EXAM 1 Flashcards
Paracelsus (1493-1541) is widely regarded as the father of toxicology. What was his real name?
Philippus Aureolus Theophrastus Bombastus von Hohenheim
True or False
Paracelsus is credited with terming the phrase “Only the dose makes the poison”.
true
The scope of toxicology encompasses:
forensic (medico legal; e.g. alcohol, workplace litigation), pharmaceutical (toxicity of common drugs), environmental (e.g. pesticides, asbestos)
Which area focuses on toxicity testing of chemicals, usually on animals and then correlates the data to human conditions?
descriptive toxicology
True or False:
Benzene is a volatile organic solvent known to cause cancer (leukemia) in humans.
true
True or False:
45% of the average person’s exposure comes from industrial pollution and an additional 3% of the total benzene exposure indoors comes from smoking (or breathing smoke exhaled by others).
false
3% due to industrial, 45% due to indoors
What is not true about the properties of carbon
monoxide (CO)?
carbon monoxide is flammable - it is not
What is true about the treatment of Carbon
monoxide (CO) poisoning?
promptly remove the patient from the source of exposure, rest the patient, if the patient is unconscious administer 100 % oxygen by mask, hyperbaric oxygen is indicated at carboxyhemoglobin levels of >30-40%
What is not true about the warning signs of chronic CO exposure?
involves sinus congestion, cough - it typically has flu-like symptoms
Hydrogen cyanide (HCN) is a colorless gas with a faint odor of….
bitter almonds
The greatest danger of exposure to cyanide today is through:
indoor fires
True or False:
Cyanide blocks the respiratory chain reaction and thus ATP production by inhibiting the cytochrome oxidase in the mitochondrial membranes.
true
What is the role of nitrite in the treatment of cyanide poisoning?
nitrite converts Hemoglobin to Methemoglobin which binds cyanide and will pull it out
True or False:
A patient’s death from cyanide (CN) poisoning occurs due to a lack of oxygen delivery.
false
death via carbon monoxide due to lack of delivery
True or False:
A patient’s death from carbon monoxide (CO) poisoning occurs due to a lack of oxygen utilization.
false
death via cyanide due to lack of utilization
True or False:
Xenobiotics are compounds that are not naturally found in or made by our bodies?
true
Which tissue is capable of metabolizing drugs?
kidney, skin, liver, lungs
What is found in phase II reactions?
methyltransferases (MT), sulfotransferases (SULTS), and glutathione-s-transferases (GST); pII reactions are conjugation rxns
What are ideal characteristics for renal excretion?
molecules with small molecular weight that are ionizable
What are Phase I drug metabolism reactions?
hydrolysis, oxidation, and reduction rxns
Metabolism of xenobiotics into toxic intermediates is known to occur via which enzyme?
CYP450s and sulfotransferases
Which co-factor is important for conjugation by N-acetyltransferases?
acetyl coenzyme A
Repeated drug administration can induce the activity of CYP450 enzymes by?
increasing CYP protein synthesis
The CYP2C9 enzyme is important for the metabolism of Warfarin, a blood thinner. Inhibition of this CYP enzyme would do what to the half-life of Warfarin in the blood?
warfarin would have a longer half-life; if it can’t be metabolized, it won’t be inactivated
What is associated with decreased drug metabolism?
hypothyroidism, old age, liver disease, genetic polymorphisms
True or False:
A polymorphism is a genetic variation that occurs in more than 1% of a population.
true
When a pregnant mom takes a drug, the fetus is protected from receiving the full dose of the drug by:
first pass effect, metabolism in placenta, and metabolism in the liver
define what a xenobiotic is
a chemical substance found within an organism that is not naturally produced or expected to be present within the organism
define mechanistic toxicology
field that tries to identify and understand the cellular, biochemical and molecular basis by which chemicals exert toxic effects.
define regulatory toxicology
field that develops, assembles models, assesses, and
communicates information about health hazards and risk
associated with exposure to agents (e.g., chemicals,
radiation) that have the potential to harm human
health and ecosystems.
define descriptive toxicology
focuses on toxicity testing of chemicals or agents of
toxicity, usually on animals and then correlated to
human conditions. It provides dose-response
information upon exposure to a harmful toxic agent.
define risk assessment toxicology
process of analyzing the information provided by mechanistic, regulatory and descriptive toxicology to determine whether an
environmental hazard might cause harm to exposed persons.
what are some examples of toxicology subfields?
forensics, pharmaceuticals (toxicity), environmental (pesticides)
what are major sources of benzene exposure?
smoking, automobile exhaust, individual activities (paint etc)
what are examples of volatile organic compounds that may be found in our homes?
trichloroethane, benzene, chloroform, formaldehyde
What types of mutations will likely affect the amino acid sequence of the protein produced from a gene?
coding non-synonymous, splicing, exon base change
Which region of a gene is most important for regulation of gene expression?
promoter
This method allows for detection of variant CYP alleles using PCR to amplify the P450 gene followed by enzymatic digestion with restriction enzymes?
PCR-RFLP
This method of DNA sample collection is pain free and least likely to be contaminated with non-human DNA?
buccal epithelial cell collection
True or False:
Pharmacogenomic testing before a medication is given to a patient can be used to prevent drug toxicities?
true
S-Warfarin is metabolized by CYP2C9. Which genotype would be associated with the slowest S-Warfarin metabolism rates?
CYP2C93/3
Which enzyme functions to activate the cellular pathways promoting blood clotting, and is inhibited by S-Warfarin?
VKORC1
Which enzyme contributes to the first pass metabolism of 5-fluorouracil (5-FU), limiting how much of this drug is delivered to stop replication of cancer cells ?
DPD
Populations with polymorphisms in this enzyme are more likely to develop anemia because they are unable to produce enough reduced glutathione to reduce oxidative stress in red blood cells?
G6PD
Which of the following proteins are classified as transporters and function to prevent entry of certain drugs and xenobiotics into our cells?
BCRP and P-glycoprotein
Polymorphisms located in ________ can result in severe hypersensitivity reactions to certain drugs.
HLA-B
SN-38 is a topoisomerase inhibitor and is an active metabolite of irinotecan. SN-38 is inactivated via a phase 2 conjugation reaction carried out by which enzyme below?
What are the physical properties of carbon monoxide?
colorless, odorless, tasteless, and non-irritating
Describe the symptoms associated with carbon monoxide poisoning.
low concentration exposure for short time = mild headache and dizziness high concentration exposure for extended period = headache and dizziness within minutes and possible unconsciousness
What are common sources of carbon monoxide?
poorly ventilated heating systems, engine exhaust, and methylene chloride (paint stripper)
Explain the mechanism behind carbon monoxide toxicity.
carbon monoxide has a high binding affinity to hemoglobin - 250 times that of oxygen -, causing a decrease in the bloods ability to carry oxygen
Describe how carbon monoxide exposure should be treated.
- remove patient from source of exposure
- admin 100% oxygen - this will reduce carboxyhemoglobin 1/2 life from 5 hours to 1
- use hyperbaric oxygen in severe cases - 3atm = 30 min 1/2 life
Identify how we can detect and prevent carbon monoxide exposures.
CO detectors, annual furnace checks, and being educated/cautious
Describe the physical properties of cyanide.
colorless gas with a bitter almond scent
Identify the chemical forms cyanide can come in.
Discuss different ways people can be exposed to cyanide.
What are cellular targets of cyanide?
What is the molecular mechanism of cyanide poisoning?
Explain how amyl nitrite, sodium nitrite, and sodium thiosulfate work as antidotes to cyanide
poisoning.
