Auto-Generated Physiological Chain Data for an Ontological Framework for Pharmacology and Mechanism of Action to Determine Suspected Drugs in Cases of Dysuria

Masayo Hayakawa (), Takeshi Imai, Yoshimasa Kawazoe, Kouji Kozaki and Kazuhiko Ohe
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Masayo Hayakawa: National Cancer Center
Takeshi Imai: The University of Tokyo
Yoshimasa Kawazoe: The University of Tokyo
Kouji Kozaki: Osaka Electro-Communication University
Kazuhiko Ohe: The University of Tokyo

Drug Safety, 2019, vol. 42, issue 9, No 4, 1055-1069

Abstract: Abstract Introduction Patients often take several different medications for multiple conditions concurrently. Therefore, when adverse drug events (ADEs) occur, it is necessary to consider the mechanisms responsible. Few approaches consider the mechanisms of ADEs, such as changes in physiological states. We proposed that the ontological framework for pharmacology and mechanism of action (pharmacodynamics) we developed could be used for this approach. However, the existing knowledge base contains little data on physiological chains (PCs). Objective We aimed to investigate a method for automatically generating missing PC from the viewpoint of anatomical structures. This study was conducted to determine dysuria-related adverse events more likely to occur during multidrug administration. Methods We adopted a systematic approach to determine drugs suspected to cause adverse events and incorporated existing data and data generated in our newly developed method into our ontological framework. The performance of automated data generation was evaluated using this newly developed system. Suspected drugs determined by the system were compared with those derived from adverse events databases. Results Of the 242 drugs involving suspected drug-induced urinary retention or dysuria, 26 suspected drugs were determined. Of these, five were drugs with side effects not listed in drug package inserts. The system derived potential mechanisms of action, PCs, and suspected drugs. Conclusion Our method is novel in that it generates PC data from anatomical structural properties and could serve as a knowledge base for determining suspected drugs by potential mechanisms of action.

Date: 2019
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DOI: 10.1007/s40264-019-00833-2

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