Module 3

Question 1

Drugs _________ into compartments in the body where they may be _______, _________, ________ or exert their ___________ effect.

Answer 1

distribute
stored
metabolized
excreted
pharmacological

Question 2

The extracellular fluid that surrounds cells. Low molecular weight, water soluble drugs distribute here.

Answer 2

Interstitial space

Question 3

Includes the fluid in the interstitial space, intracellular fluid and the plasma

Answer 3

Total body water

Question 4

The acellular component of blood.

Answer 4

plasma

Question 5

Lipid soluble drugs tend to distribute here. The body’s fat stores.

Answer 5

Adipose tissue

Question 6

Drug distribution is determined by three factors, what are they?

Answer 6

Blood flow to tissues
Ability of drug to move out of capillaries
Ability of drug to move into cells

Question 7

The more drug that distributes out of the blood, the ______ the concentration of drug in the blood.

Answer 7

lower

Question 8

What are well perfused organs/tissues (i.e. name them)?

Answer 8

Liver, kidney, brain

Question 9

What are poorly perfused tissues/organs?

Answer 9

Fat, (muscle), bone, skin

Question 10

Describe blood flow in newborns

Answer 10

Neonates have limited blood flow

Question 11

Describe how heart failure or shock affects blood flow.

Answer 11

Decreased CO or BP reduces blood flow and can limit distribution

Question 12

Describe blood flow in solid tumours.

Answer 12

The outer portion of solid tumours are well perfused; the innner region is not - hard to attain high drug concentrations within the tumour

Question 13

Describe blood flow in abscesses.

Answer 13

They have no blood supply and are thus hard to treat with antibiotics. Often drained before drug therapy.

Question 14

Drugs move out of capillaries through ________ except in the _______.

Answer 14

fenestrations

brain

Question 15

What are the different ways in which drugs can pass the cell membrane?

Answer 15

Lipophilic - pass membrane
Transporter - hydrophilc drug
- efflux - pumps out
- uptake - pumps in

Question 16

Most widely studied efflux transporter.

Answer 16

P-glycoprotein

Question 17

P-glycoprotein is an _______ transporter, meaning it requires ______ in order to transport drugs _________ a concentration gradient.

Answer 17

active
ATP
against

Question 18

How does P-gp function in the liver?

Answer 18

Pumps drugs into the bile to facilitate excretion

Question 19

How does P-gp function in the SI?

Answer 19

Pumps drugs into the lumen, preventing drug absorption into the blood

Question 20

How does P-gp function in the kidney?

Answer 20

Pumps drugs into the lumen to facilitate excretion.

Question 21

How does P-gp function in the brain?

Answer 21

Pumps drugs into the blood, limiting exposure to the brain

Question 22

For each of the following organs, describe which side (lumenal or towards the blood) that p-gp is located.
Liver
SI
Kidney
Brain

Answer 22

Liver - transcellular (bile canalicular membrane) - pumps into bile duct
SI - lumenal (apical membrane)
Kidney - lumenal (apical side)
Brain - blood

Question 23

Where is P-gp expressed in the liver?

Intestine?

Answer 23

hepatocytes

enterocytes

Question 24

Where is P-gp found in the kidney?

Answer 24

PCT

Question 25

What are the two major plasma proteins that bind drugs in the plasma?

Answer 25

Albumin | Alpha 1 acid glycoprotein

Question 26

Albumin has high affinity for what types of drugs?

Answer 26

lipophilic and anionic (weakly acidic)

Question 27

Alpha 1 acidic glycoprotein has high affinity for what types of drugs?

Answer 27

cationic (weakly basic) and very hydrophilic drugs

Question 28

Plasma protein binding is ________.

Answer 28

reversible

Question 29

What are pathologies that decrease plasma albumin concentration

Answer 29

Malnutrition, trauma, aging, liver and kidney disease

Question 30

How does decreased plasma albumin concentration affect drug concentration?

Answer 30

Will increase free drug concentration, which may lead to toxicity

Question 31

What factors/pathologies affect alpha 1 acidic glycoprotein levels?

Answer 31

Hepatic inflammation, aging, trauma cause increased alpha 1 acidic glycoprotein

Question 32

How does increased alpha 1 acidic glycoprotein affect drug concentration?

Answer 32

causes decreased free drug concentration

Question 33

apparent volume into which a drug distributes

Answer 33

Volume of distribution

Question 34

What is the equation for Vd?

Answer 34

Vd = D/C D - dose C - concentration in the blood

Question 35

What are the characteristics of drugs with a small Vd? Where do they distribute into? What volume per kg, and what percentage of body weight is their Vd?

Answer 35

High affinity for plasma proteins Large MW Distribute into the plasma 0.0057L/kg or 5.7% of body weight

Question 36

What are the characteristics of drugs with an intermediate Vd? Where do they distribute? What volume per kg, and what percentage of body weight is their Vd?

Answer 36

Low MW Very hydrophilic Intermediate affinity for plasma proteins Distribute into the ECF 0.2L/kg 20% of body weight

Question 37

What are the characteristics of drugs with a large Vd? Where do they distribute? What volume per kg, and what percentage of body weight is their Vd?

Answer 37

Low MW Lipophilic Minimal protein binding Distribute into the body compartments >0.2L/kg

Question 38

When the Vd of a displaced drug is small, where does it distribute?

Answer 38

Stays in the plasma - so free drug concentration increases

Question 39

When the Vd of a displaced drug is large, where does it distribute?

Answer 39

Distributes into the tissues. | This decreases plasma drug concentration, but increases the apparent Vd.

Question 40

Describe how age affects distribution (Vd) of certain drugs (do not describe the effects on plasma proteins).

Answer 40

There is typically more fat as part of body mass as we age - thus drugs distributing into fat will have a larger Vd. There is typically less muscle mass as we age and thus drugs distributing into muscle will have a lower Vd.

Question 41

Describe how total body water changes with age? Consider obese individuals as well.

Answer 41

Decreases from infancy to elderly. (obese people are lower than healthy adults)

Question 42

Describe how muscle mass changes with age, include obese people in your answer.

Answer 42

Highest in healthy adults, decreases to obese individuals, elderly than infants.