Drug Transporters (Exam 1)

Question 1

What are special carriers and what mechanisms accomplish this

Answer 1

primarily membrane drug transporters for endogenous substances
- transport xenobiotics
- localized to barrier membranes (intestine, liver, kidney)
- seperate susceptible organs like BBB, blood-placenta, and blood testes
used for drug absorbtion or prevent entry

Question 2

What is unique about transporters

Answer 2

7% of genes are transporters
15-30% of membrane proteins are transporters
high specificity

Question 3

Name 3 passive transporters and how they work

Answer 3

Coupled (symporter): transport 2 things simultaneously
Exchanger: 1 thing goes out another goes in
Passive: open all the time, electrical chemical gradient

found on the cell membrane and membranous structures

Question 4

What is the most important active transporter

Answer 4

Na/K ATPase Pump

Question 5

What are Drug Efflux Transporters and what are they now known as

Answer 5

Cell survivial system to pump out drugs
in cancer result in multi drug resistant
not very specific but require ATP to bnd to the nucleotide binding domains

ATP Binding Cassette (ABC) transporters

MDR, MDP

Question 6

Where are nucleotide binding domains located and how do they work (NMD)

Answer 6

located on th inside
ATP binds to them and facilitate movement out of the cell

Question 7

What are some attributes of the ABC Gene Family

Answer 7

7 families (A-G)
Diverse functions : cholesterol
Loacalization specific: apical or basal
Major drug effluc transporters; B,C,G

Question 8

What drugs do ABCB1 target, what can increase the amt of receptors, where can you find it

Answer 8

broadest specificity
- antineo, protease inhibitors, abx, antidep, antep, opiods
certain cancers can increase ABCB1
found in the GI, kidney, liver, testes
crtical for BBB

Question 9

What are some drug interaction with ABCB1

Answer 9

inhibitors
- cyclosporine A, quinidine, ritonavir
- Digoxin is transported by ABCB1 and can cause toxicity if inhibited

Question 10

How does ABCB1 work in the gut in relation to Loperamide

Answer 10

opioid, anitdiarrheal (OTC)
stays in the the gut, no CNS effects

Question 11

What can happen to loperamide when given an ABCB1 inhibitor

Answer 11

quinidine an ABCB1 inhibitor can cause systemic absorption and CNS effects like respiratory supression

Question 12

Name 2 other ABC transporters other an ABCB

Answer 12

ABCC: largest class, ubiquitous but doesnt transport as many drugs as ABCB. Mainly anitneo efflux
ABCG2: BrCx resistance protein (BRCP) targets antineo, toxins, food-borne carcinogens
-used for folate transport

Question 13

Identify a non-ABC Efflux transporter

Answer 13

SLC21: passive, work with gradients
organic anion transporter proteins (OATPs)
can influx or efflux

Question 14

What is the overall flux for drug movements in the blood to the intestine, liver,

Answer 14

intestine: mainly move in
placenta: move out
BBB: move out
Blood-CSF: not as regulated but move out
liver: move into the cell ->biotransformation
kidney: enters the glomerulus and enters the tubule ->urine

Question 15

How does the Blood-Brain Barrier prevent drugs from getting in (4)

Answer 15

ABC transporters
Vascular epithelium: tight junctions no leaky capillaries
Astrocyte
Podocytes

Question 16

How are things transported into and away from the BBB

Answer 16

active efflux transporters take things out
Into the brain:
transcellular lipophilic pathway (O2, CO2, ethanol, nicotine
carrier proteins: glucose, amino acid nucleotide
receptor-mediated endocytosis: insulin transferrin igG
adsorptive endocytosis: albumin histone

Question 17

How does the blood-CSF barrier compare to BBB

Answer 17

less than efflux and transporters than the BBB
some drugs can like bupivacaine
antineoplasitc doesnt cross

Question 18

What are the effects of the ABC transporters on the GI tract

Answer 18

ABC most commonly on the apical surface (microvilli)
ABCG2: most common
ABCC transport glucuronides from hepatic metabolism to intestinal (in the case with tylenol)

Question 19

Describe the pathway for tylenol crossing barriers

Answer 19

intestines -> blood ->liver ->glucuronidation ->back to intestine ->excretion via feces

Question 20

What receptors are found in the liver and how are they excreted

Answer 20

Many different receptors OATPs and all ABC’s
blood->liver->bile

Question 21

What are some clinical applications of drug efflux transporters

Answer 21

Expression is upregualted by PXR, steroids, xenobiotics
downregulated by endothelin acts as a partial agonist-antagonist