Pharmacogenomics of Hypersensitivity to Non-steroidal Anti-inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively prescribed in daily clinical practice. NSAIDs are the main cause of drug hypersensitivity reactions all over the world. The inhibition of cyclooxygenase enzymes by NSAIDs can perpetuate arachidonic acid metabolism, shunting to the 5-lipoxygenase pathway and its downstream inflammatory process. Clinical phenotypes of NSAID hypersensitivity are diverse and can be classified into cross-reactive or selective responses. Efforts have been made to understand pathogenic mechanisms, in which, genetic and epigenetic backgrounds are implicated in various processes of NSAID-induced hypersensitivity reactions. Although there were some similarities among patients, several genetic polymorphisms are distinct in those exhibiting respiratory or cutaneous symptoms. Moreover, the expression levels, as well as the methylation status of genes related to immune responses were demonstrated to be involved in NSAID-induced hypersensitivity reactions. There is still a lack of data on delayed type reactions. Further studies with a larger sample size, which integrate different genetic pathways, can help overcome current limitations of gen etic/epigenetic studies, and provide valuable information on NSAID hypersensitivity reactions.

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Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs

Frontiers in Pharmacology ◽

10.3389/fphar.2020.594427 ◽

2020 ◽

Vol 11 ◽

Author(s):

Raquel Jurado-Escobar ◽

Inmaculada Doña ◽

Gador Bogas-Herrera ◽

Natalia Pérez-Sánchez ◽

María Salas ◽

...

Keyword(s):

Acute Phase ◽

Drug Hypersensitivity ◽

Arachidonic Acid Metabolism ◽

Cysteinyl Leukotriene ◽

Cyclooxygenase 1 ◽

Drug Hypersensitivity Reactions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Adherent Leukocytes

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most highly consumed drugs worldwide and the main triggers of drug hypersensitivity reactions. The most frequent reaction, named cross-reactive NSAID-hypersensitivity, is due to the pharmacological activity of these drugs by blocking the cyclooxygenase-1 enzyme. Such inhibition leads to cysteinyl-leukotriene synthesis, mainly LTE4, which are responsible for the reaction. Although the complete molecular picture of the underlying mechanisms remains elusive, the participation of platelet-adherent leukocytes (CD61+) and integrins have been described for NSAID-exacerbated respiratory disease (NERD). However, there is a lack of information concerning NSAID-induced urticaria/angioedema (NIUA), by far the most frequent clinical phenotype. Here we have evaluated the potential role of CD61+ leukocytes and integrins (CD18, CD11a, CD11b, and CD11c) in patients with NIUA, and included the other two phenotypes with cutaneous involvement, NSAID-exacerbated cutaneous disease (NECD) and blended reactions (simultaneous skin and airways involvement). A group NSAID-tolerant individuals was also included. During the acute phase of the reaction, the three clinical phenotypes showed increased frequencies of CD61+ neutrophils, eosinophils, and monocytes compared to controls, which correlated with urinary LTE4 levels. However, no correlation was found between these variables at basal state. Furthermore, increased expressions of CD18 and CD11a were found in the three CD61+ leukocytes subsets in NIUA, NECD and blended reactions during the acute phase when compared with CD61−leukocyte subpopulations. During the acute phase, CD61+ neutrophils, eosinophils and monocytes showed increased CD18 and CD11a expression when compared with CD61+ leukocytes at basal state. No differences were found when comparing controls and CD61+ leukocytes at basal state. Our results support the participation of platelet-adherent leukocytes and integrins in cutaneous cross-hypersensitivity to NSAIDs and provide a link between these cells and arachidonic acid metabolism. Our findings also suggest that these reactions do not involve a systemic imbalance in the frequency of CD61+ cells/integrin expression or levels of LTE4, which represents a substantial difference to NERD. Although further studies are needed, our results shed light on the molecular basis of cutaneous cross-reactive NSAID-hypersensitivity, providing potential targets for therapy through the inhibition of platelet-leukocyte interactions.

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Ipersensibilità ai FANS: intolleranza o allergia?

Medico e Bambino ◽

10.53126/meb40037 ◽

2021 ◽

Vol 40 (1) ◽

pp. 37-43

Author(s):

Laura Levantino ◽

Cristiana Corrado ◽

Laura Badina ◽

Sara Lega ◽

Egidio Barbi

Keyword(s):

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Hypersensitivity Reactions ◽

Provocation Tests ◽

Immunological Mechanisms ◽

Drug Hypersensitivity Reactions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Drug Provocation Tests ◽

Cox 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions in children. According to the EAACI latest classification NSAIDs hypersensitivity reactions are differentiated into cross-reactive reactions, with non-immunological mechanisms (based on COX-1 inhibition), and selective reactions, with immunological mechanisms. Paediatric clinical manifestations of NSAID hypersensitivity are typically cutaneous, but sometimes, similarly to anaphylaxis, can involve other systems, especially the respiratory one. Differentiating between NSAID intolerance and NSAID allergy through drug provocation tests is crucial for the patient because the two clinical entities require different management.

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Analysis of the Costs Associated With the Elective Evaluation of Patients Labelled as Allergic to Beta-Lactams or Nonsteroidal Antiinflamatory Agents

Frontiers in Pharmacology ◽

10.3389/fphar.2020.584633 ◽

2020 ◽

Vol 11 ◽

Author(s):

Miriam Sobrino-García ◽

Esther M. Moreno ◽

Francisco J. Muñoz-Bellido ◽

Maria T. Gracia-Bara ◽

Elena Laffond ◽

...

Keyword(s):

Scientific Evidence ◽

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Inclusion Criteria ◽

Beta Lactams ◽

Drug Hypersensitivity Reactions ◽

Clinical Consequences ◽

Bibliographic Search ◽

Inflammatory Drugs ◽

Anti Inflammatory

Introduction: Being labelled as allergic to different drugs results in patients receiving other treatments, which are more toxic, less effective and more expensive. We aimed to analyze different studies of the costs of drug hypersensitivity assessment.Methods: A bibliographic search on studies regarding this issue was performed, including the available scientific evidence up to June 2020. We searched three databases with terms related to costs and allergy testing in drug hypersensitivity reactions.Results: Our search revealed 1,430 publications, of which 20 met the inclusion criteria. In the manuscript, prospective studies evaluating the costs of the evaluation of patients with suspected allergy to beta-lactams or non-steroidal anti-inflammatory drugs are analyzed. Also, comment is made on the costs associated with incorrect labeling as non-steroidal anti-inflammatory drug or penicillin hypersensitivity.Conclusions: Taking all costs into account, the study of drug hypersensitivity is not expensive, particularly considering the economic and clinical consequences of labeling a patient with hypersensitivity to drugs.

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Drugs of radiological pharmacology: Quercetin

Radiation Diagnostics, Radiation Therapy ◽

10.37336/2707-0700-2020-2-7 ◽

2020 ◽

pp. 81-83

Author(s):

Nikolay Kolotilov

Keyword(s):

Blood Circulation ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Influenza Viruses ◽

Radioprotective Activity ◽

Lipoxygenase Pathway ◽

X Ray ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Necrosis Factor

The purpose of the article is to draw attention to Quercetin as a means of radiological pharmacology within the framework of medicines’ repurposing. Spectrum of pharmacological activity. Quercetin possesses anti-inflammatory (blockade of the lipoxygenase pathway of arachidonic acid metabolism, decreased synthesis of leukotrienes, serotonin and other inflammatory mediators), antioxidant, antispasmodic, diuretic, membrane stabilizing, capillary stabilizing, regenerative, estrogen-like (effect on proline hydroxylase, inhibition of tumor necrosis factor and synthesis of interleukins), immunomodulatory, anticataractogenic, antisclerotic, angioprotective, antiviral (against influenza viruses), antitumor, proosteoclastic, gastroprotective, actoprotective action. Quercetin exhibits antiulcer action associated with the anti-inflammatory drugs, and also has a radioprotective activity (after X-ray and gamma irradiation). The cardioprotective properties of Quercetin are conditioned by an increase in the energy supply of cardiomyocytes due to its antioxidant effect and an improvement in blood circulation. Quercetin influences bone remodeling processes. Quercetin is able to normalize blood pressure and stimulate the release of insulin, accelerate platelet aggregation, and inhibit thromboxane synthesis. Key Words: Quercetin, radioprotector, senolytic effect, dietary supplement.

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