17 - Drug and Immune Resistance

Question 1

What are pre-malignant cells called?

Answer 1

dysplastic

Question 2

What are the 4 major types of treatment for cancer?

Answer 2

immunotherapy | chemotherapy | surgery | radiation

Question 3

What are MDR protein channels?

Answer 3

multiple drug resistance protein channels = pumps drugs and toxins out of cell

Question 4

What are ABC transporters?

Answer 4

ATP Binding Cassette transporters = MDR protein channels/pumps

Question 5

What are the 4 ABC proteins that are involved in MDR?

Answer 5

p-glycoprotein | multidrug-resistance-related protein (MRP) | lung resistance-related protein | breast cancer resistance-related protein

Question 6

What gene produced p-glycoprotein?

Answer 6

MDR gene

Question 7

How many transmembrane domains do ABC transporters have?

Answer 7

17 = huge

Question 8

What is p-glycoprotein?

Answer 8

ATP-dependent drug efflux pump

Question 9

Where do p-glycoproteins pump drugs from?

Answer 9

cytosol and within plasma membrane

Question 10

What is “cross-drug resistance” of some pumps?

Answer 10

one pump resistant to different kinds of drugs

Question 11

Is it better to have 3 drugs that do the same thing so it hits stronger OR 3 drugs each having a different mechanism hitting the cells in different ways?

Answer 11

different mechanisms

Question 12

What is the issue of having variants of MDR?

Answer 12

all may need different inhibitors since all are different/variants

Question 13

What are 4 solutions for overcoming MDR?

Answer 13

use chemosensitizing agents to inhibit the pump | saturate with high concentration of the drug | new drugs not subjected to known resistance mechanisms | drug combos not subject to same resistance mechanisms

Question 14

What are chemosensitizing agents (modulators)?

Answer 14

non-toxic compounds to make MDR cells more susceptible to the toxicity of drugs

Question 15

How does bioavailability affect drug efficacy and toxicity?

Answer 15

need a high drug bioavailability to be effective and toxic to tumor cell

Question 16

How can modulators be too toxic?

Answer 16

can block all of the pumps of other cells such as liver and kidney = need for detoxification

Question 17

Since cytochrome p450 metabolizes drugs, how can you overcome this to increase the efficacy of your anti-cancer drug?

Answer 17

lock and key = make a drug that will fit the cytochrome p450 enzyme = inhibit it

Question 18

What are 2 types of enzyme inhibitors?

Answer 18

competitive inhibitor = on active site | non-comepetitive inhibitor = changes shape of active site

Question 19

What is pharmacokinetics?

Answer 19

time course of ADME processes

Question 20

What does ADME stand for?

Answer 20

absorption | distribution | metabolism | excretion

Question 21

In ADME, what is the absorption process?

Answer 21

passage of drug from administration site to circulation

Question 22

In ADME, what is the distribution process?

Answer 22

protein binding followed by target specific and non-specific tissue uptake

Question 23

In ADME, what is the metabolism process?

Answer 23

Phase I and Phase II of metabolizing the drug | changes in each person = why clinical trials take long

Question 24

In ADME, what is the excretion process?

Answer 24

removal of intact drug