Distribution

Question 1

refers to the reversible transfer of drug from one location to another within the body.

Answer 1

Distribution

Question 2

Factors Affecting Distribution (5)

Answer 2

1. Regional blood flow
2. Capillary permeability
3. Physicochemical properties of the drug
4. Protein binding
5. Volume of distribution

Question 3

Regional blood flow
(Rate of distribution)
- Give 4 highly perfused organ that increases the drug distribution

Answer 3

Brain
Heart
Liver
Kidney

Question 4

Regional blood flow
(Rate of distribution)
Give 3 slow perfused organ that decreases the drug distribution

Answer 4

Fat
Tissue
Skin

Question 5

(Factor) It is the ability to pass through capillary and enter to tissues

Answer 5

Capillary permeability (volume of blood )

Question 6

What are the 2 junction types or capillary permeability

Answer 6

Discontinuous
Continuous

Question 7

junction type of capillary permeability that:
—- has spaces in between
—- easily pass through

Answer 7

Discontinuous

Question 8

Ex. Organ that has discontinuous type

Answer 8

Liver
—— fast distribution (1st factor)
—— easily pass through (2nd factor)

Question 9

Ex. Organ that has discontinuous type

Answer 9

Liver

Question 10

Ex. Organ that has continuous type

Answer 10

Brain (BBB - walls of capillary)
—— fast distribution (factor 1)
—— not easily pass through (factor 2)

Question 11

junction type of capillary permeability that:
—- w/o spaces in between
—- do not easily pass through

Answer 11

Continuous

Question 12

Ex. Of drugs that passes through continuous type

Answer 12

LUNA - passes through BBB
Super lipophilic

Ex. 1st gen. Antihistamines
Effect: sedative

Question 13

What are the 2 factors under physicochemical properties of drug.

Answer 13

Molecular weight
Solubility

Question 14

Physicochemical factors (molecular weight)
- give ex. Of VERY large molecule (upto 2000kDa)
- it stays at_____

Answer 14

Dextran
- Plasma

Question 15

Physicochemical factors (molecular weight)
- give ex. Of large molecule (5-30 kDa)
- it stays at_____

Answer 15

Heparin
- extracellular space

Question 16

Why High MW - X Pass through cell membrane ?

Answer 16

Because of large structure

Question 17

(Solubility)
Hydrophilic, ionized drug stays at_____

Answer 17

Extracellular fluid(space)

Question 18

(Solubility)
Lipophilic compounds is readily diffuse into_____

Answer 18

Tissues

Question 19

Extremely lipid soluble compounds accumulate in the _______

Answer 19

adipose tissue

Question 20

(Factor) Indicator of the extent of drug distribution into body fluids and tissues
• Relates the amount of drug in the body to the measured concentration in the plasma
𝑉𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑑𝑖𝑠𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 (𝑉d ) = 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 /𝑝𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 (𝐶”)
• Important for the calculation of loading dose

total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.

Answer 20

Volume of Distribution or apparent volume of distribution

Question 21

Correlation of Vd with body fluids
• Total body fluids =___% of BW (males); ____% of BW (females)

Intracellular fluids = ____% of BW o Extracellular fluids =____% of BW

■ Interstitial compartment =___% BW ■ Intravascularcompartment=__%BW

Answer 21

TBF male: 60%
TBF female: 50-55%

ICF: 40%
EXF: 20%

ISC: 15%
IVC: 5%

Question 22

Volume of Distribution of Warfarin

Answer 22

8

Question 23

Volume of Distribution of Gentamicin

Answer 23

18

Question 24

Volume of Distribution of Digoxin

Answer 24

440

Question 25

Volume of Distribution of Diazepam

Answer 25

80

Question 26

Volume of Distribution of Diazepam

Answer 26

80

Question 27

Volume of Distribution of Nortriptyline

Answer 27

1700

Question 28

Volume of Distribution of Chloroquine

Answer 28

>15000

Question 29

SIGNIFICANCE of determining drug__________: • Provides slow release form of a drug (repository, resulting to extended effect) • Limit access to certain body compartments • Can make the drug prone to drug-drug interaction

Answer 29

Protein binding

Question 30

(3) SIGNIFICANCE of determining drug protein binding:

Answer 30

1.Provides slow release form of a drug (repository, resulting to extended effect) 2.Limit access to certain body compartments 3.Can make the drug prone to drug-drug interaction

Question 31

Protein binding of Gentamicin

Answer 31

3

Question 32

Protein binding of Gentamicin

Answer 32

3

Question 33

Protein binding of Digoxin

Answer 33

25

Question 34

Protein binding of Vancomycin

Answer 34

30

Question 35

Protein binding of Lidocaine

Answer 35

51

Question 36

Protein binding of phenytoin

Answer 36

89

Question 37

Protein binding of warfarin

Answer 37

99

Question 38

2 types of plasma protein

Answer 38

Albumin Alpha 1 acid glycoprotein

Question 39

Types of plasma protein that bind to drug w/ neutral and acidic pH ( low pH)

Answer 39

Albumin

Question 40

Give 3 example of drug with neutral pH

Answer 40

Chloramphenicol Dexamethasone Diazepam

Question 41

Give 4 example of drug with acidic/weak acid

Answer 41

Barbiturates Penicillins Salicylates (Aspirin) Gentamicin

Question 42

Types of plasma protein that bind to weak bases

Answer 42

Alpha 1 acid glycoprotein

Question 43

Give 3 example of drug with weak base

Answer 43

Lidocaine (Xylocaine) Saquinavir Propranolol

Question 44

Significance of determining drug protein binding

Answer 44

Protein displacement