Distribution

Question 1

what molecules have a high affinity for fat?

Answer 1

lipid soluble molecules. has a very high kow

Question 2

describe endocrine disrupting chemica;s?

Answer 2

controversy! Its related to competition for binding proteins. They can compete for steroid binding globulins.

Question 3

what 2 organs concentrate more toxicants than do all the other organs combined?

Answer 3

liver and kidney.

Question 4

cellular binding proteins is especially found in what organs?

Answer 4

the liver and the kidney. These organs contain certain protein that bind certain xenobitoics.

Question 5

the xenos that are unbound (not bound to albumin) can get where/

Answer 5

into the blood stream, the systemic circulation.

Question 6

define volume of distribution:

Answer 6

the apparent fluid volume in which the xenobiotic appears to be dissolved (how widely the xenobitoic is distributed throughout the body)

Question 7

the rate of the distribution to organs or tissues is determined primarily by what?

Answer 7

blood flow and the rate of diffusion out of the capillary bed into the cells of a particular organ or tissue and usually occurs rapidly.

Question 8

Vd is used to what?

Answer 8

compare distribution of xenobitoics, especially for drugs

Question 9

What is an example of a cellular binding protein in the kidney?

Answer 9

a protein called metallothionein. It is involved in zink homeostasis which is an essential trace element we need. But it can bind to toxic cadmium. When you are exposed to cadmium these people have kidney disease becasue toxicologiccally the kidney cells express high levels of metallothioneing and it builds up when you are exposed to Cd. So you get a higher dose in the kidney

Question 10

what is the problem with polar bears and fat storage sites?

Answer 10

Polar bears before hibernation get really really fat, then lose it all. This means that legacy contaminants like DDT are very highly concentrated in the fat, then they are biotransformed and actiavted when they loose it all and this can lead to toxic effects. Such as during lactation! They mobilize those contaminates into the milke and expose their offspring to them.

Question 11

what is the problem with bone as a storag sites?

Answer 11

Both lead and strontium can replace cacloums and fluroine as well!

Question 12

example of how blood flow differs and therefore distribution differs?

Answer 12

liver, lung, brain get 25% of cardiac output, they are highly perfused tissues! Other tissues like adipose tissue (Fat) gets 3% of cardiac output.

Question 13

what would be 2 reason for two drugs t have different Vd’s?

Answer 13

1. if they have different lipophilicities? 2. the difference in binding proteins, plasma protein binding specificall! If drug is 10% bound and drug b is loike 90% bound then only 10% of drug b actually free and unbound in the blood stream to diffuse into tissues.

Question 14

Vd=

Answer 14

total drug dose (mg)/ plasma drug conc (mg/L)

Question 15

describe albumin:

Answer 15

is the most abundant protein in plasma and serves as both a depot and multivalent transport protein for many endogenous and exogenous compounds.

Question 16

what are the 4 main factors of distribution?

Answer 16

1. Blood flow to the area (perfusion) 2. Lipopilicity 3. Binding proteins 4. Barriers

Question 17

how does lead replace bone?

Answer 17

lead is not required for anything in our body. Lead mimics or competes with calcium in varioys processes and that why when your exposed to lead it gets distributed in your body but ends up in your skeleton.

Question 18

what storage site is very important in our systemic circulation?

Answer 18

plasma proteins! ex.) albumin

Question 19

question: if drug a had a Vd of 1000L and drug b had a Vd of 10L what does this mean?

Answer 19

Drug b is 100 times lower in distribution then drug A. Drug A is rapidly and widely distributed. Drug b most of it stays in the plasma!

Question 20

describe the blood brain barrier

Answer 20

Blood brain barrier: cells are tightly joined and a xenobiotic cannot enter the brain through filtration and the lipophilic vacumn cleaners prevent it from going into the brain.

Question 21

storage sites:

Answer 21

Places that can store or act as a reservoir where the xenobitoic can hang out. The compartment where a toxicant is concentrated.

Question 22

what are 5 major storage sites?

Answer 22

1. *plasma porteins 2. Cellular binding proteins 3. Fat 4. Bone 5. The liver and kidney