Drug Interactions
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Drug Research ◽  
2021 ◽  
Author(s):  
Cemal Parlak ◽  
Özgür Alver ◽  
Cecil N.M. Ouma ◽  
Lydia Rhyman ◽  
Ponnadurai Ramasami

The proverb “Old is gold” is applicable in drug discovery and the proverb “All that Glitters is not Gold” is also appropriate. In the COVID-19 era, there has been a race for drugs to be effective against SARS-CoV-2. There are reports about the uses of Remdesivir and Favipiravir as existing antivirals against virus but none have been conclusive so far. In the attempts for innovations, the combination of drugs is also under trials. Therefore, we used the density functional theory method and quantum theory of atoms in molecules to investigate drug-drug interactions involving Remdesivir and Favipiravir. The computed parameters were related to the antiviral actions of both drugs together. The results indicate enhanced antiviral activity and it will be worthy to consider additional investigations with the combination of these two drugs.


Author(s):  
Archana Balasubramanian ◽  
Raksha Sudarshan ◽  
Jhinuk Chatterjee

Abstract Background Frontotemporal dementia (FTD) is the second most common type of dementia in individuals aged below 65 years with no current cure. Current treatment plan is the administration of multiple medications. This has the issue of causing adverse effects due to unintentional drug–drug interactions. Therefore, there exists an urgent need to propose a novel targeted therapy that can maximize the benefits of FTD-specific drugs while minimizing its associated adverse side effects. In this study, we implemented the concept of network pharmacology to understand the mechanism underlying FTD and highlight specific drug–gene and drug–drug interactions that can provide an interesting perspective in proposing a targeted therapy against FTD. Results We constructed protein–protein, drug–gene and drug–drug interaction networks to identify highly connected nodes and analysed their importance in associated enriched pathways. We also performed a historeceptomics analysis to determine tissue-specific drug interactions. Through this study, we were able to shed light on the APP gene involved in FTD. The APP gene which was previously known to cause FTD cases in a small percentage is now being extensively studied owing to new reports claiming its participation in neurodegeneration. Our findings strengthen this hypothesis as the APP gene was found to have the highest node degree and betweenness centrality in our protein–protein interaction network and formed an essential hub node between disease susceptibility genes and neuroactive ligand–receptors. Our findings also support the study of FTD being presented as a case of substance abuse. Our protein–protein interaction network highlights the target genes common to substance abuse (nicotine, morphine and cocaine addiction) and neuroactive ligand–receptor interaction pathways, therefore validating the cognitive impairment caused by substance abuse as a symptom of FTD. Conclusions Our study abandons the one-target one-drug approach and uses networks to define the disease mechanism underlying FTD. We were able to highlight important genes and pathways involved in FTD and analyse their relation with existing drugs that can provide an insight into effective medication management.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Hans Kristian Råket Pedersen ◽  
Anne Mette Skov Sørensen ◽  
Astrid Blicher Schelde ◽  
Martin Erik Nyeland ◽  
Espen Jimenez-Solem

Author(s):  
Hemraj Singh Rajput ◽  
Nirmal V. Shah

Drug interaction in critically ill patient is very common and affecting patients Physically, Mentally and Financially. There are various measures which has been taken to minimize this burden on patient, such as books being prepared which include various drug interaction, maintain websites and database that provides information regarding drug interactions. With the use of these website and databases the drug interaction can be managed. It is common practice that side effects of drug interaction are being managed by additional drugs, the main reason behind it could be non-availability of alternative drugs or costlier alternative. These factors remain the main cause of treatment failure in majority of patients leading to prolong. The current study was performed for the duration of 12 months, from this study it was identified that 113 types of major drug interactions commonly found in total 250 prescriptions which were evaluated and managed accordingly. Suggestions being prescribed by various sites were, avoid concomitant use of drug, use alternative therapy, and monitor closely for any adverse effect. During suggestion made by the Clinical Pharmacist, for the same drug interactions it was identified that more of drug therapy adjustment can be done then provided by the online database. The parameter on which the drug interactions management are being suggested were focused on just type of drug interaction and its effect, it does not include the actual pharmacodynamic and pharmacokinetic changes in therapy. The suggestion made by the clinical pharmacist were includes drug removal, drug dosage changes, alternative therapy, alternative route of administration, change in time interval etc. From this study it was concluded that the drug interaction management can be done at various stages of treatment with proper therapy modification by the clinical pharmacist, and if done properly it will improve the overall outcome of patient health care.


Sensors ◽  
2021 ◽  
Vol 21 (18) ◽  
pp. 6167
Author(s):  
Linda Bertel ◽  
David A. Miranda ◽  
José Miguel García-Martín

TiO2 electrochemical biosensors represent an option for biomolecules recognition associated with diseases, food or environmental contaminants, drug interactions and related topics. The relevance of TiO2 biosensors is due to the high selectivity and sensitivity that can be achieved. The development of electrochemical biosensors based on nanostructured TiO2 surfaces requires knowing the signal extracted from them and its relationship with the properties of the transducer, such as the crystalline phase, the roughness and the morphology of the TiO2 nanostructures. Using relevant literature published in the last decade, an overview of TiO2 based biosensors is here provided. First, the principal fabrication methods of nanostructured TiO2 surfaces are presented and their properties are briefly described. Secondly, the different detection techniques and representative examples of their applications are provided. Finally, the functionalization strategies with biomolecules are discussed. This work could contribute as a reference for the design of electrochemical biosensors based on nanostructured TiO2 surfaces, considering the detection technique and the experimental electrochemical conditions needed for a specific analyte.


Author(s):  
Nisha Poonia ◽  
Aman Kumar ◽  
Vijay Kumar ◽  
Monika Yadav ◽  
Kashmiri Lal

: To overcome ever increasing cases of antifungal resistance and circumventing side effects and drug interactions related with currently available drugs has impelled the need to expedite the process of drug discovery and development of novel antifungals. 1,4-Disubstituted 1,2,3-triazole has gained tremendous interest in last two decades mainly because of its ease of synthesis via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and its broad spectrum of chemotherapeutic potential. 1,2,3-Triazole is an excellent pharmacophore which has been used as a bioisostere for obtaining libraries of new medicinally important scaffolds. The present review focus on the recent advances (2016-2021) of 1,2,3-triazole derivatives obtained by CuAAC as potential antifungal agents that may facilitate triazole based antifungal development process.


2021 ◽  
Vol 7 (9) ◽  
pp. 747
Author(s):  
Melanie T. Cushion ◽  
Alan Ashbaugh

Rezafungin is a novel echinocandin in Phase 3 development for prevention of invasive fungal disease caused by Candida spp., Aspergillus spp. and Pneumocystis jirovecii in blood and marrow transplantation patients. For such patients, standard antifungal prophylaxis currently comprises an azole for Candida and Aspergillus plus trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia (PCP) despite drug-drug-interactions and intolerability that may limit their use, thus, alternatives are desirable. Rezafungin demonstrates a favorable safety profile and pharmacokinetic properties that allow for once-weekly dosing in addition, to antifungal activity against these predominant pathogens. Herein, the in vivo effects of rezafungin against Pneumocystis murina pneumonia were evaluated in immunosuppressed mouse models of prophylaxis and treatment using microscopy and qPCR assessments. In the prophylaxis model, immunosuppressed mice inoculated with P. murina were administered TMP-SMX (50/250 mg/kg 1×/week or 3×/week), caspofungin (5 mg/kg 3×/week), rezafungin (20 mg/kg, 1×/week or 3×/week; 5 mg/kg, 3×/week) intraperitoneally for 2, 4, 6 and 8 weeks, then immunosuppressed for an additional 6 weeks. Rezafungin administered for 4 weeks prevented P. murina from developing infection after rezafungin was discontinued. In the treatment model, immunosuppressed mice with P. murina pneumonia were treated with rezafungin 20 mg/kg 3×/week intraperitoneally for 2, 4, 6 and 8 weeks. Treatment with rezafungin for 8 weeks resulted in elimination of P. murina. Collectively, these studies showed that rezafungin could both prevent infection and eliminate P. murina from the lungs of mice. These findings support the obligate role of sexual reproduction for survival and growth of Pneumocystis spp. and warrant further investigation for treatment of P. jirovecii pneumonia in humans.


Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5500
Author(s):  
Yang Li ◽  
Zahra Talebi ◽  
Xihui Chen ◽  
Alex Sparreboom ◽  
Shuiying Hu

Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The evaluation of transporter-mediated drug-drug interactions (DDIs) is an important consideration during the drug development process and can guide the safe use of polypharmacy regimens in clinical practice. In recent years, several endogenous substrates of drug transporters have been identified as potential biomarkers for predicting changes in drug transport function and the potential for DDIs associated with drug candidates in early phases of drug development. These biomarker-driven investigations have been applied in both preclinical and clinical studies and proposed as a predictive strategy that can be supplanted in order to conduct prospective DDIs trials. Here we provide an overview of this rapidly emerging field, with particular emphasis on endogenous biomarkers recently proposed for clinically relevant uptake transporters.


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