Notice bibliographique
Résumé
Abstract There is a large amount of circumstantial evidence that supports the hypothesis that most idiosyncratic drug reactions (IDRs) are caused by reactive metabolites rather than the parent drug. When the total daily dose is included in the calculation, there is a rough correlation between the amount of covalent binding and the risk that a drug will be associated with a significant incidence of IDRs, especially those affecting the liver. However, there are drugs that form a large amount of reactive metabolites and rarely cause IDRs, and there are drugs such as ximelagatran that do not appear to form reactive metabolites and yet had to be withdrawn from the market because of an unacceptable risk of IDRs. There are a wide variety of proteins that are targets of covalent binding, and clearly, not all covalent binding is associated with the same risk of causing an IDR. It is likely that most IDRs are immune mediated, although this is not without controversy, especially with respect to idiosyncratic liver toxicity. There are several hypotheses that address the issue of how drugs initiate an immune response, but in the absence of valid animal models, they are very difficult to rigorously test. These hypotheses include the hapten hypothesis, the danger hypothesis, the p‐I (pharmacological interaction) hypothesis, epigenetic effects leading to activation of the immune system, direct activation of antigen‐presenting cells, and some of the newer biological agents simply appear to alter the balance in the immune system and do not involve reactive metabolites. It is likely that the mechanism by which different drugs induce an immune response is different, at least in detail. There are also hypotheses that do not involve the immune system such as mitochondrial toxicity and the inflammagen hypothesis. In the absence of valid animal models, it is important to use the clinical characteristics of IDRs to evaluate the hypotheses. A very important characteristic is the usual delay between starting a drug and the onset of the IDR. Another important characteristic is that different drugs can cause different types of IDRs in different people and even the same drug can cause different types of IDRs in different people. This is most easily explained by an immune mechanism in which this variability is due to variability in T‐cell‐receptor specificity, which is different even in identical twins. However, until we have a much better understanding of the detailed mechanisms of IDRs, it will be difficult to predict which drug candidates are likely to cause a relatively high incidence of IDRs and which patients are at high risk of such adverse reactions.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».