scholarly journals Assessment of the cardiovascular adverse effects of drug-drug interactions through a combined analysis of spontaneous reports and predicted drug-target interactions

2019 ◽  
Author(s):  
Sergey Ivanov ◽  
Alexey Lagunin ◽  
Dmitry Filimonov ◽  
Vladimir Poroikov
Keyword(s):  
Ventricular Tachycardia ◽  
Adverse Effects ◽  
Drug Interactions ◽  
Cardiovascular System ◽  
Drug Target ◽  
Drug Effects ◽  
Classification Models ◽  
Adverse Drug Effects ◽  
Combined Analysis ◽  
Spontaneous Reports

AbstractAdverse drug effects (ADEs) are one of the leading causes of death in developed countries and are the main reason for drug recalls from the market, whereas the ADEs that are associated with action on the cardiovascular system are the most dangerous and widespread. The treatment of human diseases often requires the intake of several drugs, which can lead to undesirable drug-drug interactions (DDIs), thus causing an increase in the frequency and severity of ADEs. An evaluation of DDI-induced ADEs is a nontrivial task and requires numerous experimental and clinical studies. Therefore, we developed a computational approach to assess the cardiovascular ADEs of DDIs.This approach is based on the combined analysis of spontaneous reports (SRs) and predicted drug-target interactions to estimate the five cardiovascular ADEs that are induced by DDIs, namely, myocardial infarction, ischemic stroke, ventricular tachycardia, cardiac failure, and arterial hypertension.We applied a method based on least absolute shrinkage and selection operator (LASSO) logistic regression to SRs for the identification of interacting pairs of drugs causing corresponding ADEs, as well as noninteracting pairs of drugs. As a result, five datasets containing, on average, 3100 ADE-causing and non-ADE-causing drug pairs were created. The obtained data, along with information on the interaction of drugs with 1553 human targets predicted by PASS Targets software, were used to create five classification models using the Random Forest method. The average area under the ROC curve of the obtained models, sensitivity, specificity and balanced accuracy were 0.838, 0.764, 0.754 and 0.759, respectively.The predicted drug targets were also used to hypothesize the potential mechanisms of DDI-induced ventricular tachycardia for the top-scoring drug pairs.The created five classification models can be used for the identification of drug combinations that are potentially the most or least dangerous for the cardiovascular system.Author summaryAssessment of adverse drug effects as well as the influence of drug-drug interactions on their manifestation is a nontrivial task that requires numerous experimental and clinical studies. We developed a computational approach for the prediction of adverse effects that are induced by drug-drug interactions, which are based on a combined analysis of spontaneous reports and predicted drug-target interactions. Importantly, the approach requires only structural formulas to predict adverse effects, and, therefore, may be applied for new, insufficiently studied drugs. We applied the approach to predict five of the most important cardiovascular adverse effects, because they are the most dangerous and widespread. These effects are myocardial infarction, ischemic stroke, ventricular tachycardia, arterial hypertension and cardiac failure. The accuracies of predictive models were relatively high, in the range of 73-81%; therefore, we performed a prediction of the five cardiovascular adverse effects for the large number of drug pairs and revealed the combinations that are the most dangerous for the cardiovascular system. We consider that the developed approach can be used for the identification of pairwise drug combinations that are potentially the most or least dangerous for the cardiovascular system.

Relationship between Drug-Drug Interactions and Adverse Drug Effects: a Case-Control Study

Drug Safety ◽  
2006 ◽  
Vol 29 (10) ◽  
pp. 911-1010
Author(s):  
M.L. Laroche ◽  
D. Plats ◽  
J.P. Charmes ◽  
L. Merle
Keyword(s):  
Drug Interactions ◽  
Case Control Study ◽  
Drug Effects ◽  
Case Control ◽  
Adverse Drug Effects ◽  
Control Study

Pharmacokinetic Approach of Clinically Important Drug Interactions of Hormonal Contraceptives – A Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Naina Mohamed Pakkir Maideen ◽  
Rajkapoor Balasubramaniam ◽  
Sambath Kumar Ramanathan
Keyword(s):  
Drug Interactions ◽  
Healthcare Professionals ◽  
Plasma Concentrations ◽  
Hormonal Contraception ◽  
Drug Effects ◽  
Hormonal Contraceptives ◽  
Adverse Drug Effects ◽  
Cyp3a4 Enzyme ◽  
Pharmacokinetic Approach ◽  
Important Drug

: Hormonal contraceptives contain an Estrogen and/or a Progestin, which are the substrates of CYP3A4 enzyme and the drugs inducing CYP3A4 enzyme, can decrease the plasma concentrations and thereby therapeutic efficacy of Hormonal contraceptives resulting in unintended pregnancy. Moreover, the hormonal contraceptives associated risk of thrombotic events are further exacerbated by the simultaneous administration of drugs like Tranexamic acid and tobacco smoke. Therefore, while prescribing hormonal contraception and other drugs to women, drug interactions should always be considered, because, there could be a possible contraceptive failure or other adverse drug effects. This article provides a summary of guidance to healthcare professionals such as prescribers and pharmacists on pharmacokinetic based interactions between hormonal contraception and other drugs.

Fracture Healing

2015 ◽  
Vol 105 (2) ◽  
pp. 160-172 ◽  
Author(s):  
Robert G. Smith
Keyword(s):  
Adverse Effects ◽  
Fracture Healing ◽  
Bone Health ◽  
Case Reports ◽  
Drug Effects ◽  
Delayed Union ◽  
Adverse Drug Effects ◽  
Drug Adverse Effects ◽  
Definitive Statement ◽  
Medical Causation

Background Recognizing the existence of adverse drug effects of frequently prescribed drugs can empower a clinician with knowledge to avoid dangerous adverse effects that may result in hazardous, negative patient outcomes on either fracture healing or bone health. Pharmacovigilance reports have described the influence of medications, allowing for bone health to be quite unpredictable. Methods First, mechanisms found in the medical literature of potential drug adverse effects regarding fracture healing are presented. Second, the 100 most frequently prescribed medications in 2010 are reviewed regarding adverse effects on fracture healing. These reported adverse effects are evaluated for medical causation. Last, a data table describing the 100 reviewed medications and their reported effects on fracture healing is provided. Results The actual number of different medications in the review was 72. Reported drug adverse effects on bone and fracture healing occurred with 59 of the 72 drugs (81.9%). These adverse effects are either described as a definitive statement or represented by postmarketing case reports. Thirteen of the 72 review drugs (18.1%) did not have any description of the possible effects on bone health. A total of 301 cases reports describing delayed union, malunion, and nonunion of fractures represent 31 of the 72 medications reviewed (43.1%). Conclusions This review offers the health-care provider information regarding potential adverse drug effects on bone health. Empowered with this information, clinicians may assist their patients in maximizing pharmacologic outcomes by avoiding these reported harmful adverse effects.

scholarly journals Prevalence and Significance of Antibiotic-Associated Adverse Reactions

2021 ◽  
Author(s):  
Tânia Magalhães Silva ◽  
Eva Rebelo Gomes ◽  
Inês Ribeiro-Vaz ◽  
Fátima Roque ◽  
Maria Teresa Herdeiro
Keyword(s):  
Drug Effects ◽  
Epidemiological Data ◽  
Antibiotic Use ◽  
World Health ◽  
Pharmacovigilance System ◽  
Adverse Drug Effects ◽  
Spontaneous Reports ◽  
Safety Risks ◽  
Health Organization ◽  
Effective Use

The World Health Organization (WHO) defines Pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse drug effects. The aim is to promote the safety and effective use of medicines through an early detection and evaluation of drug safety risks. The pharmacovigilance system is essentially based in spontaneous reports of Adverse Drug Reactions (ADR). ADR can be associated with severe outcomes and significant mortality, besides, most of them are deemed to be preventable events. Globally, antibiotics are among the most widely prescribed medications and their extensive use is linked to antibiotic-associated ADR. This chapter aims to summarize available epidemiological data concerning antibiotic use related ADR and analyze the reports received by the EudraVigilance system regarding the exclusive usage of antibiotics.

scholarly journals Drug Interactions with Antidementia Drugs: Clinical Consequences

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C.A. de Mendonça Lima
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Cognitive Disorders ◽  
Public Health Problem ◽  
Cardiac Conduction ◽  
Major Public Health Problem ◽  
List Type ◽  
Spontaneous Reports ◽  
Increased Risk ◽  
Antidementia Drugs

Alzheimer" disease (AD) is a major public health problem, and it is at the origin of a significant burden: 15% of direct costs in dementia are attributed to pharmacological treatment. Persons with dementia often have comorbidities and receive multiple medications. Both factors increase the risk of drug-drug interactions (DDIs) which can result in adverse drug reactions (ADRs). In a study, a total of 1058 spontaneous reports were identified that involved cholinesterase inhibitors (ChEIs) in the French Pharmacovigilance Database; 35.5% contained at least one DDI; 118 of them (31.4%) were the cause of ADRs. Pharmacodynamic interactions play a far greater role than pharmacokinetic interactions in the significance of DDIs. Some known interactions with ChEIs are:1.atropinic drugs aggravate cognitive disorders;2.combinations of ChEIs and antipsychotics are associated with an increased risk of extrapyramidal adverse effects;3.combining ChEIs with drugs that reduce the heart rate, depress cardiac conduction, or induce torsades de pointes increases the risk of arrhythmias and cardiac conduction disorders.Recent studies suggest that the therapeutic response in Alzheimer"s disease is genotype specific, depending on genes associated with AD pathogenesis and/or genes responsible for drug metabolism. APOEe4/e4 genotype carriers are the poorest responders to treatments. Some ChEIs are metabolized via CYP-related enzymes and can interact with other drugs that are substrates, inhibitors or inducers of the CYP system. Health professionals should be aware of the potential adverse effects of ChEIs, including the possible DDIs and antagonist effects with other drugs.

scholarly journals Challenges of Pharmacovigilance in Brazil

2020 ◽  
Vol 13 (2) ◽  
pp. 1
Author(s):  
Vanessa M. de Oliveira ◽  
Vanessa T. Gubert-Matos ◽  
Alexandre A. Tutes ◽  
Cristiane M. Ferreira ◽  
Erica F. Vasconcelos-Pereira ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Drug Effects ◽  
Healthcare Spending ◽  
Adverse Drug Effects ◽  
Medicinal Products ◽  
Notification System ◽  
Safety Issues ◽  
Potential Safety ◽  
Hospital Stays ◽  
Detection Evaluation

Pharmacovigilance encompasses the detection, evaluation, understanding, and prevention of adverse effects or any other drug-related problems. Knowledge of real and independent pharmacovigilance data is essential because clinical trials with medicinal products are limited and do not reveal all adverse effects of a product. The spontaneous notification system is one of the main tools used in pharmacovigilance. However, important remaining challenges for health professionals are the accurate recognition of adverse drug reactions and reporting routinely and systematically during their work. Once low notification rates make it harder to detect and monitor potential safety issues, it is needed risk assessment, and regulatory actions to safeguard patient safety. The objective of this study is to present the challenges of pharmacovigilance in Brazil. The implementation of computerized active search tools significantly improves the identification of possible adverse drug effects. Effective pharmacovigilance is crucial to ensure the safety and integrity of healthcare systems, to avoid lengthy hospital stays and to optimize healthcare spending. However, pharmacovigilance tools remain underused, undervalued, or even unknown in Brazil.

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