scholarly journals Type B adverse drug reactions reported by an immunoallergology department

2018 ◽  
Vol 16 (1) ◽  
pp. 1070 ◽  
Author(s):  
Maria J. Costa ◽  
Maria T. Herdeiro ◽  
Jorge J. Polónia ◽  
Ines Ribeiro-Vaz ◽  
Cármen Botelho ◽  
...  
PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11774
Author(s):  
Hannah McConnell ◽  
T. Daniel Andrews ◽  
Matt A. Field

Background Pharmacogenetic variation is important to drug responses through diverse and complex mechanisms. Predictions of the functional impact of missense pharmacogenetic variants primarily rely on the degree of sequence conservation between species as a primary discriminator. However, idiosyncratic or off-target drug-variant interactions sometimes involve effects that are peripheral or accessory to the central systems in which a gene functions. Given the importance of sequence conservation to functional prediction tools—these idiosyncratic pharmacogenetic variants may violate the assumptions of predictive software commonly used to infer their effect. Methods Here we exhaustively assess the effectiveness of eleven missense mutation functional inference tools on all known pharmacogenetic missense variants contained in the Pharmacogenomics Knowledgebase (PharmGKB) repository. We categorize PharmGKB entries into sub-classes to catalog likely off-target interactions, such that we may compare predictions across different variant annotations. Results As previously demonstrated, functional inference tools perform variably across the complete set of PharmGKB variants, with large numbers of variants incorrectly classified as ‘benign’. However, we find substantial differences amongst PharmGKB variant sub-classes, particularly in variants known to cause off-target, type B adverse drug reactions, that are largely unrelated to the main pharmacological action of the drug. Specifically, variants associated with off-target effects (hence referred to as off-target variants) were most often incorrectly classified as ‘benign’. These results highlight the importance of understanding the underlying mechanism of pharmacogenetic variants and how variants associated with off-target effects will ultimately require new predictive algorithms. Conclusion In this work we demonstrate that functional inference tools perform poorly on pharmacogenetic variants, particularly on subsets enriched for variants causing off-target, type B adverse drug reactions. We describe how to identify variants associated with off-target effects within PharmGKB in order to generate a training set of variants that is needed to develop new algorithms specifically for this class of variant. Development of such tools will lead to more accurate functional predictions and pave the way for the increased wide-spread adoption of pharmacogenetics in clinical practice.


2018 ◽  
Author(s):  
James L Baldwin ◽  
Aimee L. Speck

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis


2018 ◽  
Author(s):  
James L Baldwin ◽  
Aimee L. Speck

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis


2014 ◽  
Vol 50 (2) ◽  
pp. 411-422 ◽  
Author(s):  
Marília Berlofa Visacri ◽  
Cinthia Madeira de Souza ◽  
Rafaela Pimentel ◽  
Cristina Rosa Barbosa ◽  
Catarina Miyako Shibata Sato ◽  
...  

The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs) in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kye Hwa Lee ◽  
Dong Yoon Kang ◽  
Hyun Hwa Kim ◽  
Yi Jun Kim ◽  
Hyo Jung Kim ◽  
...  

Open Medicine ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. 37-44
Author(s):  
Maria Ganeva ◽  
Tanya Gancheva ◽  
Ivan Baldaranov ◽  
Jeni Troeva ◽  
Evgenya Hristakieva

AbstractThe aim of the study was to evaluate the pattern of utilization of systemic drugs used in the management of adverse drug reactions (ADRs) leading to hospitalization. A prospective pharmacovigilance study was carried out among patients admitted to the Clinic of Dermatology and Venereology in Stara Zagora (July 1999–June 2009). ADRs were classified by type, severity and causality. Casecausality was scored according to Naranjo et al. (1981). Drug utilization was measured in defined daily doses (DDDs) per 100 hospital bed days. A total of 144 cutaneous ADRs, predominantly “type B” were the reason for hospitalization. Highest utilization for the management of ADRs was found for the drug groups “Blood and blood forming organs” (406.08 DDDs/100 bed days) and “Respiratory system” (111.15 DDDs/100 bed days). The use of DDD for measuring drug utilization reveals the importance of drug-induced exacerbations of chronic skin diseases like psoriasis which were associated with significant utilization of drugs belonging to the group “Blood and blood forming organs”. Considering the low preventability of “type B” ADRs, our findings suggest that potential reduction of drug-related hospitalizations may be achieved through the rational use of drugs in patients with comorbidities.


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