-
we find persistent proliferation in what?
Neoplastic cells
-
cancer cells are the type with this active enzyme
telomerase
-
8 barriers to successful treatment
- 1 toxicity to nl cells
- 2 low host defense
- 3 first order kinetics= a constant % of cells will be killed w/ each round, so an equally strong dose is needed each time
- 4 no visible end point
- 5 solid tumors do not respond well= most tumor cells are in G0 phase
- 6 drug resistance
- 7 heterogeneity of tumor cells
- 8 limited drug access to tumor
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what type of therapy is recommended for cancer tx?
- Combination therapy
- - resistance suppression
- - inc. cancer cell kill
- - reduced injury to nl cells
-
why are cancer drugs on of the few drugs given Intra-arterial?
direct attack on solid tumor
-
toxicities associated with cancer tx
- Bone marrow suppression- most prevalent
- GI - epithelial lining of tract
- Alopecia - b/c fast dividing cells
- Hyperuricamia - inc. uric acid breakdown of DNA
- Extravasation - tissue damage from IV site, so given central line to vena cava
- Carcinogenesis - from DNA damage
-
3 types of cancer drugs
- cytotoxic agents= direct kill
- Hormones and hormone antagonists= interfere with hormone dependent tissues
- Targeted drugs= created to bind to specific molecules
- = monoclonal antibodies
-
cytotoxic drugs
admin of
- direct attack on cells
- -cell cycle specific OR non-specific
- -Usually disrupt DNA synthesis
- admin= need to follow safe handling procedures to avoid nurse toxicity
- = Central line IV access is best
-
alkylating agents / Platinum compounds
cytotoxic dx
- Alkyl groups form abnormal cross links b/w DNA strands
- Drug resistance is common
- - inc. production of enzymes that repair DNA
SE= found in high-growth tissues like GI
-
Anti-Metabolites
cytotoxic dx
Disrupt metabolic processes (imposter)
Folic acid, Pyrimidine, and Purine analogs
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Methotrexate / Rheumatrex
Anti-metabolite (Cytotoxic)
- Folic Acid Analog (imposter)
- - DNA, RNA, and proteins
- Inhibits folic acid entry into cells, which decreases dna, rna, & protein productions
- Need LARGE doses b/c cancer cells are often resistant
-
Cytarabine / ARA-C
Anti-metabolite (Cytotoxic)
- Pyrimindine analog (imposter)
- - DNA and RNA
-
Mercaptopurine / Purinethol
anti-metab (Cytotoxic)
- Purine Analog
- -proteins and nucleic acids
-
Leucovorin Rescue
Leuc= a form of folic acid that can bypass the metabolic blocks of methotrexate
cancer cells lack uptake mechs for Leuc's
- Therefore, nl cells get folic acid
- BUT TIMING IS CRUCIAL!
-
anti-tumor antibiotics
cytotoxic agents
used only to treat cancer --> direct interaction with DNA
Administered IV only --> GI toxic
Delayed cardiomyopathy may arise after Tx
-
Mitotic Inhibitors
Cytotoxic agent
Act during the M phase of cell division
Cause peripheral nueropathy
-
Topoisomerase Inhibs
Cytotoxic agent
act during the S phase
Prevent the creation of single strand DNA for replication
-
what classification drug is used for prostate cancer?
Androgen Deprivation
-
Leuprolide / Lupron
Gonadotropin-Releasing Hormone AGONIST (GnRH)
- Initial inc. in hormone causes down regulation of receptors in testes
- Initital INCREASE and then DECREASE in cancer growth
- Does NOT block androgen from Adrenals or Prostate
1st defense for prostate cancer
-
Flutamide / Eulexin
- Androgen Receptor blocker
- -blocks recept, depriving cells of all androgen needed for growth
- -in combo with GnRH to suppress the initial growth of cancer
for advanced forms post-castration :( poor guy
-
SERMS
- Selective estrogens receptors modulators
- 'Anti-estrpgens'
Used for Breast cancer
-
Tamoxifen / Nolvodex
Raloxifene / Evista
SERMS
- Block some estrogen receptors
- - tumor deprived of estrogen needed to grow
- Stimulate other estrpgen recepts
- - Inc. bone density
- - dec. LDL, inc. HDL
used for prevention in high risk pt.s
-
Aromatase Inhibitors
SERMS used in Post-menopausal breast cancer
- block only breast tumor estrogen, NOT ovarian
- Well tolerated
-
Side effects of SERMS and Post-menopausal SERMS
SERMS= Thromboembolism, endometriosis / cancer
Post-men= flushing, headache, n/v, HTN, increased risk for osteoporosis
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Trastuzumab / Herceptin
side effects
Monoclonal Antibody used for breast cancer
- HER2 receptor controlling cell growth
- Human Epidural growth factor receptors
- -binds to receptors and stops cell prolif.
SE= cardiotoxicity, hypersensitivity, & pulmonary events
-
3 types of Targeted Drugs
Monoclonal antibodies= good, but can cause a lot of cell death and therefore toxicity
Small molecules= inhibit intra-cellular communication
Angiogenesis INhibitors= stop blood flow to tumor
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Why are Hematopoietic and Thromopoietic Growth Factors given in combo with Chemo Therapy?
They have Colony stimulating factors
They act on bone marrow to stimulate formation of blood cells
-
Hematopoietic growth factor effects what cells?
red and white
-
Thrombopoietic growth factor effects what cells?
platelets
-
Epoetin Alfa / Epogen, Proctrit
- Hemat g-factor --> RBC's
- For HCT <35%
- Need iron, folic acid, & B12 or WILL NOT work
- Uses= chronic renal failure, chemo, anemia in pt.s facing surgery
- = inc. RBC count like erythropoietin
SE= HTN-monitor and control BEFORE use
-
other info about Procrit
- Vial MUST NOT be shaken
- Should not be mixed other drugs
- Should not be frozen
Now is given SubQ
-
Filgrastim / Neupogen
Hemat g-factor --> WBC's
- uses= elevation of neutrophil counts in pt.s w/ cancer
- = Tx of severe chronic nuetropenia
SE= bone pain
-
Oprelvekin / Neumega
- (Interleukin-11)
- Thrombopoietic g-factor --> platelets
Uses= used w/ myelosuppressive chemo to minimize thrombocytopenia
- SE= fluid retention
- = cardiac dysrrhythmias
- = allergic rxns
-
What 3 things need replaced in Anemia?
- Iron --> oral or IV (Iron Dextran)
- -high incidence of anaphylactic rxns
- Vit. B12
- - essential for DNA synthesis in all cells
- - given orally, nasal, IM, IV
- Folic Acid
- - essential for DNA synthesis and cell division
- -given orally
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