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Flashcards in Pharmacokinetics I (cont.) Deck (29):
0

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

trapping

*lead to changes in absorption and/or elimination

1

What is the range of pH in the stomach?

1.9-2.6

3

What is the range of pH in the intestine

6.4-7.6

4

What is the range of pH in the urine

5.0-8.0

4

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

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

5

What is the range of pH in the breast milk

6.4-7.6
(same as intestine)

6

What four aspects affect distribution of drugs?

- 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)

7

Which organs fill quickly with drugs, large or small?

Small organs fill quickly

8

How does blood flow affect distribution of drugs?

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

9

How does solubility affect distribution of drugs?

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

10

Give an example of binding effects on distribution of drugs?

plasma protein binding

11

Drugs are distributed in multiple phases, what are these?

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

12

Example of coated tablet:
Misoprostol outer mantle which allows for what?

- 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

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

a - route of delivery

14

Propantheline ______ GI Transit; hence more absorption

decreases

*acts to slow down contractions through gut

15

Metoclopramide ______ GI Transit; hence less absorption

increases

*acts to speed up contractions to move things through gut

16

Drug delivery to which set of organs is faster:

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

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

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.

limited

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

18

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

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

19

What is apparent volume of distribution (Vd)?

- 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

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.

larger

21

What two general things does a low Vd indicate?

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

22

What can Vd be used to calculate? Give the equation

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

23

What is charcoaid?

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

24

Blood-Brain Barrier

What about the capillary barrier limits paracellular diffusion

Tight junctons as opposed to fenestrations

25

Blood-Brain Barrier

What does a high TEER indication?
(index of permeability)

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

26

Blood-Brain Barrier

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

efflux

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

27

Blood-Brain Barrier

Are Solute Carriers (SLC) efflux or uptake transporters?

uptake

- organic anion transporting polypeptides

28

What is the function of the BBB?

- maintain homeostasis
- restrict access to toxic xenobiotics/metabolites