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   Table of Contents - Current issue
Coverpage
May-June 2020
Volume 52 | Issue 3
Page Nos. 163-233

Online since Tuesday, August 4, 2020

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EDITORIAL  

Understanding the challenges and ethical aspects of compassionate use of drugs in emergency situations p. 163
Pardeep Kumar Goyal, Roli Mathur, Bikash Medhi
DOI:10.4103/ijp.IJP_665_20  
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RESEARCH ARTICLES Top

Effectiveness of Deferasirox in Pediatric Thalassemia Patients: Experience from a Tertiary Care Hospital of Odisha p. 172
Mousumee Panigrahi, Trupti Rekha Swain, Rabindra Kumar Jena, Ashutosh Panigrahi, Nishant Debta
DOI:10.4103/ijp.IJP_68_18  
BACKGROUND AND OBJECTIVES: Patients with beta-thalassemia require lifelong blood transfusions, leading to chronic iron overload, which can lead to growth retardation, as well as hinder sexual development during the adolescent period and dysfunction of organs such as heart, pancreas, and endocrine glands. These patients are in need of lifelong transfusion therapy and hence lifelong iron chelation therapy as well. Hence, this study was aimed to assess the effectiveness of deferasirox for iron chelation in pediatric thalassemia cases in a tertiary care hospital of Eastern India. SUBJECTS AND METHODS: This prospective, observational, hospital-based study was conducted from June 2015 to December 2016. Two hundred and fifty patients were assessed for eligibility, of which 174 were included. Effectiveness of deferasirox was observed by measuring serum ferritin levels which were monitored at the end of every 3 months till 1 year. We also evaluated the compliance with deferasirox therapy in the same study cohort. RESULTS: The serum ferritin level reduced significantly at the end of 12 months in comparison to baseline (P = 0.04). There was a mean absolute decrease in serum ferritin only in the dose range of 21–30 mg/kg/day. Approximately 90% of the patients had 100% compliance with deferasirox therapy. CONCLUSIONS: Deferasirox is an effective iron chelator when started at an optimum time and with optimum dose. At least 1 year of deferasirox therapy is needed for a significant lowering of serum ferritin levels of pediatric thalassemia patients on multiple blood transfusions.
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Drug utilization, rationality, and cost analysis of antimicrobial medicines in a tertiary care teaching hospital of Northern India: A prospective, observational study p. 179
HV Bimba, Vandana Roy, Angelika Batta, Mradul Kumar Daga
DOI:10.4103/ijp.IJP_225_19  
BACKGROUND: The burden of bacterial infections is huge and grossly under-represented in the current health-care system. Inappropriate use of antimicrobial medicines (AMMs) poses a potential hazard to patients by causing antibiotic resistance. This study was conducted to assess the: (i) AMM consumption and use patterns in patients attending the outpatients and inpatients of Medicine and Surgery departments of the hospital. (ii) Appropriateness of the AMM in the treatment prescribed, and (iii) cost incurred on their use in admitted patients. MATERIALS AND METHODS: An observational, prospective study was conducted among inpatients and outpatients of the Medicine and Surgery departments of a tertiary care hospital of northern India. Analysis of 2128 prescriptions and 200 inpatient records was performed using a predesigned format. The use of AMMs was reviewed using anatomical therapeutic chemical classification and defined daily doses (DDDs). To evaluate the expenditure incurred on AMMs, ABC analysis was performed. RESULTS: AMMs were prescribed to 37.9% outpatients and 73% of admitted patients. The percentage encounters with AMMs was 40.6% (medicine) and 25.6% (surgery) outpatients. The total DDDs/100 patient days of AMMs in medicine and surgery were 3369 and 2247. Bacteriological evidence of infection and AMM sensitivity was present in only 8.5% of cases. Over 90% of AMMs were prescribed from the hospital essential medicines list. Most of the AMMs were administered parenterally (64.9%). Multiple AMMs were prescribed more to inpatients (84.2% vs. 4.2% outpatients). Overall, expenditure on AMM was 33% of the total cost of treatment on medicine. ABC analysis showed that 74% of the expenditure was due to newer, expensive AMM, which constituted only 9% of the AMM used. The AMM therapy was found to be appropriate in 88% of cases as per Kunin's criteria for rationality. CONCLUSION: AMMs are being commonly prescribed without confirmation of AMM sensitivity in the hospital. A large proportion of expenditure is being incurred on expensive AMM used in a few number of patients. There is a need for developing a policy for rational use of AMM in the health facility.
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Cytochrome P4502D6 polymorphism in eastern Indian population p. 189
Monalisa Dhuya, Murari Mohan Pal, Avijit Hazra, Suparna Chatterjee, Nithya Gogtay
DOI:10.4103/ijp.IJP_530_17  
OBJECTIVES: Cytochrome P4502D6 (CYP2D6) enzyme metabolizes a quarter of prescription drugs. Polymorphisms of CYP2D6 gene and resultant phenotypic variations in metabolic activity have been described in various populations. We assessed the prevalence of CYP2D6 activity phenotypes, employing dextromethorphan (DXM) as probe drug in subjects with at least two parental generations residing in eastern India. MATERIALS AND METHODS: Unrelated healthy subjects took 60 mg DXM after fasting overnight. Blood samples were collected 3 h after dosing and plasma separated. DXM and its primary metabolite dextrorphan (DXT) were measured by liquid chromatography with tandem mass spectrometry. The DXM-to-DXT metabolic ratio (MR) was obtained for each subject. Histogram of MR values suggested bimodal distribution. A polynomial regression equation derived through probit analysis was solved to identify the antimode of the MR values. Subjects with log(MR) < antimode were extensive metabolizers (EMs). Log(MR) ≥ antimode indicated poor metabolizers (PMs). RESULTS: We evaluated the results from 97 participants. The median MR was 0.209 (interquartile range: 0.090–0.609), while the antimode for MR was 3.055. From these, it was inferred that three subjects were PMs, while the rest were EMs. CYP2D6 polymorphism prevalence is low (3.09%; 95% confidence interval: 0.35%–6.54%) in the population of eastern India and matches the prevalence in other zones of the country. CONCLUSIONS: Differences in CYP2D6 activity has treatment implications and may lead to adverse events or therapeutic failure. Phenotyping of subjects receiving CYP2D6 metabolized drugs may help clinicians personalize treatment and avert adverse drug-drug interactions. However, the frequency of the PM phenotype is low in India, and routinely phenotyping for CYP2D6 activity will not be cost-effective. We cannot recommend it at this stage.
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Evaluation of diuretic efficacy and antiurolithiatic potential of ethanolic leaf extract of Annona squamosa Linn. in experimental animal models p. 196
Mejo C Korah, Junaid Rahman, R Rajeswari, Haja Sherief, V Lalitha, S Sengottavelu, T Sivakumar
DOI:10.4103/ijp.IJP_92_18  
OBJECTIVE: The study is to investigate the diuretic and antiurolithiatic activities of ethanolic leaf extract of Annona squamosa Linn. in experimental animals. MATERIALS AND METHODS: For both studies, Wistar albino rats and two doses of extract (250 and 500 mg/kg) were used. Diuretic activity was evaluated by Lipschitz model. Urine volume and urine pH were noted, the concentration of sodium and potassium was estimated by flame photometry, and diuretic index, natriuretic index, and Lipschitz values were calculated from the results. Furosemide was used as a positive control. Ethylene glycol-induced urolithiasis model was used for antiurolithiatic study. Urine volume, urine pH, body weight, and biochemical parameters such as calcium, urea, uric acid, and creatine both from serum and urine were estimated. Antioxidant parameters and histopathological analysis of the kidney were evaluated. Cystone was used as a positive control in this study. Results were expressed as mean ± standard error of mean. Statistical analysis was carried out using one-way analysis of variance, followed by Dunnett's multiple comparison tests. RESULTS: In both diuretic and antiurolithiatic studies, both doses of the extract showed efficacy, and the dose of 500 mg/kg has shown a significant effect compared to positive control and negative control. CONCLUSION: The dose of 500 mg/kg showed a promising diuretic and antiurolithiatic activity.
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Involvement of the toll-like receptors-2/nuclear factor-kappa B signaling pathway in atherosclerosis induced by high-fat diet and zymosan A in C57BL/6 mice p. 203
Priyanka Arya, Uma Bhandari
DOI:10.4103/ijp.IJP_567_19  
OBJECTIVE: Accumulated evidence reported a link between the immune system, microbial infection, and the development of atherosclerosis. Excess intake of high-fat diet (HFD) increases blood lipid levels and induces inflammatory pathways whereas zymosan A (Zym), a microbial component, mediates inflammatory response through the stimulation of specific ligand of toll-like receptors (TLRs) of the immune system. The current research work was aimed to evaluate the mechanism behind atherosclerosis mediated by HFD and Zym in C57BL/6 mice. MATERIALS AND METHODS: The mice were orally fed with HFD for 30 days and Zym (80 mg/kg, single intraperitoneal injection on day 8th). On the 31st day, blood was withdrawn from overnight fasted mice by tail vein puncture and estimated for serum lipids and tumor necrosis factor-alpha (TNF-α). Animals were sacrificed, and cardiac, liver, and aortic tissues were isolated for the estimation of cardiac TLR-2, nuclear factor-kappa B (NF-ƙB); hepatic low-density lipoprotein receptors (LDLR); and base of aorta analyzed for histopathology. RESULTS: It was found that HFD and Zym administration increased arterial inflammation directly through modulation of the TLR-2/NF-ƙB pathway, thereby upregulate serum TNF-α, cardiac TLR-2, and NF-ƙB levels. Further, HFD and Zym treatment significantly increased serum lipid levels and marked decrease in LDLR protein expression in the liver when compared to normal control mice. Histopathological analysis showed the formation of atherosclerotic plaque. CONCLUSION: The study is first, to our current knowledge, to demonstrate the involvement of the TLR-2/NF-ƙB signaling pathway in atherosclerosis induced by HFD and Zym in C57BL/6 mice, resulting in increased degradation of LDLR protein, thereby, increasing the serum lipid levels.
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DRUG WATCH Top

A rare case of cephalexin-induced acute interstitial nephritis with hypokalemic periodic paralysis p. 210
Rajesh Kumar, Amit Kumar Singh, Kavish Sharma, Vandana Talwar
DOI:10.4103/ijp.IJP_532_19  
Drug-induced acute interstitial nephritis (AIN) is often encountered in clinical practice. Cephalexin is a first-generation cephalosporin with antimicrobial sensitivity ranging from Gram-positive to Gram-negative organisms. Cephalexin-induced AIN presenting with hypokalemic periodic paralysis (HPP) has been rarely reported. A 34-year-old female with recent history of oral cephalexin intake presented with acute onset paraplegia with deranged renal parameters and hypokalemia. She was treated conservatively with mechanical ventilator support. HPP could be a rare clinical presentation for cephalexin-induced AIN.
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Duloxetine-induced hypertensive urgency in type 2 diabetes mellitus with diabetic neuropathy p. 213
Ravindra Shukla, Sameer Khasbage, Mahendra Kumar Garg, Surjit Singh
DOI:10.4103/ijp.IJP_370_19  
We present a case of hypertensive urgency in a diabetic patient with painful diabetic neuropathy on duloxetine treatment. The patient's blood pressure was high after taking 1-day dose of duloxetine and the patient was diagnosed with hypertensive urgency. The patient was managed with labetalol, leading to reduction in blood pressure. The patient's medication was switched to telmisartan and metoprolol, which leads to resolution of increased blood pressure. This case report is a possible case of hypertensive urgency after the initiation of duloxetine managed with antihypertensives and resolves with the discontinuation of the duloxetine.
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SHORT COMMUNICATION Top

Co-abuse of alprazolam augments the hepato-renal toxic effects of methylphenidate p. 216
Meenu Dutt, Ravinder Naik Dharavath, Tanzeer Kaur, Navpreet Kaur, Kanwaljit Chopra, Shweta Sharma
DOI:10.4103/ijp.IJP_758_19  
OBJECTIVE: Methylphenidate (MPH) is a first-line treatment option for attention-deficit hyperactive disorder and narcolepsy. MPH is one of the most abused psychostimulants by the adults and young population to stay awake, perform better, or improve concentration. The scanty reports say that the medical users or abusers mostly consider the administration of benzodiazepines to overcome the adverse effects, i.e., mood- and anxiety-related problems associated with MPH chronic abuse. This work aims to study the effect of alprazolam (ALZ) on MPH-associated adverse effects on liver and kidney. MATERIALS AND METHODS: Female Wistar rats (n = 58) were administered with MPH (10, 20, and 40 mg/kg) and ALZ (5, 10, and 20 mg/kg) alone and in combination for 28 days. Bodyweight, feed intake, and water intake were monitored weekly. Parameters related to liver and renal function, oxidative stress, and histopathology were performed to evaluate the toxic impacts on the liver and kidneys. RESULTS: ALZ, along with MPH, increased the serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, and urea levels. The co-abuse also led to elevated oxidative stress and structural abnormalities in the liver and kidney tissues. CONCLUSION: The co-abuse of ALZ has amplified the hepato-renal toxic effects of MPH. Therefore, it is a significant concern for public safety, and their co-abuse must be restricted and discouraged.
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POTENTIAL PHARMACOLOGICAL TARGETS Top

Target/therapies for chronic recurrent erythema nodosum leprosum p. 222
Pugazhenthan Thangaraju, Shoban Babu Varthya, Sajitha Venkatesan
DOI:10.4103/ijp.IJP_788_19  
A Type 2 lepra reaction or erythema nodosum leprosum is an anticipated complication in the lepromatous spectrum of leprosy cases. It is an example of an immune complex-mediated complement activated disease (Type III hypersensitivity reaction). Hence, we tried to target the inflammatory mediators and the mental stressors for the possible management strategies.
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LETTER TO THE EDITOR Top

Indian perspective of remdesivir: A promising COVID-19 drug p. 227
Devendra Singh, Himika Wasan, Apoorva Mathur, Yogendra Kumar Gupta
DOI:10.4103/ijp.IJP_486_20  
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Psychiatric implications of the use of hydroxychloroquine in COVID-19 patients p. 229
Seema Rani, Sandeep Grover, Aseem Mehra, Swapnajeet Sahoo
DOI:10.4103/ijp.IJP_595_20  
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Sofosbuvir for COVID-19 infection: A potential candidate p. 232
Rohit Gupta, Puneet Dhamija
DOI:10.4103/ijp.IJP_675_20  
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