Fitzpatrick - Anti-Neoplastic Drugs, Alkylating Agents CCNSD Flashcards Preview

Hematology and Oncology > Fitzpatrick - Anti-Neoplastic Drugs, Alkylating Agents CCNSD > Flashcards

Flashcards in Fitzpatrick - Anti-Neoplastic Drugs, Alkylating Agents CCNSD Deck (23):
1

Cell cycle specific drugs are dependent on what?

Schedule dependent - Duration and timing of drug administration affect efficacy >>> dose dependent

2

DNA alkylating/cross-linking agents: MOA

- MOA - attack nucleophiles (-06, -07 N7 position of guanine)
- Damage - crosslinking (bifunctional) or alkylating (monofunctional)
- Consequences - miscoding of DNA bases, DNA breakage

3

Name repair sensitive G-G crosslinks.

N-mustards, thiotepa, busulfan

4

Name repair sensitive G-C crosslink.

Chloroethylnitrosoureas

5

Name repair insensitive G-G crosslink.

Mitomycin

6

Name repair sensitive G-CH3 (O6-G-methylation).

Dacarbazaine, procarbazine, temozolomide

7

Cell cycle non-specific drugs are dependent on what?

Efficacy weighed more heavily on Dose Dependent >>> schedule

8

Therapeutic use for mechlorethamine

Hodgkin Disease (MOPPS)

9

Adverse effect of mechlorethamine.

Blisters, necrosis if extravasation occurs. Occurs bc instantaneous activation by water upon infusion.

10

Cyclophosphamide activation in ___ location via ___ enzyme.

In liver via CYP450 activation.

11

Metabolites of Cyclophosphamide (two).

- Acrolein = urotoxic (bladder)
- Phosphoramide Mustard = active tumor metabolite drug

12

Ifosfamide activation in ___ location via ___ enzyme.

In liver via CYP450 activation and CYP2B6/CYP3A4.

13

Metabolites of ifosfamide (three).

- Acrolein = urotoxic (bladder)
- Phosphoramide Mustard = active tumor metabolite drug
- Chloracetaldehyde (CYP2B6/CYP3A4) = NEUTROTOXICITY - seizures, paralysis, coma

14

Dose limiting toxicity of nitrosoureas.

myelosuppression

15

A person has brain cancer - what class of Alkylating agents should be used and why?

bc they penetrate/have Good distribution in the CNS.
-Carmustine (Nitrosoureas) limited to brain cancer
-Temozolomide (triazene) - refractory anaplastic astrocytoma and glioblastoma

16

MOA of dacarbazine and temozolomide

- Dacarbazine - IV w/ CYP4501A activation
- Temozolomide - PO; spontaneous H+

Both result in activated metabolite MTIC --> electrophile (CH3)

17

What triazene DOES NOT penetrates the CNS effectively?

Dacrabazine

18

Status of O^6 MGMT has what effects on temozolomide alkylating DNA

- High MGMT = DNA repair nullifies damage - refractory
- Low MGMT = susceptible dt catastrophic DNA damage = GOOD

19

How does cisplatin/related compounds enter cells to cross link?

Enter via diffusion and Cu2+ transporter

20

1/2 of cisplatin is excreted in urine in 24hrs, so ____ location has a greater concentration of platinum than plasma and other organs, thus causing ____.

Renal cortex

NEPHROTOXICITY

21

MOA of cisplatin resistance.

1. Decreased uptake or increased efflux.
2. Neutralization of cisplatin by GLUTATHIONE
3. Increased DNA repair
4 Defective apoptosis

22

10 days after ___ drug administration, lower GFR, higher serum Cr, reduced serum Mg and K levels = ____

Cisplatin administration

Cisplatin nephrotoxicity (can also be secondary to tumor lysis syndrome)

23

oxaloplatin toxicity

neutropenia, cold induced neurpathy