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Gavazova E, Staynova R, Grekova-Kafalova D. Inappropriate polypharmacy during the COVID-19 pandemic: impact, challenges, and solutions - a narrative review. Folia Med (Plovdiv) 2025; 67. [PMID: 40270160 DOI: 10.3897/folmed.67.e144169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 01/13/2025] [Indexed: 04/25/2025] Open
Abstract
The COVID-19 pandemic has brought unprecedented challenges to healthcare systems worldwide, impacting various aspects of patient care. Polypharmacy, the concurrent use of multiple medications by a single patient, is a significant concern exacerbated by the pandemic. The dual threat of COVID-19 infection and polypharmacy for the same vulnerable group - the elderly and those with pre-existing multimorbidity - is particularly problematic, as polypharmacy has been shown to lead to suboptimal treatment outcomes in many chronic diseases. This comprehensive review explores the multifaceted issues surrounding polypharmacy during the COVID-19 pandemic, addressing its causes, consequences, and potential solutions.
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Nguyen TK, Vu GM, Duong VC, Pham TL, Nguyen NT, Tran TTH, Tran MH, Nguyen DT, Vo NS, Phung HT, Hoang TH. The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients. Heliyon 2024; 10:e27043. [PMID: 38509882 PMCID: PMC10950508 DOI: 10.1016/j.heliyon.2024.e27043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 12/13/2023] [Accepted: 02/22/2024] [Indexed: 03/22/2024] Open
Abstract
Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.
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Affiliation(s)
| | - Giang Minh Vu
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | - Vinh Chi Duong
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | | | | | - Trang Thi Ha Tran
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | - Mai Hoang Tran
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | - Duong Thuy Nguyen
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | - Nam S. Vo
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
| | - Huong Thanh Phung
- Faculty of Biotechnology, Hanoi University of Pharmacy, Hanoi, Viet Nam
| | - Tham Hong Hoang
- Center for Biomedical Informatics, Vingroup Big Data Institute, Hanoi, Viet Nam
- GeneStory JSC, Hanoi, Viet Nam
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Ortiz GX, Ulbrich AHDPDS, Lenhart G, dos Santos HDP, Schwambach KH, Becker MW, Blatt CR. Drug-induced liver injury and COVID-19: Use of artificial intelligence and the updated Roussel Uclaf Causality Assessment Method in clinical practice. Artif Intell Gastroenterol 2023; 4:36-47. [DOI: 10.35712/aig.v4.i2.36] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 08/18/2023] [Accepted: 09/05/2023] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Liver injury is a relevant condition in coronavirus disease 2019 (COVID-19) inpatients. Pathophysiology varies from direct infection by virus, systemic inflammation or drug-induced adverse reaction (DILI). DILI detection and monitoring is clinically relevant, as it may contribute to poor prognosis, prolonged hospitalization and increase indirect healthcare costs. Artificial Intelligence (AI) applied in data mining of electronic medical records combining abnormal liver tests, keyword searching tools, and risk factors analysis is a relevant opportunity for early DILI detection by automated algorithms.
AIM To describe DILI cases in COVID-19 inpatients detected from data mining in electronic medical records (EMR) using AI and the updated Roussel Uclaf Causality Assessment Method (RUCAM).
METHODS The study was conducted in March 2021 in a hospital in southern Brazil. The NoHarm© system uses AI to support decision making in clinical pharmacy. Hospital admissions were 100523 during this period, of which 478 met the inclusion criteria. From these, 290 inpatients were excluded due to alternative causes of liver injury and/or due to not having COVID-19. We manually reviewed the EMR of 188 patients for DILI investigation. Absence of clinical information excluded most eligible patients. The DILI assessment causality was possible via the updated RUCAM in 17 patients.
RESULTS Mean patient age was 53 years (SD ± 18.37; range 22-83), most were male (70%), and admitted to the non-intensive care unit sector (65%). Liver injury pattern was mainly mixed, mean time to normalization of liver markers was 10 d, and mean length of hospitalization was 20.5 d (SD ± 16; range 7-70). Almost all patients recovered from DILI and one patient died of multiple organ failure. There were 31 suspected drugs with the following RUCAM score: Possible (n = 24), probable (n = 5), and unlikely (n = 2). DILI agents in our study were ivermectin, bicalutamide, linezolid, azithromycin, ceftriaxone, amoxicillin-clavulanate, tocilizumab, piperacillin-tazobactam, and albendazole. Lack of essential clinical information excluded most patients. Although rare, DILI is a relevant clinical condition in COVID-19 patients and may contribute to poor prognostics.
CONCLUSION The incidence of DILI in COVID-19 inpatients is rare and the absence of relevant clinical information on EMR may underestimate DILI rates. Prospects involve creation and validation of alerts for risk factors in all DILI patients based on RUCAM assessment causality, alterations of liver biomarkers and AI and machine learning.
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Affiliation(s)
- Gabriela Xavier Ortiz
- Graduate Program in Medicine – Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | | | - Gabriele Lenhart
- Multiprofessional Residency Integrated in Health, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | | | - Karin Hepp Schwambach
- Graduate Program in Medicine – Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Matheus William Becker
- Graduate Program in Medicine – Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Carine Raquel Blatt
- Department of Pharmacoscience, Graduate Program in Medicine – Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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COVID-19-Associated Acute Psychotic Disorder-Longitudinal Case Report and Brief Review of Literature. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020408. [PMID: 36837609 PMCID: PMC9963865 DOI: 10.3390/medicina59020408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/15/2023] [Accepted: 02/18/2023] [Indexed: 02/22/2023]
Abstract
Even though since the beginning of the COVID-19 pandemic, the literature became more and more abundant on data and hypotheses about the various consequences on people's lives, more clarity needs to be added to the existing information. Besides the stressful experiences related to the COVID-19 pandemic, SARS-CoV-2 infection has been proven to impact brain functioning through direct and indirect pathogenic mechanisms. In this context, we report a case of a patient presenting with a first episode of psychosis following COVID-19. In our case, a 28-year-old male patient with no personal or family psychiatric history developed psychotic symptoms (delusions, hallucinations, and disorganized behaviour) that required antipsychotic treatment and inpatient hospitalization one week after he was discharged from the hospital after COVID-19. At the six-month and one-year follow-up, the patient was in remission without any psychotic signs or symptoms. A brief review of the literature is also provided. The case presented in this article outlines the possibility that the post-COVD-19 recovery period might be a crucial time for the onset of acute psychotic disorder, and therefore, routine psychiatric assessments should be carried out during all phases of the disease. A clearer picture of the impact of the COVID-19 pandemic on mental health will most likely be revealed in the future as many consequences need long-term evaluation.
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Khani S, Tafaroji J, Yaghoubi M, Emami Kazemabad MJ, Hejazi SA. Prevalence of COVID-19 outcomes in patients referred to opioid agonist treatment centers. Front Pharmacol 2023; 14:1105176. [PMID: 37033605 PMCID: PMC10076798 DOI: 10.3389/fphar.2023.1105176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/15/2023] [Indexed: 04/11/2023] Open
Abstract
Background: Coronavirus disease (COVID-19) is a mild to severe infectious respiratory illness caused by the SARS-CoV-2 virus. Based on the numerous pieces of evidence regarding the role of opioids in immune function, viral replication, and virus-mediated pathology, we decided to assess the incidence and severity of COVID-19 outcomes in people undergoing opioid maintenance treatment. Methods: This is a prospective, descriptive, multi-center study that included 452 patients undergoing maintenance treatment in opioid agonist treatment (OAT) clinics in different cities of Iran. Demographic information, underlying disease, history of maintenance treatment, type of drug used, history of addiction, smoking, and the kind of substance abused, were recorded. A physician evaluated the COVID-19 symptoms, and the severity of the disease was defined based on the number of observed symptoms. Results: The results have not shown any significant difference in the severity of COVID-19 symptoms in different nationalities, gender, and treatment groups. Furthermore, the history of drug abuse, including time and type of abuse and smoking, has not indicated any significant association with the occurrence of symptoms. Only the severity of COVID-19 in the mentioned cities (first and second follow-up: p < 0.001) and individuals with a history of underlying disease (first follow-up: p = 0.020; second follow-up: p = 0.043) were significantly different. Conclusion: Our results have demonstrated that the severity of symptoms in people with the underlying disease was significantly higher than in others. But there is no association between sex, race, treatment groups, and abuse history with the severity of COVID-19 symptoms in methadone maintenance treatment (MMT) patients.
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Affiliation(s)
- Samira Khani
- Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Javad Tafaroji
- Pediatric Medicine Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Mehdi Yaghoubi
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | | | - Seyed Amir Hejazi
- Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
- *Correspondence: Seyed Amir Hejazi,
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Spanakis M, Ioannou P, Tzalis S, Papakosta V, Patelarou E, Tzanakis N, Patelarou A, Kofteridis DP. Drug-Drug Interactions among Patients Hospitalized with COVID-19 in Greece. J Clin Med 2022; 11:7172. [PMID: 36498745 PMCID: PMC9740400 DOI: 10.3390/jcm11237172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/15/2022] [Accepted: 11/29/2022] [Indexed: 12/05/2022] Open
Abstract
The modulation of the pharmacological action of drugs due to drug-drug interactions (DDIs) is a critical issue in healthcare. The aim of this study was to evaluate the prevalence and the clinical significance of potential DDIs in patients admitted to the University Hospital of Heraklion in Greece with coronavirus disease 2019 (COVID-19). Cardiovascular disorders (58.4%) and diabetes (types I and II) (29.6%) were the most common comorbidities. A high occurrence of DDIs was observed, and clinically significant DDIs that may hamper response to treatment represented 40.3% of cases on admission, 21% during hospitalization, and 40.7% upon discharge. Polypharmacy and comorbidities were associated with a higher prevalence of DDIs in a statistically significant way (p < 0.05, 95% CI). Clinically significant DDIs and increased C-reactive protein values upon admission were associated with prolonged hospitalization. The results reveal that patients admitted due to COVID-19 in Greece often have an additional burden of DDIs that healthcare teams should approach and resolve.
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Affiliation(s)
- Marios Spanakis
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, 71004 Heraklion, Greece
- Computational Biomedicine Laboratory, Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), 70013 Heraklion, Greece
| | - Petros Ioannou
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Sotiris Tzalis
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Vasiliki Papakosta
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Evridiki Patelarou
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, 71004 Heraklion, Greece
| | - Nikos Tzanakis
- Department of Respiratory Medicine, University Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Athina Patelarou
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, 71004 Heraklion, Greece
| | - Diamantis P. Kofteridis
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
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Attia KAM, Serag A, Eid SM, Abbas AEF. A New Chemometrically Assisted UV Spectrophotometric Method for Simultaneous Determination of Tamsulosin and Dutasteride in Their Pharmaceutical Mixture. J AOAC Int 2022; 105:1755-1761. [PMID: 35758559 PMCID: PMC9384409 DOI: 10.1093/jaoacint/qsac080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 06/03/2022] [Accepted: 06/19/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT in terms of their ability to protect against recent COVID-19. However, very few studies were reported for their simultaneous quantification in their combined dosage form and were mainly based on chromatographic analysis. Subsequently, it is very important to offer a simple, selective, sensitive, and rapid method for the quantification of TAM and DUT in their challenging dosage form. OBJECTIVE In this study, a new chemometrically assisted ultraviolet (UV) spectrophotometric method has been presented for the quantification of TAM and DUT without any prior separation. METHOD For the calibration set, a partial factorial experimental design was used, resulting in 25 mixtures with central levels of 20 and 25 μg/mL for TAM and DUT, respectively. In addition, to assess the predictive ability of the developed approaches, another central composite design of 13 samples was used as a validation set. Post-processing by chemometric analysis of the recorded zero-order UV spectra of these sets has been applied. These chemometric approaches include partial least-squares (PLS) and genetic algorithm (GA), as an effective variable selection technique, coupled with PLS. RESULTS The models' validation criteria displayed excellent recoveries and lower errors of prediction. CONCLUSIONS The proposed models were effectively used to determine TAM/DUT in their combined dosage form, and statistical comparison with the reported method revealed satisfactory results. HIGHLIGHTS Overall, this work presents powerful simple, selective, sensitive, and precise methods for simultaneous quantification of TAM/DUT in their dosage form with satisfactory results. The predictive ability and accuracy of the developed methods offer the opportunity to be employed as a quality control technique for the routine analysis of TAM/DUT when chromatographic instruments are not available.
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Affiliation(s)
- Khalid A M Attia
- Al-Azhar University, Faculty of Pharmacy, Pharmaceutical Analytical Chemistry Department, 11751 Nasr City, Cairo, Egypt
| | - Ahmed Serag
- Al-Azhar University, Faculty of Pharmacy, Pharmaceutical Analytical Chemistry Department, 11751 Nasr City, Cairo, Egypt
| | - Sherif M Eid
- October 6 University, Faculty of Pharmacy, Analytical Chemistry Department, 6 October City, Giza 12585, Egypt
| | - Ahmed Emad F Abbas
- October 6 University, Faculty of Pharmacy, Analytical Chemistry Department, 6 October City, Giza 12585, Egypt
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A Review of Potential Therapeutic Strategies for COVID-19. Viruses 2022; 14:v14112346. [PMID: 36366444 PMCID: PMC9696587 DOI: 10.3390/v14112346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/21/2022] [Accepted: 10/23/2022] [Indexed: 02/01/2023] Open
Abstract
Coronavirus disease 2019 is a rather heterogeneous disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing pandemic is a global threat with increasing death tolls worldwide. SARS-CoV-2 belongs to lineage B β-CoV, a subgroup of Sarbecovirus. These enveloped, large, positive-sense single-stranded RNA viruses are easily spread among individuals, mainly via the respiratory system and droplets. Although the disease has been gradually controlled in many countries, once social restrictions are relaxed the virus may rebound, leading to a more severe and uncontrollable situation again, as occurred in Shanghai, China, in 2022. The current global health threat calls for the urgent development of effective therapeutic options for the treatment and prevention of SARS-CoV-2 infection. This systematic overview of possible SARS-CoV-2 therapeutic strategies from 2019 to 2022 indicates three potential targets: virus entry, virus replication, and the immune system. The information provided in this review will aid the development of more potent and specific antiviral compounds.
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9
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Zhang Q, Melchert PW, Markowitz JS. In vitro evaluation of the impact of Covid-19 therapeutic agents on the hydrolysis of the antiviral prodrug remdesivir. Chem Biol Interact 2022; 365:110097. [PMID: 35964681 PMCID: PMC9367181 DOI: 10.1016/j.cbi.2022.110097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/01/2022] [Accepted: 08/06/2022] [Indexed: 11/27/2022]
Abstract
Remdesivir (RDV, Veklury®) is an FDA-approved prodrug for the treatment of hospitalized patients with COVID-19. Recent in vitro studies have indicated that human carboxylesterase 1 (CES1) is the major metabolic enzyme catalyzing RDV activation. COVID-19 treatment for hospitalized patients typically also involves a number of antibiotics and anti-inflammatory drugs. Further, individuals who are carriers of a CES1 variant (polymorphism in exon 4 codon 143 [G143E]) may experience impairment in their ability to metabolize therapeutic agents which are CES1 substrates. The present study assessed the potential influence of nine therapeutic agents (hydroxychloroquine, ivermectin, erythromycin, clarithromycin, roxithromycin, trimethoprim, ciprofloxacin, vancomycin, and dexamethasone) commonly used in treating COVID-19 and 5 known CES1 inhibitors on the metabolism of RDV. Additionally, we further analyzed the mechanism of inhibition of cannabidiol (CBD), as well as the impact of the G143E polymorphism on RDV metabolism. An in vitro S9 fraction incubation method and in vitro to in vivo pharmacokinetic scaling were utilized. None of the nine therapeutic agents evaluated produced significant inhibition of RDV hydrolysis; CBD was found to inhibit RDV hydrolysis by a mixed type of competitive and noncompetitive partial inhibition mechanism. In vitro to in vivo modeling suggested a possible reduction of RDV clearance and increase of AUC when coadministration with CBD. The same scaling method also suggested a potentially lower clearance and higher AUC in the presence of the G143E variant. In conclusion, a potential CES1-mediated DDI between RDV and the nine assessed medications appears unlikely. However, a potential CES1-mediated DDI between RDV and CBD may be possible with sufficient exposure to the cannabinoid. Patients carrying the CES1 G143E variant may exhibit a slower biotransformation and clearance of RDV. Further clinical studies would be required to evaluate and characterize the clinical significance of a CBD-RDV interaction.
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Affiliation(s)
- Qingchen Zhang
- Department of Pharmacotherapy and Translational Research, Gainesville, FL, USA
| | - Philip W Melchert
- Department of Pharmacotherapy and Translational Research, Gainesville, FL, USA
| | - John S Markowitz
- Department of Pharmacotherapy and Translational Research, Gainesville, FL, USA; Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA.
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Panahi Y, Dadkhah M, Talei S, Gharari Z, Asghariazar V, Abdolmaleki A, Matin S, Molaei S. Can anti-parasitic drugs help control COVID-19? Future Virol 2022. [PMID: 35359702 PMCID: PMC8940209 DOI: 10.2217/fvl-2021-0160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 02/28/2022] [Indexed: 01/18/2023]
Abstract
Novel COVID-19 is a public health emergency that poses a serious threat to people worldwide. Given the virus spreading so quickly, novel antiviral medications are desperately needed. Repurposing existing drugs is the first strategy. Anti-parasitic drugs were among the first to be considered as a potential treatment option for this disease. Even though many papers have discussed the efficacy of various anti-parasitic drugs in treating COVID-19 separately, so far, no single study comprehensively discussed these drugs. This study reviews some anti-parasitic recommended drugs to treat COVID-19, in terms of function and in vitro as well as clinical results. Finally, we briefly review the advanced techniques, such as artificial intelligence, that have been used to find effective drugs for the treatment of COVID-19.
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Affiliation(s)
- Yasin Panahi
- Department of Pharmacology & Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Masoomeh Dadkhah
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sahand Talei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Gharari
- Department of Biotechnology, Faculty of Biological Sciences, Al-Zahra University, Tehran, Iran
| | - Vahid Asghariazar
- Deputy of Research & Technology, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Arash Abdolmaleki
- Department of Engineering Sciences, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran.,Bio Science & Biotechnology Research center (BBRC), Sabalan University of Advanced Technologies (SUAT), Namin, Iran
| | - Somayeh Matin
- Department of Internal Medicine, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Soheila Molaei
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.,Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
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11
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Biswas M, Sawajan N, Rungrotmongkol T, Sanachai K, Ershadian M, Sukasem C. Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies. Front Pharmacol 2022; 13:835136. [PMID: 35250581 PMCID: PMC8894812 DOI: 10.3389/fphar.2022.835136] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 01/24/2022] [Indexed: 01/18/2023] Open
Abstract
Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug-gene pairs (atazanavir-UGT1A1, ABCB1, SLCO1B1, APOA5; efavirenz-CYP2B6; nevirapine-HLA, CYP2B6, ABCB1; lopinavir-SLCO1B3, ABCC2; ribavirin-SLC28A2; tocilizumab-FCGR3A; ivermectin-ABCB1; oseltamivir-CES1, ABCB1; clopidogrel-CYP2C19, ABCB1, warfarin-CYP2C9, VKORC1; non-steroidal anti-inflammatory drugs (NSAIDs)-CYP2C9) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from in silico studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug-drug interactions (DDIs) and drug-herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and CYP2B6) and herbogenetic (e.g., andrographolide and CYP2C9) interventions, collectively called multifactorial drug-gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.
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Affiliation(s)
- Mohitosh Biswas
- Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand
- Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh
| | - Nares Sawajan
- Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand
- Department of Pathology, School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand
| | - Thanyada Rungrotmongkol
- Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
- Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Kamonpan Sanachai
- Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | - Maliheh Ershadian
- Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand
| | - Chonlaphat Sukasem
- Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand
- Pharmacogenomics and Precision Medicine, The Preventive Genomics and Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, Thailand
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
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Kably B, Launay M, Derobertmasure A, Lefeuvre S, Dannaoui E, Billaud EM. Antifungal Drugs TDM: Trends and Update. Ther Drug Monit 2022; 44:166-197. [PMID: 34923544 DOI: 10.1097/ftd.0000000000000952] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 12/09/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. METHODS We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-drug-interaction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure. RESULTS More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available. CONCLUSIONS TDM seems to be crucial for curative and/or long-term maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.
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Affiliation(s)
- Benjamin Kably
- Laboratoire de Pharmacologie-Toxicologie, Hôpital Européen Georges Pompidou, AP-HP Centre
- Faculté de Médecine, Université de Paris, Paris, France
| | - Manon Launay
- Laboratoire de Pharmacologie-Toxicologie-Gaz du sang, Hôpital Nord-CHU Saint Etienne, Saint-Etienne
| | - Audrey Derobertmasure
- Laboratoire de Pharmacologie-Toxicologie, Hôpital Européen Georges Pompidou, AP-HP Centre
| | - Sandrine Lefeuvre
- Laboratoire de Toxicologie et Pharmacocinétique, CHU de Poitiers, Poitiers; and
| | - Eric Dannaoui
- Faculté de Médecine, Université de Paris, Paris, France
- Unité de Parasitologie-Mycologie, Laboratoire de Microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Eliane M Billaud
- Laboratoire de Pharmacologie-Toxicologie, Hôpital Européen Georges Pompidou, AP-HP Centre
- Faculté de Médecine, Université de Paris, Paris, France
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13
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Pourkarim F, Pourtaghi‐Anvarian S, Rezaee H. Molnupiravir: A new candidate for COVID-19 treatment. Pharmacol Res Perspect 2022; 10:e00909. [PMID: 34968008 PMCID: PMC8929331 DOI: 10.1002/prp2.909] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 12/05/2021] [Accepted: 12/15/2021] [Indexed: 12/15/2022] Open
Abstract
The novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in china and has rapidly spread to many countries around the world. The effective pharmacotherapy can reduce the mortality of COVID-19. Antiviral medications are the candidate therapies for the management of COVID-19. Molnupiravir is an antiviral drug with anti-RNA polymerase activity and currently is under investigation for the treatment of patients with COVID-19. This review focuses on summarizing published literature for the mechanism of action, safety, efficacy, and clinical trials of molnupiravir in the treatment of COVID-19 patients.
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Affiliation(s)
- Fariba Pourkarim
- Student Research CommitteeFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | - Samira Pourtaghi‐Anvarian
- Student Research CommitteeFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | - Haleh Rezaee
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
- Infectious Diseases and Tropical Medicine Research CenterTabriz University of Medical SciencesTabrizIran
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Abstract
Background COVID-19 is an ongoing viral pandemic produced by SARS-CoV-2. In light of in vitro efficacy, several medications were repurposed for its management. During clinical use, many of these medications produced inconsistent results or had varying limitations. Objective The purpose of this literature review is to explain the variable efficacy or limitations of Lopinavir/Ritonavir, Remdesivir, Hydroxychloroquine, and Favipiravir in clinical settings. Method A study of the literature on the pharmacodynamics (PD), pharmacokinetics (PK), safety profile, and clinical trials through academic databases using relevant search terms. Results & discussion The efficacy of an antiviral drug against COVID-19 is associated with its ability to achieve therapeutic concentration in the lung and intestinal tissues. This efficacy depends on the PK properties, particularly protein binding, volume of distribution, and half-life. The PK and PD of the model drugs need to be integrated to predict their limitations. Conclusion Current antiviral drugs have varying pharmacological constraints that may associate with limited efficacy, especially in severe COVID-19 patients, or safety concerns.
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15
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Vitiello A, Ferrara F. Risk of drug-induced cardiac arrhythmia during COVID-19 therapeutic treatment. Egypt Heart J 2021; 73:103. [PMID: 34792677 PMCID: PMC8600338 DOI: 10.1186/s43044-021-00228-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 11/05/2021] [Indexed: 12/15/2022] Open
Abstract
Therapeutic treatment of severe COVID-19 infection involves the administration of multiple pharmacologic agents to reduce the risk of serious complications; this may result in drug interactions and possible adverse reactions and induced cardiotoxicity. The risk-benefit ratio associated with the use of medications to treat COVID-19 should be carefully monitored. In addition, the severe COVID-19 patient may experience cardiac damage, and alteration of normal cardiac electrophysiology function. Severe COVID-19 with cardiac involvement and the risk of drug-induced adverse reactions may cause cardiac arrhythmias, including long qt syndrome, which in some cases may lead to sudden death. In this short review we briefly review the pharmacological agents used to treat severe COVID-19 with increased risk of causing long qt forms.
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Affiliation(s)
- Antonio Vitiello
- Pharmaceutical Department, Usl Umbria 1, Via XIV Settembre 06132, Perugia, Italy
| | - Francesco Ferrara
- Pharmaceutical Department, Asl Napoli 3 Sud, Dell’amicizia street 22, 80035 Nola, Naples, Italy
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16
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Spanakis M, Patelarou A, Patelarou E, Tzanakis N. Drug Interactions for Patients with Respiratory Diseases Receiving COVID-19 Emerged Treatments. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:11711. [PMID: 34770225 PMCID: PMC8583457 DOI: 10.3390/ijerph182111711] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/31/2021] [Accepted: 11/04/2021] [Indexed: 12/28/2022]
Abstract
Pandemic of coronavirus disease (COVID-19) is still pressing the healthcare systems worldwide. Thus far, the lack of available COVID-19-targeted treatments has led scientists to look through drug repositioning practices and exploitation of available scientific evidence for potential efficient drugs that may block biological pathways of SARS-CoV-2. Till today, several molecules have emerged as promising pharmacological agents, and more than a few medication protocols are applied during hospitalization. On the other hand, given the criticality of the disease, it is important for healthcare providers, especially those in COVID-19 clinics (i.e., nursing personnel and treating physicians), to recognize potential drug interactions that may lead to adverse drug reactions that may negatively impact the therapeutic outcome. In this review, focusing on patients with respiratory diseases (i.e., asthma or chronic obstructive pulmonary disease) that are treated also for COVID-19, we discuss possible drug interactions, their underlying pharmacological mechanisms, and possible clinical signs that healthcare providers in COVID-19 clinics may need to acknowledge as adverse drug reactions due to drug-drug interactions.
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Affiliation(s)
- Marios Spanakis
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, GR-71004 Heraklion, Crete, Greece; (A.P.); (E.P.)
- Computational BioMedicine Laboratory, Institute of Computer Science, Foundation for Research & Technology-Hellas (FORTH), GR-70013 Heraklion, Crete, Greece
| | - Athina Patelarou
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, GR-71004 Heraklion, Crete, Greece; (A.P.); (E.P.)
| | - Evridiki Patelarou
- Department of Nursing, School of Health Sciences, Hellenic Mediterranean University, GR-71004 Heraklion, Crete, Greece; (A.P.); (E.P.)
| | - Nikolaos Tzanakis
- Department of Respiratory Medicine, University Hospital of Heraklion, Medical School, University of Crete, GR-71303 Heraklion, Crete, Greece;
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17
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Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M. Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects. World J Hepatol 2021; 13:1299-1315. [PMID: 34786167 PMCID: PMC8568575 DOI: 10.4254/wjh.v13.i10.1299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 06/17/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.
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Affiliation(s)
- Carmelo Loinaz-Segurola
- HBP and Transplant Surgery Unit. Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain.
| | - Alberto Marcacuzco-Quinto
- HBP and Transplant Surgery Unit. Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid 28041, Spain
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Trukhan DI, Davydov EL. Liver drug damage: possibilities of polyionic succinate-methioninic complex during the pandemic of new coronavirus infection (COVID-19). MEDITSINSKIY SOVET = MEDICAL COUNCIL 2021:110-121. [DOI: 10.21518/2079-701x-2021-15-110-121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Medicinal liver damage is an important problem not only in the framework of hepatology and gastroenterology, but also for internal medicine in general, which is due to the difficulties of correct and timely diagnosis of this pathology. In the first part of the review, the main mechanisms of liver tissue damage and clinical and formological manifestations of drug-induced liver damage are considered.The pandemic of the new coronavirus infection (COVID-19), spread by the SARS-CoV-2 virus, has become a challenge to health systems around the world. The global clinical experience gained over the past year in the management of patients with a new coronavirus infection makes it possible to highlight a number of relevant clinical aspects, one of which is drug-induced liver damage associated with the treatment of COVID-19. In the second part of the review, the possible mechanisms of influence of COVID-19 on the hepatobiliary system are considered, which include viral cytotoxicity, a secondary effect of immune dysregulation; hypoxia as a result of respiratory failure and subsequent ischemic liver damage; reactivation of already existing liver pathology and drug damage to the liver. It has been established that a large number of drugs used to treat COVID-19 - antiviral agents, antibacterials, non-steroidal anti-inflammatory drugs, steroids and others - have hepatoxic effects and can cause liver damage. In the context of the COVID-19 pandemic, for patients with a new coronavirus infection and drug-induced liver damage, a rational, pathogenetically justified choice of a hepatoprotective drug is of particular importance. In the final part of the review, the possibilities of the polyionic succinate-methionine complex in the treatment of drug-induced liver damage are considered and a clinical example of the drug application in a patient with drug-induced liver damage during treatment with COVID-19 is given.
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Affiliation(s)
| | - E. L. Davydov
- Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky
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19
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Rasouli M, Vakilian F, Ranjbari J. Therapeutic and protective potential of mesenchymal stem cells, pharmaceutical agents and current vaccines against covid-19. Curr Stem Cell Res Ther 2021; 17:166-185. [PMID: 33349221 DOI: 10.2174/1574888x16666201221151853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 07/07/2021] [Accepted: 07/19/2021] [Indexed: 11/22/2022]
Abstract
It has been almost 18 months since the first outbreak of COVID-19 disease was reported in Wuhan, China. This unexpected devastating phenomenon, raised a great deal of concerns and anxiety among people around the world and imposed a huge economic burden on the nations' health care systems. Accordingly, clinical scientists, pharmacologists and physicians worldwide felt an urgent demand for a safe, effective therapeutic agent, treatment strategy or vaccine in order to prevent or cure the recently-emerged disease. Initially, due to lack of specific pharmacological agents and approved vaccines to combat the COVID-19, the disease control in the confirmed cases was limited to supportive care. Accordingly, repositioning or repurposing current drugs and examining their possible therapeutic efficacy received a great deal of attention. Despite revealing promising results in some clinical trials, the overall results are conflicting. For this reason, there is an urgent to seek and investigate other potential therapeutics. Mesenchymal stem cells (MSC) representing immunomodulatory and regenerative capacity to treat both curable and intractable diseases, have been investigated in COVID-19 clinical trials carried out in different parts of the world. Nevertheless, up to now, none of MSC-based approaches has been approved in controlling COVID-19 infection. Thanks to the fact that the final solution for defeating the pandemic is developing a safe, effective vaccine, enormous efforts and clinical research have been carried out. In this review, we will concisely discuss the safety and efficacy of the most relevant pharmacological agents, MSC-based approaches and candidate vaccines for treating and preventing COVID-19 infection.
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Affiliation(s)
- Mehdi Rasouli
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | | | - Javad Ranjbari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran. Iran
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20
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Choi YJ, Park JY, Lee HS, Suh J, Song JY, Byun MK, Cho JH, Kim HJ, Park HJ. Variable effects of underlying diseases on the prognosis of patients with COVID-19. PLoS One 2021; 16:e0254258. [PMID: 34280188 PMCID: PMC8289057 DOI: 10.1371/journal.pone.0254258] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 06/23/2021] [Indexed: 01/08/2023] Open
Abstract
Underlying diseases might be risk factors for poor prognosis in patients with coronavirus disease (COVID-19); however, we still do not know whether these diseases are independent factors affecting prognosis, which type of underlying diseases are risk factors, and which type of clinical outcomes are affected. We retrospectively reviewed cohort data from 7,590 de-identified patients with COVID-19 who were diagnosed using severe acute respiratory syndrome-coronavirus-2 RNA polymerase chain reaction test up to May 15, 2020. We used linked-medical claims data provided by the Health Insurance Review and Assessment Service in South Korea. Underlying diseases were identified using the diagnostic codes in the patients’ files from January 1, 2019 to December 31, 2019. The total mortality rate was 3.0% in patients with COVID-19. After adjusting for age, sex, and concomitant chronic conditions, we found that congestive heart failure, chronic pulmonary diseases, diabetes without chronic complications, renal diseases, and malignancy were factors that significantly increased the cost of treatment. Cerebrovascular disease, chronic pulmonary disease, and paralysis were found to be independent factors significant in prolonging hospital stay. Diabetes with chronic complications was independently associated with intensive care unit admission. In addition, underlying congestive heart failure (odds ratio [OR], 1.724; P = 0.003), dementia (OR, 1.598; P = 0.012), diabetes with and without chronic complications (OR, 1.821; P = 0.002 and OR, 1.518; P = 0.022, respectively), renal disease (OR, 2.299; P = 0.002), and malignancy (OR, 1.529; P = 0.039) were significant factors associated with death, even after adjustments. Underlying diseases were significant independent factors of the poor prognosis in patients with COVID-19. The effects were variable according to the type of underlying disease and clinical outcome. Therefore, patients with COVID-19 with underlying diseases should be monitored more closely because they are more at risk of a poor prognosis.
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Affiliation(s)
- Yong Jun Choi
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Ju-Young Park
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin Suh
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jeung Yoon Song
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Min-Kwang Byun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Hwa Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyung Jung Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Jung Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
- * E-mail:
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21
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Olszewska-Parasiewicz J, Szarpak Ł, Rogula S, Gąsecka A, Szymańska U, Kwiatkowska M, Jaguszewski MJ, Sierpiński R, Zaczyński A, Wierzba W, Kosior DA. Statins in COVID-19 Therapy. Life (Basel) 2021; 11:life11060565. [PMID: 34208435 PMCID: PMC8234902 DOI: 10.3390/life11060565] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/03/2021] [Accepted: 06/11/2021] [Indexed: 01/08/2023] Open
Abstract
Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial.
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Affiliation(s)
- Justyna Olszewska-Parasiewicz
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
| | - Łukasz Szarpak
- Maria Sklodowska-Curie Białystok Oncology Centre, Ogrodowa 12, 15-027 Białystok, Poland
- Maria Sklodowska-Curie Medical Academy in Warsaw, Solidarnosci 12, 03-411 Warsaw, Poland
- Correspondence:
| | - Sylwester Rogula
- Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland; (S.R.); (A.G.)
| | - Aleksandra Gąsecka
- Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland; (S.R.); (A.G.)
| | - Urszula Szymańska
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
| | - Maria Kwiatkowska
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
| | - Milosz J. Jaguszewski
- Department of Cardiology, Medical University of Gdańsk, Dębinki 7, 80-952 Gdańsk, Poland;
| | - Radosław Sierpiński
- Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszyński University, 01-815 Warsaw, Poland;
| | - Artur Zaczyński
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
| | - Waldemar Wierzba
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
- UHE Satellite Campus in Warsaw, University of Humanities and Economics in Łódź, Felińskego 15, 01-513 Warsaw, Poland
| | - Dariusz A. Kosior
- Central Clinical Hospital the Ministry of the Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland; (J.O.-P.); (U.S.); (M.K.); (A.Z.); (W.W.); (D.A.K.)
- Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
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Biever P, Staudacher DL, Sommer MJ, Triebel H, Neukamm MA, Bode C, Supady A, Lother A. Hemoadsorption eliminates remdesivir from the circulation: Implications for the treatment of COVID-19. Pharmacol Res Perspect 2021; 9:e00743. [PMID: 33710753 PMCID: PMC7953359 DOI: 10.1002/prp2.743] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 01/27/2021] [Accepted: 01/28/2021] [Indexed: 02/06/2023] Open
Abstract
Both antiviral treatment with remdesivir and hemoadsorption using a CytoSorb® adsorption device are applied in the treatment of severe COVID-19. The CytoSorb® adsorber consists of porous polymer beads that adsorb a broad range of molecules, including cytokines but also several therapeutic drugs. In this study, we evaluated whether remdesivir and its main active metabolite GS-441524 would be adsorbed by CytoSorb® . Serum containing remdesivir or GS-441524 was circulated in a custom-made system containing a CytoSorb® device. Concentrations of remdesivir and GS-441524 before and after the adsorber were analyzed by liquid chromatography-tandem mass spectrometry. Measurements of remdesivir in the outgoing tube after the adsorber indicated almost complete removal of remdesivir by the device. In the reservoir, concentration of remdesivir showed an exponential decay and was not longer detectable after 60 mins. GS-441524 showed a similar exponential decay but, unlike remdesivir, it reached an adsorption-desorption equilibrium at ~48 µg/L. Remdesivir and its main active metabolite GS-441524 are rapidly eliminated from the perfusate by the CytoSorb® adsorber device in vitro. This should be considered in patients for whom both therapies are indicated, and simultaneous application should be avoided. In general, plasma levels of therapeutic drugs should be closely monitored under concurrent CytoSorb® therapy.
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Affiliation(s)
- Paul Biever
- Heart Center Freiburg UniversityDepartment of Cardiology and Angiology IFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine III (Interdisciplinary Medical Intensive Care)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine II (Division of Infectious Diseases)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
| | - Dawid L. Staudacher
- Heart Center Freiburg UniversityDepartment of Cardiology and Angiology IFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine III (Interdisciplinary Medical Intensive Care)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
| | - Michaela J. Sommer
- Institute of Forensic MedicineMedical Center‐University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Hermann Staudinger Graduate SchoolUniversity of FreiburgFreiburgGermany
| | - Hannah Triebel
- Institute of Forensic MedicineMedical Center‐University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany
| | - Merja A. Neukamm
- Institute of Forensic MedicineMedical Center‐University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany
| | - Christoph Bode
- Heart Center Freiburg UniversityDepartment of Cardiology and Angiology IFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine III (Interdisciplinary Medical Intensive Care)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
| | - Alexander Supady
- Heart Center Freiburg UniversityDepartment of Cardiology and Angiology IFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine III (Interdisciplinary Medical Intensive Care)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Heidelberg Institute of Global HealthUniversity of HeidelbergHeidelbergGermany
| | - Achim Lother
- Heart Center Freiburg UniversityDepartment of Cardiology and Angiology IFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Department of Medicine III (Interdisciplinary Medical Intensive Care)Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany
- Institute of Experimental and Clinical Pharmacology and ToxicologyFaculty of MedicineUniversity of FreiburgFreiburgGermany
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Rezaee H, Pourkarim F, Pourtaghi‐Anvarian S, Entezari‐Maleki T, Asvadi‐Kermani T, Nouri‐Vaskeh M. Drug-drug interactions with candidate medications used for COVID-19 treatment: An overview. Pharmacol Res Perspect 2021; 9:e00705. [PMID: 33421347 PMCID: PMC7796804 DOI: 10.1002/prp2.705] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/20/2020] [Accepted: 11/30/2020] [Indexed: 02/06/2023] Open
Abstract
Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.
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Affiliation(s)
- Haleh Rezaee
- Infectious Diseases and Tropical Medicine Research CenterTabriz University of Medical SciencesTabrizIran
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | - Fariba Pourkarim
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | | | - Taher Entezari‐Maleki
- Department of Clinical PharmacyFaculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | - Touraj Asvadi‐Kermani
- Department of SurgeryFaculty of MedicineTabriz University of Medical SciencesTabrizIran
| | - Masoud Nouri‐Vaskeh
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMAUniversal Scientific Education and Research Network (USERNTehranIran
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