RT Book, Section A1 Gregus, Zoltán SR Print(0) ID 1100084449 T1 Mechanisms of Toxicity T2 Casarett and Doull's Toxicology: The Basic Science of Poisons, 8e YR 2012 FD 2012 PB McGraw-Hill Education PP New York, NY SN 978-0-07-176925-9 LK accesspharmacy.mhmedical.com/content.aspx?aid=1100084449 RD 2024/03/29 AB Step 1—Delivery: From the Site of Exposure to the TargetAbsorption versus PresystemicEliminationAbsorptionPresystemic EliminationDistribution To and Away from the TargetMechanisms Facilitating Distribution to a TargetMechanisms Opposing Distribution to a TargetExcretion versus ReabsorptionExcretionReabsorptionToxication versus DetoxicationToxicationDetoxicationStep 2—Reaction of the Ultimate Toxicant with the Target MoleculeAttributes of Target MoleculesTypes of ReactionsNoncovalent BindingCovalent BindingHydrogen AbstractionElectron TransferEnzymatic ReactionsEffects of Toxicants on Target MoleculesDysfunction of Target MoleculesDestruction of Target MoleculesNeoantigen FormationToxicity Not Initiated by Reaction with Target MoleculesStep 3—Cellular Dysfunction and Resultant ToxicitiesToxicant-Induced CellularDysregulationDysregulation of Gene ExpressionDysregulation of Ongoing Cellular ActivityToxic Alteration of Cellular MaintenanceImpairment of Internal Cellular Maintenance: Mechanisms of Toxic Cell DeathImpairment of External Cellular MaintenanceStep 4—Inappropriate Repair and AdaptationMechanisms of RepairMolecular RepairCellular RepairTissue RepairMechanisms of AdaptationAdaptation by Decreasing Delivery to the TargetAdaptation by Decreasing the Target Density or ResponsivenessAdaptation by Increasing RepairAdaptation by Compensating DysfunctionWhen Repair and Adaptation FailWhen Repair FailsWhen Adaptation FailsToxicity Resulting from Inappropriate Repair and AdaptationTissue NecrosisFibrosisCarcinogenesisConclusions