CHAPTER 35: ANTICANCER DRUGS Flashcards
Antimetabolites
- folic acid analogs: methotrexate
- pyrimidine analogs: 5-fluorouracil
- purine analogs: 6-mercaptopurine
Methotrexate: MOA
- antifolate
- folic acid role in metabolic rxns and cell replication
MOA: inhibit DHFR, enz that converts folic acid to active form FH4
Methotrexate: therapeutic use
- combo w other drugs
- acute lymphocytic leukemia, burkitt lymphoma in CHILDREN
- bladder cancer
- head/neck carcinomas
- low dose single agent for inflamm diseases (arthritis, psoriasis, Crohns)
Methotrexate: adverse effects and drug-drug interactions
AE: rash, alopecia, myelosuprresion, stomatitis
high dose AE: renal damage
drug-drug: omeprazole, folic acid, warfarin, NSAIDs, penicillin
Antitumor Antibiotics
- names
- how does it work
- cell cycle specific?
- doxorubicin
- interfere w DNA synth, insert between base pairs (intercalation)
- inhibit topoisomerase too ( form free radicals)
- cell cycle phase nonspecific
Doxorubicin: therapeutic uses
- combo for sarcomas and carcinomas
- breast cancer
- acute lymphocytic leukemia
- lymphomas
Doxorubicin: MOA
- free radicals can induce membrane lipid peroxidation, DNA strand scission
- oxidation purine/pyrimidine bases, thiols and amines
Doxorubicin: Adverse effects
- bone marrow suppressin
- GI disturbances
- tissue damage/extravasation
- alopecia
- cardiotoxicity
- RED color urine and sweat
Doxorubicin: drug interactions
- calcium channel blockers (inc cardiotox)
- phenobarbital (inc metab doxo)
- paclitaxel (dec metab doxo)
- phenytoin levels reduced
Microtubule Inhibitors
- names
- how does it work
- cell cycle specific?
- vinca alkaloids (vincristine/vinblastine)
- taxanes (paclitaxel)
- stop cell division during mitosis, affect equilibrium of polymerized and depolym forms of the microtubules
- M phase cell cycle specific
Vincristine and Vinblastine
- USED AS COMBO w other drugs
Vincristine: treat acute lymphoblastic leukemia in children, wilms tumor, soft tissue sarcoma, Hodgkin lymphomas
Vinblastine: give w bleomycin and cisplatin to treat metastatic testicular carcinoma
- treat hodgkin lymphomas
Vincristine and Vinblastine: MOA
bind to microtubular protein, tubulin
- block tubulin to polymerize and form microtubules
- aggregates consisting of tubulin dimers and drug are formed–> dysfunc spindle apparatus, freeze in metaphase, prevent chromosome segregation and cell proliferation
Vincristine and Vinblastine: adverse effects
- phlebitis or cellulitis (from extravasation)
- nausea, vomit, diarrhea, alopecia
Vinblastine: myelosuppression
Vincristine: peripheral neuropathy (paresthesia, loss reflex, ataxia), and constipation
DO NOT deliver intratheca
Noncytotoxic Agents: steroid hormones and antagonists
tumors sensitive to steroid hormones can be…
- hormone responsive: tumor regress following treatment w specific hormone
- hormone dep: removal of hormone stimulus causes tumor regression
- BOTH
Noncytotoxic Chemo agents: agonists vs antagonists
Agonists: GnRH (gonadotropin releasing hormone)
Antagonists: anti estrogen for estrogenic dep cancer, anti testosterone for test. dep cancer
Hormonal Agents- Prostate Cancer
- GnRH
- Leuprolide
- occupy GnRH receptor in pituitary–> desensitize–> inhibit release FSH and LH
- testes stop producing testosterone
Hormonal Agents- Prostate Cancer
- Androgen Receptor Antagonists
- flutamide
- block testosterone at receptor site
Hormonal Agents- Prostate Cancer
- leuprolide AE and contraindications
AE: hot flash, dec libido, gynecomastia, dec bone density, arrhythmia, pulm edema
contraindicate: PT w hypersensitivity
Hormonal Agents- Prostate Cancer
-Flutamide AE, contraindications, interactions
AE: hot flash, dec libido, gynecomastia, GI disturbances, hepatitis
contraindicated: PT w liver disease
interactions: warfarin (inc anticoag effect)
Hormonal Agents- Breast Cancer
- estrogen receptor antag
- tamoxifen
- stop breast cancer growth
- first live treat and prevention
Hormonal Agents- Breast Cancer
- Aromatase Inhibitors
- anastrozole
- stop growth by blocking estrogen production
- first line in postmenopausal women
Hormonal Agents- Breast Cancer
- monoclonal antibody
- trastuzumab
- prevent growth by causing cell death
- treat metastatic breast cancer
- along OR combo w paclitaxel
Hormonal Agents: Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS
TAMOXIFEN
- AE: endometrial cancer, hypercalcemia, nausea/vomit, pul embolus, hot flash, vag discharge/bleeding
- contraindicated: pregnancy, PT taking warfarin, history of blood clots or pulm embolism
Hormonal Agents- Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS
ANASTRAZOLE
- AE: muscle/joint pain, osteoporosis, nausea, hot flash
- contraindicated: pregnancy, women before menopause, PT liver disease
Hormonal Agents- Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS
TRASTUZUMAB
- AE: cardiac toxicity, tachy, HF, hypersensitivity, nausea/vomit
- contraindicated: pregnancy, hypersensitive PT, heart disease PT
Antibodies treatment: EGFR Tyrosine kinase inhibitors
- cetuximab
- inhibit epidermal growth factor receptor
- treat metastatic colorectal cancer, metastatic non small cell lung cancer, head/neck cancer
Antibodies treatment: CD20 directed antibodies
- rituximab
- antibody against protein CD20, on surface of immune sys B cells
- binds to protein and trigger cell death
- treat various cancers, ex) non hodgkins lymphoma
Antibodies treatment: angiogenesis inhibitors
- bevacizumab
- block angiogenesis, inhibit vascular endothelial growth factor A (VEGF-A)
- treat colorectal and lung cancers
