Distribution Flashcards

1
Q

What are compartments?

A

diff locations in body where drug is distributed (referred to theoretically)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

describe initial absorption & distribution of drug:

A

initial absorption into “central compartment” (systemic circulation) is followed by distribution to “peripheral compartments” (ex: liver, brain, other organs & tissues);

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

After absorption & entry into systemic circulation, there is…

A

… an immediate rapid distribution throughout body, esp to well perfused tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 4 main factors influencing distribution?

A
  1. blood flow (perfusion) - depending on tissue, can range frm 3-30% of cardiac output
  2. drug physiochemical properties (lipid solubility, pKa, molecular size)
  3. binding of drug to plasma prots & cellular binding prots
  4. barriers to distribution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is most abundant plasma protein?

A

Albumin; many drugs have varying affinities (weak interactions - hydrostatic interactions, van der waals, not covalent bonds)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The Free:bound equilibrium in blood plasma is due to?

A

reversible binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What kind of drug can diffuse out of bloodstream and into tissues & why?

A

Free drug only; b/c plasma proteins are huge & cannot cross capillary walls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

explain the dynamic nature of free drug diffusing from blood into tissues:

A

as free drug diffuses from blood to tissue, more is released from plasma prots until tissue sites become saturated. also, as free drug is excreted, more is released from plasma prots

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is albumin?

A

The bus; has many sites where interactions w/ chemicals/drugs can occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is tissue (cellular) protein binding like in adipose tissue?

A

It’s an important storage depot for highly lipophilic drugs (& persistent organic pollutants)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is tissue (cellular) protein binding like in the liver & kidney?

A

they have high binding capacity for certain drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is tissue (cellular) protein binding like in bone?

A

bone binds certain drugs (ex: tetracyclines) & heavy metals (ex: lead)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Consider tissue (cellular) protein binding in lean vs obese individuals:

A

Might need to give more drug in obese animals if it is lipophilic drug that accumulates in fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Consider tissue (cellular) protein binding in lactating individuals:

A

breast milk is high in fat & can accumulate lipophilic drugs where they can become route of exposure for neonate (but route of excretion for mom)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some barriers to drug distribution?

A

BBB & placental “barrier”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does the blood brain barrier affect drug distribution?

A
  • mjr barrier to many drugs b/c of tightly joined endothelial cells surrounding CNS & active (ATP-dependent) transporters for removal (MDR prots)
16
Q

when is the blood brain barrier not fully developed and what are the implications of this?

A

not fully developed in embryo & at birth; this has important toxicological implications

17
Q

How does the placental “barrier” affect drug administration?

A
  • must assume that any drug entering maternal circulation is capable of crossing placenta unless proven otherwise
  • drugs are tested extensively for their ability to cross placenta & cause teratogenic effects in offspring
18
Q

What is the volume of distribution? (V subscriptD)

A
  • apparent fluid volume in which a drug appears to be dissolved (how widely a drug is distributed throughout body)
  • “proportionality constant” used to compare distribution of drugs
  • total drug dose (mg) / plasma drug conc (mg/L)
19
Q

what does high volume of distribution mean?

A

extensive distribution of drug & high affinity for tissues

20
Q

what does low volume of distribution mean?

A

drug is restricted mainly to blood plasma, mainly due to high plasma protein binding

21
Q
A