Flashcards in Final Study Guide: Toxicology and Heavy Metals Deck (72)
Definition of Toxicology
The study of the adverse effects of a chemical, physical or biological agent on living organisms and the ecosystem including the prevention of such adverse effects in...
What is Toxicity?
The ability of a material to damage a biological system, cause injury, or impair function.
What factors affect toxicity?
Dose, route of exposure, chemical species, along with age, gender, genetics, and nutritional status of exposed individuals.
What is a hazard?
Something that can cause harm and is defined by the inherent properties of the harmful agent.
What is a risk?
The chance or probability that a defined harm will actually occur from a specific hazard.
What is risk assessment?
takes into account both the probability of harm (based on expected frequency and duration of exposure to a hazardous agent) as well as the severity of the hazard itself.
Risk = Hazard + Exposure
What is Toxicokinetics?
It refers to the ADME and clearance of a toxic substance
What is Toxicodynamics?
It refers to the interaction of toxic substance and the body.
What is ADME?
Adsorption, Distribution, Metabolism, and Excretion
What is Clearance?
plasma cleared per unit time
*Includes both the renal and hepatic contributions
In what two ways does Clearance occur?
-Drug or toxin is METABOLIZED into other chemical species
-Drug or toxin is removed from the body by ELIMINATION from a specific organ
If a substance is 95% metabolized by the liver to a totally inactive from and the remaining 5% excreted by the kidney then will a therapy that increases the renal excretion of it be of much benefit for improving clearance?
Under normal conditions Elimination of most drugs/chemicals is proportional to what?
Their plasma concentration
(1st order kinetics)
What happens when plasma levels become very high?
Protein binding and normal metabolism can both become saturated.
What happens when protein binding and normal metabolism both become saturated?
The rate of elimination can become fixed,
(Zero order Kinetics), and more drug will be delivered directly to the circulation in unbound fraction that is not readily able to be metabolized and cleared by renal and hepatic mechanisms.
What happens at toxic doses of a drug or toxin?
Normal kinetics may be altered to reflect prolonged half-life and increased toxicity (Larger, unbound free fractions)
What is volume of Distribution (Vd)?
apparent volume in which a substance is distributed throughout the body.
What are characteristics of compounds with large Vd's?
Implies a substance will not be easily accessible to purification attempts (e.g. hemodialysis)
Examples: antidepressants, antipsychotics, antimalarials, and opioids.
What are characteristics of compounds with smaller Vd's?
Are generally more accessible and thus better candidates for hemodialysis.
Examples: Salicylates, ethanol, phenobarbital.
What is Bioaccumulation?
accumulation of toxic agent in an individual when the uptake of the agent exceeds the organism's ability to metabolize/excrete it across time.
*one organism across time
What is Biomagnification?
Increases in relative amount of a contaminant in member of a population as it passes up the food chain.
What is a heavy metal?
Natural elements (metals) that have a high atomic weight and possess a density at least five dimes greater that that of water. (i.e. specific density > 5 gm/cm3)
What are the 4 (toxic?) heavy metals in this lecture?
*chromium, nickel, and tin are also examples of heavy metals widely used in commercial manufacturing.
At low doses some heavy metals are what?
(Typically iron, manganese, cobalt, and zinc)
*large amounts can be toxic
Deficiencies in essential metals may cause what?
Worsening of outcomes from heavy metal poisoning.
What are the exposure sources for Lead (#1)
Soil and Dust, pre-1977 paint chips, lead based paint on toys, contaminated water, industrial pollution, folk remedies for colic (Azarcon) and pica.
Does lead serve any physiological role in the body?
At what level of exposure does lead have an adverse effect?
Any level of exposure
*Lead levels >5 micrograms per deciliter is the reference level at which CDC recommends public health actions be initiated.
Where is lead absorbed by the body?
Respiratory tract via lungs (50-70%)
GI tract (5-10%)
Also poorly absorbed through the skin