Midterm Flashcards
The amount of a substance administered at one time = ?
Dose
What is exposure dose?
The amount of xenobiotics encountered in the environment
The actual amount of the exposed dose that enters the body = ?
Absorbed dose
The quantity administered usually orally or by injection = ?
Administered Dose
What is total dose?
The sum of all individual doses.
What does Fractionating mean?
When you split up the total dose as to decrease the probability that the total dose will cause toxicity.
** reason = the body often can repair the effect of each subtoxic dose if sufficient time passes before receiving the next dose.
The clinical and toxic effects of a dose must be related to ___ , ___ & ___
Age, body size & time
A common dose measurement is?
mg/kg
Why is knowledge of the dose-response relationship important? (3)
- Establishes causality that the chemical has in fact induced the observed effects.
- Establishes the lowest dose where an induced effect occurs - the threshold effect.
- Determines the rate at which injury builds up - the slope for the dose response.
What form dose the dose response curve normally take?
Sigmoid curve
The point at which toxicity first appears is known as?
The Threshold dose level
When does the threshold for toxic effects occur?
At the point where the body’s ability to detoxify a xenobiotic or repair toxic injury has been exceeded.
The usual measure for variability of a toxic response is the standard deviation. One standard deviation represents what percent of the responses?
68%
What is LD50?
This is a common dose estimate for acute toxicity. This is a statistically derived dose at which 50% of the individuals will be expected to die.
The toxicity of a substance depends on what factors?
Form, and innate chemical activity Dosage Exposure route Species Age Sex Ability to absorb Metabolism Distribution within the body Excretion Presence of other chemicals
The innate chemical activity of substances varies greatly. Some can quickly damage cells causing immediate death while others slowly interfere. For example hydrogen cyanid binds to _________ resulting in ________.
Cytochrome oxidase resulting in hypoxia and rapid death.
Nicotine binds to what type of receptors in the CNS?
Cholinergic
______ is the most important critical factor in determining if a substance will be an acute or chronic toxicant.
Dosage
Ingested chemicals, when absorbed from the intestine distribute first to?
Liver and may be immediately detoxified.
What is meant by selective toxicity?
Refers to species differences in toxicity between two species simultaneously exposed.
what are the two types of metabolism?
Detoxification and bioactivation
What is meant by detoxification?
The process by which a xenobiotic is converted to a less toxic form.
This is a natural defence mechanism of the organism.
Generally detox = converting lipid-soluble compounds to polar compounds.
What is Bioactivation?
Bioactivation is the process by which a xenobiotic may be converted to more reactive or toxic form.
What is a major determinant of whether or not a toxicant will damage cells?
Its lipid solubility.
Lipid soluble = readily penetrates cell membranes
What is the primary excretory organ? What are the other two organs that follow in function?
Kidney
GI Tract
Lungs (for gases)
**xenobiotics may also be excreted in sweat, tears, and milk.
When the presence of other chemicals decreases toxicity this is known as?
Antagonism
When a chemical adds to the toxicity this is termed?
Additivity
When a chemical increases toxicity this is termed?
Synergism or potentiation
Define interaction
The effect that one chemical has on the toxic effect of another chemical.
T or F
Additivity is the least common type of drug interaction
False
Most common
T or F
Antagonism is often a desirable effect in toxicology
True
Often the basis for most antidotes.
Give an example of a chemical antagonism
Mercury toxicity can be reduced by chelating (binding) the mercury ions with dimercaprol
Swallowed poison is absorbed by introducing charcoal into the stomach is what type of antagonism
Disposition Antagonism
_______ occurs when a chemical that does not have a specific toxic effect makes another chemical more toxic.
Potentiation
What is disposition?
Often used in place of toxicokinetics to describe the time-course of movement of chemicals through the body
Ingested and inhaled materials are still considered outside the body until when?
They cross the cellular barriers of the GI tract or respiratory system.
What are the factors that affect the likelihood that a xenobiotic will be absorbed?
Route of exposure
Concentration of the substance at the site of contact.
Chemical and physical properties of the substance.
T or F
Due to such route-specific differences in absorption, xenobitocis are often ranked for hazard in accordance with the route of exposure.
True
What route of exposure is the main route for many pharmaceuticals?
GI
**environment to food and water contaminants as well
What are the primary types of specialized transport mechanisms?
Facilitated Diffusion
Active Transport
Endocytosis (phagocytosis & pinocytosis)
Whittier the properties of a chemical substance that affects its ability for passive transfer?
Lipid Solubility
Molecular Size
Degree of ionization
T or F
In general, highly ionized chemicals have low lipid solubility and pass with difficulty through the lipid membrane
True
Most aqueous pores allow chemicals of what molecular weight to pass through?
100-200
What pores allow for larger sized chemicals to pass through? What is the molecular weight of these chemicals?
Capillaries and Kidney Glomeruli
- 50 000
Phagocytosis is very important process in what areas of the body?
Lung
Certain liver and spleen cells.
What are the three main factors that affect absorption within the various sites of the gastrointestinal tract?
Types of cells at the specific site
Period of time that the substance remains at the site
pH of stomach or intestinal contents at the site.
T or F
In the stomach weak acids are absorbed and bases are not
True
T or F
The small intestine has a pH near neutral and both weak bases and weak acids are ionized and are usually readily absorbed by passive diffusion
False
are UNIONIZED
What are the three basic regions to the respiratory tract
- nasopharyngeal
- Tracheobronchial
- Pulmonary
Absorption through the alveolar membrane is by?
Passive Diffusion
The only way to increase the amount of a toxin to absorbed is to increase the rate and depth of breathing. What is the term describing this?
Ventilation-limitation
What is flow-limitation
When you increase absorption by increasing the rate of blood supply to the lung.
Why does minimal absorption take place in the nasopharyngeal region?
Due to the cell thickness of the mucosa and the rapid movement of gases and particles through the region.
Coal dust and asbestos fibres may lead to what conditions?
Black lung or asbestosis respectively
Which of the following can passthrough the skin and cause nerve damage: Hexane Carbon Tetrachloride Ether Organophosphate pesticides
Hexane
What layer is the most important in regulation penetration of a skin contaminant?
Epidermis particularly the stratum corneum
What is the stratum corneum made of?
Keratin
Where is the stratum corneum the thinnest?
Axillary
Inquinal and Scrotum especially.
The most prevalent skin conditions that enhance dermal absorption are?
Skin burns and dermatitis
What is meant by parenteral route?
Injection into the body via syringe and hollow needle.
The total volume of body fluids in which toxicant is distributed is known as?
The apparent volume of distribution Vd and is expressed in litres
T or F
If a toxicant is distributed only in the plasma a high Vd results, and if a toxicant is distributed in all sites there is a lower Vd
True
Greater dilution in all the sites compared to just the plasma
body burden = _____ x ______
plasma conc x VD
What is meant by the first pass effect?
Toxicants entering the GI tract or peritoneum are immediately subject to biotransformation or excretion by the liver and elimination by the lung.
The term used to integrate all the processes of distribution, biotransformation, and elimination is?
Disposition
Disposition models are named for the number of areas of the body that the chemical may go to. What are these areas termed?
Compartments
What is the one-compartment model?
This describes the disposition of a substance that is introduced and distributed instantaneously and evenly in the body, and eliminated at a rate and amount that is proportional to the amount left in the body.
T or F
A half-life for a chemical whose kinetic behaviour fits a one-compartment model is often referred to as the “biological half-life”
False
Two-compartment model
1 compartment = Half life which is just the time it takes for half of the chemical to be lost from the plasma.
The liver receives what percent of cardiac output?
roughly 28%
What is the most abundant plasma protein that binds toxicants?
Albumin
What are the primary sites for toxicant storage?
Adipose tissue
Bone
Liver
Kidneys
T or F
Toxicants that are lipophobic, polar and high molecular weight are readily absorbed through the cell membranes of the skin, GI and lung
False
Lipophilic, non-polar, and low molecular weight.
