Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IHO Week 3 > Fitz-Drugs that disrupt DNA > Flashcards

Fitz-Drugs that disrupt DNA Flashcards

1
Q

What is the MOA of cross-linking agents?

A

Cross-linking agents are strong electrophiles that attack cell nucleophiles like SH of protein, N of protein/DNA base (esp N7 position of Guanine), and O of DNA base or phosphate.

This leads to cross-linking, miscoding of DNA bases and strand breakage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why are cross-linking agents CCNS?

A

While they ARE dependent on cell proliferation they are CCNS because the alkylations that INITIATE cell death occur during ANY phase of the cell cycle.

**Primary toxicity occurs in late G1 and S pahse w/ cell cycle arrest in G2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why are cross-linking agents AWESOME at treating the majority of human cancers?

*clue: it involves p 53

A

DNA damage usually activates a cell cycle checkpoint dependent on p53.

50% of human cancers have a mutated/absent p53 gene. These cells CANNOT repair DNA alkylation and therefore DIE. This makes these DNA alkylating drugs more effective in those types of cancers.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do you activate cyclophosphamide?

A
  1. Activation by cyp450 enzymes
  2. 4-OH cyclphosphamide
  3. aldophosphamide
  4. Phosphoramide mustard + alcrolein (in all tissues)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the negative affects of Acrolein and how does MESNA help?

A

ACROLEIN, a by-product of cylophosphamide activation, causes hemorrhagic cystitis.

LUCKILY, because it’s a by-product, it can be removed by administering MESNA w/ no change in therapeutic effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Induction of CYPB6 will have what effect on cyclophosphamide?

A

It will INCREASE enzyme activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the common toxicities associated w/ all cross linking agents?

A 
(common cytotoxic effects)
Myelosuppression
N and V
Strong vesicants (blistering)
immunosuppression
gonadal failure
carcinogenesis
mutagenesis
teratogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Unique toxicity:

Mechlorethamine

A

potent vesicant

most emetic antineoplastic drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Unique toxicity:

cyclophosphamide

A

Hemorrhagic cystitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Unique toxicity:

Ifosfamide

A

most neurotoxic of the alkylating agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Unique toxicity:
Nitrosourea
Carmustine, Lomustine

A

lung/liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Unique toxicity:

Cisplatin

A

most EMETIC
kidney
ototoxic
peripheral neuropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Unique toxicity:

Busulfan

A

BUSULFAN TAN= hyperpigmentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Unique toxicity:

Chlorambucil

A

lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Unique toxicity:

Mitomycin

A

irreversible kidney damage (hemolytic uremic syndrome)

lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the primary MOA of anthracycline antibiotics?

A

Intercalation in a major groove of DNA–> cytotoxic actions:
inhibition of TOPO II
single/double strand breaks (mutagenic)
sister chromatid exchange (carcinogenic)

17
Q

What is the secondary MOA of anthracycline antibiotics?

A

Interact w/ cell membranes to alter fluidity and ion transport

In the presence of NADPH, react w/ cytochrome p450 to form superoxide anion radicals

18
Q

Why is cardiotoxicity unique to anthracycline antibiotics?

A

Secondary mechanisms of the drugs lead to superoxide anion radicals that cause cardiotoxicity

19
Q

What are the acute effects of cardiomyopathy?

A

increased HR, arrythmias

20
Q

What are the delayed effects of cardiomyopathy?

A

CHF that is unresponsive to digitalis YEARS after tx

21
Q

What is the mechanism of resistance for Doxorubicin?

A
  1. Decreased accum: via Increased P-glyco
  2. Changes in target proteins (decrease in topo II activity)
  3. increased inactivation (increased glutathione activity)
22
Q

With what mechanism of resistance is MDR most likely to develop in doxorubicin?

A

Decreased acccum via increased p-glyco leads to MDR

23
Q

Chemical class?

Bleomycin

A

Antibiotic

24
Q

Chemical class?
etoposide
Irinoitecan/topotecan

A

Plant alkaloids:
epipodophyllotoxin
camptothecins

25
Q

Chemical class?

procarbazine

A

Alkylating agent

26
Q

What do all drugs that cause DNA strand breaks require?

A

functional apoptotic machinery (esp p 53) to complete the cell kill

27
Q

How does bleomycin cause strand breaks?

A

Bleomycin BLASTS DNA
Binds to DNA through amino-terminal peptide–> generates free radicals that CUT the DNA into pieces–> accumulation of cells in G2 that have chromosomal aberrations–> apoptosis

28
Q

How does Etoposide cause strand breaks?

A

Etoposide forms a complex w/ TOPO II and DNA–> double strand breaks. The complex remains bound to the enzyme so repair can’t occur

29
Q

How do irinotecan and topotecan cause strand breaks?

A

Both inhibit TOPO I and lead to single strand breaks.

30
Q

How does procarbazine cause strand breaks?

A

Inhibits DNA, RNA adn protein synthesis and leads to DNA strand scission (we don’t really know though….)

31
Q

What are the unique properties of bleomycin that make it useful in many drug regimens?

A

It can be used in combination w/ other drugs and it has a unique MOA.

It is part of the PVB regimen for testicular cancer.

IHO Week 3 (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions