Toxicologic Principles - Review Questions Flashcards
Chemical or cellular tolerance
may result from a lower availability of receptors and/or mediators (e.g., neurotransmitters).
Drugs of abuse such as morphine interact with the opioid receptor; with repeated exposure to morphine, a protein called beta-arrestin-2 binds to the opioid receptor leading to desensitization and tolerance.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 32). McGraw-Hill Education. Kindle Edition.
mechanisms of toxin delivery in order from most effective to least effective
intravenous > inhalation > subcutaneous > oral > dermal
Klaassen, Curtis D.; Watkins, John B.. Casarett & Doull’s Essentials of Toxicology, Third Edition (Lange) . McGraw-Hill Education. Kindle Edition.
Hazard Index
hazard indices (the ratio between the estimated dose and the AEL; see “Acceptable Exposure Level” section) are summed across chemicals and routes of exposure to obtain a total hazard index for a particular exposure setting.
If the decision criterion of a total hazard index of 1 is exceeded, further review is performed to determine which chemicals act at the same target organ.
Hayes’ Principles and Methods of Toxicology (p. 77). CRC Press. Kindle Edition.
Dispositional antagonism
when the disposition—that is, the absorption, distribution, biotransformation, or excretion of a chemical—is altered such that the concentration and/or duration of the chemical at the target organ is reduced.
the prevention of absorption of a toxicant by use of activated charcoal
the increased excretion of a chemical by administration of an osmotic diuretic or alteration of the pH of the urine.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 31). McGraw-Hill Education. Kindle Edition.
EC50 versus ED50:
EC50 is the dose required for an individual to experience 50% of the maximum effect. ED50 is the dose for 50% of the population to obtain the therapeutic effect.
ED50 used to estimate TI, EC50 used to compare potency.
Additive Effect
two chemicals is equal to the sum of the responses to each chemical given alone (e.g., 2 + 3 = 5)
when two organophosphorous insecticides are given together, inhibition of acetylcholinesterase enzymes (AChE) is usually additive, based on the relative ability of each one to inhibit AChE.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 31). McGraw-Hill Education. Kindle Edition.
viability index
(percentage of animals that survive 4 days or longer),
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 53). McGraw-Hill Education. Kindle Edition.
efficacy
assessment of the extent to which a chemical can elicit a response and is often interpreted using the ordinate axis (or y-axis).
Maximal efficacy reflects the magnitude achieved on the response axis, regardless of drug concentration
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 42). McGraw-Hill Education. Kindle Edition.
Synergistic Effect
combined responses of two chemicals are much greater than the sum of the response to each chemical when given alone (e.g., 2 + 2 = 20).
carbon tetrachloride and ethanol are hepatotoxic compounds, but together they produce much more liver injury than expected based on the extent of damage at a given dose when administered alone.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 31). McGraw-Hill Education. Kindle Edition.
Receptor antagonism
two chemicals that bind to the same receptor produce less of an effect when given together relative to the addition of their separate effects (e.g., 4 + 6 = 8) or when one chemical antagonizes the effect of the second chemical (e.g., 0 + 4 = 1).
receptor antagonist naloxone treats the respiratory depressive effects of morphine
antiestrogen drug tamoxifen to lower breast cancer risk among women at high risk for this estrogen-related cancer. As a partial agonist, tamoxifen competitively blocks estradiol from binding to its receptor.
Treatment of organophosphorous insecticide poisoning with atropine. atropine binds to the acetylcholine receptor
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 31). McGraw-Hill Education. Kindle Edition.
dominant lethal test
This test is usually performed in rodents. The male is exposed to a single dose of the test compound and then is mated with two untreated females weekly for 8 weeks. The females are killed before term, and the number of live embryos and the number of corpora lutea are determined.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 53). McGraw-Hill Education. Kindle Edition.
Dispositional tolerance
the amount of chemical reaching the site of action decreases over time, leading to the reduced responsiveness of the tissue
The barbiturate, phenobarbital, produces tolerance to itself by increasing the expression of enzymes in the liver that are responsible for its biotransformation to pharmacologically inactive products, a process known as “biotransformation enzyme induction.”
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 32). McGraw-Hill Education. Kindle Edition.
Reference dose
A reference dose (RfD) is the United States Environmental Protection Agency’s maximum acceptable oral dose of a toxic substance.
Potentiation
one substance does not produce any toxicity on a particular tissue or system but when added to another chemical makes that chemical much more toxic (e.g., 0 + 2 = 10).
Isopropanol is not hepatotoxic on its own, but when it is administered in combination with carbon tetrachloride, the hepatotoxicity of carbon tetrachloride is much greater than when it is given alone.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 31). McGraw-Hill Education. Kindle Edition.
Functional antagonism
two chemicals counterbalance each other by producing opposing effects on the same physiological function, often through different signaling pathways.
blood pressure can markedly fall during severe intoxication with a barbiturate, which can be effectively antagonized by the intravenous administration of a vasopressor such as norepinephrine.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 32). McGraw-Hill Education. Kindle Edition.
