Brainscape's Knowledge GenomeTM

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


See full index

Med Chem 3 - Final Exam > DNA Cross-Linking Agents II > Flashcards

DNA Cross-Linking Agents II Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

What (3) toxic compounds are generated in the metabolism of Nitrosourea via the vinyl diazotic acid pathway? Which metabolite is the main alkylator of DNA?

A
  1. acetaldehyde
  2. isocyanate
  3. 2-Chloroethyl carbocation (MAIN ALKYLATOR)

*acetaldehyde + isocyanate are generated via the diazotic acid pathway

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

Explain how the 2-Chloroethyl carbocation metabolite, generated from metabolism of a nitrosourea, alkylates DNA?

A

2-Chloroethyl carbocation attaches (2) adjacent guanines through an ethyl linkage on the SAME STRAND

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

True or False - alkylation of DNA on the same strand is more difficult to repair than alkylation of DNA on two different strands?

A

False - alkylation of DNA on same strand is EASIER to repair

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

What compound is necessary for the decomposition of nitrosoureas?

A

H2O

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

All of the following regarding Carmustine are true, except?

A. highly lipophilic
B. can be administered IV or biodegradable wafer
C. IV administration must be diluted with ethanol
D. wafers are very stable at room temperature
E. used in brain tumors and blood cancers

A

(D) Carmustine wafers must be stored in the refrigerator since it is a low melt solid

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

Which of the following statements regarding nitrosoureas is incorrect?

A. Lomustine is more stable than Carmustine
B. Thrombocytopenia and leukopenia are common SE’s
C. Lomustine is orally available and via wafer
D. Pulmonary toxicity SE is seen after the 1st Tx
E. Seizures are a common SE of nitrosourea wafers

A

(D) pulmonary toxicity is a delayed reaction seen only after several rounds of chemotherapy with Carmustine and Lomustine

*pulmonary toxicity is also dose related

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

Which of the following statements is true?

A. Streptozocin has good water solubility
B. Procarbazine is orally available
C. Dacarbazine is orally available
D. Both A & B
E. None of the above
A

(D) Steptozocin is administered IV so yes, it does have good water solubility AND Procarbazine is orally available

*Dacarbazine is administered IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What would you monitor for safety in patients taking Streptozocin?

A

Kidney function - this drug is nephrotoxic b/c kidney cells have same type of receptors (for the sugar moiety) and use similar transporters so these cells are very sensitive to this drug and can be killed

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

True or False - procarbazine generates a diazomethane metabolite?

A

True

*So does Dacarbazine and Temozolomide. Remember, diazomethane is a reactive intermediate that will methylate DNA, introducing a mutation so the G will pair with T instead of C leading to cell destruction

MOA: “O-6 methylation of guanine nucleotides”

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

What is needed for the metabolism of procarbazine?

A

oxygen

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

What (2) major metabolites are generated from metabolism of Procarbazine? Indicate which is the major reactive DNA methylator and which is the major urinary metabolite?

A
  1. Diazomethane - methylates guanine
  2. N-Isopropylterephthalamic acid - excreted in urine

*Diazomethane methylation of guanine results in guanine pairing with thymine (instead of cytosine) which will lead to apoptosis if not repaired

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

Why would resistance to Procarbazine be seen in patients with upregulated repair mechanisms?

A

Procarbazine is metabolized to diazomethane which introduces a methyl group to guanine. This can easily be repaired in cancers with upregulated repair mechanisms and thus the drug is less effective in killing cancer

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

Which alkylator can have significant drug-drug and drug-food interactions b/c of inhibition of MAO and enzymes involved in ethanol metabolism?

A

Procarbazine b/c it inhibits monoamine oxidase

*it also inhibits enzymes involved in ethanol metabolism - so patients can’t drink any booze

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

All of the following DNA alkylators are orally available except?

A. Procarbazine
B. Lomustine
C. Dacarbazine
D. Temozolomide
E. Busulfan
A

(C) Dacarbazine is NOT orally available; it is administered IV

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

All of the following anti-cancer agents can be administered IV except?

A. Busulfan 
B. Carmustine
C. Streptozocin
D. Cisplatin
E. Satraplatin
A

(E) Satraplatin is orally available

*Busulfan can be administered orally OR IV

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

Which DNA alkylator is used in the Tx of malignant melanoma?

A

Dacarbazine

17
Q

Which DNA alkylator is used in the Tx of glioblastoma and astrocytoma?

A

Temozolomide

18
Q

All of the following are true regarding the metabolism of triazenes, except?

A. CYP’s are involved in Dacarbazine metabolism but not Temozolomide
B. AIC and diazomethane are the main metabolites
C. Temozolomide is safer than Dacarbazine
D. Toxic formaldehyde is generated from metabolism of Temozolomide
E. Diazomethane is the main alkylator

A

(D) Formadlehyde is generated from metabolism of DACARBAZINE and significantly contributes to its toxicity

Metabolism of Temozolomide is non-enzymatic and therefore does not produce toxic formaldehyde

19
Q

True or False - More Dacarbazine is excreted unchanged in the urine than Temozolomide?

A

True

40% of Dacarbazine is excreted unchanged while
6% of Temozolomide is excreted unchanged

20
Q

All of the following are prodrugs except?

A. Procarbazine
B. Dacarbazine
C. Temozolomide
D. Altretamine
E. Both A & D
A

(E) only DACARBAZINE and Temozolomide are PRODRUGS

21
Q

Why is Temozolomide less toxic than Dacarbazine?

A

Temozolomide is metabolized non-enzymatically and therefore does NOT produce formaldehyde.

22
Q

What is the major urinary metabolite of triazines? How does this metabolite contribute to triazine MOA?

A

Triazines: Dacarbazine and Temozolomide major urinary metabolite is AIC

AIC interferes with purine biosynthesis in cancer cells

23
Q

All of the following contribute to anti-cancer MOA of Dacarbazine, except?

A. production of formaldehyde
B. alkylation by diazomethane
C. Interference with cancer cell purine biosynthesis 
D. none of the above
E. all of the above
A

(E) all contribute toward anti-cancer MOA

24
Q

Which of the following regarding Altretamine is true?

A. causes GI problems and peripheral nerve damage
B. majority of anti-cancer activity through production of multiple formaldehyde cross-linking DNA
C. Iminium ion metabolite alkylates DNA causing more damage to cancer cells
D. B & C only
E. All of the above

A

(E) all of the above

25
Q

What is Altretamine used to treat?

A

Ovarian cancer - only used in patients non-responsive to organoplatinum therapy - so it’s a 2nd line agent in Tx of ovarian cancer

*DOC for ovarian cancer is Cisplatin

26
Q

True or False - Busulfan can methylate bases on the same strand AND opposite strands of DNA?

A

True - Busulfan forms a covalent linkage between two guanines

27
Q

What is Busulfan’s secondary anti-cancer MOA?

A

depletes glutathione of cancer cells

28
Q

Which of the following regarding Busulfan is incorrect?

A. only administered IV
B. selective agent specific for bone marrow
C. major toxicity associated with myelosuppression
D. allopurinol can be used for Tx of hyperuricemia SE
E. Used in Tx of chronic myelogenous leukemia

A

(A) Busulfan is orally available AND administered IV

29
Q

All of the following regarding organoplatinum complexes are true, except?

A. cross-links adjacent DNA bases with covalent bonds on the same strand
B. Pt-NH3 bond is stronger than Pt-Cl bond
C. water is required for activation
D. NH3 (ammonia) ligands are not required for Cisplatin & Carboplatin anti-cancer activity
E. cross-linking occurs more frequently between adjacent guanine residues

A

(D) NH3 (ammonia) ligands ARE required for anti-cancer activity – they stabilize the kinked cross-linked DNA conformation by interacting with phosphate groups from DNA backbone

30
Q

All of the following regarding cisplatin are true, except?

A. highly nephrotoxic and can also cause irreversible hearing loss
B. sodium thiosulfate can be co-administered to protect the kidneys
C. DOC for ovarian cancer
D. administered IV
E. long half-life

A

(E) Cisplatin has a very short half-life (

31
Q

Which of the following statements is incorrect?

A. Slower hydration dynamics make carboplatin less potent than cisplatin
B. Oxaliplatin is activated by water
C. Oxaliplatin is often administered with basic (pH) drugs
D. Less resistance to Tx is seen with oxaliplatin mostly b/c of the conformation formed due to its structure
E. Satraplatin is metabolized into 6 different metabolites

A

(C) Oxaliplatin decomposes in alkaline media so it should NEVER be given with basic drugs

32
Q

Which organoplatinum complex is used in the Tx of head and neck cancers?

A

Carboplatin

33
Q

True or False - Patients that overdose on cisplatin can be saved by dialysis since this drug is eliminated predominantly via kidneys?

A

False - Cisplatin is strongly bound to plasma proteins and patients CANNOT be rescued from cisplatin toxicity through dialysis

34
Q

How does Satraplatin differ from two of its specific metabolites (Desacetoxysatraplatin and Diaquo satraplatin)?

A

Satraplatin contains Pt IV while its two metabolites contain Pt II

35
Q

Which organoplatinum complex is used in the Tx of metastatic colon, rectal cancer?

A

oxaliplatin

Med Chem 3 - Final Exam (5 decks)

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