Distribution Of Drugs

Question 1

Distribution of drugs is determined by what 4 things?

Answer 1

1) size of organ
2) blood flow
3) capillary permeability (large plasma proteins cross liver and spleen capillaries; BBB prevents proteins from crossing)
4) hydrophobic vs hydrophilic nature of the drug

Question 2

What is the primary binding protein to plasma proteins?

Answer 2

Plasma albumin

Question 3

What will happen to drug concentration in a compartment where the drug is binding to plasma proteins in the blood or tissue?

Answer 3

It will increase the drug concentration in that compartment

Also can cause competition for binding

Question 4

If you have a drug that is more hydrophilic (water soluble), does it need to bind to plasma proteins?

Answer 4

No; it doesn’t need a carrier

Question 5

What are the requirements for drugs to get past the permeability of brain capillary?

Answer 5

Must be lipid-soluble and/or use carrier-mediated transport

Question 6

What type of drug can not breach the brain capillaries?

Answer 6

Charged (ionized) drugs

Question 7

A hypothetical volume of fluid in which a drug is disseminated?

Answer 7

Volume of distribution (Vd)

Question 8

How much water is in the plasma compartment of the body?

Answer 8

6% of body weight, or 4 L in a 70 kg individual (154 lbs)

Question 9

How much water is in the extracellular fluid compartment of the body?

Answer 9

20% of body weight, 14 L in 70 kg individual = 154 lbs

=plasma water plus interstitial fluid

Question 10

How much water makes up the total body water?

Answer 10

60% of body weight, 42 L in 70 kg individual = 154 lbs

Question 11

How many liters make up the total body water?

Answer 11

42 liters

Question 12

How many liters of water make up the intracellular volume?

Answer 12

28 liters

Question 13

How many liters of water make up the extracellular volume?

Answer 13

14 liters

Question 14

How many liters of water make up the interstitial volume?

Answer 14

10 liters

Question 15

How many liters of water make up the plasma volume?

Answer 15

4 liters

Question 16

What does Vd (volume of distribution) relate?

Answer 16

The amount of drug in the body to the plasma concentration of the drug

Question 17

Equation for finding the volume of distribution (Vd) of a drug

Answer 17

Vd (volume of distribution) = (amount of drug in the body)/(concentration in the blood)

Question 18

When talking about volume distribution, if the plasma concentration (in blood) is high, then volume distribution (in tissue) is what?

Answer 18

Low

Question 19

When talking about volume distribution, if the plasma concentration (in blood) is low, then volume distribution (in tissue) is what?

Answer 19

High

Question 20

Example
If the amount of drug in the body is 20 units, and the concentration in the blood is 2 units, what is the volume of distribution (in the tissues)?

Answer 20

Vd = 20/2 = 10 (low)

Question 21

Example
If the amount of drug in the body is 200 units, and the concentration in the blood is 2 units, what is the volume of distribution (in the tissues)?

Answer 21

Vd = 200/2 = 100 (high)

Question 22

Can Vd (volume of distribution) be larger than the total volume in the body? If so, when?

Answer 22

Yes, if a drug is given in large doses and rapidly leaves the vascular compartment

Question 23

If Vd does not necessarily refer to an identifiable physiological volume, what does it refer to?

Answer 23

The volume that would be required to contain all of the drug in the body at the same concentration as in the plasma

Question 24

Because Vd refers to the volume that would be required to contain all of the drug in the body at the same concentration as in the plasma, what is it referred to?

Answer 24

Apparent Vd

Question 25

What is apparent Vd?

Answer 25

It refers to the volume that would be required to contain all of the drug in the body at the same concentration as in the plasma

Question 26

What is the distribution phase?

Answer 26

The initial phase after drug administration where a drug is distributed to the various compartments

Question 27

What is the elimination phase?

Answer 27

The much slower phase after administration of a drug, after the distribution phase, and represents the drug leaving the plasma and being lost from the body

Question 28

If the serum concentration starts close to 4 (the high peak) upon rapid injection of the drug, then this drug had to have been administered through what technique?

Answer 28

IV (intravenous); slope only decreases from here due to distribution and elimination

Question 29

You can use Vd to calculate what?

Answer 29

The amount of drug needed to achieve a desired plasma concentration

Question 30

What does a large Vd tell you?

Answer 30

Most of the drug is in the extraplasmic space

Question 31

Example: A drug has a Vd of 25 L and you desire a plasma concentration of 1 mg/L; what is the amount of drug you would give the pt?

Answer 31

25 L x 1 mg/L = 25 mg

Question 32

Units for the answer if he asks for the amount?

Answer 32

Mg

Question 33

Units for the answer if he asks for the concentration?

Answer 33

mg/L

Question 34

Example: A cardiac patient with arrhythmia is not well controlled due to inadequate levels of digoxin; suppose plasma concentration is 1 ug/L (C1) and the desired level of digoxin is 3 ug/L (C2); the clinical needs to know how much additional drug to give to bring the circulating level of digoxin from C1 to C2.

Answer 34

Vd x C1 = amount of drug initially in body Vd x C2 = amount of drug in the body needed to achieve the desired plasma level Vd(C2-C1) = difference between the 2 values is how much is needed Vd for digoxin is 440L, so 440L(3ug/L-1ug/L) = 880 ug

Question 35

Where are drugs that are not being delivered to the organs of elimination (liver, kidney)?

Answer 35

Extraplasmic space

Question 36

A factor that increases Vd does what to the drug's half life?

Answer 36

Increase the half-life and extends the duration of action of the drug (because it's not being eliminated from the body)

Question 37

What is used well for drugs with low Vd, meaning the drug is in the blood, not the tissue?

Answer 37

Hemodialysis

Question 38

Why is placental transfer of drugs important?

Answer 38

Drugs can cause congenital abnormalities

Question 39

How do drugs cross the placenta?

Answer 39

Primarily by simple diffusion

Question 40

What type of drugs readily enter the fetal blood from the maternal circulation?

Answer 40

Lipid-soluble, non-ionized drugs

Question 41

Is the placenta a barrier to drugs?

Answer 41

NO

Question 42

If a drug can get into the CNS, it can definitely get past what?

Answer 42

The placenta