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Printable Handouts
Navigable Slide Index
- Introduction
- Overview
- Adverse drug reactions
- Mechanistic classification of drug reactions
- Classification of adverse drug reactions
- Products withdrawn from UK due to hepatotoxicity
- Drug metabolism: pharmacology - background
- Reminder: drug metabolism
- Variation in drug metabolism - toxicity
- Perhexilene maleate and CYP2D7
- Lipidosis induced by amphiphilic cationic drugs
- Prediction of variation in drug metabolism
- Off target clinical adverse drug reactions
- Drug metabolism: pharmacology - toxicity
- Immune mediated hepatotoxicity and bioactivation
- Metabolic basis of bioactivation and toxicity
- Prediction of toxic metabolites - methods
- Prediction of toxic metabolites - screens
- Screens for metabolic reactivity
- GSH conjugation
- Nucleophile traps for electrophilic intermediates
- Furosemide: hepatotoxicity (1)
- Characterisation of a reactive FS intermediate
- Trapping of FS intermediate by NAL and NAC
- Furosemide: hepatotoxicity (2)
- Screens for metabolic reactivity - covalent binding
- Covalent binding to protein
- How much covalent binding is acceptable: data
- How much covalent binding is acceptable: results
- Qualifying considerations
- Prediction of toxic metabolites - design
- 4-aminoquinoline antimalarials
- Amodiaquine: metabolism and toxicity
- 4-aminoquinolines: safety and efficacy in vitro
- Isoquine: glucuronylation
- Prediction of toxic metabolites - biology
- Acetaminophen/paracetamol
- Metabolism and toxicity of acetaminophen
- Functional consequences of adduct formation
- Mechanism of cell damage and critical proteins
- Hepatocyte: defence against drug-induced stress
- Mechanism of Nrf2-regulated gene induction
- Hepatic nuclear translocation of Nrf2 (1)
- Hepatic nuclear translocation of Nrf2 (2)
- Acetaminophen hepatotoxicity in mice
- Induction of Nrf2 by model hepatotoxins (1)
- Induction of Nrf2 by model hepatotoxins (2)
- Induction of Nrf2 by model hepatotoxins (3)
- Nrf2 activation: NAPQI
- Role of the adrenergic system
- Drug metabolism: toxicology
- Mechanism of cell damage: cell death (1)
- Mechanism of HMGB1 in acetaminophen toxicity
- Mechanism of cell damage: cell death (2)
- HMGB1 compared with serum ALT levels
- Effect of caspase inhibition: CK-18 and HMBG2
- Chain of events from drug to toxicity
- Making toxic or safe drugs
- Conclusions
Topics Covered
- Classification of adverse drug reactions
- How this relates to the chemical structure of the offending drug
- Understanding how variation in drug metabolism can contribute to clinical toxicity is important in designing pre-clinical models and screens
- Case studies of drugs which can form reactive metabolites and can irreversibly modify cellular protein
- Examples of structural modifications to chemicals containing toxicophores
- Novel and traditional serum and cellular biomarkers of adaptation, apoptosis and necrosis
Links
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Talk Citation
Williams, D. (2009, July 30). Cellular and molecular toxicology [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 7, 2024, from https://doi.org/10.69645/KPJD4996.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Dominic Williams has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.