A review of potential pharmacological treatments of COVID-19: an evidence-based perspective

Coronaviruses (CoVs) typically manifest as mild to severe respiratory tract infections. No drug is approved by US food and drug administration (FDA) for the treatment of patients with coronaviruses infection. With growing COVID-19 pandemic globally, need of hour is to work on potential prophylactic and therapeutic drugs to prevent local and community transmission. A literature search for eligible studies published till March 2020 was conducted in the PubMed, Medline, EMBASE, OVID, and Google Scholar databases by two reviewers. Therapeutic efficacy and safety of different drug regimens targeting treatment pathway acting against corona virus-2019 (COVID-19) were reviewed. Possible mechanism of actions of these potential repurposed drugs against COVID-19 were reviewed to develop effective prevention and treatment strategies. Many potential pharmacological therapies are being studied in various clinical trials. No FDA-approved repurposed drugs have shown safety and efficacy in randomized controlled trials for patients with COVID-19. Vaccines are under development and only few vaccines are under clinical evaluation. This review highlights potential drug actions against COVID-19 and their safety issues. It could help researchers and physicians to use these potential agents judiciously in clinical trials as well as in treatment protocols

Painful neuropathy: comparative observational analysis of safety profile of pregabalin and amitriptyline

Background: Chronic neuropathic pain, caused by a lesion or disease of the somatosensory nervous system is a common debilitating condition in clinical practice. Pregabalin and Amitriptyline are most commonly used drugs for its management. The aim of the study was to study the safety of Pregabalin and Amitriptyline in chronic neuropathic pain.Methods: Prospective observational study at Department of Medicine and Orthopaedics at All India Institute of Medical Sciences, Rishikesh. Newly diagnosed patients of neuropathic pain who were prescribed either Pregabalin or Amitriptyline were included in the study. Patients were followed up telephonically or during routine visits for a period of 3 months after initiation of any of these drugs. Appropriate measures of central tendency were used to describe demographic and clinical parameters and Correlation test was used between different variables and occurrence of adverse drug reactions.Results: 317 patients were prescribed these drugs. A total of 276 ADRs were observed (128 with Pregabalin and 148 with Amitriptyline). Central nervous system symptoms like sedation and dizziness were most commonly present in both the groups. Diabetes mellitus (47.1%) was most common etiology for neuropathic pain. Causality assessment showed probable association with Amitriptyline (n=140) and Pregabalin (n=118). Majority of ADRs with Amitriptyline group (49.32%) were moderate in severity whereas it was mild with Pregabalin (59.7%). A weak positive correlation (R=0.273) was seen with number of ADRs occurrence and total drug exposure in patients taking Pregabalin whereas a weak negative correlation (R=-0.623) was seen in Amitriptyline treated group.Conclusions: Safety profile of Pregabalin was better than Amitriptyline in the present study. The study findings must be replicated in larger patient population and for a prolonged duration for better understanding of the pattern of adverse drug reactions.

Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study

Background: Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. Methods: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8;P= 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3;P< 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5;P= 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, r2 = 0.23). Conclusion: Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population