Lecture 7

Question 1

Distribution depends on… (4)

Answer 1

1. Blood flow to and through tissue
2. Drug solubility
3. Drug ionization
4. Binding to plasma proteins of tissues

Distribution is required for drug to reach its target, must get to target and USUALLY into cells

Question 2

Where can drugs distribute? (6)

Answer 2

1. Total water - small water-soluble molecules ex: ethanol
2. Extracellular water - larger water-soluble molecules ex: gentamycin
3. Plasma restricted - strongly plasma protein-bound molecules and very large molecules ex: heparin
4. Fat - highly lipid soluble molecules ex: DDT
5. Bone - certain ions ex: lead, fluoride, tetracycline
6. Muscle, etc.

Question 3

Distribution in Pharmacology

Answer 3

Vd = Volume of Distribution

Vd = Amount of drug in body / C

C = concentration of drug in blood, plasma, or water

Vd can be greater than actual volume in body

Tissue can be storage depot for drugs

Question 4

Protein Binding + Distribution

Answer 4

• Plasma protein binding is related to metabolism, excretion, and drug effect
• Drug deposits in tissue “free up” plasma protein binding sites
• Binding is in equilibrium based on relative binding constants (affinities)

Question 5

Capillary Permeability

Answer 5

• One cell thick
• Absorption properties apply (diffusion, etc.)
• Gaps between endothelial cells differ in specialized tissue (large in excretory tissue, small/tight in barriers)

Question 6

Specialized Barriers

Answer 6

1. Blood-Brain Barrier
2. Placenta

Exclude certain drugs

Question 7

Blood-Brain Barrier

Answer 7

AKA BBB

• Tight junctions of endothelium
• Astrocytes form additional barrier around capillaries
• Decrease in permeability to water-soluble or ionized molecules
• Lipid-soluble substances diffuse easily
• More permeable when disrupted by infection or injury
• Also has drug efflux transporters
• Not fully formed until about 6 months of age

Question 8

Placenta

Answer 8

• Connects fetus with maternal uterine wall and has sinuses to take maternal blood to baby
• Lipid-soluble materials move easily
• Water-soluble materials move more slowly
• Large molecules are less likely to pass barrier
• Fastest equilibrium possible between mother and fetus is 40 minutes

Question 9

Limited entry to body compartments can occur by…

Answer 9

1. Physical barriers (tight junctions)

2. Transporter barriers - high concentrations of efflux transporters or low concentrations of influx transporters

Question 10

Half-life

Answer 10

• Denoted by t1/2
• Time it takes for half a drug concentrations to be eliminated
• Simplest case is a single compartment
• Drug residence depends on Vd and CL (CL = clearance)

Question 11

Delayed Effections

Answer 11

• Drug effect doesn’t usually parallel drug concentrations
• Can occur due to distribution to site of action
• Drug action can be indirect or require a cellular response for an affect to manifest

Question 12

Therapeutic Window Definition

Answer 12

The range of dosage of a drug or of its concentration that provides safe effective therapy.

Question 13

Distribution Definition

Answer 13

The dispersion or dissemination of substances throughout the fluids and tissues of the body.

Question 14

Volume of Distribution Definition

Answer 14

The apparent volume in which a drug is

distributed (Vd).

Question 15

Pregnancy Class A

Answer 15

Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

Question 16

Pregnancy Class B

Answer 16

Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women. Or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.

Question 17

Pregnancy Class C

Answer 17

Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. Or no animal studies have been conducted and there are no adequate and well controlled studies in pregnant women.

Question 18

Pregnancy Class D

Answer 18

Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.

Question 19

Pregnancy Class E

Answer 19

Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.