Pharmacokinetics I (cont.)

Question 0

What is the range of pH in the stomach?

Answer 0

1.9-2.6

Question 1

Differences in the pH of body fluids can lead to drug _______ in certain compartments.

Answer 1

trapping

*lead to changes in absorption and/or elimination

Question 3

What is the range of pH in the intestine

Answer 3

6.4-7.6

Question 4

What is the range of pH in the urine

Answer 4

5.0-8.0

Question 4

In lower pH, will weak acid be charged or uncharged?

Answer 4

Uncharged (HA), which will allow it to cross membrane

Question 5

What is the range of pH in the breast milk

Answer 5

6.4-7.6

same as intestine

Question 6

What four aspects affect distribution of drugs?

Answer 6

• size of organ
  ex: skeletal muscle: large organ hard to fill vs brain: small organ fills quickly
• blood flow: well-perfused organs will achieve high tissue concentrations (e.g. brain, heart, kidneys, liver)
• solubility (e.g. highly lipid soluble drugs like high lipid content like the brain)
• binding (e.g. plasma protein binding)

Question 7

Which organs fill quickly with drugs, large or small?

Answer 7

Small organs fill quickly

Question 8

How does blood flow affect distribution of drugs?

Answer 8

Well-perfused organs will achieve high tissue concentrations
e.g. brain, heart, kidneys, liver

Question 9

How does solubility affect distribution of drugs?

Answer 9

Highly lipid soluble drugs like high lipid content (like the brain)

Question 10

Give an example of binding effects on distribution of drugs?

Answer 10

plasma protein binding

Question 11

Drugs are distributed in multiple phases, what are these?

Answer 11

First phase drugs
- distributed to “high flow” areas (heart, liver, kidneys, brain)

Later phase drugs
- distributed to “low flow” areas such as bones, fat, and skin

Question 12

Example of coated tablet:

Misoprostol outer mantle which allows for what?

Answer 12

• replenishes GI-protective COX-1 prostaglandins
• the second layer (enteric coating) delays NSAID release until the lower GI tract)
• do not give to pregnant women, induces smooth muscle contractions

Question 13

The rate of movement of a drug across a barrier (membrane) is governed by Fick’s law which considers all of the following except:
a - route of delivery
b - surface area
c - drug permeability coefficient
d - thickness of the barrier
e - concentration on both sides of the barrier

Answer 13

a - route of delivery

Question 14

Propantheline ______ GI Transit; hence more absorption

Answer 14

decreases

*acts to slow down contractions through gut

Question 15

Metoclopramide ______ GI Transit; hence less absorption

Answer 15

increases

*acts to speed up contractions to move things through gut

Question 16

Drug delivery to which set of organs is faster:

1 - heart, liver, kidney, and other well-perfused organs
2 - muscle, skin, fat

Answer 16

1 - heart, liver, kidney, and other well-perfused organs

Question 17

It is the free fraction of drug that distributes from blood to other tissues. As such, distribution may be ____ by drug binding to plasma proteins.

Answer 17

limited

*particularly to albumin for acidic drugs and to alpha-1 acid glycoprotein for basic drugs

Question 18

What are a few reasons that drugs may accumulate in tissues in higher concentrations than the free concentration in plasma?

Answer 18

• pH gradients
• binding to intracellular constituents
• partitioning into lipid

Question 19

What is apparent volume of distribution (Vd)?

Answer 19

• relates the amount of drug in the body to the concentration (C) of drug in the plasma (extracellular portion of blood)
• the volume that relates the amount of drug in the body to the plasma concentration (units of volume)

Vd = amount of drug in the body (mg)/plasma drug concentration (mg/L)

*the larger the value of Vd, the greater distribution of drug into tissues/body

Question 20

Vd (volume of distribution) may be affected by the individual person. For example, a lipophilic drug that has affinity for fat would be predicted to have a ______ volume of distribution in an obese person.

Answer 20

larger

Question 21

What two general things does a low Vd indicate?

Answer 21

• drug does not have high affinity for tissues
  and/or
• drug is extensively bound to plasma proteins

Question 22

What can Vd be used to calculate? Give the equation

Answer 22

the dose of drug that needs to be administered to achieve a desired plasma concentration

Dose = Vd * Cp

Vd = volume of distribution
Cp = plasma concentration

Question 23

What is charcoaid?

Answer 23

activated charcoal used to treat acute poisoning/overdose; should be given within one hour of drug intake

Question 24

Blood-Brain Barrier

What about the capillary barrier limits paracellular diffusion

Answer 24

Tight junctons as opposed to fenestrations

Question 25

Blood-Brain Barrier

What does a high TEER indication?
index of permeability

Answer 25

higher value, more restrictive vessel is going to be for drug to cross it

Question 26

Blood-Brain Barrier

Are ATP-binding cassettes (ABC) efflux or uptake transporters?

Answer 26

efflux

• P-glycoprotein
• multidrug resistance proteins
• breast cancer resistance protein

Question 27

Blood-Brain Barrier

Are Solute Carriers (SLC) efflux or uptake transporters?

Answer 27

uptake

• organic anion transporting polypeptides

Question 28

What is the function of the BBB?

Answer 28

• maintain homeostasis

- restrict access to toxic xenobiotics/metabolites