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Drug hypersensitivity

Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Chouki Chenaf, Eric Chapuy, Frédéric Libert, Fabien Marchand, Christine Courteix, Marianne Bertrand, Cecilia Gabriel, Elisabeth Mocaër, Alain Eschalier, Nicolas Authier
Antidepressants are first-line treatments of neuropathic pain but not all of these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as a MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect noradrenaline release. Melatonin, serotonin and noradrenaline have been involved in the pathophysiology of neuropathic pain. Yet no study has been conducted to determine agomelatine effects on neuropathic pain in animal models.Using three rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ) and traumatic (sciatic nerve ligation/CCI) etiologies, we investigated the anti-hypersensitivity effect of acute and repeated agomelatine administration...
October 1, 2016: Pain
Tara F Carr
OBJECTIVE: The aim of this paper was to review the classification of adverse drug reactions, highlight the known pathophysiology of immediate hypersensitivity reactions, and discuss the utility of diagnostic testing for immunologically mediated immediate reactions to gadolinium-based contrast agents (GBCAs). METHODS: Current literature on immediate reactions to GBCA was reviewed and summarized. RESULTS: Adverse drug reactions to GBCA are rare, and can be attributed to physiologic, immunologic, and nonimmunologic processes...
June 29, 2016: Topics in Magnetic Resonance Imaging: TMRI
James R Costello, Bobby Kalb, Diego R Martin
Since their clinical introduction in 1988, gadolinium-based contrast agents (GBCAs) have demonstrated an excellent safety profile with a reported acute adverse reaction rate ranging from 0.01% to 2%. By comparison, the acute adverse reaction rate of low osmolar nonionic computed tomography contrast agents (CTCs) ranges from 0.7% to 3.1%. Many of the risk factors associated with CTC reactions (drug allergies, asthma, atopy, prior contrast reaction) also point toward an increased incidence of acute adverse events to GBCAs...
June 29, 2016: Topics in Magnetic Resonance Imaging: TMRI
Dario Gulin, Jozica Sikic, Jasna Cerkez Habek, Sandra Jerkovic Gulin, Edvard Galic
Eosinophilic myocarditis (EM) is a rare and potentially fatal disease if left untreated. Because the disease can have a delayed presentation and can appear even after 2 years, its underlying causes often remain unknown. We report the case of a 63-year-old man with an atypical clinical presentation of hypersensitive EM and significant coronary artery disease, which was confirmed through coronary angiography. The patient was treated with hydrochlorothiazide (12.5 mg once daily for 2 years) and budesonide/formoterol (160/4...
December 2016: Drug Saf Case Rep
Marc D Cohen, Edward Keystone
Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors...
December 2015: Rheumatol Ther
Gemma Amo, José A Cornejo-García, Jesus M García-Menaya, Concepcion Cordobes, M J Torres, Gara Esguevillas, Cristobalina Mayorga, Carmen Martinez, Natalia Blanca-Lopez, Gabriela Canto, Alfonso Ramos, Miguel Blanca, José A G Agúndez, Elena García-Martín
The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity...
2016: Frontiers in Pharmacology
Jiawei Guan, Qian Zhao, Weifeng Mao
PTEN is a tumor suppressor gene characterized as a phosphatase that antagonizes the phosphatidylinositol 3-kinase signaling pathway in the cytoplasm. Nuclear PTEN plays roles in chromosomal stability, in which the double-strand breaks (DSB) repair mediated by homologous recombination (HR) and non-homologous end joining (NHEJ) is critical. Herein, the role of nuclear PTEN in DSB repair and the underlying molecular mechanism was investigated in this study. Using human breast cancer BT549 and MDA-MB-231 cell lines, we reveal a specific feature of PTEN that controls poly(ADP-ribosyl)ation of Ku70 and interferes with binding of Ku70 at DSB...
October 11, 2016: Biochimica et Biophysica Acta
Thomas Schluep, Jason Lickliter, James Hamilton, David L Lewis, Ching-Lung Lai, Johnson Yn Lau, Stephen A Locarnini, Robert G Gish, Bruce D Given
ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase I, randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (N = 36) or placebo (N = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement)...
October 14, 2016: Clinical Pharmacology in Drug Development
G Cortellini, A Romano, A Santucci, A Barbaud, S Bavbek, D Bignardi, M Blanca, P Bonadonna, M T Costantino, J J Laguna, C Lombardo, L Losappio, J Makowska, A Nakonechna, O Quercia, E A Pastorello, V Patella, I Terreehorst, S Testi, J R Cernadas, J Dionicio Elera, D Lippolis, S Voltolini, D Grosseto
BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, the present study aims to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel...
October 12, 2016: Allergy
Jiwon Lee, Eu Gene Park, Munhyang Lee, Jeehun Lee
BACKGROUND AND PURPOSE: Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. METHODS: This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses...
October 7, 2016: Journal of Clinical Neurology
Ankush Gupta, Uma A Bhosale, Priyank Shah, Radha Yegnanarayan, Shalini Sardesai
BACKGROUND: Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy...
September 2016: Annals of Neurosciences
Namrata Balaraddiyavar, Aruna Bhushan, Basavaraj C Kotinatot, Gouramma Huggi
Here, we report a case of a 30-year-old male who was prescribed eperisone hydrochloride for body pain and loose stools after which he developed severe maculopapular rash. Eperisone hydrochloride is an analgesic and antispastic drug used for spastic diseases such as spastic paralysis in cerebrovascular diseases, cervical spondylosis, and periarthritis. The drug is marketed in most of the Asian countries including India, but it is not licensed. Studies show the history of hypersensitivity in other countries, but this is the first reported case in India...
September 2016: Indian Journal of Pharmacology
Yanbing Zu, Min-Han Tan, Chee Ren Ee, Jackie Y Ying
A number of human leukocyte antigen (HLA) gene alleles have been found to be genetic risk markers for immunologically mediated drug hypersensitivity. Clinical adoption of HLA pharmacogenomics requires facile and accurate allele screening assays. As HLA genes are highly polymorphic, currently available methods are usually labor-intensive and liable to generate false positives. Herein we report a general strategy for screening HLA alleles with nanoparticle probes. Specific HLA alleles can be identified by gauging three to five sequence variants...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
David A Khan
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively...
October 2016: Journal of Allergy and Clinical Immunology
Tatiana Duarte, Sara Gonçalves, Catarina Sá, Rita Marinheiro, Rita Rodrigues, Filipe Seixo, Elza Tomas, Rui Caria
Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are common and five types of reactions have been defined. The prevalence of such reactions in patients with myocardial infarction is unclear, and so antiplatelet therapy in this population is a challenge. Various desensitization protocols have been developed but there are no specific guidelines for their use. The authors present the case of a patient with acute coronary syndrome and aspirin hypersensitivity referred for urgent coronary angiography...
October 4, 2016: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
Adam N Williams
Aspirin-exacerbated respiratory disease (AERD) is a distinct clinical condition characterized by chronic sinusitis with nasal polyps, asthma, and hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Distinguishing AERD from other forms of chronic sinusitis, asthma, and NSAID reactivity has important clinical implications for management. The clinical history is helpful, but not adequate for confirming the diagnosis of AERD, in most cases. Diagnostic provocation challenge remains the only way to confirm or exclude the diagnosis of AERD...
November 2016: Immunology and Allergy Clinics of North America
Kristen M Walters, Katharine M Woessner
Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the most commonly used drugs worldwide. They account for a large number of adverse drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing. Distinguishing between a predicted side effect of a drug and a potentially life-threatening hypersensitivity reaction is essential to manage the affected patient. However, most clinicians find it difficult to diagnose these types of reactions despite published classification schemes...
November 2016: Immunology and Allergy Clinics of North America
Francesco Gaeta, Maria J Torres, Rocco Luigi Valluzzi, Cristiano Caruso, Cristobalina Mayorga, Antonino Romano
Hypersensitivity reactions to β-lactam antibiotics are commonly reported. They can be classified as immediate or non-immediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within one hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. Non-immediate reactions occur more than one hour after the last drug administration...
October 4, 2016: Current Pharmaceutical Design
Lene H Garvey
Perioperative hypersensitivity reactions are rare, often life-threatening events, and subsequent investigations to identify the culprit are important to avoid re-exposure. All exposures in the perioperative setting may potentially be the cause of a hypersensitivity reaction, but drugs administered intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns and performance and interpretation of investigations...
October 4, 2016: Current Pharmaceutical Design
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