Antineoplastic therapy- Alkylating agents 1-18 Flashcards
Are alkylatic agents synthetic or natural?
They’re synthetic, so are antimetabolites
In general, what do alkylatic agents do?
Alkylate purine/pyrimidine bases, block DNA synthesis
Name the nitrogen mustards
Mechlorethamine Cyclophosphamide Ifosfamide Chlorambucil Melphalan Bendamustine
Name the nitrosureas
Carmustine
Lomustine
Streptozocin
What are the “other” alkylatic agents
Dacarbazine Procarbazine Temozolamide Altretamine Busulfan
Name the platinum coordination complexes
Cistplatin
Carboplatin
Oxaliplatin
Where do alkylating agents work in the cell cycle?
Non-specific! G1 and S
What 3 general properties are there of alkylatic agents?
Mutagenic, carcinogenic, teratogenic
What is the MOA of alkylatic agents?
Form carbonium ion or transition intermediates. They alkylate the nitrogen on: 7 of guanine, 1 and 3 of adenosine, 3 of cytosine, and 6 O of guanine
- They form cross-links with adjacent bases to prevent strand from coming apart to block transcription
- Cross-linking also increases p53 activity to cause apoptosis
Can cause abnormal pairing of G with T, removal of purines, and increased ring cleavage due to binding
Which agents were used during WW1 as chemical warfare agents? Why were they dangerous?
Nitrogen mustards; they had significant vesicant actions and caused tissue damage
How is Mechlorethamine administered?
IV
What is Mechlorethamine used for?
Hodgkin’s disease (part of MOPP’s regimen) - LIMITED use
Adverse effects of mechlorethamine?
Nausea, vomiting, leukopenia, thrombocytopenia, reduced reproductive function
Does mechlorethamine have a rescue?
You can treat extravasation with sodium thiosulfate
How is cyclophosphamide administered?
Oral, IV
Does mechlorethamine require activation?
Quick activation, quick inactivation
Does cyclophosphamide require activation?
Yes by p-450 system
What is cyclophosphamide used for?
Chronic and acute lymphytic leukemia
Lymphoma
Used in combination for breast, lung, testicular, ovarian, sarcoma, non-hodgkins and hodgkins
What toxicities are associated with cyclophosphamide?
Nausea, vomiting, cystitis, GI ulceration, alopecia, pulmonary fibrosis, immunosuppression
Does cyclophosphamide have a rescue?
Give mercaptoethane sulfonate (MESNA) to reduce cystitis in the bladder, MUST hydrate patient
Does Ifosfamide require activation?
Yes CYP3A4 activation
What is Ifosfamide usually compared to?
Cyclophosphamide
It is less potent, but has CNS side effects and more nephrotoxicity, platelet suppression
Does Ifosfamide have a rescue?
Mercaptoethane sulfonate (MESNA) to prevent cystitis, MUST hydrate patient
What is Ifosfamide used for?
Sarcoma, testicular cancer, bone marrow ablation
Used to deplete bone marrow before transplants
What drug is used for bone marrow ablation?
Ifosfamide, Melphalan
What is Melphalan used for?
Multiple myeloma, bone marrow ablation
How is Melphalan administered?
Oral, IV
Toxicities of Melphalan?
Bone marrow suppression, less nausea and vomiting and no alopecia!
Leukemias
Teratogenic
What is Chlorambucil used for?
Chronic lymphocytic leukemia (CLL)
How is Chlorambucil administered?
Given orally only
Toxicities with Chlorambucil?
GI discomfort, pulmonary fibrosis, seizures, dermatitis, bone marrow suppression, teratogenic, infertility
What is Bendamustine used for?
CLL and Non-hodgkin’s lymphoma
How is Bendamustine administered?
IV infusion on day 1 and 2 of a 28 day cycle
Toxicities with bendamustine?
Myelosuppression, mucositis, nausea, vomiting
How does Bendamustine compare to other agents?
Lacks resistance to other alkylating agents
