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 ◽  
Vol 15 (7) ◽  
pp. e1006851 ◽  
Author(s):  
Sergey Ivanov ◽  
Alexey Lagunin ◽  
Dmitry Filimonov ◽  
Vladimir Poroikov
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Drug Target ◽  
Combined Analysis ◽  
Spontaneous Reports

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.

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.

Characteristics of the Analgesic Effects and Drug Interactions of Intrathecal Carbachol in Rats

1995 ◽  
Vol 83 (4) ◽  
pp. 844-849. ◽  
Author(s):  
Stephen E. Abram ◽  
Therese C. O'Connor
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Stimulus Intensity ◽  
Hind Limb ◽  
Intrathecal Morphine ◽  
Radiant Heat ◽  
Limb Weakness ◽  
Analgesic Effects ◽  
Low Intensity ◽  
Significant Difference

Background Intrathecal carbachol produces consistent analgesia in animals without appreciable adverse effects. Little is known about the ability of this drug to provide analgesia as stimulus intensity is increased. Likewise, there are few data regarding interactions between carbachol and other intrathecal analgesics. Methods Using two different noxious radiant heat intensities, one applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms intrathecal carbachol on paw withdrawal latencies were measured. Similar testing was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8, 1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were administered, responses to the low intensity stimulus were recorded, and the ED50 of each combination was established and isobolographic analysis of the drug interactions was carried out. Results The 30-micrograms dose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED50 (95% confidence interval) of intrathecal carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64 micrograms (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED50 values for intrathecal morphine and clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive effects. The ED50 for the carbachol-morphine combination was 12% of the expected additive value and the ED50 for the carbachol-clonidine combination was 30% of the expected additive value. Conclusions Intrathecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing analgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine.

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

Nimesulide – A Drug to be Banned completely

2021 ◽  
pp. 132-137
Author(s):  
C. Muralikrishna Goud ◽  
Syeda Mariya Ghazanfar
Keyword(s):  
United States ◽  
Adverse Effects ◽  
Drug Interactions ◽  
Acute Hepatitis ◽  
Family Welfare ◽  
Over The Counter ◽  
High Court ◽  
Human Use ◽  
The Government ◽  
Pediatric Use

The Aim of present work is to report Nimesulide a Nonsteroildal Anti Inflammatory Drug is being sold as over the counter drug has to banned completely due to occurrence of Nimesulide induced acute hepatitis. On February 12, 2011, the Union Ministry of Health and Family Welfare finally had decided to suspend the pediatric use of the Nimesulide suspension. From 10 March 2011 Nimesulide formulations are not indicated for human use in children below 12 years of age. On September 13, 2011 Madras High Court revoked a suspension on manufacture and sale of pediatric drugs Nimesulide and phenylpropanolamine (PPA). Though the government of India has banned the pediatric use of Nimesulide for common fever and pain due to its adverse effects on the liver, its usage by adults is being increased everyday without any prescription. The drug was banned in 2000 in various countries like Switzerland, Spain, United states etc, whereas in India it was banned in 2011 which was too late to be banned and still available in India for adult use despite of its hepatotoxicity and possible drug interactions.

Non-Steroidal Anti-Inflammatory Drugs: Usage and Co-prescription with Other Potentially Interacting Drugs in Elderly: a Cross-sectional Study

2019 ◽  
Author(s):  
Nuru Abdu ◽  
Samuel Teweldemedhin ◽  
Asmerom Mosazghi ◽  
Luwam Asfaha ◽  
Makda Teshale ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
The Elderly ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Female Ratio ◽  
Protective Agents ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract Introduction: Globally, non-steroidal anti-inflammatory drugs (NSAIDs) usage in the elderly with chronic pain has been reported as frequent. Though it is fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse effects is of paramount importance as the elderly usually require multiple medications for their co-morbidities. If prescriptions are not appropriately monitored and managed, they are likely to expose patients to serious drug interactions and potentially fatal adverse effects. Thus, the objective of the study was to assess the appropriateness of NSAIDs use and incidence of NSAIDs related potential interactions in elderly. Methods: A descriptive cross-sectional study was conducted among elderly out-patients (aged 60 and above) who visited three hospitals in Asmara between August 22 and September 29, 2018. The sampling design was two-stage random sampling and data was collected using a questionnaire, exit interview and by abstracting information from patients’ clinical cards. Descriptive and analytical statistics including chi-square test and logistic regression were employed using SPSS. Results: A total of 285 elderly respondents were enrolled in the study with similar male to female ratio. One in four of all respondents were chronic NSAIDs users, of which 74.6% were not prescribed prophylactic gastro-protective agents (GPAs). About 20% of the elderly were involved in polypharmacy and nearly all of the encountered potential NSAIDs related interactions (n=322) with prescribed drugs were moderate. Diabetes and hypertension were significantly associated with chronic NSAIDs use (OR=3, 95% CI: 1.54, 5.84; OR=9.99, 95% CI: 4.46, 22.38) and incidence of drug interactions (OR=3.95, 95%CI: 1.92, 8.13; OR=3.12, 95%CI: 1.81, 5.33) while diabetes and cardiac problem were significantly associated with incidence of polypharmacy (OR=4.33, 95% CI: 2.36, 7.96; OR=3.56, 95% CI: 1.05, 12.11). Conclusion: Though the overall reflection of prescription pattern of NSAIDs during the study period was almost satisfactory, gastro-protective agents were poorly prescribed as a prophylaxis.

Herbal Drug Interactions

2017 ◽  
pp. 201-231 ◽  
Author(s):  
Mymoona Akhter
Keyword(s):  
Drug Interaction ◽  
Side Effects ◽  
Adverse Effects ◽  
Drug Interactions ◽  
Herbal Medicines ◽  
Herbal Drugs ◽  
Herbal Drug ◽  
Herbal Therapy ◽  
Alternative Medicines ◽  
Regulatory Bodies

Use of complementary and alternative medicines (CAM) for preventive and therapeutic purposes has increased tremendously in the last two decades internationally. The manufacturers of these products are not required to submit proof of safety or efficacy to the Food and Drug Administration. As a result, the adverse effects and drug interactions associated with them are largely unknown. In this chapter, the author presents interactions of herbal medicines with other medicines (herbal or non-herbal). A large number of herbal drugs, including from single drug to a variety of mixtures have been used to treat kidney disorders. Herb-herb or herb drug interaction has been reported intensively during last decade, therefore it becomes important to keep an eye on the use of combination herbal therapy in order to avoid serious results because of interactions with each other. Due to the growing awareness about the interactions and side effects of herbal drugs/supplements over the past few years, regulatory bodies are working on these issues and pharmacopoeias are being developed for reference.

scholarly journals Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents

2020 ◽  
Vol 10 ◽  
pp. 204512532093530 ◽  
Author(s):  
Delia Bishara ◽  
Chris Kalafatis ◽  
David Taylor
Keyword(s):  
Drug Interaction ◽  
Adverse Effects ◽  
Drug Interactions ◽  
Clinical Trial Data ◽  
Potential Drug ◽  
Qtc Prolongation ◽  
Experimental Drugs ◽  
Psychotropic Agents ◽  
The Common ◽  
Experimental Treatments

As yet, no agents have been approved for the treatment of COVID-19, although several experimental drugs are being used off licence. These may have serious adverse effects and potential drug interactions with psychotropic agents. We reviewed the common agents being used across the world for the treatment of COVID-19 and investigated their drug interaction potential with psychotropic agents using several drug interaction databases and resources. A preliminary search identified the following drugs as being used to treat COVID-19 symptoms: atazanavir (ATV), azithromycin (AZI), chloroquine (CLQ)/hydroxychloroquine (HCLQ), dipyridamole, famotidine (FAM), favipiravir, lopinavir/ritonavir (LPV/r), nitazoxanide, remdesivir, ribavirin and tocilizumab. Many serious adverse effects and potential drug interactions with psychotropic agents were identified. The most problematic agents were found to be ATV, AZI, CLQ, HCLQ, FAM and LPV/r in terms of both pharmacokinetic as well as serious pharmacodynamic drug interactions, including QTc prolongation and neutropenia. Significant caution should be exercised if using any of the medications being trialled for the treatment of COVID-19 until robust clinical trial data are available. An even higher threshold of vigilance should be maintained for patients with pre-existing conditions and older adults due to added toxicity and drug interactions, especially with psychotropic agents.

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