Excretion

Question 1

what is the most important xenobiotic elimination pathway in vertebrate animals?

Answer 1

renal excretion

Question 2

is first order or zero order most common?

Answer 2

first order

Question 3

Potentiation:

Answer 3

2+0=10. it potentiats that effect. One drug has no effect on what you are measuring but it has an effect on the other drug and enhances that! ex.) grapefruit juice inhibits the major p450 enzyme and so if you take a drug this juice will get a more enhanced effect because it will have longer time in your body (half-life)

Question 4

Cp (concentration of plasma)=

Answer 4

Co(initial concentration) e^-kt

Question 5

half life of xeno equation:

Answer 5

t1/2=0.693/kel

Question 6

when you plot the concentration vs time and you get the curved line this tells you it follows first order toxicokinetics: what does this mean?

Answer 6

this measn that the elimination of that xeno from the body is proportional to that plasma concentration. elimination is proportional to Cp

Question 7

how do acid and base excretion differ?

Answer 7

remember that like is not ionized in like. Urine is slightly acidic and therefore acid xenobiotices will not get ionized and will be reabsorbed. However if it is a weak base and goes into the slightly acidic pH of the glomerulus it will become ionized and promote excretion of bases whereas acids it promotes reabsorption.

Question 8

what does alpha and beta mean in the two compartment model?

Answer 8

akpha is absorption and distribution and betta is metabolism and excretion

Question 9

Synergism:

Answer 9

2+2=10, ex.) opioids +advil= you get an enhances pain relieving effect because they attack pain from differnt angles

Question 10

describe enterohepatic cycling:

Answer 10

drugs and drug metabolites with molecular weights higher than 300 may be excreted via the bile, stored in the gall bladder, delivered to the intestines by the bile duct, and then reabsorbed into the circulation. This process reduces the elimination of drugs and prolongs their half-life and duration of action in the body.

Question 11

rate constant for absorption::

Answer 11

ka

Question 12

draw a 2 compartment model:

Answer 12

Question 13

up to what percent of the maternal dose can be excreted in the break milk

Answer 13

2%

Question 14

what are the difference routes of excretion:

Answer 14

1. Renal 2. Biliary 3. Pulomnary (exhalations/lungs) 4. Lactation 5. Minor routes: sweat, saliva, hair, nails

Question 15

interactions during excretion

Answer 15

competition for facilitated diffusion (OAT, OCT) and active transport pumps (MDR, MRP). The xenobiotics can compete for the pumps! The ones that loose will have a higher concentration and longer half life in the body.

Question 16

whats the principle for how the breathalyzer works?

Answer 16

2% of the dose of ethanol is excreted in our exhaled breath

Question 17

what does zero order mean?

Answer 17

elimination is independent of Cp

Question 18

basic formula for one department model?

Answer 18

Cp= Co * e^-kel*t

Question 19

3 key concepts to the course of disposition of xenobiotics in the body:

Answer 19

1.) Bioavailability- lower bioavailbility means better bio transformation 2. Volume distribution- apparent space or volume of the body its occupying. High volume of distribution means very lipid soluble, unbound and gets all throughout the body. means low volume means trapped in plasma and confined to central compartment 3. Clearance! efficiency of xenobiotic removal from body.

Question 20

Summation (additivity)

Answer 20

most important and common interaction. There is actually no interaction between the xenobiotics! You just add the effects of the xenobiotics. ex.) 2 xenobitoics with same mode of action, they just combine to produce an additive response 2+2=4

Question 21

the biliary route is important route for excretion for what?

Answer 21

larger molecules greater than 350 g/mol like benzo(a)pyrene which is cancer causing

Question 22

antagonism-

Answer 22

getting a reduced effect 2+2=1 one of the xenobiotics has sort of blocked that response.

Question 23

if kel =0.2 min-1 what does this mean?

Answer 23

that 20% of the xeno is eliminated from the body every minute

Question 24

describe two model compartment

Answer 24

its like the tide in the ocean once you get first wave of xeno it pushes into the peripheral but once that concentration gets too high it starts pushing back towards central

Question 25

what kind of xenobiotics follow a two compartment model?

Answer 25

water soluble xenobiotics

Question 26

example of zero order:

Answer 26

ethanol follows zero order kinetics and why you can die from it. If you increase the dose your enzymes can only work so hard and get to the point where your sedation of alcohol is too much. If ethanol did not follow zero order the breathalyzer would not work! is because when youve had 3 beers or 30 beers you will have constant elimination of 2% in your breathe.

Question 27

draw a one compartment model

Answer 27

Question 28

what are the 3 processes involved in changing blood level of a xenobiotic:

Answer 28

1. Glomerular filtration 2. Tubular reabsorption 3. Tubular secretion

Question 29

what does 7 half lives mean?

Answer 29

99% of drug excreted after 7 days.

Question 30

clearance:

Answer 30

removal of a xenobiotic

Question 31

Interactions in GI tract:

Answer 31

can affect absorption like pka!

Question 32

what model does this describe?

Answer 32

two compartment model

Question 33

what model does this graph follow?

Answer 33

could either by one compartment or 2 compartment

Question 34

How can you get high concentrations in your tubular cells?

Answer 34

You have a xenobiotic in the blood stream and transporters like OCT will pump that into the proximate conjugate tubular cell and it does so readily. But they do not get pumped very readily out into the filtrate. remember dose defines the poison so sometimes you can get a very high concentration in your tubular cells.

Question 35

in the two compartment model what des central meand and peripheral mean?

Answer 35

there are two compartments in the body, there are the central the blood streamd the circulation and then theres everything else with the tissues and muscles and organs which is peripheral

Question 36

clearance=

Answer 36

Vd*kel (or Vd*B for a two compartment model) remember that clearance is in unit mL/min so it is a rate of flow.

Question 37

Interactions during distribution:

Answer 37

the xenobitoics may compete for the binding site on proteins! dieldrin binds with really high affinity to albumin greater than 99% bound. its going to stick there more readily than other xenobiotics. the other xenobiotics will then have more concentration for free unbound which can cause trouble in the body

Question 38

the one-compartment model works for what?

Answer 38

for many xenobitoics, especially very lipid soluble xeno’s one with high log kow

Question 39

what model does this graph follow?

Answer 39

one compartment

Question 40

draw the zero order kinetics graph:

Answer 40

Question 41

rate constant for elimination

Answer 41

kel

Question 42

describe glomerular filtration and into tubular reabsorption:

Answer 42

the glomerular capillaries have large pores (70nm), therefore most toxicants will be filtered at the glomerulus, except tose that are very large or are tightly bound to plasma protein. Once a toxicant enters the glomerulus filtrate it will either by passively reasborbed across the tubular cells if it has a high lipid/water partition coefficnet or remain in the tubular lumen and be excreted if it is a polar compound.