Term
| 3 types of computerized literature searches |
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Definition
| MEDLINE-pubmed, TOXLINE, NIOSHTIC-2 |
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Term
| ___ is a computerized "Digested" material, web-based source of info |
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Definition
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Term
| 6 subcategories of TOXNET |
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Definition
| HSDB (hazardous substances data bank), IRIS (integrated risk information system -- by EPA), CCRIS (chemical carcinogenesis research information system -- NCI), TRI (Toxic chemical release inventory), GENE-TOX (peer-reviewed mutagenicity test date -- EPA), ChemIDplus (chemical names, synonyms and structures) |
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Term
| 2 sources of government, criteria documents |
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Definition
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Term
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Definition
| chemical specific info in detail -- government document |
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Term
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Definition
| emergency response safety and health database, also occupational safety and health guidelines for chemical hazards |
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Term
| ___ is a computerized clinical information system that you can get by going throguh the purdue libraries pharmacy |
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Definition
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Term
| ___ is considered the EPAs "Bible", with the most relevant regulatory levels |
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Definition
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Term
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Definition
| agency for toxic substances and disease registry -- organizes and prioritizes hazardous waste sites |
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Term
| Where do you go to get info on poisons? |
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Definition
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Term
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Definition
| economic, clinical, forensic, ecotox, and environmental |
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Term
| ___ is the subdivision of toxicology that focuses on how chemicals are made to be toxic. example? |
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Definition
| economic -- pesticides - try to discriminate between pests and humans and increase crop yield |
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Term
| ___ toxicology focuses on antidotes, drug abuse and overdose. they mainly look for ___ and ___. |
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Definition
| clinical -- signs and symptoms |
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Term
| ___ toxicology focuses on medical and legal issues. example? |
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Definition
| forensic -- ex: analyzing toxicity in foods |
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Term
| ___ is the subdivision of tox that focuses on "the birds and the bees", specifically non-target organisms. |
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Definition
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Term
| ____ toxicology focuses on human exposures, mainly through occupational, food, and water. |
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Definition
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Term
| acute effects and example |
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Definition
| occur from a single dose, effect occurs fairly quickly (hours) and terminates quickly ... ex: overdose |
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Term
| subchronic effect. examples? |
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Definition
due to repeated dose, over days or weeks.
... ex: farmers spraying crops, or taking an antibiotic |
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Term
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Definition
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Term
| 2 things that can happen with a chronic effect |
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Definition
| build up a chemical over time :: increase in damage to organs (cumulative) |
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Term
| 3 major types of exposures and example of each |
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Definition
| incidental (something gets in the water supply), accidental (child gets into cleaner), intentional (drugs) |
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Term
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Definition
| threshold limit value - set by ACGIH - means most workers will not be affected |
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Term
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Definition
| Permissable Exposure Limits - set by OSHA - very outdated |
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Term
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Definition
| Maximum Contaminant Levels - set by EPA - used for water |
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Term
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Definition
| minimal risk levels - ATSDR - concerned wtih general public at all ages from something they're exposed to all the time |
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Term
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Definition
| agency for toxic substances and disease registry - organize and prioritize hazardous waste sites |
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Term
| Chemicals not intended for introduction into a biological system tend to exert their effects depending on ___, ___, and ___. |
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Definition
| nonspecific caustic or corrosive actions, specific toxicological actions, and production of pathological sequelae |
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Term
| chemicals not intended for introduction into biological systems exert abnormal effects depending on ? |
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Definition
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Term
| Chemicals intended for introduction into biological systems can exert unwanted effects with normal doses depending on what 3 things? |
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Definition
| malfunction of mechanisms for terminating the action of the agent, actions on the wrong target system, synergism with other chemicals |
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Term
| chemicals intended for introduction into biological systems exert effects due to excessive doses based on what 5 things? |
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Definition
| nonspecific caustic or corrosive actions, exaggerated pharmacologic effects, specific toxicologic actions, production of pathological sequelae, sociologic complications |
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Term
| What are examples of non-specific caustic or corrosive actions that a chemical could exert? |
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Definition
| primary irritants, like spilling something on the skin |
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Term
| what are 3 "specific toxicologic actions" that chemicals can exert? |
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Definition
| pharmacokinetic (distribution), metabolic activation, receptor |
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Term
| receptors provide ___ and ___ |
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Definition
| selectivity and specificity |
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Term
| ___ are cell components that interact with a chemcial which leads to a chain of events that produces some effect |
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Definition
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Term
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Definition
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Term
| ___ is how much of a chemical you need to achieve a desired effect |
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Definition
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Term
| 2 chemicals' potencies can only be compared if? |
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Definition
| they are both capable of reaching the desired effect |
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Term
| The property of a drug which determines the amount of biological effect produced per unit of drug-receptor complex formed |
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Definition
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Term
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Definition
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Term
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Definition
| Greater than additive effect: 1+1=3 |
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Term
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Definition
| chemical has no effect by itself but can increase the activity of another chemical: 0+1=4 |
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Term
| Chemical-Chemical Antagonism |
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Definition
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Term
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Definition
| one chemical's action increases while the other chemical's action decreases |
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Term
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Definition
| happens at receptor -- antidotes |
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Term
| ___ antagonism has to do with pharmacokinetics. |
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Definition
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Term
| transport from site of exposure to blood |
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Definition
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Term
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Definition
| oral, respiratory, dermal, injections |
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Term
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Definition
| from high concentrations to low (fick's principle of concentration gradients) |
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Term
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Definition
| from low concentration to high, needs a transporter molecule -- body has these for all endogenous and some exogenous compounds |
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Term
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Definition
| organic anion and cation transporters (active transport) |
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Term
| 2 factors that affect absorption |
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Definition
| transport mechanism (active or passive), molecule (size, ionization, ph, etc) |
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Term
| the most readily-absorbed molecules are ___, ___ and ___. |
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Definition
| non-polar, non-ionized, and lipid soluble |
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Term
| When you ingest a toxicant, it first goes to the gut, where it is taken up by the blood and delivered to the ___ by the ____ system. |
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Definition
| liver, hepatic portal system |
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Term
| ___% of what you eat goes through the liver before any other organ |
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Definition
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Term
| a "portal system" means it has a ___ at both ends |
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Definition
| vein ... hepatic portal: vein in gut and liver |
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Term
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Definition
| liver is the target tissue for everything absorbed by the GI tract |
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Term
| Why is it important that the lungs are highly vascular? |
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Definition
| they are good for converting O2 to CO2 but also good at picking up toxins and distributing them throughout the blood. |
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Term
| ___% of the blood supply is pumped through the lungs at some point |
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Definition
| 100 ... why inhaled toxins work so quickly |
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Term
| in the skin, what layer is of most concern in regards to toxins |
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Definition
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Term
| 6 factors that affect how quickly a toxin is absorbed by the skin |
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Definition
| the nature of the chemical, location (thick skin or thin skin), hydration (quicker uptake), temperature (higher temp=faster absorption), damage, solvents |
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Term
| Almost all distribution in the body is done by the blood plasma, with the exception of ___. Why? |
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Definition
| lead... it binds to the RBCs |
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Term
| In plasma, toxins can either be free or bound. if they are bound, it is usually to ___. why is this important? |
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Definition
| albumin.... it prevents activity and prolongs half life in the body. |
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Term
| 3 "barriers" to distribution and their significance |
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Definition
| capillaries - have a junction between them, so stuff can still pass through :: fat - stores things easily, like DDT :: Blood-Brain Barrier - no gap between so it is hard for chemicals to get through to the brain, especially large, polar molecules |
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Term
| detoxification vs. bioactivation |
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Definition
| detox - results in decreased activity and duration of the chemical :: bioactivation - opposite |
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Term
| In terms of clinical drugs, we want to make things that are ___, ___, and ___. Why? In terms of toxins, we want things that are ___, ___, and ___. Why? |
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Definition
| drugs: non-polar, non-ionized, lipid soluble -- so they are easily absorbed. :: toxins - polar, ionized, water soluble -- so they are NOT absorbed and easily excreted |
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Term
| example of detoxification/bioactivation of a compound |
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Definition
| halogenated compounds -- can be detoxed by the liver and activated by the CNS |
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Term
| Classical Metabolism cosists of ___ and ___ rxns |
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Definition
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Term
| Phase I reactions are considered to be ____. |
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Definition
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Term
| Where do Phase I reactions take place? If they wanted to isolate this organelle, how would they do it? |
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Definition
| endoplasmic reticulum -- spin it into a microsome (protein pellet) |
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Term
| Phase I/II reactions involve hydrolases and esterases |
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Definition
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Term
| The ___ is the most important excretory organ |
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Definition
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Term
| the ___ is an important excretory organ for volatile compounds and gases |
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Definition
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Term
| the __ is an important excretory organ for foreign chemicals |
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Definition
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Term
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Definition
| How people respond differently to drugs and toxins based on their genetics |
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Term
| how often do SNPs appear, and how often are they "silent"? |
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Definition
| 1 out of every 1000-2000 base pairs -- 99% are silent |
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Term
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Definition
| when people respond to toxins at lower doses than others |
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Term
| what are some factors that can cause hypersusceptibility |
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Definition
| genetics, racial/ethnic groups |
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Term
| what is the importance of glutathione? |
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Definition
| primaquine is an anti-malarial drug, but can cause hemolytic anemia if you don't have glutathione. ... see notecard |
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Term
| Why do so many asians have trouble metabolizing alcohol? |
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Definition
| low Alcohol Dehydrogenase activity -- see notecard |
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Term
| ____ is the enzyme that determines fast and slow acetylators. A ___ in this enzyme causes slow acetylation |
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Definition
| N-acetyltransferase ... genetic mutation (NOT deficiency) |
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Term
| What is the significance of Isoniazid? |
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Definition
| treats TB, but can build up in the blood of slow-acetylators and cause peripheral neuropathy |
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Term
| about __% of white americans are slow-acetylators |
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Definition
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Term
| what is the significance of carcinogenic arylamines? |
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Definition
| can cause cancer in slow acetylators who can't break it down |
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Term
| What is a metabolic ratio? |
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Definition
| ratio of parent compound to metabolite |
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Term
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Definition
| metabolizes a lot of different drugs, but contains 80 alleles, which leaves plenty of room for mutations. people with mutations are "poor metabolizers" of all of these otherwise useful drugs and the drug builds up in their bodies |
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Term
| Drugs that are CYP2D6-mediated |
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Definition
| debrisoquine, beta blockers, antihiarrhythmics, neuroleptics |
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Term
| MHC restriction and its importance |
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Definition
Tcells can only recognize antigens that are bound to MHC. ex: H1N1 - since we have never been exposed, MHC 1 can't bind and present the antigen so our Tcells can't attack it.
::: also helps recognize self vs. non-self |
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Term
| 3 components of innate immunity |
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Definition
| anatomical barriers, humoral components, and cellular components |
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Term
| 3 anatomical barriers that are part of innate immunity |
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Definition
| mechanical factors (peristalsis, mucociliary escalator), chemical factors (pH), biological factors |
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Term
| 3 Humoral components that are part of innate immunity |
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Definition
| complement, Coagulation system, cytokines |
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Term
| 4 cellular components in innate immunity |
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Definition
| neutrophils, monocytes and macrophages, NK cells, eosinophils |
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Term
| What are the roles of innate immunity? |
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Definition
| control infections during the time that is needed to engage the adaptive immune system (usually the first 5-7 days) :: activates and directs the adaptive immune system, primarily through signals delivered by dendritic cells |
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Term
| Adaptive immunity also goes by what other 2 names? |
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Definition
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Term
| 2 general functions of acquired immunity |
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Definition
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Term
| 3 general cell types of adaptive immunity |
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Definition
| B lymphs, T lymphs, and antigen presenting cells |
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Term
| 2 general types of immunity provided by the acquired immune system and their components |
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Definition
| humoral - serum proteins, complement, antibodies :: cell mediated immunity (CMI) - T lymphs |
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Term
| Primary lymphoid tissues and the cells they create |
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Definition
| Bone Marrow - b cells :: thymus - t cells |
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Term
| Secondary lymphoid tissues -- types and function |
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Definition
| function: where cells go after they develop to wait for contact with an antigen :: spleen and lymph nodes |
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Term
| Tertiary lymphoid tissues |
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Definition
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Term
| What are the 2 major, general cell types of the immune system |
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Definition
| myeloid cells, lymphoid cells |
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Term
| what 2 types of cells are involved in the innate immune system? |
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Definition
| granulocytes (basophils, neutrophils, eosinophils) and NK cells |
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Term
| Suppressor T cells are AKA ___. What is their function? |
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Definition
| Tregs -- downplay immune response |
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Term
| The B cell antigen receptor is? |
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Definition
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Term
| Upon antigen exposure, B cells can develop into __ or ___ |
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Definition
| plasma cells (IgM, IgG, etc) or memory cells |
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Term
| Why can you be immunized as a kid and be good to go for life? |
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Definition
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Term
| ___% of Tcells die before exiting the thymus |
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Definition
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Term
| antigen receptor for T cells |
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Definition
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Term
| 2 types of selection for Tcells in the thymus |
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Definition
| Positive - MHC restriction is "taught" -- if a cell can't recognize MHC, it is eliminated :: Negative - Tolerance - eliminate cells that recognize self antigens |
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Term
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Definition
| helpers (CD4) and Cytotoxic (CD8) |
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Term
| 2 types of T helper cells and their functions |
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Definition
| Th-1 - cell mediated to cytokines :: Th-2: humoral (bcell) immunity |
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Term
| 5 types of autoimmune mechanisms |
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Definition
| self-recognition molecules, hypersensitivity, antibody-dependent cytotoxicity, complement-mediated lysis, cytotoxic T lymphs |
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Term
| example of localized and systemic anaphalaxis |
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Definition
| localized: bee sting, systemic: peanut allergy |
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Term
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Definition
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Term
| ___ is the most toxic/potent chemical |
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Definition
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Term
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Definition
| foreign chemicals the body is exposed to that have little or no value in sustaining normal biochemistry. |
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Term
| how can reabsorption of metabolites of molecules broken down by the kidneys be controlled? |
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Definition
| adjusting urine pH --> weak acids can be caused to be excreted rather than reabsorbed by adding bicarbonate and therefore making the urine alkyline. |
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Term
| how does disease in the liver and kidney affect metabolism in these organs? |
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Definition
| increases half life of compounds |
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Term
| hepatic first pass effect |
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Definition
| most toxicants absorbed by the GI tract are eliminated by the liver before they can reach systemic circulation |
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Term
| heavier molecules tend to be metabolized by the ___ |
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Definition
| liver -- to be excreted through bile (as opposed to kidneys and urine) |
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Term
| What are the implications of a Glucose-6-Dehydrogenase deficiency? |
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Definition
| deficient G-6-P = reduced ability to maintain sufficient levels of reduced Glutathione (GSH) in RBCs --> in the event of oxidative stress, they will suffer damage to RBc membrane proteins = hemolytic anemia |
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