7/11/16

Question 1

Toxic action of a substance

Answer 1

a consequence of the physical/chemical interaction of the active form of that substance with a molecular target within the living organism

Question 2

Magnitude of toxic effect

Answer 2

a function of the concentration of altered molecular targets, which in turn is related to the concentration of the active form of the toxicant at the site where the molecular targets are located

Question 3

Toxicokinetics

Answer 3

what the body does to the agent 
Absorption 
Distribution
Metabolism
Excretion
Storage

Question 4

Toxicodynamics

Answer 4

what the agent does to the body - the active form of the agent at the sensitive target

Question 5

TK/TD are affected by

Answer 5

• other drugs/xenobiotics
• genetic polymorphisms
• infection/GI flora
• age, weight, diet

Question 6

Absorption and distribution

Answer 6

enteral (oral, sublingual, rectal)
parenteral (IV, IM, SC)
other routes (inhalation, topical, transderaml)

Question 7

What is the common feature of all routes of administration (except IV)?

Answer 7

Absorption - epithelial cells line our body cavities and surfaces (epithelial cells lines our body cavities and surfaces)

Question 8

Physicochemical factors that affect kinetics of absorption

Answer 8

pH, blood flow, gastric emptying, bowel transit, surface area (lung 140m2, GI 300m2, skin 1.5-2m2)

Question 9

Diffusion

Answer 9

low MW, lipophilic compounds, requires concentration gradient

Question 10

Carrier-mediated transport

Answer 10

ligand binds receptor on cell surface

ex: cholesterol/lipoprotein bind to LDL

Question 11

Facilitated transport

Answer 11

mediated by membrane transport proteins
energy provided by concentration gradient
- glucose transporter

Question 12

Active transport

Answer 12

major form of drug transport

• mediated by membrane transport proteins
• transports AGAINST a concentration gradient
• temeperature-dependent and saturable

Question 13

Why is the blood-brain barrier less permeable to toxicants?

Answer 13

Capillary endothelial cells (tightly joined, contains ATP transporter - efflux pump)
Capillaries in CNS are surrounded by glial cells
Low protein content of interstitial fluid in brain limits movement of water-insoluble molecules by paracellular transport

Question 14

Purpose of biotransformation (metabolism)

Answer 14

convert xenobiotics to water soluble forms so that they can be excreted in feces and urine

Question 15

Why does biotransformation make resulting compound more toxic?

Answer 15

Most xenobiotics are liophilic and body readily excretes water soluble compounds so the body transform via Phase 1 or 2 reaction to make them more soluble.

Question 16

Primary enzyme in phase 1 reactions

Answer 16

cytochrome p-450 (mixed function oxidase)

Question 17

Phase 2 reaction enzymes

Answer 17

glucuronyltransferase
sulfotransferase
glutathione-S-transferase
acetyltransferase

Question 18

Excretion pathways

Answer 18

respiratory (mucociliary exchange, gas exchange)
GI (biliary excretion, entero-hepatic circulation)
urinary excretion (glomerular filtration, trans-tubular secretion)

Question 19

Other routes of excretion

Answer 19

milk, sweat, hair, nails, saliva

Question 20

biological half-life

Answer 20

time required for chemical in the body to decrease to 1/2 its current value

Question 21

toxicological endpoints

Answer 21

cell death, cellular/organ dysfunction, teratology, genetic changes, cancer

Question 22

LD50

Answer 22

lethal dose to 50% of test population, lower ld50 - more toxic

Question 23

Exposure

Answer 23

any condition which provides an opportunity for an external environmental agent to enter the body

Question 24

Agent

Answer 24

any chemical, biological, or physical material capable of eliciting a biological response (diff than vector or carrier - air, water, soil, food)

Question 25

Dose

Answer 25

amount of agent actually deposited within the body, distinction between exposure and dose is blurred

Question 26

exposure assessment

Answer 26

exposure = intensity x frequency x duration

Question 27

Vectors for exposure in context of environmental health

Answer 27

water, air, food, soil

Question 28

toxicokinetics in the toxicological paradigm

Answer 28

exposure, internal dose, biologic effective dose

Question 29

toxicodynamics in the toxicological paradigm

Answer 29

early biologic effects, altered structure & function, clinical disease

Question 30

Patterns of exposure

Answer 30

``` continuous (cigarette) intermittent (uranium mining) cyclic random concentrated ```

Question 31

Hierarchy of "exposure" data

Answer 31

Quantitative personal dosimeter measurements quantitative ambient measurements in the vicinity quantitative surrogates of exposure (estimates of drinking water or food consumption x conc.) residence or employment in proximity to the source of exposure residence or employment in the general geographic area of the source of exposure

Question 32

Uncertainties in toxicology

Answer 32

high to low dose extrapolation | interspecies comparisons

Question 33

Define dose-responser relationship

Answer 33

the relationship between the quantity of response and the dose of the drug or toxicant - response is due to agent - degree of response is due to compound concentration - have a quantifiable response parament

Question 34

Potency

Answer 34

Range of doses over which a drug produces increasing responses

Question 35

Efficacy

Answer 35

maximal response; plateau of the dose-response curve

Question 36

"Random" model

Answer 36

Risk of response is a function of dose, assumes no threshold, no dose is safe, any dose increases the risk (ex cancer)

Question 37

"Deterministic" Model

Answer 37

Severity of response is a function of dose, assumes a threshold, a "safe" dose exist(ex radiation, chloracne)

Question 38

Interactive responses

Answer 38

Additive (2+4=6) Synergistic (2+5=20) Potentiation (0+4=10) Antagonism (2+6=3; 4+1=0)

Question 39

Interactions of chemicals - additive

Answer 39

operating through same molecular mechanism - specific receptor or very specific interaction (ex 2 diff organophosphates interacting with cholinesterase receptor)

Question 40

Interactions of chemicals -synergistic

Answer 40

Carbon tetrachloride w/ ethyl alcohol - people living above dry cleaning exposed and drink alcohol - synergy response -> liver toxicity lung cancer & asbestos

Question 41

Interactions of chemicals - potentiation

Answer 41

only one chemical has toxic effect at site of action ex: isopropyl alcohol (rubbing alcohol, antifreeze, solvent not toxic to liver CNS depression w/ gastritis, pain, N+V) -> potentiates CCl4 * In the absence of pretreatment, little response

Question 42

Interactions of chemicals - antagonism

Answer 42

1) functional mechanism, 2 chemicals counterbalance each other - chemical producing convulsions plus anticonvulsant drug (diazepam) 2) dispositional mechanism, alters concentrations or residence time of toxin (ipecac, charcoal) 3) metabolic mechanism - modulation of CP450 4) receptor block mechanism (competitive inhibitors - naloxone, tamoxifen, atropine)