Print Options

Card layout: ?

← Back to notecard set|Easy Notecards home page

Instructions for Side by Side Printing
  1. Print the notecards
  2. Fold each page in half along the solid vertical line
  3. Cut out the notecards by cutting along each horizontal dotted line
  4. Optional: Glue, tape or staple the ends of each notecard together
  1. Verify Front of pages is selected for Viewing and print the front of the notecards
  2. Select Back of pages for Viewing and print the back of the notecards
    NOTE: Since the back of the pages are printed in reverse order (last page is printed first), keep the pages in the same order as they were after Step 1. Also, be sure to feed the pages in the same direction as you did in Step 1.
  3. Cut out the notecards by cutting along each horizontal and vertical dotted line
To print: Ctrl+PPrint as a list

46 notecards = 12 pages (4 cards per page)

Viewing:

Molecular Toxicology Exam 1 Prep (Exam Review Based)

front 1

Define toxicology

back 1

Study of the adverse affects of xenobiotics

front 2

Why is toxicology important and what did it form the basics of

back 2

  • formed basics of therapeutics, experimental medicine, environmental health, and fundamental science
  • It's important in risk assessment for chemical compounds, medicines, food, etc

front 3

Who is Paracelsus

back 3

  • father of modern toxicology (1493-1541)
  • Chemical toxic and therapeutic properties are dependent on the dose
  • Specifically studied water intoxication

front 4

What is thalidomide

back 4

  • was a morning sickness medicine
  • caused more than 10,000 children to be born with birth defects in Europe and Africa
  • Led to discovery of placenta-crossing by Francis Kelsey

front 5

Who is Francis Kelsey?

back 5

Discovered placenta-crossing

front 6

What is the FDC Act?

back 6

  • Federal food Drug Cosmetic Act (1938)
  • Substances had to be tested for safety of human consumption
  • Led to the founding of the FDA (food & drug administration)

front 7

What is the FIFRA Act

back 7

  • Federal Insecticide, Rodenticide, and Fungicide Act (1947)
  • States that a non-food/drug item must be effective and safe

front 8

What was the importance of sulfanimide in toxicology history?

back 8

  • Antifreeze
  • Was added to children's medicine to make it sweet before FDC Act

front 9

What was Agent Orange

back 9

  • TCDD (dioxin)
  • Carcinogen used during times of war as a jungle defoliant

front 10

What did prohibition lead to?

back 10

  • Substances like methanol, lead, and triorthocresyl phosphate being added to alcohol to pass as medicine
  • Triorthocresyl phosphate was added to rum to make Jamaican ginger

front 11

Toxicokinetics vs toxicodynamics

back 11

  • Kinetics: concentration of compound in your body
  • Very dependent on bioavailability as it has to be able to take up the toxin to have effect as well as uptake and transport
  • Dynamics: determines the effect of the toxin
  • Dependent on binding type and induction of toxic effects

front 12

Define toxic response and the three different types

back 12

the phenotypic outcomes of the toxicity of a chemical

  • three types: Adaptation, stress response, and toxic response

front 13

What is the adaptation toxic response?

back 13

  • physiological response to a "consistent" exposure
  • Is possible within a given exposure/time range
  • If exposure increases in time or concentration, it becomes toxic

front 14

What is the stress response toxic response?

back 14

  • cellular stress
  • Intended to limit the damage to the cell and tissue
  • often non-specific
  • Variety of conditions: oxidative stress, energy homeostasis, heat stress, and reactive metabolites

front 15

What is hormesis? What is the hormetic region?

back 15

  • biological phenomenon where a toxic substance in low doses could be beneficial
  • The hormetic region is the thin region between the substance being helpful and harmful to the receiving organism

front 16

How are toxicants delivered into the body?

back 16

  • Main routes: skin, ingestion (GI tract), respiratory
  • Lesser routes: injection, maternal transfer (placenta), bite, thorn, abrasion

front 17

What is an uptake barrier and give examples

back 17

  • mechanism your body has to prevent drug uptake
  • cell membrane, epithelial cells of GI tract, respiratory surface aka lung, and body surface

front 18

What factors affect the distribution of a toxicant

back 18

  1. How easy it moves across cell membranes

- lipophilicity, movement through ion channels, active or passive transport

2. Characteristics of the epithelium

- mainly epithelial thickness

3. Toxin concentration

- more concentration=faster delivery

4. Structure of capillary beds

- how much vasculature (fenestrated (extremely porous) or no)

5. Does it bind reversibly

front 19

What factors oppose distribution?

back 19

  1. Plasma proteins: bind to make toxin unavailable
  2. Barriers: (ie. BBB) keep toxins out
  3. Long term storage: (ie. fat cells) stores toxins to mitigate damage
  4. Binding proteins: (ie.metallothionine) to bind and attempt to make toxins useless
  5. Metabolism and elimination: break down toxin and excrete out of the body

front 20

What is lipophilicity?

back 20

How hydrophobic or fat soluble is the compound

front 21

What is the big difference between organic compounds and their inorganic form?

back 21

Their degree of lipophilicity is different

front 22

What is the molecular importance of compounds like MeHG---Cystine

back 22

This is a specific example of a compound that partakes in molecular mimicry

  • in this specific one, MeHg----Cystine can mimic methionine and cross the BBB to cause neurological issues

front 23

What was an important example of reversible binding from the lecture?

back 23

Cadmium

  • Compound induces production of metallothionine in the liver
  • The Cd enters the liver and binds reversibly to the metallothionine
  • It runs through your blood stream into your kidney
  • Detaches from the metallothionine
  • Causes tumor growth in your kidney

front 24

What are the four mechanisms of transmembrane transport?

back 24

  1. Diffusion
  2. Facilitated Diffusion
  3. Active transport
  4. Endocytosis

front 25

Briefly explain diffusion

back 25

  • movement of small lipophilic compounds
  • most toxins and compounds pass through this mechanism

front 26

Briefly explain facilitated diffusion

back 26

  • High transport rate thanks to carrier proteins and ion channels (aka mediators)
  • highly selective transport option and often temperature dependent
  • The transport rate can be inactivated or inhibited (ie.metals)

front 27

Briefly explain active transport

back 27

  • Requires ATP-pumps
  • Na-K-ATPase
  • often important in transport of material out of cells

front 28

What are xenobiotic transport pumps

back 28

  • actively transport material out of cells
  • extremely important from liver and kidneys
  • Part of the ABC transporter family

front 29

What are p-glycoproteins?

back 29

  • Form of active transport
  • MDR protein
  • Encoded by the MDR-1 gene
  • Very little specificity; most lipophilic compounds can bind/be moved
  • PGP/MDR pumps out chemo drugs from tumor cells which renders the drug ineffective
  • Inhibitors are given to keep drug in the tumor cells

front 30

What is endocytosis? Explain and draw

back 30

  • ATP expensive transport/dissolution of large molecule

Drawing: should include macrophage removing stuck molecule in lipid bilayer, dissolution of the molecule, and repair of the bilayer

front 31

What is frustrated phagocytosis? Explain and draw examples (2).

back 31

  • Explanation should include more macrophages coming to attempt to digest large molecule and being unsuccessful and emitting reactive oxygen species (ROS)

front 32

What leads to cell specific toxicity and give an example

back 32

  • differences in cellular transport as it determines how, what form, and where the toxicant enters the cell
  • not all cells express specific transporter

MPTP (heroin)

  • MPTP is the byproduct of heroin synthesis/metabolization
  • leads to parkinsons like symptoms (loss of dopaminergic neurons)
  • mimics dopamine enough to use dopamine transporters in brain

front 33

What are the basics of phase 1 metabolism

back 33

  • Chemical modifications that introduce a functional group on a xenobiotic that provides sites for phase II metabolism
  • "putting a handle on it"
  • Takes place in smooth ER of a hepatocyte
  • Major enzymes are cytochrome P450 (CYP) or mixed function oxygenase (MFO)

front 34

What are the basics of phase 2 metabolism

back 34

  • Synthetic reaction of a xenobiotic with an endogenous substance that results in a product in which is more water soluble and will enhance excretion
  • "Something grabs the handle"
  • Neutralization of active metabolic intermediates
  • Cytoplasm in hepatocyte is the area where reaction takes place
  • Important enzymes: GST, EH, UDP-GTS, ST

front 35

What phase is the enzyme GST in and what does it do?

back 35

  • GST is in phase II
  • takes phase I metabolite and adds glutathionine (protein)

front 36

What phase is the enzyme EH in and what does it do?

back 36

  • Phase II
  • Detoxifies epoxides

front 37

What phase is UDP-GTS (or UGT) in and what does it do?

back 37

  • Phase II
  • adds glucuronic acid

front 38

What phase is ST in and what does it do?

back 38

  • Phase II
  • adds sulfer groups

front 39

What is tamoxifen and what is it an example of?

back 39

  • Cancer drug
  • Causes different types of cancer in rats
  • ST enzyme example differences in rats and humans

front 40

What was the in class example of biotransformation with UGT enzyme?

back 40

  • NSAID pain relievers (like ibuprofen)

front 41

What was the in class example of bioactivation with UGT enzyme?

back 41

  • 2-napthylamine
  • intermediate formed is more toxic
  • Toxicity of the compound is determined by your bladder pH
  • Acidic: connection w/acid is unstable which produces protonated compounds in the bladder which leads to bladder cancer
  • basic: excreted normally

front 42

What is biotransformation?

back 42

  • change in chemical structure through metabolism
  • the parent compound structure is altered

front 43

What is bioactivation?

back 43

  • change in the chemical structure through metabolism that makes the compound MORE reactive/toxic
  • not all that are transformed are activated
  • Does not occur in all tissues
  • has different toxicokinetics and mechanisms
  • May be species specific

front 44

What was the lecture example when discussing bioactivation?

back 44

  • 4-ipomeanol
  • fungal derived toxin that causes bronchiolar necrosis in most mammals but not humans
  • Most mammals produce CYP4B1 enzymes in lungs which means the toxic response is in the lungs
  • For humans CYP1A2 and CYP3A4 in liver so the toxic reaction for us is in our liver

front 45

Break down the components of the liver in 4 drawings stopping at the portal triad, make sure to label (slide 4 of metabolism ppt).

back 45

front 46

Draw and label the interior of the sinusoids

back 46