Nedim Lecture Review: Absorption, Disposition, Excretion of Toxicants Drug development/Drug toxicology Flashcards
What are the composite actions for the disposition of a chemical(s)?
absorption, distribution, biotransformation,
and elimination
How are toxins transported?
Passive, active, special, facilitated transport
What are the factors that determine which molecules can pass through the membrane?
Physicochemical properties such as molecular weight, hydrophilicity, and polarity
Define Passive Transport ( in this case)
Fick’s law - chemicals move from regions of higher concentration to
regions of lower concentration without any energy expenditure.
Define special transport (in this case.)
Particles that are too large to pass through aqueous pores/ insoluble in lipids to diffuse across the lipid domains of membranes.
Nevertheless, they are often transported very rapidly across membranes, even against concentration gradients.
Define active transport ( in this case)
Movement of chemicals against electrochemical or concentration gradients
Saturability at high substrate concentrations
Selectivity for certain structural features of chemicals
Competitive inhibition by chemical congeners or compounds that are carried by the same transporter
Requirement for expenditure of energy, so that metabolic inhibitors block the transport process.
Define facilitated transport (in this case)
This process facilitates transport carrier-mediated transport that exhibits the properties of active transport except that the substrate
is not moved against an electrochemical or concentration gradient, and the transport process does not require the input of energy
Define absorption. Where does absorption occur?
the process by which toxicants cross body membranes to enter the bloodstream is called absorption.
location: GI tract, lungs, and skin.
Absorption and acid/base
If a toxicant is an organic acid or base, it can be absorbed by simple diffusion in the part of the GI tract where it exists in its most lipid-soluble (nonionized) form.
Other factors that influence the
absorption of xenobiotics?
pH,
* presence of food,
* digestive enzymes,
* bile acids,
* bacterial microflora in the GI tract,
* motility and permeability of the GI tract.
* For example, snake venoms, which are proteinaceous moieties, are much less toxic by
the oral route relative to intravenous exposure because they are degraded by digestive
enzymes of the GI tract.
What are the several factors that can influence the absorption of toxicants through the skin?
(1) the integrity of the stratum corneum,
(2) the hydration state of the stratum corneum,
(3) temperature, solvents as carriers,
(4) molecular size.
Distribution
primarily by blood flow and the rate
of diffusion out of the capillary bed into the cells of a particular organ or tissue, and usually
occurs rapidly.
volume of distribution (Vd),
Which organ has high-capacity storage?
kidney and liver
Which compounds are found in the bone matri x
fluoride, lead, and strontium
What are the 2 barriers that protect the brain?
the blood–brain barrier (BBB) and blood–cerebral spinal fluid barrier (BCSFB).