Exam 9: Anti Cancer Agents Flashcards
What do we need to know for each agent?
Category
Mechanism
Toxicity
Only need to know specific uses when noted explicitly (seriously, don’t try to memorize a bunch of other shit)
Name 2 nitrogen mustards
Mechlorethamine
Cyclophosphamide
Name 1 nitrosourea
Carmustine
Name one platinum complex
Cisplatin
Name 1 folic acid analog
Methotrexate
Name 1 purine analog
Mercaptopurine
Name 2 pyrimidine analogs
Fluorouracil
Cytarabine
Name 2 anthacycline antibiotics
Daunorubicin
Doxorubicin
Name 4 vinca alkaloids, epipodophylotoxins, and taxanes
Vinblastine
Vincristine
Etoposide
Paclitaxel
Name 2 corticosteroids used in cancer treatment
Prednisone
Dexamethasone
Name one estrogen/antiestrogen
Tamoxifen
Name one Tyrosine Kinase inhibitor
Imatinib
Name one monoclonal antibody used for cancer treatment
Trastuzumab
What is a difference in general usefulness in cell cycle specific vs cell cycle non-specific agents?
CCS are better at treating tumors with lots of cells that are proliferating
CCNS are better in low-growth solid tumors
What are the cell cycle non specific agents?
All the alkylators and the 2 antibiotics:
Mechlorethamine, Cyclophosphamide, Carmustine, Cisplatin
and
Daunorubicin
Doxorubicin
What are three alkylating agents?
Mechlorethamine
Cyclophosphamide
Carmustine
Cisplatin (kind of, causes cross linking without actual alkylation)
What is the mechanism of alkylating agents?
Alkylation of Nitrogen 7 on Guanine
What are 3 consequences of alkylation of Guanine?
- Miscoding of DNA strands (won’t interact with complementary base)
- Incomplete repair of alkylated segment (breaks/depurination)
- Excessive cross linking of DNA and inability for strand separation
Are alkylating agents CCS or CCNS?
CCNS
What are toxicities of Alkylating agents?
Acute- Nausea, vomiting
Long Term- Bone marrow depression
These are the main toxicities seen in most cancer drugs, except when explicitly noted
Mechlorethamine mechanism
Alkylation of Nitrogen 7 on Guanine
Cyclophosphamide mechanism
Alkylation of Nitrogen 7 on Guanine
Cyclophosphamide pharmacokinetic consideration
Prodrug
Must be activated by p450 enzyme
Carmustine mechanism
Alkylation of Nitrogen 7 on Guanine
Nirtosurea
What is a pharmacodynamic feature of carmustine?
Highly lipid soluble
Cisplatin mechanism
Bifunctional alkylating agent
Causes cross linking
Cisplatin toxicity
Nephrotoxic and Ototoxic
Cisplatin class
Platinum complex
Are antimetabolites CCS or CCNS?
CCS
Methotrexate Mechanism
Folic acid analog
Inhibits dihydrofolate reductase, preventing creation of Tetrohydrofolate needed for DNA synthesis
What protects normal cells with methotrexate use?
Leucovorin (Folinic acid)
Bypasses metabolic block by methotrexate
What phase is affected by Methotrexate?
S phase (DNA synthesis)
Methotrexate toxicity
Acute- Nausea, vomiting
Long Term- Bone marrow depression
Methotrexate uses
Psoriasis, Rheumatoid arthritis
Mercaptopurine mechanism
Purine analog
Inhibits enzymes of purine interconversion, decreasing nucleotide synthesis
What cell cycle phase is affected by Mercaptopurine?
S phase
5-Fluorouracil mechanism
Pyrimidine analog
Inhibits thymidylate synthetase covalently, inhibiting DNA synthesis (S phase)
5-Fluorouracil toxicity
Less GI effects than other cancer drugs
Cytarabine mechanism
Pyrimidine analog
Converted to cytarabine triphosphate
Inhibits DNA polymerase by competing with deoxycitidine triphosphate
S phase specific
Daunorubicin and Doxorubicin mechanism
Intercalate and bind to DNA between base pairs, uncoiling DNA, destroying template (Not CCS)
When is the most effect seen with Daunorubicin and Doxorubicin
S phase, but still considered non specific
Daunorubicin and Doxorubicin toxicity
Cardiomyopathy (Dilated)
*** Pretty sure this will be a test question.
Vinblastine and Vincristine Mechanism
Vinca Alkaloids
Bind to tubulin and disrupt the mitotic spindle apparatus
Prevents segregation of chromosomes in metaphase
What phase are Vinca alkaloids specific for?
Mitosis phase (Metaphase)
What toxicity is associate with Vincristine and Vinblastine?
Neurological side effects (eg. peripheral neuropathy)
Also general toxicities seen in most cancer drugs
Etoposide mechanism
Forms a complex with Topoisomerase II and DNA resulting in DNA breaks and cell death.
Specific for G2 phase
What cell cycle phase is Etoposide specific for?
G2
Paclitaxel mechanism
Antimicrotubule agent.
Enhances microtubule assembly
Stabilizes microtubules (they can’t depolymerize)
Specific for G2 and M phase
What cell cycle phase is Paclitaxel specific for?
G2 and M phases
Prednisone and Dexamethasone mechanism
Lipid soluble, diffuse into cells, affect transcription of genes in the nucleus.
Suppress mitosis in lymphocytes
G1 phase specific
What cell cycle phase are corticosteroids specific for?
G1
Tamoxifen mechanism
Non steroidal anti estrogen
Blocks estrogen receptors (nuclear transcription factors) that stimulate growth
G1 phase specific
What cell cycle phase is Tamoxifen specific for?
G1
Tamoxifen toxicities
Short term: Menopausal symptoms (Hot flashes, headaches, fatigue, etc.)
Long term: visual changes, vaginal bleeding, ocular toxicity, thromboembolism, thrombocytopenia
Most Serious: Can promote tumor growth and increase incidence of endometrial cancer
Tamoxifen use
Estrogen receptor positive invasive breast cancer
Often used for breast cancer in men
Imantinib mechanism
Inhibits Bcr-Abl tyrosine kinase
Inhibits proliferation and triggers apoptosis in Bcr-Abl-positive leukemia cell lines
Imantinib uses (2)
Acute Lymphocytic Leukemia (ALL)
Ph+ (Philadelphia chromosome + 9:22) Chronic Myeloid Leukemia (CML)
Trastuzumab mechanism
(Herceptin)
IgG1 monoclonal antibody that binds to the the EGF receptor HER-2
Down regulates the receptor’s tyrosine kinase activity which are involved in metastasis
Phase G1 specific
Trastuzumab uses
Breast cancers that overexpress EGF2
In combo with paclitaxel is the first line treatment for HER2-overexpressing metastatic breast cancer
What is the first line treatment for HER2-overexpressing metastatic breast cancer?
Trastuzumab and Paclitaxel
