Chapter 4 lecture 5-6 Flashcards
Give another definition of toxicokinetics
- The time-course of movement of chemicals through the body
- how does the body dispose of a xenobiotic
What does the severity of toxicity depend on?
its concentration at the site
of action.
Recall what ADME are
- Absorption: How do toxicant enter to our body?
- Distribution: Whether the absorbed compound could move from the site of entry to the target organ to elicit toxic reaction
- Metabolism: Whether the chemical could be metabolized to a more or less toxic compound
- Excretion: How and how rapidly the chemical is removed from the body
What are the 7 aspects that are important for toxic disposition?
- Duration and concentration of substance at the site of entry
- Rate and amount that can be absorbed
- Distribution in the body and concentration at specific body sites
- Efficiency of biotransformation and nature of the metabolites
- The ability of the substance or it’s metabolites to pass through cell membranes and contact with specific cell components (e.g., DNA).
- The amount and duration of storage of the substance (or it’s metabolites) in body tissues
- The rate and sites of excretion
ADME are interelated, T/F?
True
What is the precise definition of absorption?
the process whereby toxicants cross body
membranes and enter the bloodstream
if the ingested material has not passed the ceullular barriers, should it be considered inside the body?
No, must pass through cellular barriers
What does route of absorption describe?
different pathway which chemical enters to our body
What does amount of absorption describe?
The amount of chemical absorbed determine how much it reaches the site of action
How is cell membrane related to absorption?
- formidable barriers
- a major body defense that prevents foreign invaders or substances from entering body tissues.
- cells are so tightly that can barely be pass through
What is the basic requirement for xenobiotics to cause adverse effects?
Must be able to penetrate multiple cell membranes.
Why many toxicants are hydrophobic?
The phospholipid bilayers of cell mem is hydrophobic.
What are the physiochemical characteristics of the substance that determine absorption?
- Size/shape
- Lipid solubility/ hydrophobicity
- Structural similarity to endogenous molecules
- Charge/ polarity
Bisphenol A (BPA) an endocrine disruptor. Structure similar to estrogen
Name some features of passive diffusion
- Along concentration gradient
- Diffusion will continue until the concentration is equal on both sides of the membrane
- Substances with high lipid solubility can move either through small pores or directly through membrane
- Non-polar/ionized substance
- Small hydrophilic molecules can pass through channel proteins
Name some features of facilitated diffusion
- Does not require energy
- carrier-mediated
- Move larger molecules
- transport of sugar and amino acids
- Process is saturated and competitively inhibited
Passive diffusion vs Facilitated diffusion
- Passive diffusion:
-no limit to the number that can fit through the membrane
-rate of diffusion increases linearly when more particles at one side of the membrane. - Facilitated diffusion:
-the rate of diffusion is determined by the number of channels and number of particles
Both do not require ATP
Name some features of active transport
- Transport xenobiotics into liver, kidney and CNS
- Electrolyte and nutrient balance
- Specific membrane carrier -> low to high conc
- Needs metabolic energy -> ATP
- Can be inhibited by metabolic poison
- May be saturated at high conc/ compete for uptake
