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   Table of Contents - Current issue
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April-June 2021
Volume 12 | Issue 2
Page Nos. 29-105

Online since Friday, September 17, 2021

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REVIEW ARTICLE  

Career vistas for Indian medical pharmacologists: A comprehensive review Highly accessed article p. 29
Avinash Arivazhahan, Gerard Marshall Raj, Deepthi Shridhar Puttur, Sarjana Atal, Manu Mathew George, Laxminarayana Bairy
DOI:10.4103/jpp.jpp_37_21  
Medical postgraduation in India is available across various disciplines, one among them being pharmacology. As with the other MD courses, MD Pharmacology is a 3-year-long course that involves strenuous theoretical, practical, and clinical training. However, the curriculum does not clearly enlighten MD residents on the career vistas available for them once they pass out. The awareness level of majority of MD pharmacology postgraduates or freshers on these career options is meagre due to lack of professional guidance or literature, and hence, majority of them tend to travel along the path that is most commonly traversed by their seniors and peers. This comprehensive review details a few of the different vistas that an MD pharmacologist can pursue, highlighting the scope, roles, responsibilities, and monetary compensation of each, in an honest attempt to educate and enlighten the MD pharmacology fraternity.
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RESEARCH ARTICLE Top

Is a glucocorticoid antagonist a potential treatment alternative for antipsychotic-induced weight gain? p. 37
Wisam Al Jumaili, Chintan Trivedi, Kaushal Shah, Mahwish Adnan, Zeeshan Mansuri, Shailesh Jain
DOI:10.4103/jpp.jpp_33_21  
Objective: To evaluate the efficacy and safety of mifepristone as a new treatment modality for antipsychotic-induced weight gain. Methods: We searched databases up to March 2021, for the published English-language literature including a Medical Subject Heading “Mifepristone,” “Receptors, Glucocorticoid,” “Weight gain,” “Overweight,” “Obesity,” “Body Weight Change,” “Antipsychotics Agents,” “Glucocorticoid Receptor Blocker,” “Glucocorticoid Receptor antagonist.” We identified two clinical and four preclinical studies utilizing mifepristone as a treatment modality. Results: The results of the olanzapine clinical trial showed that mean increase in weight from baseline to day 14 was greater in the olanzapine with the placebo group (3.2 ± 0.9 kg) than the olanzapine with mifepristone group (2.0 ± 1.2 kg) and the mifepristone with placebo (2.0 ± 0.7 kg), and a similar effect was observed in the risperidone with mifepristone clinical trial. Conclusions: Mifepristone shows potential in the management of AIWG. Glucocorticoid antagonists can be a viable alternative to curb this side effect. Large-scale clinical studies are warranted to determine the medication's safety and efficacy based on this mechanism of action.
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MINI REVIEW Top

Fostemsavir, a drug with novel mechanism for the treatment of HIV-1 infection p. 42
Raman Palanisamy Priyadharsini, CM Divyashanthi, Dhivya Elango
DOI:10.4103/jpp.jpp_19_21  
HIV is a global problem with increased mortality and morbidity. The highly active antiretroviral therapy is effective in reducing the HIV RNA and improving the immune response. The drugs in the current regimen have certain disadvantages such as adverse effects, drug intolerance, and drug resistance. Since there is a demand for identifying the drugs with new mechanism of action, the compounds which target the viral gp120 receptor were screened and the most suitable drug among them was identified. In a Phase II and Phase III trial, the drug BMS-663068 fostemsavir was found to be efficacious in reducing the viral RNA levels. The drug is a prodrug that gets converted into metabolite temsavir BMS-626529. The preferred dose is 600 mg orally 12 hourly in patients who had undergone many treatment schedules with multidrug-resistant infection and those who cannot tolerate the drug regimen due to resistance and safety issues. The drug is metabolized by CYP3A4 and has drug interactions with CYP3A4 inducers and inhibitors. This review mainly comprises the mechanism of action, clinical trials, pharmacological properties, and adverse effects of the drug fostemsavir.
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RESEARCH PAPERS Top

Vitamin D3 attenuates type 3 diabetic-associated cognitive deficits in rats through regulating neurotrophins and enhancing cholinergic transmission pathway p. 47
Yahya Abdullah Al-Zahrani, Mai A. Alim A. Sattar, Sameer E Al-Harthi, Ayed A Alkatheeri, Yahya Mohammed Al-Zahrani
DOI:10.4103/jpp.jpp_20_21  
Objective: To examine the protective effect of Vitamin D3 against Type 3 diabetes-induced cognitive dysfunction in rats. Materials and Methods: Type 3 diabetes was induced by a high-fat diet plus streptozotocin in rats. Rats were divided into seven groups: negative control, positive control, Vitamin D3 groups (100, 500 and 1000 IU/kg/day), Vitamin D3 plus rivastigmine, and rivastigmine monotherapy. A radial arm maze test was used to assess cognitive function. Levels of acetylcholinesterase (AChE), dopamine (DA), nerve growth factor, neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus were estimated by the enzyme-linked immunosorbent assay kits. Results: Chronic treatment with Vitamin D3 significantly (P < 0.05) and dose dependently alleviated cognitive deficits, with enhancing cholinergic transmission pathway activity through attenuated hippocampal AChE and increased DA level (P < 0.001). Moreover, Vitamin D3 significantly increased (P < 0.001) neurotrophin levels as an underlying mechanism for the resulted improvement. Conclusion: Vitamin D3 plus rivastigmine (combined group) is better than Vitamin D (100 and 500 mg/kg/day) for improvement of AChE, DA, NT-3, and GDNF levels. Vitamin D (500 and 1000 IU/kg/day) was effective as a combined group in terms of the behavioral test.
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Effect of atorvastatin and rosuvastatin on the glycemic control in patients with type II diabetes mellitus: A Comparative, randomized, double-blind study p. 54
Mohini Sachin Mahatme, Mukunda Bharat Bargade, Sachin K Hiware, MM Motlag
DOI:10.4103/jpp.jpp_8_21  
Objectives: To compare the effects of atorvastatin and rosuvastatin in type II diabetes mellitus (T2DM) patients with dyslipidemia. Materials and Methods: Eighty patients with history of T2DM of more than 3 months duration, glycated hemoglobin <7%, dyslipidemia, and normal electrocardiogram were included in the randomized double-blind trial. The patients received either tablet atorvastatin 20 mg or rosuvastatin 10 mg once a day along with metformin and glimepiride twice daily orally. Patients were evaluated by the change in estimated average glucose (eAG), lipid profile, and incidence of adverse drug reactions (ADRs). Results: Rise in fasting blood sugar (FBS), postprandial blood sugar, and eAG were significant in the atorvastatin group as compared to the rosuvastatin group where there was a significant increase only in FBS levels. Changes in lipid parameters and incidence of ADR were similar in both the groups. Conclusion: Rosuvastatin can be preferred to atorvastatin in T2DM with dyslipidemia due to less variation in the blood sugar parameters, effective control over lipid profile, pleiotropic effects, and less microsomal interactions.
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Therapeutic drug monitoring of imatinib in patients of chronic myeloid leukemia – Chronic phase p. 61
Harshit Khurana, Ashwini Kumar, Abha Khurana, Kumar Abhisheka, Vijoy Kumar Jha
DOI:10.4103/jpp.jpp_28_21  
Introduction: Tyrosine kinase inhibitor is recommended for the initial management of chronic phase chronic myeloid leukemia (CP CML) based on the more favorable balance of toxicity and long-term disease control. Background: Mean trough plasma Imatinib Mesylate (IM) levels are detected to be significantly higher in patients with a complete cytogenetic response or major molecular response (MMR). Methodology: The primary objective of the study was to correlate the IM drug levels with MMR on two different occasions at least 3 months apart and to study the variation in the plasma trough levels of IM during the treatment with standard dose for at least 12 months. Results: After exclusion, 30 patients of CML-CP in MMR, on standard dose over a period of 2 years were finally analyzed. The mean IM plasma levels (IPLs) of the first sample for all patients were 1722 ± 566 ng/ml (IPL-1) with a corresponding mean molecular response (MR) 0.0257 ± 0.0279 breakpoint cluster region-abelson murine leukemia (BCR-ABL) IS % (MR-1). The mean IPLs of the second sample for all patients were 1549 ± 375 ng/ml (IPL-2) with a corresponding mean MR 0.0143 ± 0.0184 BCR-ABL IS % (MR-2). Area under the receiver operating characteristic curve for IPL-1 was 0.565 and IPL-2 was 0.639. For IM level at second point of 1800 ng/ml, the specificity for predicting MMR was 81.8% and sensitivity was 31.6%. Conclusion: Monitoring of trough IM plasma concentrations may become the part of standard management of CML patients.
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Role of Vitamin B complex as an add-on therapy to diclofenac in patients with primary osteoarthritis of the knee p. 68
Jasmine Kaur, Seema Rani, Anil Gulia, Garima Bhutani, Sanjeev Kumar, Arvind Narwat
DOI:10.4103/jpp.jpp_32_21  
Objective: This study was conducted with the aim to evaluate the efficacy and safety of Vitamin B complex as an add-on therapy to diclofenac in patients with primary osteoarthritis (OA) of the knee. Materials and Methods: In this prospective, open-labeled, randomized, and comparative clinical study, a total of 130 patients of age >40 years with primary OA of knee attending orthopedics OPD were randomly allocated into two groups of 65 each, i.e., Group D and Group B. In Group D, patients received tablet diclofenac 75 mg and in Group B, patients received tablet Vitamin B complex along with diclofenac once daily for 4 weeks, respectively. Clinical assessment was done at baseline and at the end of 4 weeks and 8 weeks by the visual analog scale (VAS), WOMAC index, and Lequesne index. Results: During the intergroup comparison, it was found that Vitamin B complex as an add-on therapy to diclofenac produced statistically significant reduction in mean VAS pain score (P < 0.05). However, the difference in mean WOMAC index and Lequesne index was not statistically different at 4 and 8 weeks between the two groups (P > 0.05). Mild side effects were seen at 4 weeks, but no side effects persisted up to 8 weeks in both the groups. Conclusion: The present study suggested that Vitamin B complex as an add-on therapy was found to cause a significant reduction in pain score. It could be a promising drug in patients with OA to improve the analgesic effect, when combined can reduce the dose of diclofenac, thereby minimizing the side effects.
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Correlation between breakthrough seizures and serum level of phenytoin and valproate in Indian patients p. 73
Neena Katoch, Ankit Bhardwaj, Kapil Suchal, Sangeeta Sharma
DOI:10.4103/jpp.jpp_3_21  
Objectives: To determine the optimum range of phenytoin (PHT) and valproate (VAP) levels and find out the critical drug levels below which chances of breakthrough seizures increase in North Indian population. Methodology: A cross-sectional, case-controlled, record-based study was conducted in a quaternary care hospital from September 2018–2019. The case group comprised epilepsy patients on monotherapy with PHT/VAP presenting with breakthrough seizures after at least 6 months of seizure control. Noncompliant, overdose, toxicity, no or partial response, any other psychiatric or neurological disorder, adverse effects, and patients taking two or more antiepileptic drugs were excluded. Results: Data of 100 patients in each group were analyzed. Significantly lower mean levels in cases were observed in PHT (5.74 ± 3.68 mg/L vs. 13.75 ± 4.27 mg/L control) and VAP (24.13 ± 27.39 mg/L vs. 76.37 ± 17.71 mg/L control). A negative correlation of drug levels was observed with age and weight in both the groups. The level/dose ratio in controls (0.05 ± 0.03; 0.09 ± 0.06) was significantly (P < 0.0001) higher than cases (0.02 ± 0.01; 0.02 ± 0.03) in PHT and VAP, respectively. Conclusions: This study identifies the critical levels and level/dose ratio at which the risk of breakthrough seizures increases. A wide level/dose ratio was found in controls, more so in the VAP group. A prospective study with larger group size along with genetic studies should be done to evaluate further.
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Assessment of potential drug - Drug interaction among the patients receiving cancer chemotherapy: A cross-sectional study p. 79
KM Venkatesh, Swathi Acharya, Rajendra Holla
DOI:10.4103/jpp.jpp_16_21  
Objectives: To identify and assess the various potential drug-drug interactions (pDDIs) among the patients receiving cancer chemotherapy, using the database from Lexicomp® Solutions with the ultimate goal of raising awareness among clinicians for safe medication usage. Materials and Methods: It is a prospective, cross-sectional study engaged at a tertiary care hospital in South India. Data regarding clinically prescribed drugs were obtained from the patients admitted to the oncology unit of a tertiary care hospital within the time frame of 6 months (June 2018 to December 2018). Frequency and clinical relevance, the onset, and Severity of pDDIs were assessed using the database from Lexicomp® Solutions version 4.1.2. Data were analyzed using the descriptive statistics. Statistical significance was analyzed using the Mann–Whitney and Chi-square tests. Pearson's correlation coefficient was used to identify the correlation between the incidence of drug-drug interactions with age, the number of drugs prescribed, and the type of cancer. Results: A total of 895 pDDIs were seen, including 261 with chemotherapeutic drugs and 634 with supportive medication. It was observed that around 14.18% of cyclophosphamide showing interaction with Ondansetron among chemotherapeutic drugs, whereas 9.14% of lithium presenting interaction with Ondansetron among supportive therapy. A statistically significant higher interaction was noted among supportive medications provided when compared to anticancer drugs (P = 0.001). Conclusions: The majority of pDDIs observed among the patients receiving chemotherapy with supportive medications as compared to anticancer chemotherapy. There is an urgent need for special safety measures to monitor and prevent drug interactions in the oncology unit.
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Prevalence, risk factors, and prescribing trends in chronic renal failure in the Indian population p. 86
Jalpa Suthar, Rutvi D Patel, Shubha Desai
DOI:10.4103/jpp.JPP_149_20  
Objective: To estimate the prevalence of Chronic renal failure (CRF) in the Indian subcontinent and to identify risk factors and treatment regimens for CRF. Methods: A prospective observational study was carried out for 7 months. A total of 200 patients with a level of creatinine >1.5 mg/dl were enrolled. CRF prevalence was measured using the hospital's inpatient department registry and medical records. The risk factors and prescribing were evaluated from the patient file report. Results: The prevalence rate of CRF was 13.7%. Male patients (59%) dominate the entire group of patients. Most patients (n = 52) were found between the age group of 71–80 years with a mean age of 62.67 ± 16.33 years. Drugs such as diuretics, and hypoglycemics were indicated to treat comorbidities. The average number of drugs per prescription were 7.43 ± 2.75 with high use of antimicrobial agents (88%). Out of 156 drugs prescribed, 76 were from essential as per essential Drug List 2017. Hypertension (P = 0.0072) and diabetes (P = 0.0084) were major concerns as risk factors followed by the drugs used for dyslipidemia, and recurrent infections. Conclusion: The prevalence rate was found to be 13.7% with significant association with risk factors such as hypertension, diabetes, and nonsteroidal anti-inflammatory drugs, dyslipidemia, chronic infections, smoking, and renal calculus for CRF. The pattern of prescribing was suitable and with few irrationalities.
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RESEARCH LETTERS Top

Impact of oral cannabis consumption on health: A cross-sectional study p. 91
Sneha R Ambwani, Rimplejeet Kaur
DOI:10.4103/jpp.JPP_143_20  
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Risk factors and prescription pattern among patients with congestive heart failure p. 94
Jison Jose, Betty Baby, Shabeer Ahammed, Sharad Chand, UP Nandakumar, BC Vinay, K Subramanyam, Juno J Joel
DOI:10.4103/jpp.jpp_25_21  
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Evaluation of recent prescription pattern in cornea clinic of a tertiary care hospital: A developing country's perspective p. 97
Niraj Niraj, Nusrat Shafiq, Chakrant Mothsara, Gaurav Garg, Amit Gupta, Samir Malhotra
DOI:10.4103/jpp.JPP_34_21  
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CASE REPORTS Top

Monday blues – Rare cause of hypoglycemia in a child with leukemia p. 100
Gowshika Krishnakumar, Dhaarani Jayaraman, Dhivyalakshmi Jeevarathnam, Peter Prasanth Kumar Kommu, Julius Xavier Scott
DOI:10.4103/jpp.jpp_57_21  
Hypoglycemia in a child with acute lymphoblastic leukemia (ALL) often makes the clinician think of sepsis or metabolic disturbances due to relative adrenal insufficiency with steroid withdrawal. We report a rare scenario of drug-induced hypoglycemia in a child on treatment for ALL. Recurrent symptomatic episodes of hypoglycemia in a 4-year-girl on treatment for high-risk ALL were analyzed and it was surprising to note that the episodes were noted on early hours on Monday and Sunday nights. Detailed evaluation for the etiology and the workup was not contributory. With the background of drug history for ALL maintenance and occurrence of episodes on Mondays, possibility of drug-induced hypoglycemia secondary to cotrimoxazole was considered. Dose alteration for trimethoprim-sulfamethoxazole was considered stopping the drug is not feasible. Malnutrition was attributed as the coexisting risk factor in our child.
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A survival case of premature infant with hepatoblastoma (fetal pattern) along with other serious comorbidities and surgical interventions p. 102
Mohammed Fardan, A Priya Shiva, Aswathy M Shaji, K Arun Chander Yadav
DOI:10.4103/jpp.JPP_146_20  
An estimated ratio (i.e., 1 in 10) babies are born too early every year. Roughly 1 million children die each year due to impediments raised pertaining to preterm birth. One such extreme preterm male baby was presented in the neonatal care unit with respiratory distress and grunting. Baby was confirmed to have ventricular septal defect along with patent ductus arteriosus and craniosynostosis which was treated with medications and surgical managements. He was also engaged with various prophylactic and empirical antibiotic therapies to cover the microbial growth. The most disturbing stage here was the appearance of liver mass sizing 5.8 cm × 1.3 cm accompanied with area of necrosis, diagnosed with hepatoblastoma which was evident with the aid of ultrasound. Hence, chemotherapy was commenced which was in accordance with Societe Internationale d Oncologie Pediatrique Epithelial Liver Tumor Study Group-3. Although the existing comorbidities haunted the baby for a long time, he finally made it successfully to get into track by fighting all the hurdles bravely, which was a sheer miracle. Along with the clinicians/surgeons, we Clinical Pharmacists worked hand in hand to ensure the baby to be receiving optimized drug regimen keeping in mind the risk-benefit ratio.
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