Dataset Information

Common causes and characteristics of adverse drug reactions in older adults: a retrospective study.

ABSTRACT: Background: Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (?65?years) in comparison to younger individuals (
Methods: Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults.

Results: In total, 4152 (22.0%) ADRs were reported for 3437 older adults (mean age, 74.6?years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21-1.44; P?
Conclusion: For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.

SUBMITTER: Woo SD

PROVIDER: S-EPMC7727226 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Common causes and characteristics of adverse drug reactions in older adults: a retrospective study.

Woo Seong-Dae SD Yoon Jiwon J Doo Go-Eun GE Park Youjin Y Lee Youngsoo Y Lee So-Hee SH Lee Young-Hee YH Ye Young-Min YM

BMC pharmacology & toxicology 20201210 1

<h4>Background</h4>Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (< 65 years).<h4>Methods</h4>Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the nu ...[more]

PMID: 33303036

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Project description:BackgroundOlder adults are more prone to develop adverse drug reactions (ADRs) since they exhibit numerous risk factors. The first aim was to analyse the number of spontaneous ADR reports regarding older adults (> 65) in the ADR database of the German Federal Institute for Drugs and Medical Devices (BfArM) and to set them in relation to i) the number of ADR reports concerning younger adults (19-65), and ii) the number of inhabitants and assumed drug-exposed inhabitants. The second aim was to analyse, if reported characteristics occurred more often in older vs. younger adults.MethodsAll spontaneous ADR reports involving older or younger adults within the period 01/01/2000-10/31/2017 were identified in the ADR database. Ratios concerning the number of ADR reports/number of inhabitants and ADR reports/drug-exposed inhabitants were calculated. The reports for older (n = 69,914) and younger adults (n = 111,463) were compared using descriptive and inferential statistics.ResultsThe absolute number of ADR reports involving older adults increased from 1615 (2000) up to 5367 ADR reports (2016). The age groups 76-84 and 70-79 had the highest number of ADR reports with 25 ADR reports per 100,000 inhabitants and 27 ADR reports per 100,000 assumed drug-exposed inhabitants. For both ratios, the number of reports was higher for males (26 and 28 ADR reports) than for females (24 and 26 ADR reports). Fatal outcome was reported almost three times more often in older vs. younger adults. Six out of ten drug substances most frequently suspected were antithrombotics (vs. 1/10 in younger adults). For some drug substances (e.g. rivaroxaban) the ADRs reported most frequently differed between older (epistaxis) and younger adults (menorrhagia).ConclusionsThere is a need to further investigate ADRs in older adults since they occurred more frequently in older vs. younger adults and will likely increase in future. Physicians should be aware of different ADRs being attributed to the same drug substances which may be more prominent in older adults. Regular monitoring of older adults taking antithrombotics is recommended.

Project description:BackgroundHuman leukocyte antigen (HLA) surface proteins are directly involved in idiosyncratic adverse drug reactions. Herein, we present a structure-based analysis of the common HLA-B*57:01 variant known to be responsible for several HLA-linked adverse effects such as the abacavir hypersensitivity syndrome.MethodsFirst, we analyzed three X-ray crystal structures involving the HLA-B*57:01 protein variant, the anti-HIV drug abacavir, and different co-binding peptides present in the antigen-binding cleft. We superimposed the three complexes and showed that abacavir had no significant conformational variation whatever the co-binding peptide. Second, we self-docked abacavir in the HLA-B*57:01 antigen binding cleft with and without peptide using Glide. Third, we docked a small test set of 13 drugs with known ADRs and suspected HLA associations.ResultsIn the presence of an endogenous co-binding peptide, we found a significant stabilization (~2 kcal/mol) of the docking scores and identified several modified abacavir-peptide interactions indicating that the peptide does play a role in stabilizing the HLA-abacavir complex. Next, our model was used to dock a test set of 13 drugs at HLA-B*57:01 and measured their predicted binding affinities. Drug-specific interactions were observed at the antigen-binding cleft and we were able to discriminate the compounds with known HLA-B*57:01 liability from inactives.ConclusionsOverall, our study highlights the relevance of molecular docking for evaluating and analyzing complex HLA-drug interactions. This is particularly important for virtual drug screening over thousands of HLA variants as other experimental techniques (e.g., in vitro HTS) and computational approaches (e.g., molecular dynamics) are more time consuming and expensive to conduct. As the attention for drugs' HLA liability is on the rise, we believe this work participates in encouraging the use of molecular modeling for reliably studying and predicting HLA-drug interactions. Graphical abstract.

Dataset Information

Common causes and characteristics of adverse drug reactions in older adults: a retrospective study.

Publications

Common causes and characteristics of adverse drug reactions in older adults: a retrospective study.

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