Term
| What are the stages of the cell cycle? |
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Definition
- G1 - 1st gap phase
- S - synthesis. Genome is duplicated
- G2 - 2nd gap phase
- M - mitotic phase
- G0 - Quiescent. Cells not actively dividing.
**Bone marrow and mucosal lining of GI constantly divide |
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Term
| How are drugs resistant to cancer therapy? |
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Definition
- Intrinsic resistance - innate to tumor cells
- Acquired - mutation. Decr levels, increased repair/detox, defects in apoptosis, mutation of drug targets |
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Term
| What are general common cytotoxic drug toxicities? |
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Definition
- myelosuppression - bone marrow toxicity. Leuko, thrombo, granulo, and anemia
- GI - N/V, diarrhea
- Major organs
- 2ndary malignancy
- Alopecia - hair loss
- Infertility |
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Term
| What drugs are alkylating agents: nitrogen mustards? |
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Definition
cyclophosphamide - PO (often), IV
ifosfamide
chlorambucil
mechlorethanamine |
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Term
| What drugs are alkylating agents: platinum complexes? |
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Definition
Cisplatin
Carboplatin
Oxaliplatin |
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Term
| How do all alkylating agents work? |
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Definition
- Activate to form carbonium intermediates which attack atoms --> covalent bond to DNA to form Cross-link
- Inhibition of replication and transcription
**NOT cell cycle specific |
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Term
| What is the structure of a nitrogen mustard - reduces electron density of nitrogen forming a positive intermediate? |
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Definition
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Term
| How do nitrogen mustards work? |
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Definition
| Guanine is the main target - alkylation causes cross linkage |
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Term
| What counteracts the hemorrhagic cystitis of cyclophosphamide and ifosfamide? |
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Definition
Mesna
**Cardiotoxic in high doses |
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Term
| How does Ifosfamide compare to cyclophosphamide? |
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Definition
- Nephrotoxic instead of cardiotoxic
- Only IV
- SEVERE myelosuppression |
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Term
| What nitrogen mustard can be used orally and continuously? |
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Definition
| Chlorambucil - rapid oral absorption |
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Term
| Which nitrogen mustard are vesicants? |
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Definition
- Mechlorethamine - Rapid IV injection, a very short half life b/c it degrades in water and bodily fluids
- Bendamustine - IV |
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Term
What drug has this structure?
[image] |
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Definition
| Busulfan - PO. Still functions as an alkylating agent. An alkyl sulfonate |
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Term
| What are the triazenes/hydrazine? |
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Definition
A type of alkylating agent:
- Dacarbazine - IV
- Procarbazine - PO |
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Term
| How do platinum coordination complexes work? |
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Definition
- Alkylating agents that use platinum to crosslink
- Aquation activates intracellularly, attacks intrastrand guanine to crosslink. Also NOT cell cycle specific
**Do not use aluminum needles, can precipitate drug |
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Term
| What are the adverse effects of cisplatin? |
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Definition
- Cisplatin - Covalent bound to proteins, IV. AEs:
- Nephrotoxic - alleviated by chloride diuresis, amifostine
- Serious peripheral neuropathy
- OTOTOXIC
- GI - give aprepitant/Emend
- Vesicant |
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Term
| What other drugs besides cisplatin are platinum complexes? |
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Definition
- Carboplatin - IV, AEs less severe
- Oxaliplatin - DO NOT use any chloride containing sln to reconstitute. Mild myelosuppression |
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