Pharm- Alkylating Agents & CCNS Drugs

Question 1

Bifunctional agents

Answer 1

cross-link DNA

Question 2

Monofunctional agents

Answer 2

insert a methyl or ethyl molecule into DNA

Question 3

Monofunctional agents

Answer 3

triazenes, nitrosoureas

Question 4

bifunctional agents

Answer 4

nitrogen mustards, aziridines, melphalan, chlorambucil, busulfan

Question 5

Triazenes

Answer 5

dacarbazine, procarbazine, temozolomide

• DNA alkylation. Methylation, guanosine O6,N7
• donate a methyl group and alkylate the guanosine O6,N7 that is in DNA
• Can tx advanced forms of brain tumors

Question 6

Dacarbazine therapeutic uses

Answer 6

metastatic melanoma

Question 7

Procarbazine therapeutic uses

Answer 7

malignant glioma

Question 8

Temozolomide

Answer 8

tx resistant glioma & astrocytoma

Question 9

Nitrosoureas

Answer 9

DNA alkylation. Alkylation, guanosine O6,N7

• brain tumors or large melanomas
• used for brain cancers bc these tend to be tumors that have cells escaping the cell cycle bc they are physically limited in their growth

Question 10

Nitrosoureas

Answer 10

Carmustine, Lomustine, Streptozocin

Question 11

Carmustine therapeutic uses

Answer 11

brain tumors, lymphoma, melanoma

Question 12

Lomustine therapeutic uses

Answer 12

brain tumors, lymphoma, melanoma

Question 13

Streptozocin

Answer 13

used as a chemical to model diabetes
-selective at islet B cells
Insulinomas -> create Type 1 diabetes

Question 14

Nitrogen Mustards

Answer 14

Cyclophosphamide, Ifosfamide, mechlorethamine

Question 15

Cyclohosphamide, Ifosfamide

Answer 15

• crosslinks
• PO, liver CYP450 activation
• various uses

Question 16

Mechlorethamine (vesicant)

Answer 16

spontaneous activation

Historical- MOPP regiment in lymphoma

Question 17

Melphalan

Answer 17

PO

-multiple myeloma

Question 18

Chlorambucil

Answer 18

• PO

- CLL

Question 19

Busulfan

Answer 19

• PO

- CML

Question 20

Aziridines

Answer 20

G-G crosslinks

Thiotepa, Mitomycin C, Altretamine

Question 21

Thiotepa therapeutic uses

Answer 21

breast, ovarian, bladder cancer

Question 22

Mitomycin C therapeutic uses

Answer 22

breast & gastrointestinal cancer

Question 23

Altretamine therapeutic uses

Answer 23

Recurrent ovarian cancer - resistant to other alkylating agents

Question 24

Cisplatin & related compounds

Answer 24

organoplatinum drugs

Question 25

Organoplatinum drugs

Answer 25

cisplatin, carboplatin, oxaloplatin

Question 26

Cisplatin distinctions

Answer 26

- platinum-Cl complex - stable in plasma and high Cl milieu - hydrolyses in cell to active agent - Complex elimination due to cell uptake

Question 27

Carboplatin distinctions

Answer 27

more stable analog | -primarily renal elimation, t1/2 ~ 2hrs

Question 28

Oxaloplatin distinctions

Answer 28

complex elimination due to cell uptake

Question 29

cisplatin therapeutic uses

Answer 29

testicular cancer (w/ bleomycin, vinblastin or etoposide); ovarian cancer; NSCL

Question 30

carboplatin therapeutic uses

Answer 30

ovarian cancer

Question 31

oxaloplatin therapeutic uses

Answer 31

Colorectal cancer (FOLFOX regimen). Folinic acid, FU, Oxaliplatin

Question 32

cisplatin dose limiting toxicity

Answer 32

renal; severe nausea/vomiting; ototoxicity- acoustic nerve damage

Question 33

carboplatin dose limiting toxicity

Answer 33

neutropenia

Question 34

oxaloplatin dose limiting toxicity

Answer 34

neutropenia, neuropathy- cold induced