Exam 1: Drug Transporters

Question 1

Drugs must pass through several _____ to reach site of action.

Answer 1

Barriers

Question 2

The drugs ability to be absorbed and be spread through the body is called:

Answer 2

Permeation

Question 3

Molecules that bind a drug and allow it to move across a membrane.

Answer 3

Special Carriers

Question 4

Drugs can pass through barriers by:

Answer 4

Active Transport or Facilitated Diffusion

Question 5

Primary functions of Special Carriers

Answer 5

Transport of endogenous substances (hormones, glucose, amino acids).

Question 6

Membrane Drug Transporters (a type of Special Carrier) are localized where?

Answer 6

Barrier membranes of the body (intestines, liver, kidney)
(And)
Membranes of susceptible organs (BBB, B Placenta B, B Testes B)

Question 7

Transporters have a role in?

Answer 7

Both absorption and removal of drugs/endogenous ligands from the body.

Question 8

Solute Carrier Proteins

Answer 8

-15-30% of all membrane proteins
-Substrate Specificity
-52 Different gene families
-7% of all genes
Can be Passive or Active!

Question 9

Most Drug Efflux Transporters are called?

Answer 9

ATP Binding Cassette Proteins (ABC Proteins)

Question 10

Drug Efflux Pumps

Answer 10

-Pump a drug into/out of the cell (depends on protein orientation)
-Is a cell survival mechanism
-Has broad substrate specificity

Question 11

Most important ABC Proteins we need to know? How many total?

Answer 11

B, C, and G
7 Families total

Question 12

The side of a cell that lines a barrier?

Answer 12

Apical

Question 13

The side of the cell that is attached to connective tissue?

Answer 13

Basal

Question 14

T/F ABC transporters are located only on the Apical side of cells?

Answer 14

False. Drugs can cross at both the Apical (absorption) side of the cell and on the Basal (into the blood) side.

Question 15

ABC B1

Answer 15

-Broadest Substrate Specificity (high affinity for all drugs)
-Widely distributed throughout the body
-Critical in Maintenance of the BBB

Question 16

What drugs inhibit ABC B1? What drug did he mention is affected by this?

Answer 16

Cyclosporine A, Quinidine, Ritonavir

Digoxin removal is affected, leading to increased toxicity.

Question 17

What drug do people abuse and take ABCB1 inhibitors?

Answer 17

Loperamide (weak opioid)
Can cause CNS effects (ie respiratory depression)

Question 18

ABC C

Answer 18

• Largest Class of ABCs (“ubiquitous”)
• Very specific (mainly antineoplastic drugs)
  -High Affinity for its associated drugs

Question 19

ABC G2

Answer 19

• Smaller Class
  -Specific transports
  -Antineoplastics, Toxins, Carcinogens (food)
  -Important for Folate transport in pregnancy

Question 20

Non-ABC Drug Efflux Transporter mentioned in class?

Answer 20

SLC21

Question 21

SLC21 transport substances using what?

Answer 21

Passive Transport relying on gradients

Question 22

Which two organ systems have almost all of the ABC transporters?

Answer 22

GI tract and Liver

Question 23

One does not simply…

Answer 23

Cross the Blood Brain Barrier
(or into Mordor) - Boromir

Question 24

BBB vascular epithelium is hard to cross because of:

Answer 24

Tight Junctions, Astrocytes, and Podocytes
Also presence of ABCs that pump back into the blood

Question 25

BBB ABC transporters can pump via:

Answer 25

-Active efflux (including lipids) -Carrier Protein Pathways -Receptor Mediated Endocytosis/Exocytosis -Absorptive Endocytosis/Exocytosis

Question 26

What Barrier has access to the brain but is less restrictive?

Answer 26

Blood CSF Barrier (still not great for a lot of drugs)

Question 27

GI tract transporters are localized to the ______

Answer 27

Microvilli

Question 28

Most common GI tract ABC transporter?

Answer 28

ABC G2 (BCRP)

Question 29

What do the ABC transporters transport out into the intestinal system?

Answer 29

Glucuronides from hepatic metabolism (think Acetaminophen)

Question 30

Where does the liver excrete processed drugs transported by the ABC cells?

Answer 30

The Bile

Question 31

These can pass the Blood Placental Barrier Easily

Answer 31

Small and Lipophilic (nicotine, EtOH)

Question 32

Endothelin does what?

Answer 32

Body's physiologic response to pulmonary HTN Has partial agonist (antagonist) function to block ABC transporters.