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Oncology > Alkylating Agents and Platinums > Flashcards

Alkylating Agents and Platinums Flashcards

1
Q

Alkylating agents are cytotoxic and mutagenic, but they are not carcinogenic. True or false?

A

False. They are carcinogenic = they can cause other cancers

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2
Q

Alkylating agents are cell-cycle specific. True or False?

A

False. They do not rely on cells being in a certain phase, and work on all phases of the cell cycle.

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3
Q 
What are 2 common toxicities related to alkylating agents due to bone marrow damage?
A) Hand Foot Syndrome
B) Hematopoietic suppression
C) Immunosuppression
D) N/V/D
A

B & C

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4
Q

Alkylating agents covalently bind to alkyl groups to important cellular molecules and damage DNA. True or False?

A

True

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5
Q

Alkylation includes which 2 mechanisms?
A) Methylation: addition of a methyl group causing problems with base pairing
B) Intercalation: incorporating itself into the DNA to cause cell death
C) Cross linking: formation of cross-bridges between bases either inter- or intra-strand binding
D) Microtubule Inhibition: Prevent the function of microtubules for DNA replication

A

A & C

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6
Q 
The following are subgroups of Alkylating agents EXCEPT: 
A) Nitrogen mustard gas derivatives
B) Nitroureas 
C) Triazenes
D) Alkylsulfonate
E) Cytidine analogs
A

E, that is a class of antimetabolites

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7
Q

Cyclophosphamide, ifosfamide, and melphalan are part of which subgroup and which class of agents?

A

Nitrogen mustard gas derivatives in alkylating agents

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8
Q 
Which are following are notable toxicities for cyclophosphamide? Select all that apply
A) N/V/D
B) Hemorrhagic cystitis 
C) Leukopenia
D) SIADH
A

B, C, D

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9
Q

What are ways to reduce incidence of hemorrhagic cystitis when administering cyclophosphamide? Select all that apply
A) Hyperhydration
B) Mesna
C) Continuous bladder irrigation
D) Pre-med with steriods, antihistamines, APAP

A

A B C

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10
Q

Cyclophosphamide metabolism occurs more quickly than ifosfamide even though it is a prodrug, and its dose limiting toxicity is hemorrhagic cystitis. True or False?

A

False. Cyclophosphamide’s dose limiting toxicity is leukopenia

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11
Q 
What are Ifosfamide's 2 dose limiting toxicities?
A) Hemorrhagic cystitis
B) Leukopenia
C) Neurotoxicity 
D) HFS
A

A & C

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12
Q

Ifosfamide is a prodrug requiring metabolic activation, but it has a slower activation rate resulting in more prolonged exposure to the bladder. True or False?

A

True

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13
Q 
Match the metabolite. \_\_\_\_ is the toxic metabolite in both cyclophosphamide and ifosfamide causing hemorrhagic cystitis, while \_\_\_\_ is the toxic metabolite only found with ifosfamide causing dose limiting neurotoxicity -- encephalopathy--and renal tubular damage. 
A) Aldophosphamide, Acrolein
B) Acrolein, Chloroacetaldehyde
C) Chloroacetaldehyde, Acrolein
D) Nitrogen mustard, Acrolein
A

B

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14
Q 
What is the mandatory administration agent needed with Ifosfamide?
A) Hyperhydration
B) Pre-meds 
C) Continuous bladder irrigation
D) Mesna
A

D because it is a disulfide detoxifier to help make acrolein a non toxic compound

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15
Q

Ifosfamide is considered a bifunctional alkylating agent that alkylates both DNA and RNA. True or false?

A

False, Melphalan does this

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16
Q

Which the following is a false statement about Melphalan?
A) The dose limiting toxicities are bone marrow suppression and mucositis.
B) It requires mesna to reduce risk of hemorrhagic cystitis
C) As an alkylating agent, it is recognized as carcinogenic
D) It has potent ability to ablate bone marrow and has potent immunosuppressive effects
E) As a bifunctional alkylating agent, it can cause intrastrand linking and cross linking

A

B. This is true for Ifosfamide (mandatory administration) and cyclophosphamide (along with hyperhydration and continuous bladder irrigation)

17
Q

Busulfan is the only one in its subgroup of alkylsulfonate, and it can cross link between DNA strands. True or false?

A

True

18
Q 
What are the main toxicities related to Busulfan? Select all that apply
A) Neurotoxicitiy/Seizures
B) Liver toxicity/VOD/SOS
C) Pulmonary fibrosis and injury
D) Severe myelosuppression
A

All of the above
A) Neurotoxicitiy/Seizures: readily penetrates brain and CSF
B) Liver toxicity/VOD/SOS: extensive hepatic metabolism
C) Pulmonary fibrosis and injury: high concentrations in lungs
D) Severe myelosuppression: high concentration in bone marrow

19
Q

Busulfan is based on a trough-based dosing for closer monitoring because low exposures are associated with relapses while high exposures are associated with liver toxicity and other fatal adverse effects. True or False?

A

False. AUC dosing

20
Q 
Why would Bulsulfan have DDIs with azoles, metronidazole, APAP, and phenytoin?
A) Because they got beef with everyone
B) It has extensive renal metabolism 
C) It has extensive hepatic metabolism 
D) It goes through p-gp enzymes
A

C = potential CYP/GST DDIs

21
Q

Triazenes - Dacarbazine and Temozolamide - can do methylation and cross linking. True or False?

A

False. Only methylation. 3 adjacent nitrogens are responsible for the alkylation/methylation activity `

22
Q

Dacarbazine can be best described by which of the following statements:
A) 100% oral bioavailability that can easily cross the BBB
B) Spontaneously forms MTIC in cellular pH to cause methylation that leads to apoptosis
C) Methylation of DNA generates base/base mismatches with cytosine and thymine
D) All of these are true about Dacarbazine

A

C; A & B describe Temozolomide

23
Q

Temozolamide of the triazene class within alkylating agents can cause NV, loss of appetite/anorexia, and neuropathy. True or False?

A

False; Dacarbazine does

24
Q

Carboplatin, Cisplatin, and Oxaliplatin are all considered alkylating agents. True or False?

A

False. They do not have an alkyl group but they damage DNA in a similar manner. They are considered metal salts (including platinum analogs)

25
Q

What is the MOA of Carboplatin, Cisplatin and Oxaliplatin?
A) Crosslinking and Methylation
B) Crosslinking (inter- and intra-strand linking)
C) Intra-strand linking only
D) Methylation

A

B: Cross linking between DNA strands by replacing chloride ligands with water molecules so they can covalently bind to DNA bases.

26
Q

Platinum agents are most well known to have adverse effects of nephrotoxicity, neurotoxicity, and emetogenic. What is the order of highest to least concern?
A) Amifostine > Cisplatin > Carboplatin
B) Cisplatin > Carboplatin > Oxaliplatin
C) Oxaliplatin > Carboplatin > Cisplatin
D) Carboplatin > Amifostine > Oxaliplatin

A

B

27
Q

Cisplatin accumulates in the kidney cells and cochlear hair cells, causing ototoxicity & tinnitus unique to cisplatin. True or False?

A

True

28
Q

What supportive care measures that need to be taken while administering Cisplatin? Select all that apply
A) Mesna, hyperhydration, continuous bladder irrigation
B) Forced diuresis and replaced Mg, K, and Ca
C) Mesna only
D) None. It is well tolerated.

A

B. Forced diuresis to reduce nephrotoxicity and replace Mg, K, Ca due to renal tubular damage

29
Q 
Fill in the blank: \_\_\_\_ is used to reduce cumulative renal toxicity with cisplatin because it traps alkylating electrophiles and scavenges free radicals. 
A) Mesna
B) Leucovorin 
C) Glucarpidase
D) Amifostine
A

D : prodrug into a cytoprotective thiol metobolite

30
Q 
Carboplatin is generally dose by AUC, and carboplatin is more of which adverse effect than the other agents in its class?
A) Ototoxicity
B) Emetogenic
C) Neurotoxic
D) Myelosuppressive
A

D
Dose = AUC x [CrCl +25]
AUC range 2-6 mg/mL*min

31
Q 
On ChemoMan, Cisplatin and Carboplatin are seen where?
A) Nephrotoxicity and Ototoxicity
B) Neurotoxic
C) Hemorrhagic cystitis 
D) Peripheral neuropathy
A

A

32
Q 
Which third generation platinum causes cumulative peripheral neurotoxicity and neurotoxicity?
A) Cisplatin
B) Carboplatin
C) Oxaliplatin
D) Ifosfamide
A

C

33
Q

Carboplatin causes peripheral neuropathy that causes DNA damage-induced apoptosis of dorsal root ganglion neurons and mitochondrial dysfunction. True or false?

A

False. Oxaliplatin

34
Q

Oxaliplatin has which of the following unique side effect within the platinum agents?
A) Ototoxicity
B) Cold sensitivities/pain in distal extremities and throat pain
C) Extreme N/V/D
D) A & B

A

B

35
Q 
Because alkylating agents greatly affect rapidly dividing cells, there are significant toxicities in the...
A) Hair follicles
B) Bone marrow
C) Gut lining
D) A and B only
E) All of the above
A

E

Oncology (6 decks)

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