Wk 12: Alkylating + platinating agents (Nitrosoureas, platinum compounds etc.) Flashcards
1
Q
What is thiotepa?
A
Thioplex
- Aziridine
- Less reactive than nitrogen mustards: more reactive at acidic pH
- For bladder cancer
- Oral or IV
2
Q
How is thiotepa administered?
A
Directly into bladder by catheter:
- Dehydrate patient 8-12hrs
- 60mg thiotepa in 30-60ml sterile water
- Retaine for 2hr once a week for 4 wks
3
Q
Give an example of an alkyl sulfonates
A
Busulfan - busulfex/myleran
4
Q
How is busulfan administered?
A
- W/ phenytoin as it cross bbb + induces seizures
- IV: Sterile sol in 10ml ampule
- Tabs: 2mg for remission/maintenance
5
Q
What is busulfan commonly used for?
A
Chronic myelogenous leukemia:
- Selective effect on bone marrow
- Little effect: lymphoid tissue + GI tract
6
Q
What type of alkylating agent is busuflan?
A
Bifunctional:
- Sn2 mechanism
- Sulfonate group better leaving group than Cl on nitrogen mustards
- Reacts w/ thiol on aa
7
Q
Give examples of nitrosoureas
A
- Lomustine
- Carmustine
- Streptozotocin
8
Q
What is chloroethylnitrosoureas?
A
Carmustine:
- Bifunction
- Derivative of urea
- Cross links DNA (N-7, O-6 of guanine, N-3 of cytosine)
- Cross BBB
- Pro-drug
- Non-selective + very toxic (bone marrow depression)
9
Q
What is lomustine?
A
- 40mg caps
- Used for: CNS tumours, hodgkin’s disease + lung cancer
10
Q
Outline the mode of action of Carmustine
A
- Nitro + urea = bioactivated
- Prod isocyanate
- This reacts w/ lysine residues to produce protein that inactivates DNA repair enzymes
- 2 active prods: Chloroethyl diazonium ion OR chloroethyl carbonium ion - cross links DNA
11
Q
What is Streptozotocin?
A
Zanosar:
- Naturally occuring nitrosourea
- From Streptomyces achromogenes
- MOA: formation of methyl diazonium ion + carbamylation of proteins (no cross links)
12
Q
What is the mode of action of temozolomide + dacarbazine?
A
- Prodrugs
- Active prod: methyldiazonium ion
- DNA methylation of guanine bases O6 + N7
- Red activity of O6-alkylguanine-DNA-alkyltransferase
13
Q
How are cisplatin similar to alkylating agents?
A
- Platinating agent
- Cross links DNA
- N-7 guanine + N-7 adenine involved
14
Q
How is cisplatin administered?
A
- Slow IV
- Clear liquid in amber vile
- Opened: stable for 28 days from light
- Reacts w/ aluminium
15
Q
What is the structure of cisplatin?
A
- Pt central atom surround by 2 Cl + 2 NH3 in cis position
- Tetra-coordinate transition metal w/ square planar geometry
