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   Table of Contents - Current issue
Coverpage
April-June 2019
Volume 10 | Issue 2
Page Nos. 45-76

Online since Wednesday, August 14, 2019

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EDITORIAL  

Of mice and men: The murine intrigues in drug discovery p. 45
MK Unnikrishnan
DOI:10.4103/jpp.JPP_40_19  
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RESEARCH PAPERS Top

Myocardial preconditioning potential of hedgehog activator purmorphamine (smoothened receptor agonist) against ischemia-reperfusion in deoxycortisone acetate salt-induced hypertensive rat hearts p. 47
Himanshi Khera, Anupam Awasthi, Sidharth Mehan
DOI:10.4103/jpp.JPP_8_19  
Aim: To investigate the myocardial preconditioning potential of hedgehog activator smoothened (SMO) receptor agonist purmorphamine (PUR) against ischemia-reperfusion (I/R) injury in deoxycortisone acetate (DOCA) salt-induced hypertensive rat heart. Methods: Hypertension in rats was produced by surgical removal of the kidney and DOCA salt administration for 6 weeks. Isolated rat heart was subjected to 30 min ischemia followed by 120 min of I/R. The heart was subjected to pharmacological preconditioning with the hedgehog (Hh) activator PUR (1 μM), PUR (2 μM), and atractyloside (4 μM), an mPTP opener, in the last episode of reperfusion before I/R. Elevated blood pressure was evaluated through tail-cuff method. Myocardial infarction was assessed in terms of the increase in lactate dehydrogenase, creatinine kinase-muscle/brain, and infarct size through triphenyltetrazolium chloride staining. Further, there were a decrease in the release of nitrite and coronary flow rate. Immunohistochemistry was performed for the assessment of tumor necrosis factor-α level in cardiac tissue. Results: Pharmacological preconditioning with PUR significantly attenuated I/R-induced myocardial infarction. However, atractyloside limits the ameliorative preconditioning potential of PUR and confirmed the role of Hh pathway in ischemic preconditioning. Conclusion: It may be concluded that the Hh activator PUR (SMO receptor agonist) prevents I/R injury in DOCA salt-induced hypertensive rat heart.
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Transdermal buprenorphine versus intramuscular diclofenac for postoperative analgesia following upper abdominal surgery under general anesthesia: A randomized controlled trial p. 57
Sandip Roy Basunia, Baisakhi Laha, Avijit Hazra
DOI:10.4103/jpp.JPP_6_19  
Aim: To compare the post-operative analgesic effect of of buprenorphine 20 μg/h patch with diclofenac 75 mg intramuscular injection following upper abdominal surgery under general anesthesia (GA). Materials and Methods: An open-label, randomized, controlled trial (CTRI/2018/03/012694) was conducted with adult subjects of either sex, undergoing planned major upper abdominal surgery under GA. Preoperative medication regimen and anesthesia protocol were uniform for all patients. Buprenorphine patch was applied to a hairless area of the chest or upper arm 12 h before surgery. Diclofenac 75 mg was injected into the deltoid muscle just after extubation. Postoperatively, vital signs were monitored along with Ramsay sedation scale (RSS) score. Postoperative analgesia was assessed using visual analog scale (VAS) scoring, at 4-h interval for the first 12 h and then 12-hourly for the next 2 days. Tramadol 2 mg/kg intravenous was permitted as a rescue analgesic. Results: Each arm had 35 patients without dropouts. The groups remained comparable in VAS pain score at all time points. However, with buprenorphine, although VAS score declined over time, the reduction attained statistical significance in comparison to the baseline (4 h) VAS score only at 72 h. In contrast, with diclofenac, VAS score achieved statistically significant reduction from 8 h onward and this was maintained throughout. In the buprenorphine arm, 21 patients (60.00%) required rescue analgesia in contrast to 10 (28.57%) on diclofenac (P = 0.016). Vital parameters and RSS remained essentially unchanged in both groups. Conclusion: Although the primary outcome measure was comparable between the groups, the pattern of rescue analgesia use suggests that postoperative analgesia experience with buprenorphine patch was less satisfactory than diclofenac injection in this study.
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Potential drug–drug interactions in the pediatric intensive care unit of a tertiary care hospital p. 63
Chandini Rao, Varadaraj Shenoy, Padmaja Udaykumar
DOI:10.4103/jpp.JPP_27_19  
Aim: To identify and evaluate the potential drug–drug interactions (PDDI) in hospitalized patients in a pediatric intensive care unit (PICU). Materials and Methods: In this cross-sectional observational study, we analyzed prescriptions of children aged 1 month–15 years admitted to PICU for PDDIs, and categorized them based on the severity (mild, moderate, and severe), underlying mechanisms, number of concomitant drugs used and potential outcomes of these PDDIs, using a drug interaction checking software. Results: Of the 122 prescriptions, we found 175 PDDIs in 77 prescriptions, of which 75.43% were of moderate, 17.71% minor, 6.86% major severity, and none was contraindicated.. The number of PDDIs increased with the number of medications per prescription. The average number of PDDIs per prescription was the highest in those that had >10 drugs (4.29). Pharmacodynamic interactions constituted the majority (73.71%) compared to pharmacokinetic interactions (23.43%). Common PDDIs encountered were between salbutamol and phenylephrine (11.43%), between anti-epileptic drugs (10.86%) and 3rd generation cephalosporins and aminoglycosides (10.29%). The most common potential outcome of these DDIs was hypokalemia (13.71%). Conclusion: There is a high prevalence of PDDIs in PICUs, mostly of moderate severity, with a significant relationship with the number of concomitant medications prescribed. Precaution is required while implementing polypharmacy in children.
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Application of a new “pharmvigill© ”app for the analysis of dermatological adverse drug reaction in a tertiary care hospital p. 69
Shalini Chawla, Ankur Tiwari, Shariq Naeem Syed,
DOI:10.4103/jpp.JPP_105_18  
Aim: To assess the patterns of dermatological adverse drug reactions (ADRs) and drugs responsible to formulate a strategy for prevention and treatment using a new app. Materials and Methods: In the present study, 870 patients in dermatology outpatient department were screened, out of which sixty cutaneous ADRs were included in the study. The ADRs were categorized and assessed by Causality Assessment Scale and Preventability Scale using an innovative mobile software application named “Pharmvigill©-ADR analyzer App. ”Results: It was observed that rashes and acneiform eruption (25% and 16.7%, respectively) were the most common cutaneous ADRs. Nonsteroidal anti-inflammatory drugs (25%) were the most common group of drugs causing cutaneous ADRs followed by antimicrobial drugs (23.3%) and steroids (20%). Similarly, betamethasone, paracetamol, and phenytoin were the most common drugs causing ADRs. In the causality assessment, almost 81% fell into the category of “probable, ”whereas 58.8% of the ADRs were “probably preventable ”and almost 40% were “not preventable. ”There was no statistically significant difference (P > 0.05) between scores in manual assessment and software-based assessment. Conclusion: Cutaneous ADRs are caused by some of the very commonly prescribed medicines. A high degree of suspicion is required to identify the “preventable ”type of ADR. The ADR analysis app “Pharmvigill ”is accurate and can decrease the analysis time of the ADRs in a dynamic clinical scenario.
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CASE REPORT Top

Presumed antihistamine-induced cataract in two young males p. 75
Md Shahid Alam, Ashwin Cherusheril Somarajan
DOI:10.4103/jpp.JPP_31_19  
The use of systemic and topical steroids, amiodarone, and phenothiazines has been established as risk factors for the development of cataract. Antihistaminics are commonly prescribed drugs for a wide range of allergic disorders but have rarely been associated with cataract formation. We herewith report cases of two young males who were on long-term antihistaminics for allergic conditions and presented with blurring of vision. Slit lamp examination revealed bilateral posterior subcapsular cataract. The patients did not have any other systemic or ocular condition predisposing for cataract formation; hence, a diagnosis of antihistaminic-induced cataract was made.
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