scholarly journals Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs

2019 ◽  
Vol 16 (17) ◽  
pp. 3161 ◽  
Author(s):  
Ren ◽  
Wang ◽  
Xu ◽  
Li ◽  
Han
Keyword(s):  
Adverse Drug Reactions ◽  
Comprehensive Evaluation ◽  
Metabolic Activation ◽  
Fuzzy Comprehensive Evaluation ◽  
3D Qsar ◽  
New Drugs ◽  
Drug Reactions ◽  
Improved Method ◽  
Biological Studies

Most studies on adverse drug reactions (ADRs) of fluoroquinolones (FQs) have focused on the mechanisms of single ADRs, and no quantitative structure–activity relationship (QSAR) method studies have been carried out that combine several ADRs of FQs. In this study, an improved three-dimensional (3D) QSAR method was established using fuzzy comprehensive evaluation. This method could simultaneously consider three common ADRs of FQs using molecular parameters. The improved method could comprehensively predict three ADRs of FQs and provide direction for the development of new drugs with lower ADRs than the originals. According to the improved method, 48 derivatives with lower ADRs (decreased by 4.86% to 50.92%) were designed from pazufloxacin. Three derivatives with a higher genotoxicity, higher photodegradation, and lower bioconcentration than pazufloxacin were selected using the constructed QSAR methods of the FQs. Finally, three traditional 3D-QSAR methods of single ADR were constructed to validate the improved method. The improved method was reasonable, with a relative error range of 0.96% to 4.30%. This study provides valuable reference data and will be useful for the development of strategies to produce new drugs with few ADRs. In the absence of complementary biological studies of these adverse drug reactions, the results reported here may be quite divergent from those found in humans or experimental animals in vivo. One major reason for this is that many adverse drug reactions are dependent upon enzyme-catalyzed metabolic activation (toxication) or on non-enzymatic conversion to toxic products and are not due to the parent drug moiety.

scholarly journals Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

2019 ◽  
pp. 1-10
Author(s):  
Md. Jahidul Hasan
Keyword(s):  
Respiratory Tract ◽  
Adverse Drug Reactions ◽  
Intravenous Administration ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Drug Reactions ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Gram Negative ◽  
Tract Infections

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

New drugs, new adverse drug reactions, and bibliographic databases

The Lancet ◽  
1999 ◽  
Vol 353 (9162) ◽  
pp. 1447-1448 ◽  
Author(s):  
A Figueras ◽  
F Estévez ◽  
J-R Laporte
Keyword(s):  
Adverse Drug Reactions ◽  
New Drugs ◽  
Bibliographic Databases ◽  
Drug Reactions

The determination of epigenetic target specificity and identification of epigenetics-related in vivo adverse drug reactions

2013 ◽  
Vol 68 (1) ◽  
pp. e18-e19
Author(s):  
Annie Otto-Bruc ◽  
Boryeu Mao ◽  
Jacques C. Migeon ◽  
Fabien Tillier ◽  
Benoît Fouchaq
Keyword(s):  
Adverse Drug Reactions ◽  
Target Specificity ◽  
Drug Reactions

scholarly journals Nurse knowledge about potentially inappropriate medications for elderly

2021 ◽  
Vol 37 ◽  
pp. e37037
Author(s):  
Gabriela Garcia Soares ◽  
Ana Luisa Zanardo Buso ◽  
Bruna Stephanie Sousa Malaquias ◽  
Rodrigo Rodrigues Silva ◽  
Juliana Maria Soares ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Population Aging ◽  
The Elderly ◽  
New Drugs ◽  
Potentially Inappropriate Medications ◽  
Drug Reactions ◽  
Cross Sectional ◽  
Elderly Health ◽  
The Individual ◽  
Inappropriate Medications

Due to the consequences of changes in fertility and mortality rates, there is an increase in population aging. In this context, the use of potentially inappropriate medications in this population makes nurses important agents in the identification of adverse reactions, requiring their knowledge about these drugs and their effects. The study aimed to verify nurses knowledge about the 2015 AGS BeersCriteria, regarding the potentially inappropriate medications for the elderly, and their adverse effects. It is a cross-sectional, descriptive, and analytical study with a quantitative and qualitative approach performed in a teaching hospital in the Triângulo Mineiro, Minas Gerais. Of the 80 professionals, 74.1% reported attending the elderly frequently, and only 3.8% had a specialization course in elderly health. Only 13.8% reported knowing the Beers Criteria. And 69% believe that adverse drug reactions can be confused as a new symptom and because of this, new drugs can be inserted into the therapeutic plan. Three categories emerged: The importance of assertive knowledge about PIMs, The nurse as a fundamental character in ADR, and Knowledge as a reinforcer of care. There is evidence of the need to train nurses to better identify adverse drug reactions so that they can act on these events avoiding the worsening of the individual.

The Influence of Primary Care Prescribing Rates for New Drugs on Spontaneous Reporting of Adverse Drug Reactions

Drug Safety ◽  
2007 ◽  
Vol 30 (4) ◽  
pp. 357-366 ◽  
Author(s):  
Richard C Clark ◽  
Simon R J Maxwell ◽  
Sheena Kerr ◽  
Melinda Cuthbert ◽  
Duncan Buchanan ◽  
...  
Keyword(s):  
Primary Care ◽  
Adverse Drug Reactions ◽  
Spontaneous Reporting ◽  
New Drugs ◽  
Drug Reactions

scholarly journals Detection of Unknown Ototoxic Adverse Drug Reactions: An Electronic Healthcare Record-Based Longitudinal Nationwide Cohort Analysis

2021 ◽  
Author(s):  
Suehyun Lee ◽  
Jaehun Cha ◽  
Jong-Yeup Kim ◽  
Gil Myeong Son ◽  
Dong-Kyu Kim
Keyword(s):  
Hearing Loss ◽  
Adverse Drug Reactions ◽  
Proportional Hazards ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
New Drugs ◽  
Rank Test ◽  
Drug Reactions ◽  
Bilateral Hearing Loss

Abstract Ototoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider the risk of ototoxicity when prescribing these drugs.

Abstract 229: Correlation of in vitro Studies and Human Drug Interaction Studies with Gemcabene

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Margaret McShane ◽  
Louis Radulovic ◽  
Charles L Bisgaier
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Multiple Dose ◽  
Drug Reactions ◽  
Open Label ◽  
Transport Pathways ◽  
Dose Study

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for dyslipidemia treatment. Patients with dyslipidemia typically take many medications often including statins and it is essential to understand potential risk of drug-drug interactions (DDI) to minimize the risk of adverse drug reactions. In the best circumstances, drugs entering the market will provide metabolic or transport pathways that do not interfere with commonly co-administered drugs. The current studies provide the analysis of potential drug interactions with gemcabene both in vitro and in vivo . Methods: Caco-2 cells were used to assess the potential P-gp substrate and inhibitor interaction and the major drug-metabolizing CYP450 isozymes and FMO-3 were used to assess the potential CYP450 and FM0-3 metabolism interaction. The results from the in vitro P-gp and CYP450 studies was correlated with the results of three DDI clinical studies with digoxin, atorvastatin and simvastatin. Results: In an open-label, multiple-dose study in 12 healthy subjects, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of digoxin (0.25 mg). Specifically, the 90% confidence interval for digoxin AUC (0-24) ratios were within the 80% to 125% range, thus confirming the in vitro results of no DDI with a P-gp substrate. In two open-label, multiple-dose studies in healthy volunteers, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of atorvastatin (80 mg) or simvastatin (80 mg) thus confirming the in vitro results of no DDI with CYP450 (see Figure below). Conclusion: These results suggest gemcabene is unlikely to elicit a metabolic (i.e., CYP450 or FMO3) or P-gp-mediated drug interaction. Gemcabene (900 mg) was well-tolerated in combination with highest dose of atorvastatin and simvastatin. Clinical Implications: Understanding potential for drug interactions minimizes the risk of adverse drug reactions.

Assessment of urban water security based on catastrophe theory

2012 ◽  
Vol 66 (3) ◽  
pp. 487-493 ◽  
Author(s):  
Fengshun Yang ◽  
Dongguo Shao ◽  
Chun Xiao ◽  
Xuezhi Tan
Keyword(s):  
Catastrophe Theory ◽  
Evaluation Method ◽  
Comprehensive Evaluation ◽  
Water Security ◽  
Fuzzy Comprehensive Evaluation ◽  
Urban Water ◽  
Improved Method ◽  
Comprehensive Evaluation Method ◽  
Scope Of Application ◽  
Cramer’S Rule

In this study, a model for assessing urban water security is developed using an evaluation method of catastrophe theory. To overcome the defects of the traditional catastrophe evaluation method, two aspects of improvement are assessed. One is expanding the scope of application of the traditional catastrophe approach, i.e., new normalization formulae for five lower level indicators contained in the index at the higher level is proposed in theory. The other is solving the problem that the synthetic values are generally high and the differences are not obvious based on the theories of Cramer's Rule and Vander monde determinant. The assessment results in Wuhan city are in good agreement with the actual situation. The comparison between the results of the improved method and a fuzzy comprehensive evaluation method verifies the science and reliability of the developed method. Consequently, it is concluded that the improved method can be an effective tool for assessment of urban water security and provide a valuable reference for improving inadequacies in urban water security.

scholarly journals Detection of unknown ototoxic adverse drug reactions: an electronic healthcare record-based longitudinal nationwide cohort analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suehyun Lee ◽  
Jaehun Cha ◽  
Jong-Yeup Kim ◽  
Gil Myeong Son ◽  
Dong-Kyu Kim
Keyword(s):  
Hearing Loss ◽  
Adverse Drug Reactions ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
New Drugs ◽  
Rank Test ◽  
Drug Reactions ◽  
Bilateral Hearing Loss ◽  
Ototoxic Drugs

AbstractOtotoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider avoiding co-administration of these drugs with other well-confirmed ototoxic drugs should be emphasized.

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