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Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized
Ghazwan A Raouf1, Fouad K Mohammad2,3, Muayad A Merza4
1Department of Pharmacology, College of Pharmacy, University of Duhok, Duhok, IRQ.
Abstract:
Background and objective Polypharmacy is prevalent in coronavirus disease 2019 (COVID-19) patients with severe disease. However, information on polypharmacy among COVID-19 patients who also suffer from cytokine storm is scarce. In light of this, the purpose of the present study was to assess the incidence of polypharmacy and in silico prediction of potential body proteins targeted by these drugs among hospitalized COVID-19 patients who were identified to have the additional burden of cytokine storm in the city of Duhok, Kurdistan Region, Iraq. Methods This was a cross-sectional observational study conducted from June 2021 to April 2022; the phenomena of major polypharmacy (six to nine medications) and excessive polypharmacy (≥10 medications) were documented among 33 (15 males and 18 females) COVID-19 patients with cytokine storm during their hospital stay (8-45 days) in Duhok, Kurdistan Region, Iraq. The SwissTargetPrediction program was utilized in silico to predict and identify human body proteins that could be potentially targeted by selected medications involved in polypharmacy. Results All patients had tested positive for COVID-19 via PCR testing, and they showed different signs and symptoms of the disease. None of the patients recovered and all of them deceased. All 33 patients received many therapeutic agents that ranged in number from eight to 20/patient during their hospital stay. The mean number of medications was 15 ± 3. We identified 2/33 (6%) patients with major polypharmacy (eight and nine) and 31/33 (94%) with excessive polypharmacy (15.5 ± 2.7). The total number of medications identified in polypharmacy was 37, excluding vitamins, minerals, and intravenous solutions. The frequency of medications administered was as follows: antibiotics (67, 13.7%), mucolytic agents (56, 11.5%), corticosteroids (54, 11%), anticoagulants (48, 9.8%), antiviral agents (41, 8.4%), antihypertensive agents (32, 6.5%), analgesics (28, 5.7%), antifungal drugs (27, 5.5%), antidiabetics (26, 5.3%), and other medications (2-19, 0.41-3.9%). Using the SwissTargetPrediction program, various drugs including antiviral agents involved in polypharmacy were found to target, in silico, body proteins at a prediction percentage that ranged from 6.7% to 40%. Conclusions Major and extensive polypharmacy conditions were identified in hospitalized COVID-19 patients suffering from cytokine storm. The severity of COVID-19 with cytokine storm, comorbidities, and hospitalization were key factors associated with polypharmacy in the patients. The SwissTargetPrediction web server is useful for predicting in silico potential human body protein targets that could possibly be sources of additional information on the adverse/toxic effects of polypharmacy medications administered concurrently. Further research in current medication protocols prescribed for advanced COVID-19 illness with cytokine storm is warranted to gain deeper insights into the topic.
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