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Adverse drug-drug interaction

Ying Han, Yangmin Zheng, Jingpu Zhang, Changqin Hu
Most third- and fourth-generation cephalosporins, such as cefotaxime, cefmenoxime, cefepime, and cefpirome, contain an aminothiazoyl ring at the C-7 position. Drug impurity, which may be produced either during synthesis or upon degradation, can induce adverse effects. Various reports have indicated that neurotoxicity is a side effect of cephalosporin. In this study, we developed methods for assessing the free-swimming activities and behaviors in zebrafish larvae in response to continuous darkness and stimulation of light-to-dark photoperiod transition by chemical treatments...
2018: Frontiers in Pharmacology
Jae-Il Lee, Yun-Jung Choi, Hi-Jung Park, Kyeong Cheon Jung, Seong Hoe Park
Antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and Factor VIII, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. It is well known that anti-CD154 antibodies have the highest potential to inhibit these types of adverse immune responses. Nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-CD154 blocking antibodies. For this, we attempted to derive an idea as to how this major complication can be eliminated...
March 16, 2018: Biochemical and Biophysical Research Communications
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
L Lafarge, L Bourguignon, N Bernard, T Vial, M-J Dehan-Moya, B De La Gastine, S Goutelle
Beta-blockers are widely prescribed in elderly patients and may induce severe adverse drug reactions. We report a case of bisoprolol-induced bradycardia in an elderly patient with impaired renal function and use of cytochrome P450 inhibitors. A literature review has been performed in order to analyze pharmacokinetic risk factors of beta-blockers overdosing in geriatrics. Various mechanisms can result in decreased elimination of beta-blockers. These mechanisms vary according to the beta-blocker agent and may be combined in some individuals, especially elderly patients...
March 12, 2018: Annales de Cardiologie et D'angéiologie
Patrick Darken, Paolo DePetrillo, Colin Reisner, Earl St Rose, Paul Dorinsky
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14...
March 12, 2018: Pulmonary Pharmacology & Therapeutics
Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
Khondoker Alam, Alexandra Crowe, Xueying Wang, Pengyue Zhang, Kai Ding, Lang Li, Wei Yue
Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics...
March 14, 2018: International Journal of Molecular Sciences
Cynthia Cheng, Fatima Mithoowani, Thomas Ungar, Monica Lee
Background: Interaction between alcohol and certain medications can lead to adverse consequences. Individuals with mental health disorders are particularly vulnerable because of their psychotropic medications, which are typically taken over extended periods and which are known to have pharmacokinetic and pharmacodynamic interactions with alcohol. It is unknown what education these patients receive from their health care providers and how such interactions are managed. Objectives: To determine whether individuals with mental health disorders are aware of alcohol-drug interactions and if so, how they use such information...
January 2018: Canadian Journal of Hospital Pharmacy
Md Fazlur Rahman, Radhika Raj, Rajgopal Govindarajan
Combination antiretroviral drug treatments depend on 3'-deoxy-nucleoside analogs such as AZT (3'-azido-3'-deoxythymidine) and DDI (2'3'-dideoxyinosine). Despite being effective in inhibiting HIV viral replication, these drugs produce a range of toxicities, including myopathy, pancreatitis, neuropathy and lactic acidosis, that are generally considered as sequelae to mitochondrial damage. While the cell surface localized nucleoside transporters (e.g., human equilibrative nucleoside transporter 2 (hENT2), human concentrative nucleoside transporter 1 (hCNT1)) are known to increase the carrier mediated uptake of 3'-deoxy-nucleoside analogs into cells, another ubiquitously expressed intracellular nucleoside transporter, namely, hENT3, has been implicated in the mitochondrial transport of 3'-deoxy-nucleoside analogs...
March 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rosario Palacios, M Mayorga, C M González-Domenech, C Hidalgo-Tenorio, C Gálvez, L Muñoz-Medina, J de la Torre, A Lozano, M Castaño, M Omar, Jesús Santos
OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42...
January 2018: Journal of the International Association of Providers of AIDS Care
Mary V Seeman, Alexandre González-Rodríguez
PURPOSE OF REVIEW: Drugs have been extensively prescribed for the treatment of psychotic symptoms in schizophrenia and related disorders, as well as for the management of psychotic features in delirium, dementia and affective disorders. The aim of this narrative review is to focus on the recent literature on drug treatment in women with psychosis at the transition to menopause and subsequently. RECENT FINDINGS: The recent literature emphasizes the following points: the efficacy of antipsychotic medication in psychosis is largely confined to the alleviation of delusions and hallucinations; menopause and ageing alter the kinetics and dynamics of drug action; drugs other than antipsychotics are currently being tested to address the cognitive, affective and negative symptoms of psychotic illnesses; menopausal symptoms add to comorbidities and require simultaneous treatment, raising the probability of deleterious drug interactions; antipsychotic drugs have many side effects and contribute to high mortality rates in the older psychosis population...
March 9, 2018: Current Opinion in Psychiatry
Jose de Leon, Edoardo Spina
PURPOSE OF REVIEW: Patients with bipolar disorder are frequently treated with polypharmacy. This article should provide clinicians with an understanding of how polypharmacy can contribute to pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs). RECENT FINDINGS: The pharmacokinetics and pharmacodynamics of lithium and other mood stabilizers (valproate, lamotrigine, carbamazepine, oxcarbazepine, and eslicarbazepine), antipsychotics, and selective serotonin reuptake inhibitors (SSRIs) were reviewed and summarized in the first four tables describing their pharmacokinetic and pharmacodynamic mechanisms...
March 12, 2018: Current Psychiatry Reports
Vaia Lambadiari, George Dimitriadis, Nikolaos P E Kadoglou
The prevalence of heart failure (HF) in the diabetic population has rapidly increased over the past 2 decades, triggering research about the impact of oral anti-diabetic medications on it. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. On the other hand, recent promising clinical data from oral SGLT2 inhibitors mainly lack mechanistic explanation from experimental studies. Hence, it is critical to understand the lessons learned from prior translational studies to gain a better knowledge of the mechanisms of oral anti-diabetic drugs in HF...
March 10, 2018: Heart Failure Reviews
A L Sennesael, A S Larock, B Devalet, V Mathieux, F Verschuren, X Muschart, O Dalleur, J M Dogné, A Spinewine
AIMS: To determine the preventability of serious adverse drug reactions (ADR) related to the use of direct oral anticoagulants (DOAC), and to explore contributing factors to preventable ADRs. Results were compared with vitamin K antagonists (VKA). METHODS: We conducted a prospective observational study in the emergency departments of two teaching hospitals from July 2015 to January 2016. Patients admitted with a thrombotic or bleeding event while under DOAC or VKA were included...
March 9, 2018: British Journal of Clinical Pharmacology
M W Petersen, A Perner, M Bahador, F Sjövall, M H Møller
INTRODUCTION: Anaerobic bacteria are believed to be common pathogens in severe infections. Yet, they are difficult to culture and consequently often unrecognised in clinical infections. Metronidazole is often used empirically for potential anaerobic infections, as the resistance to metronidazole is low. However, disadvantages of metronidazole use exist, including drug interactions, side effects and economical expenses. Currently, the balance between the benefits and harms of empirical metronidazole for severe bacterial infections is unknown...
March 8, 2018: Acta Anaesthesiologica Scandinavica
Austin C Korgan, Elizabeth O'Leary, Jillian L King, Ian C G Weaver, Tara S Perrot
Paternal preconception risk factors (e.g. stress, diet, drug use) correlate with metabolic dysfunction in offspring, which is often comorbid with depressive and anxiety-like phenotypes. Detection of these risk factors or deleterious phenotypes informs a female about prevailing ecological demands, in addition to potential adverse environment-induced phenotypes that may be disseminated to her offspring. We examined whether a F0 male rat's prior exposure to an obesogenic high-fat diet (HFD) influences a female's attraction towards a male, subsequent mother-infant interactions and the development of defensive (emotional) responses in the F1 offspring...
February 21, 2018: Psychoneuroendocrinology
Benjamin David Thumamo Pokam, Jude E Enoh, Aniekan-Augusta O Eyo, Nse O Umoh, Prisca W Guemdjom
Background: Antituberculosis drugs (ATDs) efficiently combat Mycobacterium tuberculosis either through direct molecular interactions or those of its metabolites. However, a variety of adverse effects have been reported, leading to frequent interruptions of treatment. To investigate the possible metabolic disturbances resulting from antituberculosis (TB) treatment, the uric acid (UA) level of patients on ATDs was measured in the southwest region of Cameroon. Methods: This hospital-based cross-sectional study involved 96 TB patients on ATDs and 32 controls who were neither on ATDs nor any other treatment that could increase UA levels...
January 2018: International Journal of Mycobacteriology
Rebecca R Crawford, Praveen K Potukuchi, Erin G Schuetz, John D Schuetz
ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs. The ABC transporters are also recognized as important contributors to pharmacokinetics, especially in drug-drug interactions and adverse drug effects. Drugs and xenobiotics, as well as pathological conditions, can influence the transcription of ABC transporters, or modify their activity or intracellular localization...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Aviv Ouanounou, Michael Goldberg, Daniel A Haas
Temporomandibular disorder (TMD) is a collective term that includes disorders of the temporomandibular joint (TMJ) and of the masticatory muscles and their associated structures. TMDs are characterized by pain, joint sounds and restricted mandibular movement, and drugs are widely used in the management of that pain. Pharmacological agents commonly used for the treatment of TMDs include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids, muscle relaxants, antidepressants, anticonvulsants and benzodiazepines...
July 2017: Journal—Canadian Dental Association, Journal de L'Association Dentaire Canadienne
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