Lecture 2: Drug Absorption

Question 1

Factors determining movement of drug through membrane

Answer 1

-characteristics of membrane
-mechanisms of passage
-dwell time of drug-mem interface
-physiochemical properties
-pH
-surface area

Question 2

Small intestine

Answer 2

-site of most absorption
-folds of Kerckring

Question 3

Folds of Kerckring

Answer 3

-plicae circulares
-surface has villi and microvilli
-increase surface area for absorption

Question 4

Transit time to small intestine affects

Answer 4

-peak concentration of drug

Question 5

Mechanisms by which drugs cross biological membranes

Answer 5

-intracellular junctions
-through lipid membranes
-carriers (diffusion/transport)
-endocytosis

Question 6

Transcellular diffusion

Answer 6

~95% of drug absorption
-dependent on pKa and pH

Question 7

Increase transcellular diffusion by:

Answer 7

-remove charged groups
-increase lipophilicity
-reduce size

-compromise between solubility and permeability

Question 8

pKa < pH of basic drug

Answer 8

BH+ < B

Question 9

pKa > pH of basic drug

Answer 9

BH+ > B

Question 10

pKa > pH of acidic drug

Answer 10

AH > A-

Question 11

pKa < pH of acidic drug

Answer 11

AH < A-

Question 12

Paracellular diffusion

Answer 12

-between tight junctions
-polar molecules
-small channels and small molecules
-very few drugs

Question 13

Increased permeability of tight junctions by

Answer 13

toxins and insults opening junctionss

Question 14

selective opening of tight junctions

Answer 14

may be a means to achieve oral absorption of insulin and other proteins

Question 15

Fick’s Law of Diffusion

Answer 15

dQ/dt (rate of diffusion)= (DAKp/h)(C1-C2)

-D, Kp, and h constant

Question 16

C1-C2

Answer 16

concentration difference
-usually C1&raquo_space;C2

Question 17

rate of transport given C1&raquo_space; C2

Answer 17

dQ/dt = PC1

-P is permeability constant

Question 18

Rate of transport graph

Answer 18

SLIDE 16
-facilitated diffusion (transport) curve
-simple diffusion y=x slope

Question 19

Taking riboflavin with food

Answer 19

increase absorption

Question 20

Facilitated diffusion

Answer 20

concentration gradient only

Question 21

Active transport

Answer 21

may go against gradient

Question 22

Transport proteins

Answer 22

-can be on apical and basolateral membrane
-move in or out
-efflux if out

Question 23

P-glycoprotein

Answer 23

-efflux transporter
-limit drug absorption
-enhance elimination
-limit distribution

Question 24

syncytiotrophoblast

Answer 24

-lots of pgps to prevent drugs from maternal blood going to fetal blood

Question 25

Endocytosis

Answer 25

-large molecules
-nanoparticle drug delivery
-phagocytosis, macropinocytosis, caveolar and clathrin mediated endocytosis, endocytosis

Question 26

efflux transporters

Answer 26

move drugs OUT of cell

Question 27

If a drug is a substrate for pgp in the enterocyte (to gut lumen), how would co-administration with another drug that inhibits pgp change the amount of drug that entered sytemic circulation?

Answer 27

increase

Question 28

enterocyte pgps

Answer 28

-limit drug absorption to gut lumen

Question 29

proximal tubule cell pgps

Answer 29

-enhance drug elimination into tubule lumen

Question 30

Endothelial Cell pgps

Answer 30

-limit drug distribution
-pump out drugs trying yo go to brain or testes

Question 31

phagocytosis

Answer 31

-solid particle eaten
=phagosome

Question 32

macropinocytosis

Answer 32

-particle and ECF eaten
=vesicle

Question 33

caveolar-mediated endocytosis

Answer 33

-caveolar surface proteins recognize what is to be eaten

Question 34

clathrin-mediated endocytosis

Answer 34

-bind to receptor
-clathrin-coated pit
-clathrin-coated vesicle

Question 35

non-clathrin and non-caveolar mediated endocytosis

Answer 35

-works the same just dint know which molecule