Unit 2 Mechanism of Toxicity and Toxicokinetics Flashcards
Immunologically mediated adverse reaction to a chemical
Chemical Allergy
Situation when pre-exposure of chemical is required to produce
toxic effect
- Allergic reaction
- Sensitization reaction
refers to a genetically determined abnormal reactivity to a chemical
Chemical idiosyncrasy
Order of frequency of involvement in systemic toxicity
- CNS
- Circulatory system
- Blood and hematopoietic system
- Visceral organs (liver, kidney, lungs and skin)
Sources of Ultimate toxicant include:
- Parent compound from a biological source
- Metabolite
- Reactive Oxygen or Nitrogen Species produced by biotransformation reactions.
he intensity of the toxic effect depends on the concentration and persistence of the __________
ultimate toxicant
The_____________ is responsible for causing the toxicity
ultimate toxicant
Mechanisms Facilitating Distribution to a target
✔Porosity of the Capillary Endothelium
✔Specialized Transport across the Plasma membrane
✔Accumulation in cell organelles
✔Reversible Intracellular binding
Mechanisms Opposing distribution to a target
✔Binding to Plasma Proteins
✔Specialized Barriers
✔Distribution to Storage sites
✔Association with intracellular Binding Proteins
✔Export from Cells
possesses very long duration due to inability of effective elimination. This results to repeated exposure.
Highly Lipophilic Compounds
Excretion for Highly Lipophilic Compounds
- From the mammary gland (breast milk)
- Bile
- Intestinal lumen from blood
EXcretion for Volatile, nonreactive toxicants (gas and volatile liquids)
Pulmonary Capillaries and alveoli
Reabsorption happnes wherein the product can go back again into the system via
tubular fluid reabsorption
Possible production of Toxication (metabolic activation)
- Electrophiles
- Free Radicals
- Nucleophiles
- RedOx active reactants
Different mechanisms of detoxification
⮚Detoxification of Toxicants with no Functional Group
⮚Detoxification of Nucleophiles
⮚Detoxification of Electrophiles
⮚Detoxification of Free Radicals
⮚Detoxification of Protein Toxins
Detoxification Process and Enzyme of Toxicants with no Functional Group
Hydroxylation/c arboxylation Conjugation - CYP 450 Tranferase
Detoxification Process and Enzyme of Nucleophiles
Conjugation, Tranferases
Detoxification Process and Enzyme of Electrophiles
Conjugation, Glutathione S transferase
Detoxification Process and Enzyme of Free Radicals
ReDoX, Superoxide dismutase Glutathione peroxidase Catalase
Detoxification Process and Enzyme of Protein Toxins
Reduction, Thioredexin
Reasons for Failed Detoxification:
- Toxicant overwhelms the detoxification process
- Reactive toxicant inactivates a detoxifying agent enzyme
- Detoxification is reversed after transfer to other tissues
- Harmful by products are produced by the detoxification process
