Toxicokinetics -AD Flashcards
how a substance gets in the body and what happen to it in the body
Toxicokinetics
Four processes involved in toxicokinetics
- Administration
- Distribution
- Biotransformation
- Excretion
The substance enters the body
Absorption
Substance move from the site of entry to other areas of the body
Distribution
The body changes the substances into new chemicals
Biotransformations
The substance or its metabolite leave the body
Excretions
Studying the kinetics of all substances
Toxicokinetics
Use to describe the time course of movement of chemicals through the body
Disposition
Factors that determine the severity of toxicity that results when a xenobiotic enters the body
Toxicants disposition and its biological activity
Toxicants gain entry to the body
Absorption
Most important several factors affect the xenobiotic to be absorbed
- Route of exposure
- Concentration of substance at the site of contact
- chemical and physical properties of the substance
Primary routes of exposure by which xenobiotic can gain entry into the body are
- GI tract
- Respiratory tract
- Skin
The main route for many pharmaceuticals
GI tract
Some pharmaceuticals that is absorbed in respiratory tract
Aerosols and inhalers
Other routes of exposure
- Implants
- Injection
- Conjunctival instillations
- Suppositories
This permit slow and time release. (Ex)
For minimal absorptions (Ex)
Implants
Hormones
Artificial lenses or tendons
Primarily used for pharmaceuticals
Injection
Primarily treatment of ocular conditions
Conjunctival instillations
For drugs intended for local effect, usually __
Suppositories; vagina and rectal
Are formidable barriers, and an effective body defense that prevents foreign invaders or substances from entering the body
Cell membranes
Surrounds all body cells and are similar in structure
Cell membrane
Head is
Polar; hydrophilic; outward
Tail
Nonpoalr; lipophilic; inward
Those that can cross the cell membrane 2 methods
Passive transfer or facilitated transport
Consist of simple diffuse across the cell membrane; no cellular energy is required
Passive transfer
Require assistance or are facilitated by specialized transport mechanism
Facilitated transport
Example of specialized transport mechanism
- Facilitated diffusion
- active transport
- endocytosis
Most common way that xenobiotics cross the cell membrane
Passive diffusion
Two factors that determine the rate of passive diffusion of cell membrane
- concentration of the substance on both sides
- ability of the substance to move
Properties of the chemical substance that affects its ability for passive transfer
Lipid solubility
Molecular size
Degree of ionization
Most aqueous pore are about __ in size and allow chemicals of molecular weight of __ to pass through
4A in size; 100-200
similar to diffusion in a way that it does not energy and follows a concentration gradient
Facilitated diffusion
Carrier mediated transport; faster and capable of moving larger molecules
Facilitated diffusion
Examples of facilitated diffusion
Transport of sugar and amino acid
Movement through the membrane may be against the concentration gradient, from lower conc to higher conc
Active transport
Active transport require this energy
cellular energy from ADP
A toxicant can leave the interstitial fluid by:
- entering local tissue
- entering blood capillaries or blood circulatory system
- entering lymphatic cells
Active transport is essential in transporting xenobiotics into the ___.
Liver, kidney, CNS
When the substance cannot enter cells via passive or active mechanism, they may still enter through a process known as
Phagocytosis and pinocytosis
In this process the cell surrounds the substance with a section of its cell wall
Endocytosis
The two primary forms of endocytosis
Phagocytosis, Pinocytosis
Large particles suspended in the extracellular fluid are engulfed and transported into cells or destroyed
Phagocytosis
Engulfing liquids or tiny particles in suspension within extracellular fluid
Pinocytosis
Primary distribution of absorbed chemical is by __?
Blood
The total volume of body fluids in which a toxicant is distributed is the __.
apparent volume of distribution (Vd)
The VD is expressed in __
Liters
Formula for calculation of volume of distribution
VD = dose (mg)/ plasma conc (mg/L)
Provide reasonable estimates of how extensively the toxicant is distributed in the body
Volume of distribution
The body burden for a toxicant can be estimated from knowledge of Vd by using the formula __.?
body burden (mg) = plasma conc (mg/L) x VD (L)
Once a chemical is in the bloodstream, it may be __.?
ESBIT
Excreted
Stored
Biotransformed into different chemicals
Its metabolite may be excreted or stored
The chemical or metabolites may interact or bind with cellular component
