Toxicology_Flashcards
(36 cards)
What is Toxicology?
The study of the potential harmful effects of chemicals on living organisms, biological systems and human health.
Who is considered the Father of Toxicology?
Philippus Aureolus Theophrastus Bombastus von Hohenheim, a.k.a. Paracelsus.
“All chemicals are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy.” - Paracelsus (1493 – 1541)
What are examples of toxic substances?
Drugs and their metabolites, occupational, environmental, household chemicals, pesticides, natural toxins (e.g. snake venom), food additives, and contaminants.
What was the mistake associated with Thalidomide?
Prescribed to relieve morning sickness during pregnancy, leading to malformations in new-borns. Withdrawn in 1961 after the link was proven.
Resulted in more rigorous drug testing before licensing.
What are examples of occupational toxicology?
Chimney sweeps’ carcinoma, nasal carcinomas in woodworkers, bladder cancer in dye workers, and neuropathy from hexane or carbon disulphide exposure.
What organs are most susceptible to toxic exposure?
Lungs, liver, kidneys, and the central nervous system.
What is the difference between acute and chronic toxic effects?
Acute effects develop rapidly and may be lethal, while chronic effects develop after the chemical is excreted and may result from long-term exposure.
Examples include cancer and neurodegenerative diseases.
What does ADME stand for in pharmacokinetics?
Absorption, Distribution, Metabolism, and Elimination.
How does absorption occur in pharmacokinetics?
Most therapeutics are orally administered and absorbed through the buccal/oral mucosa, stomach, and intestine.
What is the role of the Blood-Brain Barrier?
It is not an absolute barrier and has tight junctions between endothelial cells, with transmembrane transporters for efflux.
What are the phases of metabolism for xenobiotics?
Phase I involves modification (e.g. oxidation), and Phase II involves conjugation to increase solubility for excretion.
What is the role of Cytochrome P450?
A multigene superfamily involved in the metabolism of a broad range of compounds, with inhibition potentially leading to adverse effects.
What is the process of glucuronidation?
Modification of amine and hydroxyl groups to improve solubility, using UDP-glucuronosyltransferases.
What is the main organ for detoxification?
The liver, which contains high levels of phase I and conjugating enzymes.
What are the routes of elimination for metabolites?
Conjugated metabolites can be excreted via urine (major route) or via the biliary route.
What are the mechanisms of toxicity?
Involves exposure to toxic substances leading to adverse effects, including oxidative stress and generation of reactive oxygen species.
What is oxidative stress?
An imbalance between cellular production of reactive oxygen species and the ability to detoxify them or repair damage.
How does the body defend against reactive oxygen species?
By keeping free iron concentrations low and removing hydrogen peroxide and superoxide.
What is oxidative stress?
Imbalance between cellular production of reactive oxygen species (ROS) and the ability to detoxify ROS or repair damage.
How does low free iron concentration affect hydroxyl radical formation?
Keeping free iron (Fe2+/Fe3+) concentration low slows down hydroxyl radical formation.
What is the role of superoxide dismutase (SOD)?
Removes hydrogen peroxide and superoxide. This enzyme in isolation would not be enough.
What happens when SOD is combined with catalase?
Both superoxide and hydrogen peroxide are neutralized.
What is an alternative to catalase?
Glutathione peroxidase (GP) turns hydrogen peroxide into harmless water.
How is reduced glutathione regenerated?
Oxidized glutathione (GSSG) is regenerated to reduced glutathione (GSH) by glutathione reductase (GR).
