Study Set Content:
Therapeutic Index formula
TI = TD50/ED50
One way to overcome the limitation of comparing variable scopes between the effective and toxic dose response curve is to calculate the ED99 for the desired effect and the LD1 for the undesired effect. Typically, after a single administration of a chemical.
Margins of Safety and Exposure
Margins of Safety and Exposure formula
Margin of safety = LD1/ED99
refers to the range of doses over which a chemical produces increasing responses.
Potency
is the maximal efficacy that reflects the limit of the dose–response relationship on the response axis (yaxis) to a certain chemical.
Efficacy
Chemical produces injury to one kind of living matter (such as a cell or organism) without harming another form of life even though the two may exist in intimate contact.
Selective Toxicity
Are both quantitative and qualitative differences in response to toxic substances may occur among different species even though you can extrapolate those data.
Species Differences
Not all humans respond to toxicants in the same manner and to the same degree as each other. Multiple factors modify one’s susceptibility to adverse outcomes
o Genetics o Age o Sex o Circadian Rhythm o Microbiome
The intensity of a toxic effect depends on the () and () of the ultimate toxicant
concentration, persistence
is the chemical species that reacts with the endogenous target molecule or critically alters the biological environment
ultimate toxicant
The ultimate toxicant can be the original chemical to which the organism is exposed (), a metabolite, or a reactive oxygen or nitrogen species () generated during the biotransformation of the toxicant, or an endogenous molecule.
parent compound, ROS or RNS
STEP 1
DELIVERY FROM THE SITE OF EXPOSURE TO THE TARGET
Transfer of a chemical from the site of exposure, usually an external or internal body surface, into the systemic circulation.
Absorption
First pass elimination
Presystemic Elimination
Mechanisms Facilitating Distribution to a Target
1. Porosity of the Capillary Endothelium 2. Specialized Transport across the PM (Plasma Membrane) 3. Accumulation in Cell Organelles 4. Reversible Intracellular Binding
Mechanisms Oppose Distribution to a Target
1. Binding to Plasma Proteins 2. Specialized Barriers 3. Distribution to Storage Sites 4. Association with Intracellular Binding Proteins 5. Export from Cells
Removal of xenobiotics from blood and their return to the external environment.
Excretion
Re-entry of toxicants in to the blood by tubular reabsorption
Reabsorption
Biotransformation to harmful products. Also known as metabolic activation.
Toxication
Biotransformation that eliminates the ultimate toxicant or prevent its formation.
Detoxication
