Anti-Neoplastic Drugs Flashcards
Classification of Anti-Neoplastic Drugs
Alkylating Agents Antimetabolites Natural Products Misc. Agents Hormone and Hormone Antagonists
Alkylating Agents: Cell Cycle Specificity
Cell cycle non-specific: also affects G0 ex: mechlorethamine, carmustine (nitrosoureas)
cell-specific phase non-specific: ex: cyclophosphamide
Alkylating Agents: Side effects
“typical” side effects: Hematopoiesis suppression GI Effects Alopecia
Mechlorethamine
Alkylating Agent – Prototype cell-cycle nonspecific produces DNA cross-linking Does not cross CNS Hodgkin’s and non-Hodgkin’s lymphoma
Cyclophosphamide
Alkylating Agent– cell-cycle phase nonspecific Pro-drug activated by liver cP450s Bladder toxicity: sterile hemorrhagic cystitis (can be partially prevented with mesna)
Carmustine
Akylating Agent - cell-nonspecific
crosses BBB very well
Treatment of: brain tumors, multiple myeloma, melanoma
Antimetabolites
many are phase specific (usually S-phase)
structural ananlogs of compounds required for itermediary metabolism.
Folate Analogs: Methotrexate
Pyrimidine Analongs: Flourouricil (5-FU)
Cytarabine
Purine Analongs: Mercaptopurine (6-MP)
Misc. Antimetabolites: Hydroxyurea
Methotrexate (MTX)
Antimetabolite: Binds to dihydrofolate reductase and prevents formation of tetrahydrofolate
High doses necessary to bind all DHFR followed by rescue of host cells with Leucovorin
Side Effects: intestinal epithelium damage
bone marrow suppression
**renal tubular necrosis **
**displaces other drugs from serum albumin **
Indications: Acute Lymphocytic Leukemia (ALL)
Choriocarcinoma
Fluorouracil (5-FU)
Antimetabolite : pyrimadine analog
interferes with thymidylate synthesis and ultimately DNA synthesis
**S-Phase Specific **
Broad spectrum of uses: stomach, **colon, **pancreas, ovary head and neck, **breast, **bladder
Cytarabine
Antimetabolite : pyrimadine analog
competes for integration into DNA and causes chain termination
**S-Phase Specific **
Side Effect: **myelosuppression, neurotoxicity **
Uses: Acute Leukemias, Acute Myelocytic Leukemia (AML)
Mercaptopurine (6-MP)
Antimetabolite: Purine Analog
Inhibits DNA and RNA synthesis
**S Phase Specific **
treatment of acute leukemias
Hydroxyurea
Antimetabolite
inhibits ribonucleotide reductase – prevent DNA synthesis
**Arrests Cells at G1-S interfaces **
Useful in conjunction with radiation
Major use: ** granulocytic leukemia **
Vinca Alkaloids
Vincristine
Vinblastine
Bind to tubulin, inhibiting proper formation of microtubules and mitotic spindles
Taxanes
enhances assembly and stability of microtubules by binding to the Beta subunit of tubulin
**blocks late in G2 phase **
Paclitaxel
Epipodophyllotoxins
Etoposide
Monoclonal Antibodies
Trastuzumab
Antibiotics
Doxorubicin
Bleomycin
Vinblastine
Blocks tubulin and spindle formation
Strongly myelosuppressive
side effects: epithelial ulcerations
uses: **lymphomas, breast cancer **
Vincristine
Blocks tubulin and spindle formation
side effects: alopecia, **neuromuscular abnormalities **
uses: **ALL, lymphomas. Wilm’s Tumor, neuroblastoma **
Paclitaxel
Taxane
interfere with DNA repair, intensifying the effects of DNA damage by cisplatin or cyclophosphamide
side effects: **dose-limiting leukopenia, peripheral neuropathy, myalgia/arthalgia **
uses: refractory ovarian cancer; breast cancer
Doxorubicin
Antibiotics
cycle-specific phase non-specific
wide spectrum of activity: most widely prescribed agent
lymphomas, breast, orvary, small cell lung cancers
_One of the few drugs with some anti-angiogenic properties _
**Interculates in DNA, distorting DNA helix **
**Causes Lipid peroxidation and free radical generation **
**Binds to DNA and Topoisomerase II **
Side Effects: ****Cardiomyopathy***
**bone marrow suppression **
alopecia
**GI issues **
Bleomycin
Antibiotics
mixture of iron-contianing glycopeptides that bind to DNA
causes oxidative-like damage to DNA which leads to DNA strand breaks
Phase Specific for G2
uses: **germ cell tumors of testes and ovaries **
**head, neck, lung, lymphomas **
Side Effects: minimal myelosupression
_Pulmonary toxicity _
**skin vesiculation, hyperpigmentation **
Etoposide
Irreversibily stabilized DNA-topoisomerase II complexes
results in dsDNA breaks that cannot be repaired
**Blocks in late G2 Phase **
uses: **Lymphomas, acute leukemias, small cell lung, testes **
Typical side effects
Filgrastim
Biological Response Modifier
Granulocyte colony stimulating factor
**Goal is to limit chemotherapy-induced neutropenia **
**-promotes progenitors of neutrophils **
**-expands the absolute population of neutrophils, providing for quicker recovery from bone marrow suppression **
