Distribution

Question 1

Compartments

Answer 1

-different locations in body where drug is distributed

-involves central compartment (systemic circulation) and peripheral compartments (liver, brain, organs, tissues)

Question 2

Drug in systemic central compartment

Answer 2

Will be equilibrium between free drug and protein bound drug.
-occurs because reversible binding
-dynamic! As some drug diffuses out into tissues or is excreted, proteins will release more drug.

Question 3

What version of drug can diffuse out of blood?

Answer 3

Must be free form of drug! Cannot be bound to protein

Question 4

Factors effecting distribution

Answer 4

1. Blood flow (perfusion)
2. Drug physiocochemical properties (lipid solubility, pKa, size)
3. Binding of drug to plasma proteins and cellular binding proteins
4. Barriers to distribution

Question 5

Blood flow/cardiac output for distribution to target tissues

Answer 5

Can range from 3-30% of cardiac output

Question 6

Plasma protein binding

Answer 6

-usually to albumin
- drugs have varying affinity

Question 7

Tissue protein binding

Answer 7

High binding capacity: liver and kidney

Storage (for highly lipophilic drugs): Adipose tissue

Bone: binds certain drugs (eg.tetracyclines) and heavy metals (eg. lead)

Question 8

Adipose tissue and forever drugs

Answer 8

Highly resistant and lipophilic drugs can persist in individuals and therefore the environment

**Individuals in arctic ingesting high fat diets can often accumulate forever chemicals

Question 9

Adipose tissue and obese individuals

Answer 9

More drug diffusing into more adipose tissue reservoirs rather than going to the actual target area. So may need more drug to have desired effect

Question 10

Adipose tissue and lactation

Answer 10

Breast milk is high in fat and can accumulate lipophilic drugs which can then result in a route of exposure to neonate

Question 11

Barriers to distribution

Answer 11

1. Blood-brain barrier
2. Placental barrier

Question 12

Blood brain barrier

Answer 12

-major barrier to many drugs because tightly joined endothelial cells surrounding CNS and active transporter for removal (MDR proteins)

**not fully developed in embryo and at birth… toxicological implications (eg.fetal alcohol syndrome)

Question 13

Placental barrier

Answer 13

-Assume that any drug in maternal circulation is capable of crossing placenta and may cause teratogenic effects in offspring

**number of layers of placenta which vary among animals will play a role

Question 14

Volume of distribution (VD)

Answer 14

the apparent fluid volume in which a drug appears to dissolve OR in other words, how widely a drug is distributed throughout the body

Question 15

What is volume of distribution used for?

Answer 15

A proportionality constant use to compare distribution of drugs

Question 16

Volume of distribution equation

Answer 16

VD= total drug dose (mg)/ plasma drug concentration (mg/L)

Question 17

High vs. low VD

Answer 17

High: extensive distribution of drug and high affinity for tissues

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

Question 18

What would a high volume of distribution indicate?

Answer 18

• likely lipophilic and a low plasma protein binding affinity