Dr. E Exam 1

Question 1

What is drug distribution?

Answer 1

The movement of drug after absorption from one location in the body to another

Question 2

Why cant we use one compartment models for drug distribution?

Answer 2

One compartment models assume that drug distribution occurs instantaneously at time = 0

Use multicompartment models

Question 3

What are the two parts of drug distribution?

Answer 3

Rate and extent

Question 4

What is distributional clearance?

Answer 4

The rate of drug transfer between compartments

How long distribution phase lasts

Question 5

What are the other names for distributional clearance?

Answer 5

Intercompartmental clearance
Rate of perfusion

Question 6

What is the extent of drug distribution determined by?

Answer 6

Determined by volume of distribution

Question 7

What does the rate of distribution tell?

Answer 7

How fast the drug distribution takes place

Question 8

What are the two phases of drug distribution?

Answer 8

Presentation of drug to tissues by blood
Diffusion or uptake of drug from the blood to the tissue

Rate is limited by the slower of the two steps

Question 9

What is the rate of tissue perfusion?

Answer 9

Rate of drug presentation (mL/min)

Question 10

What happens during perfusion-controlled drug distribution?

Answer 10

Some drugs tend to distribute less to tissues because of lower perfusion rate

Question 11

What can cause perfusion controlled drug distribution?

Answer 11

Congestive heart failure

Question 12

What does hydrostatic pressure do?

Answer 12

Creates the pressure gradient between artierial end entering tissue and venous end leaving tissue

Question 13

What is hydrostatic pressure responsible for?

Answer 13

Penetration of water soluble drugs into spaces between endothelial cells and into the lymph

Question 14

What happens during diffusion controlled drug distribution?

Answer 14

Drug arrives to the tissue site, diffuses into interstitial fluid of capillaries and across tissue membrane into tissues through passive diffusion and is controlled by slow diffusion

Question 15

What can cause diffusion controlled drug distribution?

Answer 15

Inflammation

Question 16

What is the equation for distribution half life?

Answer 16

0.693/alpha

Question 17

What happens at tss?

Answer 17

Distribution equals redistribution

Question 18

What is extent of drug distribution?

Answer 18

Relative distribution of drug molecules between plasma and the rest of the body

Question 19

What is the volume of plasma?

Answer 19

3L

Question 20

What is the volume of blood?

Answer 20

5L

Question 21

What is the volume of interstitual H2O?

Answer 21

12 L

Question 22

What is the volume of intracellular H20?

Answer 22

27L

Question 23

What is the volume of extracellular fluid?

Answer 23

15 L

Question 24

What is the volume of total body fluid?

Answer 24

42 L

Question 25

How do you calculate the volume in plasma?

Answer 25

0.04L/kg

Question 26

How do drugs get into plasma?

Answer 26

Drug molecules are in systemic circulation and distribute throughout plasma

Question 27

What factors affect the drug distribution in plasma?

Answer 27

Lipid solubility (increase causes more drug out of plasma) Molecular size (decrease causes more drug out of plasma) Plasma protein binding (more means more in plasma) Permeability of membrane

Question 28

How do you calculate drug in EC fluid?

Answer 28

0.2L/kg

Question 29

Why are most drugs distributed to the EC fluid?

Answer 29

Epithelial membrane of capillary cells is very loose and allows passage of even polar and protein molecules

Question 30

How do you calculate drug in total body fluid?

Answer 30

0.6L/kg

Question 31

How do drugs get into total body fluid?

Answer 31

Drug exposed to individual cells by entering into intracellular fluid of tissues

Question 32

What does the drug's ability to get past total body fluid depend on?

Answer 32

Lipophilicity Tissue structure binding

Question 33

What is volume of distribution?

Answer 33

Hypothetical volume of fluid required to contain the total dose of a drug in the body at the same concentration as that measured in plasma

Question 34

What does Vd relate?

Answer 34

Amount in the body to concentration in plasma

Question 35

What is Vd affected by?

Answer 35

Pathological conditions Weight Otherwise it is the same for the same drug

Question 36

Why is Vd at steady state clinically important/

Answer 36

Has physiological relevance reflecting the extent of the drug distribution from the plasma pool into tissues

Question 37

Why can Vd exceed physiological total body volume?

Answer 37

Because of drug binding to peripheral tissue structures

Question 38

What are the plasma proteins?

Answer 38

Albumin (55% and synthesized in liver) Globulins Alpha 1 acid glycoprotein lipoproteins

Question 39

What are the tissue structures?

Answer 39

Nucleic acids Ligands Calcified tissues ATPhosphotases

Question 40

What happens to volume of distribution when plasma protein binding increases?

Answer 40

It decreases

Question 41

What happens to Vd when tissue binding increases?

Answer 41

Vd increases

Question 42

How do you find Abody?

Answer 42

Aplasma+Atissue VdxCplasma

Question 43

How do you find fplasma?

Answer 43

Aplasma/Abody Vplasma/Vd

Question 44

How do you find ftissue?

Answer 44

1-fplasma

Question 45

How do you find Aplasma?

Answer 45

Vplasma x Cplasma

Question 46

What form of drug undergoes passive diffusion?

Answer 46

Unbound drug concentrations in plasma

Question 47

How do you find fuplasma during Steady state?

Answer 47

same as futissue

Question 48

How do you find Cuplasma?

Answer 48

Cplasma x fuplasma

Question 49

How do you find Cutissue?

Answer 49

Ctissue x futissue

Question 50

What happens if the concentration of drug unbound decreases?

Answer 50

Drug dissociated from bound

Question 51

What does Cu,plasma do?

Answer 51

Diffuses across membranes to the drug's site of action Interacts with receptors to cause pharmacological and toxicological activities and is available for distribution and elimination

Question 52

What is k1/k2?

Answer 52

Affinity between the drug and plasma protein | Magnitude association constant

Question 53

What happens when K1 is much greater than K2?

Answer 53

affinity increases and drug binding is favored

Question 54

What happens to plasma protein amount when concentration of drug increases?

Answer 54

Increases

Question 55

What causes a decrease in albumin?

Answer 55

liver disease age pregnancy burns trauma

Question 56

What causes an increase in albumin?

Answer 56

Thyroid hormone Corticosteroids Growth hormone Insulin

Question 57

What causes an increase in AAG?

Answer 57

Stress caused by MI Cancer Surgery

Question 58

What causes a decrease in lipoprotein?

Answer 58

dieting statins

Question 59

What causes an increase in lipoprotein?

Answer 59

alcoholism diabetes

Question 60

What does renal disease cause?

Answer 60

decrease in albumin decrease in drug binding increase in accumulation

Question 61

What does liver disease cause?

Answer 61

Decrease in plasma protien binding decrease in albumin and AAG

Question 62

What is concetration dependent displacement?

Answer 62

Binding of one drug might displace a second drug from binding site ## Footnote Competition for a limited number of binding sites on the protien

Question 63

What can decrease the consequences of toxicity due to decreased binding?

Answer 63

Increase in elimination Changes in drug concetration outside the plasma (plasma is very low in concentration while the outside is large)

Question 64

How do you calculate loading dose?

Answer 64

Vss x Target Cp

Question 65

What is Vd affected by?

Answer 65

Weight Age Concentration of plasma protein