17 - Drug and Immune Resistance Flashcards Preview

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Flashcards in 17 - Drug and Immune Resistance Deck (24)
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1
Q

What are pre-malignant cells called?

A

dysplastic

2
Q

What are the 4 major types of treatment for cancer?

A

immunotherapy | chemotherapy | surgery | radiation

3
Q

What are MDR protein channels?

A

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

4
Q

What are ABC transporters?

A

ATP Binding Cassette transporters = MDR protein channels/pumps

5
Q

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

A

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

6
Q

What gene produced p-glycoprotein?

A

MDR gene

7
Q

How many transmembrane domains do ABC transporters have?

A

17 = huge

8
Q

What is p-glycoprotein?

A

ATP-dependent drug efflux pump

9
Q

Where do p-glycoproteins pump drugs from?

A

cytosol and within plasma membrane

10
Q

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

A

one pump resistant to different kinds of drugs

11
Q

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?

A

different mechanisms

12
Q

What is the issue of having variants of MDR?

A

all may need different inhibitors since all are different/variants

13
Q

What are 4 solutions for overcoming MDR?

A

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

14
Q

What are chemosensitizing agents (modulators)?

A

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

15
Q

How does bioavailability affect drug efficacy and toxicity?

A

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

16
Q

How can modulators be too toxic?

A

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

17
Q

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

A

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

18
Q

What are 2 types of enzyme inhibitors?

A

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

19
Q

What is pharmacokinetics?

A

time course of ADME processes

20
Q

What does ADME stand for?

A

absorption | distribution | metabolism | excretion

21
Q

In ADME, what is the absorption process?

A

passage of drug from administration site to circulation

22
Q

In ADME, what is the distribution process?

A

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

23
Q

In ADME, what is the metabolism process?

A

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

24
Q

In ADME, what is the excretion process?

A

removal of intact drug