rats p. 198
Ruckmani Arunachalam, Venu Gopala Rao Konda, Madhavi Eerike, Arun Kumar Radhakrishnan, Sobita Devi
DOI:10.4103/ijp.IJP_552_19  PMID:34169904
OBJECTIVES:
  1. To evaluate the effects of ethanolic root Ethanolic extract of Azima tetracantha. Lam roots (EEATR) in adenine-induced chronic kidney failure in Wistar albino rats
  2. To assess the antioxidant activity of EEATR.
MATERIALS AND METHODS: Thirty rats were selected and allocated to five groups with six animals in each group. Group 1 was given normal saline (control), Group 2 – adenine, 0.75% 40 mg/kg, Group 3 – adenine and 250 mg/kg of EEATR, Group 4 – adenine and 500 mg/kg EEATR, and Group 5 – EEATR 500 mg/kg. Saline, adenine, and EEATR were given orally once daily for 28 days. EEATR was given 60 min before adenine administration. Urine output, blood urea nitrogen (BUN), creatinine, albumin, and total proteins were estimated. The histopathological changes in the kidneys were examined, and antioxidant property of the extract was assessed in the renal tissue. RESULTS: Adenine treated rats had a reduction in urine output (‒45%), food intake (‒46%), body weight (‒28%), total proteins (‒66%) and albumin (‒59%) and an increase in creatinine (950%), BUN (73.6%), and kidney weight (43.75%). Histological examination of the kidneys showed capillary congestion, tubular damage, glomerular distortion, and many oxalate crystals. Rats co-administered with EEATR 250 and 500 mg/kg had marked improvement (P ≤ 0.0001%) in all the above parameters with a marked reduction in size and number of oxalate crystals in the kidney. In the anti-oxidant assays, EEATR exhibited significant antioxidant activity. CONCLUSION: EEATR was found to be an effective nephroprotective agent in adenine-induced chronic renal failure in Wistar albino rats.
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Effect of combined colistin and meropenem against meropenem resistant Acinetobacter baumannii and Pseudomonas aeruginosa by checkerboard method: A cross sectional analytical study p. 207
Anitha Gunalan, Dhandapani Sarumathi, Apurba Sankar Sastry, Venkateswaran Ramanathan, Sathish Rajaa, Sujatha Sistla
DOI:10.4103/ijp.ijp_1013_20  PMID:34169905
BACKGROUND: Meropenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are the two most common nosocomial pathogens causing ventilator-associated pneumonia. To combat this resistance, different combinations of antibiotics have been evaluated for their efficacy in laboratories as well as in clinical situations. AIM: The aim of the study was to investigate the effect of combined colistin and meropenem against meropenem-resistant isolates of A. baumannii and P. aeruginosa by checkerboard method. MATERIALS AND METHODS: Fifty meropenem-resistant isolates of A. baumannii (n = 25) and P. aeruginosa (n = 25) from endotracheal aspirates were studied. The MIC of colistin and meropenem was found using the microbroth dilution method. The fractional inhibitory concentration was calculated for the combination of antibiotics by checkerboard assay and the antibiotic interactions were assessed. Fisher's exact test was carried out for statistical comparison of categorical variables. RESULTS: A synergistic effect between colistin and meropenem was observed in 18/25 (72%) and 6/25 (24%) isolates of Acinetobacter baumannnii and P. Aeruginosa, respectively, with fractional inhibitory concentration indices of ≤0.5. None of the tested isolates exhibited antagonism. CONCLUSION: Our results showed that combinations of colistin and meropenem are associated with improvement in minimum inhibitory concentration and may be a promising strategy in treating meropenem-resistant A. baumannii respiratory tract infections.
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Evaluation of vanillin as a probe drug for aldehyde oxidase and phenotyping for its activity in a Western Indian Cohort p. 213
Sandhya Subash, Nithya J Gogtay, Krishna R Iyer, Prajakta Gandhe, Ritu Budania, Urmila M Thatte
DOI:10.4103/ijp.IJP_463_18  PMID:34169906
BACKGROUND: Aldehyde oxidase (AO), a molybdoflavoenzyme, is emerging as a key player in drug discovery and metabolism. Despite having several known substrates, there are no validated probes reported for studying the activity of AO in vivo. Vanillin (4-hydroxy 3-methoxy benzaldehyde) is an excellent substrate of AO, in vitro. In the present study, vanillin has been validated as an in vivo probe for AO. Subsequently, a phenotyping study was carried out using vanillin in a subset of Indian population with 100 human volunteers. METHODS: For the purposes of in vitro probe validation, initially the metabolism of vanillin was characterized in partially purified guinea pig AO fraction. Further, vanillin was incubated with partially purified xanthine oxidase fraction and AO fractions, and liver microsomes obtained from different species (in presence and absence of specific inhibitors). For the phenotyping study, an oral dose of 500 mg of vanillin was administered to the participants in the study and cumulative urine samples were obtained up to 8 h after giving the dose. The samples were analyzed by high-performance liquid chromatography and metabolic ratios were calculated as peak area ratio of vanillic acid/vanillin. RESULTS: (a) The results of the in vitro validation studies clearly indicated that vanillin is preferentially metabolized by AO. (b) Normal distribution tests and probit analysis revealed that AO activity was not normally distributed and that 73.72% of the participants were fast metabolizers, 24.28% intermediate metabolizers, and 2% were slow metabolizers. CONCLUSIONS: Data of the phenotyping study suggest the existence of AO polymorphism, in a Western Indian cohort.
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EDUCATIONAL FORUM Top

Copper-lowering agents as an adjuvant in chemotherapy p. 221
Pramod Kadu, Bhakti Sawant, Pravin Popatrao Kale, Kedar Prabhavalkar
DOI:10.4103/ijp.IJP_68_20  PMID:34169907
Copper is an important element essential for metabolism and normal human body function. Although it is an essential element, related imbalance leads to toxic effects. Studies have proved that there is an increase in copper level in cancer cells. Evidences suggest the link between increase in copper levels and progression of various types of cancers. Different strategies have been utilized to decrease the level of copper in various types of cancer cells. However, it was observed that cell machinery involved in copper homeostasis plays critical factor in lowering copper levels in cancer cells. The outcomes of many monotherapies consisting copper-lowering agents for the treatment of different types of cancers showed that the inhibition of single factor is not sufficient to inhibit the growth of cancer cells. The combination of copper-lowering agent with chemotherapeutic agent showed synergistic effect. Interestingly, the presence of copper-lowering agent in such combinations significantly improved the efficacy of chemotherapeutic agent. The present work has focused on the discussion of outcomes of studies involving anti-copper agent and chemotherapeutic agent and related future strategies.
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SHORT COMMUNICATION Top

Can emapalumab be life saving for refractory, recurrent, and progressive cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and Janus kinase inhibitors p. 226
Erkan Cure, Adem Kucuk, Medine Cumhur Cure
DOI:10.4103/ijp.IJP_615_20  PMID:34169908
Although many potent drugs have been used for cytokine storm, mortality is high for patients with coronavirus disease-2019 (COVID-19), which is followed up in the intensive care unit. Interferons (IFNs) are the major cytokines of the antiviral defense system released from many cell types. However, IFN-γ plays a key role in both primary and secondary cytokine storms. If the cytokine storm is not treated urgently, it will be fatal; therefore, it should be treated immediately. Anakinra, an interleukin-1 (IL-1) antagonist, tocilizumab, an IL-6 antagonist, and Janus kinase (JAK) inhibitors are successfully used in cytokine storm caused by COVID-19. However, sometimes, despite these treatments, the patient's clinical course does not improve. Emapalumab (Eb) is the human immunoglobulin G1 monoclonal antibody and is a potent and noncompetitive antagonist of IFN-γ. Eb can be life saving for cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and JAK inhibitors.
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DRUG WATCH Top

The effects of empagliflozin on cardiometabolic risk factors in patients with type 2 diabetes: A short-term observational study p. 229
Jithin Chacko, Shankar Dhandapani, Vidhya Jahagiridhar, Krishnan Swaminathan
DOI:10.4103/ijp.IJP_669_18  PMID:34169909
The aim of this study was to assess the short-term cardiometabolic outcomes in type 2 diabetes patients receiving empagliflozin in a tertiary referral center. Three hundred and fifteen consecutive patients started on empagliflozin were followed for a 4-month period after local ethics committee approval for a range of outcomes. Data were recorded on Microsoft Excel and transposed to SPSS for further analysis. Empagliflozin treatment resulted in statistically significant reductions in weight, glycosylated hemoglobin, and systolic and diastolic blood pressures along with favorable lipid profile outcomes over a 4-month period. The rates of discontinuation of the medications due to genomycotic infections were extremely low at 0.6% with no episodes of severe hypoglycemia or euglycemic diabetic ketoacidosis. Empagliflozin therapy, either in addition to other oral agents or insulin, seems to result in favorable outcomes in cardiometabolic risk factors in the immediate short term. Long-term follow-up of this cohort will shed light on cardiovascular outcomes and adverse effects in our population in real-world clinical practice.
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A case report on azathioprine-induced euprolactinemic galactorrhea p. 234
Deepa Chaudhary, Ratinder Jhaj
DOI:10.4103/ijp.ijp_159_18  PMID:34169910
Galactorrhea is characterized as an inappropriate discharge of milk-containing fluid from the breast. It has various causes including physiological and pathological. It may also be caused by many drugs. Although galactorrhea is usually associated with increased serum prolactin levels, it has been reported to occur in the absence of hyperprolactinemia. Cases of azathioprine-induced galactorrhea with normal prolactin level in a 22-year-old female patient with prurigo have been reported. It was noticed that the patient had no history of galactorrhea in the past.
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SYSTEMATIC REVIEW Top

Efficacy and safety of inhaled nitric oxide in the treatment of severe/critical COVID-19 patients: A systematic review p. 236
Ajay Prakash, Sukhmeet Kaur, Charanjeet Kaur, Praisy K Prabha, Anusuya Bhatacharya, Phulen Sarma, Bikash Medhi
DOI:10.4103/ijp.ijp_382_21  PMID:34169911
OBJECTIVE: Present systematic review aimed to analyze the effect of inhaled nitric oxide (iNO) in the treatment of severe COVID-19 and to compare it to standard of care (SOC), antiviral medications, and other medicines. MATERIALS AND METHODS: Medline (PubMed), Scopus, Embase, Ovid, Web of Science, Science Direct, Wiley Online Library, BioRxiv and MedRxiv, and Cochrane (up to April 20, 2021) were the search databases. Two reviewers (SK and CK) independently selected the electronic published literature that studied the effect of nitric oxide with SOC or control. The clinical and physiological outcomes such as prevention of progressive systemic de-oxygenation/clinical improvement, mortality, duration of mechanical ventilation, improvement in pulmonary arterial pressure, and adverse events were assessed. RESULTS: The 14 retrospective/protective studies randomly assigning 423 patients met the inclusion criteria. Cumulative study of the selected articles showed that iNO has a mild impact on ventilation time or ventilator-free days. iNO has increased the partial pressure of oxygen/fraction of inspired oxygen ratio of fraction of inspired oxygen in a few patients as compared to baseline. However, in most of the studies, it does not have better outcome when compared to the baseline improvement. CONCLUSIONS: In patients with COVID-19 with acute respiratory distress syndrome, nitric oxide is linked to a slight increase in oxygenation but has no effect on mortality.
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LETTERS TO THE EDITOR Top

Candidiasis in patients treated with interleukin-17 inhibitors p. 244
Nerea BŠez-Gutierrez, Hťctor RodrŪguez-Ramallo
DOI:10.4103/ijp.ijp_1178_20  PMID:34169912
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Potential effects of itolizumab treatment on plasma interleukin-6 levels in patients with severe COVID-19 p. 246
Yethindra Vityala, Tugolbai Tagaev, Sagynali Mamatov, Ziiabidin Aidarov, Panchadcharam Harinath
DOI:10.4103/ijp.IJP_33_21  PMID:34169913
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Written informed consent to virtual e-consent in clinical research: Changing necessity during COVID times p. 248
Apoorva Mathur
DOI:10.4103/ijp.ijp_331_21  PMID:34169914
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Attitude toward COVID-19 vaccination: A cross-sectional study on healthcare professionals p. 250
Suresh Velumani, Patel Arpita, Ramachandran Balaraman
DOI:10.4103/ijp.ijp_173_21  PMID:34169915
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