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Idiosyncratic Drug Reactions: Current Understanding

2006· review· en· W2161643992 on OpenAlexaff
Jack Uetrecht

Bibliographic record

VenueThe Annual Review of Pharmacology and Toxicology · 2006
Typereview
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsIdiosyncrasyCircumstantial evidenceDrugMechanism (biology)BiologyComputational biologyPharmacologyEpistemology

Abstract

fetched live from OpenAlex

Clinical characteristics and circumstantial evidence suggest that idiosyncratic drug reactions are caused by reactive metabolites and are immune-mediated; however, there are few definitive data and there are likely exceptions. There are three principal hypotheses for how reactive metabolites might induce an immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger hypothesis, and the PI hypothesis. It has been proposed that some idiosyncratic reactions, especially those involving the liver, represent metabolic idiosyncrasy; however, there are even less data to support this hypothesis. The unpredictable nature of these reactions makes mechanistic studies difficult. There is a very strong association with specific human leukocyte antigen (HLA) genes for certain reactions, but this has only been demonstrated for very few drugs. Animal models represent a very powerful tool for mechanistic studies, but the number of valid models is also limited. There may be biomarkers of risk; however, much more work needs to be done.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.006
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0030.003
Science and technology studies0.0000.002
Scholarly communication0.0030.004
Open science0.0020.001
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0060.004

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.222
GPT teacher head0.498
Teacher spread0.276 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations299
Published2006
Admission routes1
Has abstractyes

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