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)
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1
Q

Cell cycle specific drugs are dependent on what?

A

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

2
Q

DNA alkylating/cross-linking agents: MOA

A
  • MOA - attack nucleophiles (-06, -07 N7 position of guanine)
  • Damage - crosslinking (bifunctional) or alkylating (monofunctional)
  • Consequences - miscoding of DNA bases, DNA breakage
3
Q

Name repair sensitive G-G crosslinks.

A

N-mustards, thiotepa, busulfan

4
Q

Name repair sensitive G-C crosslink.

A

Chloroethylnitrosoureas

5
Q

Name repair insensitive G-G crosslink.

A

Mitomycin

6
Q

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

A

Dacarbazaine, procarbazine, temozolomide

7
Q

Cell cycle non-specific drugs are dependent on what?

A

Efficacy weighed more heavily on Dose Dependent&raquo_space;> schedule

8
Q

Therapeutic use for mechlorethamine

A

Hodgkin Disease (MOPPS)

9
Q

Adverse effect of mechlorethamine.

A

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

10
Q

Cyclophosphamide activation in ___ location via ___ enzyme.

A

In liver via CYP450 activation.

11
Q

Metabolites of Cyclophosphamide (two).

A
  • Acrolein = urotoxic (bladder)

- Phosphoramide Mustard = active tumor metabolite drug

12
Q

Ifosfamide activation in ___ location via ___ enzyme.

A

In liver via CYP450 activation and CYP2B6/CYP3A4.

13
Q

Metabolites of ifosfamide (three).

A
  • Acrolein = urotoxic (bladder)
  • Phosphoramide Mustard = active tumor metabolite drug
  • Chloracetaldehyde (CYP2B6/CYP3A4) = NEUTROTOXICITY - seizures, paralysis, coma
14
Q

Dose limiting toxicity of nitrosoureas.

A

myelosuppression

15
Q

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

A

bc they penetrate/have Good distribution in the CNS.

  • Carmustine (Nitrosoureas) limited to brain cancer
  • Temozolomide (triazene) - refractory anaplastic astrocytoma and glioblastoma
16
Q

MOA of dacarbazine and temozolomide

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

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

17
Q

What triazene DOES NOT penetrates the CNS effectively?

A

Dacrabazine

18
Q

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

A
  • High MGMT = DNA repair nullifies damage - refractory

- Low MGMT = susceptible dt catastrophic DNA damage = GOOD

19
Q

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

A

Enter via diffusion and Cu2+ transporter

20
Q

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 ____.

A

Renal cortex

NEPHROTOXICITY

21
Q

MOA of cisplatin resistance.

A
  1. Decreased uptake or increased efflux.
  2. Neutralization of cisplatin by GLUTATHIONE
  3. Increased DNA repair
    4 Defective apoptosis
22
Q

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

A

Cisplatin administration

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

23
Q

oxaloplatin toxicity

A

neutropenia, cold induced neurpathy