Pharm 5 set 1

Neoplastic cells

telomerase

• 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

• Combination therapy
• - resistance suppression
• - inc. cancer cell kill
• - reduced injury to nl cells

direct attack on solid tumor

• 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

• cytotoxic agents= direct kill
• Hormones and hormone antagonists= interfere with hormone dependent tissues
• Targeted drugs= created to bind to specific molecules
•   = monoclonal antibodies

• 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

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

cytotoxic dx

Disrupt metabolic processes (imposter)

Folic acid, Pyrimidine, and Purine analogs

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

Anti-metabolite (Cytotoxic)

• Pyrimindine analog (imposter)
• - DNA and RNA

anti-metab (Cytotoxic)

• Purine Analog
• -proteins and nucleic acids

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!

cytotoxic agents

used only to treat cancer --> direct interaction with DNA

Administered IV only --> GI toxic

Delayed cardiomyopathy may arise after Tx

Cytotoxic agent

Act during the M phase of cell division

Cause peripheral nueropathy

Cytotoxic agent

act during the S phase

Prevent the creation of single strand DNA for replication

Androgen Deprivation

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

• 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

• Selective estrogens receptors modulators
• 'Anti-estrpgens'

Used for Breast cancer

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

SERMS used in Post-menopausal breast cancer

• block only breast tumor estrogen, NOT ovarian
• Well tolerated

SERMS= Thromboembolism, endometriosis / cancer

Post-men= flushing, headache, n/v, HTN, increased risk for osteoporosis

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

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

They have Colony stimulating factors

They act on bone marrow to stimulate formation of blood cells

red and white

platelets

• 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

• Vial MUST NOT be shaken
• Should not be mixed other drugs
• Should not be frozen

Now is given SubQ

Hemat g-factor --> WBC's

• uses= elevation of neutrophil counts in pt.s w/ cancer
•   = Tx of severe chronic nuetropenia

SE= bone pain

• (Interleukin-11)
• Thrombopoietic g-factor  --> platelets

Uses= used w/ myelosuppressive chemo to minimize thrombocytopenia

• SE= fluid retention
•  = cardiac dysrrhythmias
•  = allergic rxns

• 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