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

Pharmacotherapeutic audit meetings as a tool of improving prescribing practices

Background: Pharmacotherapeutic audit meeting (PTAM) is a good tool to review prescriptions for rationality and suggest measures for improving quality of prescriptions. To promote this, World Health Organization (WHO) and International Network for Rational Use of Drugs (INRUD) provided drug prescribing and drug use indicators. To assess the impact of PTAMs as an intervention for improving quality and rationality of prescriptions.Methods: This was a single centre, prospective study conducted from December 2018-February 2020. Prescriptions from outpatient surgical departments were collected, screened using WHO/INRUD core indicators and discussed in PTAMs. The same process was repeated over next 2 months to assess change in prescribing patterns after PTAM. Chi-square and Student’s t-test was used for statistical analysis.Results: The difference in proportions for antibiotic prescribing was 8.7% [95% CI (1.0%-16.7%), p=0.02]; injectable preparation use was 0.7% [95% CI (-0.4%-2.3%) p=0.23]; prescriptions with generic name drugs was 10.9% [95% CI (5.6-16.2%) p<0.0001] and prescriptions from Essential drug list (EDL) was 8.1% [95% CI (2.5%-13.5%) p=0.0046].Conclusions: Our research showed PTAM could be an effective tool to implement WHO/INRUD drug prescribing indicators robustly. Hence, it could be included in WHO/INRUD policies as an intricate part of institutional healthcare delivery system

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.

Awareness among tertiary care doctors about Pharmacovigilance Programme of India: Do endocrinologists differ from others?

Background and Objectives: Reporting adverse drug reactions (ADRs) associated with drug use is an important factor in patient safety. Majority of ADRs are preventable through improved prescribing and monitoring. Endocrinologists prescribe drugs with actions on almost all organs and for relatively longer durations. ADR are expected following the use of these drugs. Pharmacovigilance is the study of drug-related adverse effects aimed at protecting patients and public from drug-related harms. The concept of pharmacovigilance is relatively new in India, and this survey is an attempt to explore awareness among doctors of an establishing institution of national importance. Materials and Methods: The survey was conducted on faculty and resident doctors by administering a written structured questionnaire in a voluntary manner. The questionnaire contained questions meant to evaluate their awareness, understanding, and misconception about ADR reporting. Identity of the responder was kept confidential. Results: A total of 106 (faculty = 56; residents = 50) participated in survey. The most common cause cited for not reporting an ADR was “do not know how to report” by 64.15%. Majority of them (64%) had no information about the Pharmacovigilance Programme of India (PvPI), and only few (8.5%) had actually reported or published an ADR. Interpretation and Conclusions: ADRs are major public health problem that needs to be addressed at all levels of health care. High index of clinical suspicion are crucial for their timely detection and management. Various educational interventions have shown to improve medical professionals' awareness, understanding about ADRs and in their reporting behavior. PvPI is an important initiative toward ensuring patient safety

A rare adverse drug reaction to escitalopram

Selective serotonin reuptake inhibitors are considered to be low side effect profile drugs as compared to conventional antidepressants. The primary care physicians should be aware of the rare and depressing side effect of these drugs when they are prescribed in young, nonpregnant females. Mastalgia has been reported in <1% of the cases. Galactorrhea as an adverse drug reaction has been reported in very few case reports, and the frequency of this side effect is unknown

Identification and in-vitro analysis of potential proteasome inhibitors targeting PSMβ5 for multiple myeloma

The proteasome subunit β5 (PSMβ5) is a chief target of proteasome inhibitors (PIs) for treatment of multiple myeloma (MM). The relevance of PSMβ5 mutations and their functional impact on the development of resistance to PIs have been demonstrated recently. Therefore, this present study deals with an in-depth E-pharmacophore based screening and repurposing of FDA-approved drugs that could target PSMβ5 for MM. Our molecular docking-based investigation revealed risedronate and zoledronate as potential alternative therapeutic molecules for targeting the PSMβ5 gene. Risedronate and zoledronate displayed high binding affinity (−9.51 and −8.56&nbsp;kcal/mol respectively) to PSMβ5. Moreover, 100&nbsp;ns molecular dynamics simulation analysis of docking complexes revealed risedronate and zoledronate with a superior binding free energies and stable interactions with PSMβ5. The RMSD plot shows that the risedronate-PSMβ5 (mean: 0.24&nbsp;nm) and zoledronate-PSMβ5 (mean: 0.25&nbsp;nm) complexes are identical and stays stable until 100&nbsp;ns. We further validated the activity of zoledronate in MM cell lines RPMI8226 and U266 where zoledronate showed significant anti-proliferative and apoptotic activity. Importantly, zoledronate showed an enhanced anti-proliferative activity when combined with bortezomib in MM cell lines. Thus, this study demonstrates that combining bortezomib with zoledronate could have a significant impact on reducing MM cell growth and can be an alternative strategy for treating MM.</p

Effectiveness of Kabasura Kudineer tablets in the management of asymptomatic and mild cases of COVID-19: A pilot double-blinded, randomized controlled trial

Introduction: COVID-19 was declared a pandemic in 2020. It has had a devastating effect on human life and the global economy. To date, there is no proven therapy for COVID-19, even though rigorous research is ongoing to test multiple compounds across all systems of medicine. A need was felt to systematically explore the Indian system of medicine to assess its efficacy against COVID-19. The objective of the present study was to examine the effect of Kabasura Kudineer as a standalone therapy on the following: time required to achieve symptom relief &amp; resolution, virological clearance, and levels of IL6, CRP and IgG, and compare it to the standard therapy available for treatment of COVID-19. Methodology: A double-blinded randomized controlled trial was conducted in 110 participants. 55 participants were enrolled in the Kabasura Kudineer arm and 55 in the control (standard therapy + Kabasura Kudineer placebo) arm. Study participants were randomly allocated into the two study arms. They were assessed for symptoms at baseline, and on Day 5 and Day 10. RT PCR, CRP, IL6 and IgG levels were measured at baseline, Day 5 and Day 10. On day 28, participants were interviewed telephonically for symptom assessment alone. Statistical analysis: A per-protocol approach was used. Significant difference between two groups was assessed at baseline, day 5 and day 10 using the Chi-square and Mann Whitney test. Result: A total of 110 patients participated in study. Four patients in the Kabasura Kudineer arm and 9 in the Standard therapy arm were lost to follow-up. Baseline characteristics for both the groups were matched at baseline. 83.9% and 93.9% patients were relieved of all symptoms by the 10th day in Kabasura and standard therapy groups respectively. Decrease in CRP level was more pronounced in the Kabasura group compared to standard therapy viz. 3 mg/l and 1.26 mg/l. No significant difference was found in IgG level and IL6 levels in both the study groups. However, it was noticed that among the unvaccinated group, the surge in IgG levels was much higher in Kabasura Kudineer group than the standard therapy group. Conclusion: Kabasura Kudineer as a standalone therapy was as effective and safe as the standard therapy among patients with asymptomatic to mild COVID-19