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Active Components of Commonly Prescribed Medicines Affect Influenza A Virus-Host Cell Interaction: A Pilot Study.

ABSTRACT: Background: Every year, millions of people are hospitalized and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among the elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection and thus contribute to the morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds from a list of commonly prescribed medicines. Then, we constructed a drug-target interaction network and identified the potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on the viability, transcription, and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that drugs such as atorvastatin, candesartan, and hydroxocobalamin could target and modulate FLUAV-host cell interaction. In vitro experiments showed that at non-cytotoxic concentrations, these compounds affected the transcription and metabolism of FLUAV- and mock-infected cells. Conclusion: Many commonly prescribed drugs were found to modulate FLUAV-host cell interactions in silico and in vitro and could therefore affect their interplay in vivo, thus contributing to the morbidity and mortality of patients with influenza virus infections.

SUBMITTER: Ianevski A

PROVIDER: S-EPMC8402715 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIdentification of internationally comparable indicators of medicines use are important for a country to implement strategies and regulations to improve usage of medicines. Sri Lanka established a new National Medicines Regulatory Authority in 2015 and this survey evaluated the medication use indicators in Sri Lanka, according to the International Network on Rational Use of Drugs (INRUD), prior to its implementation.MethodsThis descriptive-cross-sectional study was conducted in 80 pharmacies, representing all 25 districts of the country. Three pharmacy categories were included; privately owned pharmacies, 'Rajya Osusala' pharmacies operated by the State Pharmaceuticals Corporation (SPC) of Sri Lanka and SPC Franchisee pharmacy outlets. Selection of pharmacies from respective districts were done proportionate to estimated population. Data were collected to identify WHO/INRUD core drug use indicators and the commonly prescribed medicines.ResultsTotal of 2328 prescriptions were included ('Rajya Osusala 559; SPC Franchise 711; private pharmacies 1058). Altogether 7,255 medicines were prescribed, and the 3 most commonly prescribed medicines were atorvastatin, losartan and metformin. Average number of medicines per encounter was 3.1±1.9 (Median: 3; range 1-12) Highest average number of medicines per encounter was reported in prescriptions received at 'Rajya Osusala' pharmacies (3.6±2.2), significantly higher than in other categories of pharmacies (p<0.001). Percentage of medicines prescribed by generic name was only 35.5%, highest at the 'Rajya Osusala' pharmacies (40.6%), significantly higher than other categories of pharmacies. The overall percentage of medicines prescribed from essential medicine list (EML) was 68.8%, without any significant variation between different categories of pharmacies. The percentage of medicines actually dispensed and accurately labelled were 92.4 and 98.5% respectively.ConclusionsThe average number of medicines per encounter was higher than the WHO recommended value but the usage of antibiotic and injectable drugs were within recommended standards. Generic prescribing, was very much lower. The EML prescribing, labelling and percentage dispensed medicines fared much better although lower than the WHO recommended 100% compliance. This island wide study has provided national wide data before the implementation of key changes in regulation of medicines in Sri Lanka and a repeat survey will be useful to identify impact of the new legislations.

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Project description:BACKGROUND:Achieving good medication adherence is a major challenge for patients with chronic conditions. Our study aimed to assess the Threshold for Unacceptable Risk of Non-adherence (TURN), defined as the threshold at which physicians consider the health risks incurred by patients due to medication non-adherence unacceptable, for the most commonly prescribed drugs in France. METHODS:We conducted an online study using a crowdsourcing approach among French general practitioners and specialists from September 2016 to August 2017. Physicians assessed the TURN for various levels of missed doses by evaluating a series of randomly presented clinical vignettes, each presenting a given medication with a given therapeutic indication. For each "drug-indication group" (i.e., all drugs from the same pharmacological class with a similar therapeutic indication): 1) we described the distribution of physicians' assessments, 2) we provided a summary estimate of the TURN, defined as the frequency of missed doses above which 75% of the physicians' assessments were located; 3) we computed the number of pill boxes reimbursed in France in 2016 to put our results into context. RESULTS:We collected a total of 5365 assessments from 544 physicians, each of whom evaluated a random sample among 528 distinct clinical vignettes. Estimates of the TURN varied widely across drug-indication groups, ranging from risk considered unacceptable with 1 daily dose missed per month (e.g., insulin for diabetes) to risk always considered acceptable (e.g., anti-dementia drugs). Drugs with an estimated TURN of over one missing daily dose per week represented 44.9% of the prescription volume of the medications assessed in our study. CONCLUSIONS:According to physicians, the impact of non-adherence may vary greatly. Patient-physician discussions on the variable consequences of non-adherence could lead to a paradigm shift by seeking to reach "optimal adherence" depending on drugs rather than unrealistic "perfect adherence" to all drugs.

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Active Components of Commonly Prescribed Medicines Affect Influenza A Virus-Host Cell Interaction: A Pilot Study.

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