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Toxicology Exam

What is the definition of toxicology? The study of adverse effects of chemicals in living organisms
What is the definition of a poison? An agent that can cause a deleterious response in a biological system.
What is the definition of a toxin? Toxic substances produced by biological systems
What is the definition of a toxicant? Toxic substances produced by, or are by-products, of anthropogenic activities.
What is a xenobiotic? A compound in an organism that is not produced or meant to be present in the organism
What are the five principles of toxicology? Source,Exposure, ADMET, Dose,Target/MOA
How can the “target” of toxicology be described? Where and how the toxin is causing damage.
What are four possible sources of toxins? Environmental exposure, Occupational exposure,Bug bites and stings, Medications
List all factors of exposure that can affect potential toxic response Route, Duration, Single vs. repeated, Frequency
What are the major routes of toxic exposure? Oral, Inhalation, Topical, Parenteral
In descending order of effectiveness, list the major and minor routes of exposure for toxic agents. IV->Inhalation->IP->SQ->SubQ->IM->ID->PO->Dermal
Describe possible short-term exposure durations. Single exposure, Acute exposure: Less than 24 hours
Describe possible long-term exposure durations. ▪ Subacute: 1 month or less ▪ Sub chronic: 1-3 months ▪ Chronic: More than 3 months
Can effects from single vs. repeated doses be different? Yes.
Describe the possible effects of a fast absorbing compound. Likely to produce immediate effect but can also produce a delayed effect.
Describe the possible effects of chronic exposure. An immediate effect may be produced after each exposure.
Describe toxication/metabolic activation Potential poisons are bioactivated in the body to a harmful form.
Describe detoxification Biotransformations that eliminate the ultimate toxicant or prevent its formation.
What is the therapeutic index? A comparison of therapeutically effective dose to toxic dose
What equation describes the therapeutic index? TI = toxic dose / therapeutic dose
Describe the margin of safety. Provides information about the slope for different compounds
What equation describes the margin of safety? MOS = TD1 / ED99
Describe the margin of exposure. This describes how much someone can be exposed to.
What equation describes margin of exposure? MOE = NOAEL / Exposure
What do the varying slopes in toxicologic dose-response curves describe? The mechanism of action is different for efficacy, toxicity, and lethality
Will the target organ always be the site of highest concentration? No, the target organ is not always the place of highest concentration.
What determines toxicity? The dose at the target.
Can the mechanism of action be different at different targets? Yes
What are the three approaches to toxicology? Descriptive, Mechanistic, Regulatory
What does descriptive toxicology describe? Gross toxic responses using in vitro and in vivo systems
What is data from descriptive studies used for? Safety evaluations for human health and environmental risk assessments, Providing a starting point for elucidating mechanisms
What is the purpose of mechanistic toxicology? To identify and understand cellular, biochemical, and molecular mechanisms causing toxic effects.
What is data from mechanistic toxicology used for? Risk assessment, Design/production of safer alternative chemicals, therapy for poisonings, and treatment of disease, Contributes to knowledge of basic physiology, pharmacology, cell biology, and biochemistry.
What is regulatory toxicology? The science of determining if drugs and chemicals are safe for use.
How is regulatory toxicology studied? Using data from descriptive and mechanistic toxicity, and possibly epidemiology.
List the regulatory agencies that use toxicologists. FDA, EPA, OSHA, NIOSH, CPSC, DOT
What fields of study are present when including all three approaches to toxicology? Risk assessment and toxicogenomics.
What is risk assessment? The process to evaluate the potential for adverse health or environmental effects from exposure to naturally occurring or synthetic agents.
What is the goal of risk assessment? To provide risk managers with a rotational basis for making decisions about managing the use of chemicals or physical agents to protect health and the environment.
What factors does risk assessment involve? Social values, Technical feasibility, Economic factors
What is an “Immediate effect”? Those that occur rapidly after a single administration of a substance
What is a “delayed effect”? Those that occur after the lapse of some time after administration of a substance.
What are some extreme examples of delayed effects? DES and vaginal cancer, TOCP and neurotoxicity
Are all toxic effects reversible? No, some are irreversible
What determines reversibility/irreversibility? The ability of a tissue to regenerate.
What organ has a very high ability to regenerate? The liver
In which organ are most injuries irreversible? The CNS, due to inability of differentiated cells to divide and be replaced.
Give two examples of irreversible toxic effects Cancer and birth defects
Where do local toxic effects occur? Site of first contact
Give an example of a toxin that cause local effects? Chlorine gas
What do systemic effects require to induce the effect? Absorption at the site of entry and distribution to site of action.
What kinds of effects do most toxins cause? Systemic effects.
Give an example of a poison that has both local and systemic effects? Tetraethyl lead
Give an example of a poison that can cause indirect systemic effects. Acid burns
List the possible mechanisms of chemical interactions? Changes in absorption, protein binding, biotransformation, and excretion of one or both interacting compounds. ▪ The response may be increased or decreased due to toxic response at site of action. ▪ Additive, synergistic, potentiation, antagonism
Describe the concept of tolerance to a toxic compound The decreased responsiveness to a toxic effect resulting from prior exposure to a chemical or related compound.
What are the two major mechanisms for tolerance? Dispositional tolerance: decreased amount of toxicant reaching site where toxic effect is produced.Reduced responsiveness of a tissue to a compound
What is selective toxicity? When a toxin is lethal to one species but not the other
How can toxic endpoints be described? On/Off target ▪ Non-organ specific ▪ Organ specific ▪ Idiosyncratic ▪ Allergic reactions
Give examples of “On-target” toxicity. The dose at the receptor is too high, Drug pharmacokinetics change, Receptor numbers change, Drug interacts with correct receptor but wrong tissue (Sleepiness with Benadryl)
Describe the pathogenesis of Fibrosis (non-organ specific) Excessive deposition of collagen and EC matrix proteins cause loss of organ function as tissue is destroyed
Where does pulmonary fibrosis occur? In the alveolar Interstitium.
What drugs can cause pulmonary fibrosis? Amiodarone, Bleomycin, Paraquot
What can cause liver fibrosis? Possibly alcohol
What is genotoxicity? Unscheduled DNA synthesis, sister chromatid exchanges, DNA strand breaks.
Is genotoxicity transferrable from cell to cell? No
What is mutagenicity? Transmissible genetic alterations
Where can genotoxicity occur? Somatic and germ cells
What can be the outcomes of genotoxicity? Cancer, teratogenesis, genetic disorders
What are the top causes of non-organ specific cancer? Tobacco and diet/obesity
How does a genotoxic carcinogen damage DNA in cancer patients? It physically interacts with it to damage or change its structure
How does a nongenotoxic carcinogen damage DNA in cancer patients? It can modify gene expression but does not affect DNA structure, can cause cell to be more susceptible to DNA damage from other sources
Describe the initiation step in cancer progression. A mutation occurs in one or more genes that control key regulatory pathways of the cell
Describe the promotion step in cancer progression Signal transduction pathways are enhanced that are in the initiated cell and its progeny by continuous exposure to the promoting agent (carcinogen)
Describe the progression step in cancer progression A second mutation in the cellular DNA, the cell becomes unstable and malignant
What is a complete carcinogen? Substance capable of initiation, promotion, and progression
What is fetal exposure to teratogens determined by? Maternal ADME of the teratogen, and whether the compound can cross the placenta
Do malformations and growth retardation in fetuses always occur together? No, they can occur separately.
Why are lungs susceptible to pulmonary toxicity? Oxidative burden (imbalance of antioxidants and free radicals, allowing more harmful reactions to occur), Site of deposition of gas exposure, Water solubility of gases
What determines deposition location of particles in pulmonary toxicity? Particle size
What determines particle deposition in pulmonary toxicity? Breathing patterns
List acute pulmonary toxicity examples Airway reactivity (bronchoconstriction/dilation), Pulmonary edema
List chronic pulmonary toxicity examples Fibrosis, Emphysema, Asthma
How do airborne pulmonary toxins cause toxicity? They overload the lungs reducing available oxygen
List systemic pulmonary toxins Bleomycin, Cyclophosphamide, Monocrotaline, Paraquat
Why is the nervous system susceptible to neurotoxicity? Axonal transport , High energy requirements,Presence of myelin Neurotransmission function
How does high energy requirements cause nervous system susceptibility? Neurons are highly dependent on aerobic metabolism. Without it, they cannot function.
How does axonal transport cause nervous system susceptibility? Cells in the NS are very long, and neurons must transport intracellular products down and up the axon.
How does the presence of myelin cause susceptibility to neurotoxicity? Myelin is susceptible to damage by toxic compounds, which can overall interfere with the cells ability to send signals to the rest of the body.
How does neurotransmission cause susceptibility to neurotoxicity? Many drugs and compounds affect the neurons ability to transmit signals.
Why is the liver susceptible to hepatotoxicity? Uptake and concentration roles ,Bioactivation and detoxification capabilities ,Inflammatory and immune response ,Propensity for idiosyncratic responses
Why is the kidney susceptible to nephrotoxicity? Potential toxins in systemic circulation , Process for concentrating urine also concentrates toxins ,Renal transport, accumulation, and metabolism contributes to probability of “In Situ” toxicity, Kidney is sensitive to endogenous vasoconstrictors
For what reasons can nephrotoxicity be site-specific? Blood flow ,Transport and accumulation of chemicals Physiochemical properties of epithelium ,Reactivity of cellular targets ,Balance of bioactivation reactions ,Cellular energetics,Repair mechanisms
What can molecules smaller than 600 daltons act as? Haptens
What can large drugs do to the immune system? Direct activation
What are the two main mechanisms in which drugs can activate the immune system? Hypersensitivity, Autoimmune reactions
List the six specialties in toxicology. Food,Forensic,Occupational,Regulatory,Environmental,Clinical
Food is presumed safe unless…? It contains a poisonous/deleterious substance in an amount injurious to health.
What if forensic toxicology the hybrid of? Analytical chemistry and toxicological principles
What is a major challenge of forensic toxicology? The toxic agent must be isolated from a biological matrix
How does forensic toxicology aid in crime solving? Helps establish cause of death, circumstance of death, and identifies agents used in crimes toward the living.
What principles does occupational toxicology use? Methodology of toxicology towards chemical and biological hazards in the workplace
What is the objective of occupational toxicology? Prevent adverse health effects in workers that arise from work environments.
What is the purpose of a regulatory toxicologist? They set the levels for safe exposure to ▪ environmental contaminants ▪ food additives ▪ medicinals
What are environmental toxicologist concerned with? Impacts of environmental pollutants on non-human organisms and human health. ▪ Ecotoxicology focuses on the impact of toxic substances on population dynamics ▪ Transport, fate, interaction are most important components of these specialties
What is clinical toxicology mainly concerned with? Disease caused by or associated with toxic substances
Can pharmacists be clinical toxicologists? Yes
What is the universal telephone number for poison control center access? 800-222-1222
What is a CSPI? Certified specialist in poison information
What is a DABAT? Diplomat of the American board of applied toxicology
What are the further treatment approaches to treating a poisoned patient after emergency care? Toxicokinetic based, Pharmacologically based, Inactivation of poison
Describe initial emergency care? Eliminating further exposure, supportive care, and determining poisoning agent.
What is the goal of toxicokinetic based treatment? To decrease the amount of poison in the body to reduce potential end-organ damage.
What are the four approaches to toxicokinetic based treatment? Prevention of absorption, Inhibition of toxication, Enhancement of metabolism, Enhancement of elimination
Prevention of absorption Gastric lavage, emesis, activated charcoal, MD activated charcoal
Inhibition of toxication Inhibiting involved enzymes, such as alcohol dehydrogenase with methanol and EG poisoning by giving ethanol of fomepizole
Enhancement of metabolism Administering cofactors to accelerate metabolic actions of enzymes, but not inducing enzymes themselves. Treating cyanide and acetaminophen poisoning.
Why is inactivation of poison used? To reduce activity of toxins that have entered circulation and are not readily eliminated
What is the mechanism of toxin inactivation? Inactivator binds to the toxin and prevents tissue interaction, Toxin-inactivator complex is cleared, Inactivators must have high affinity for the toxin, Complex must have low toxicity
Describe the general structure of heavy metal chelators. Small molecules with a nucleophilic electron donor to form a metal ligand complex, have higher affinity for binding metal than tissue
What are three requirements for heavy metal chelators to work? Soluble, non-toxic, readily cleared.
What does the ideal chelator have low affinity for? Endogenous ions such as calcium
What is an antivenom? Antibodies against a venom
How are antivenoms produced? Inoculating animals with small amounts of venom to get a humoral response
What do antivenoms want to have an affinity for? High affinity/specificity for its substrate
What is the danger with using antivenoms? Type 3 hypersensitivity reactions
Antivenom example Digoxin immune fab
What is the purpose of pharmacological treatment of poison? To counteract a toxins pharmacological response by administering a drug with opposite pharmacological action, or that bypasses the metabolic pathway that’s been inhibited.
What are the four categories of pharm. Mediated treatments? Receptor antagonist, Receptor agonist, treatment removes poison from active site, treatment passes an inhibited pathway by stimulating down stream targets.
Receptor antagonist Blocks effects of toxin that acts as an agonist. ▪ Examples: Naloxone, atropine, flumazenil (GABAA antagonist to treat benzo overdose)
Receptor agonist Treats agonist effects of the toxin ▪ Examples: physostigmine (increase cholinergic tone, reverse atropine)
Treatment removes poison from active site Treating CN poisoning ▪ Treating CO poisoning with O2 ▪ Treating organophosphate poisoning with pralidoxime
Created by: Bmcgraw



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