Antineoplastic Drugs Flashcards
What are 3 Characteristics of cancer cells?
- persistent proliferation
- Grow invasively; beyond typical borders
- cells form metastases; they spread to remote sites through lymph or blood vessels.
Strategy 1 for antineoplastic drug treatment
Treatment of choice for disseminated, metastatic cancer
Strategy 2 for antineoplastic drug treatment
Adjuvant to surgery or radiation for solid tumors
Strategy 3 for antineoplastic drug treatment
Smart drugs are chemically linked to antibodies that target only cells with specific tumor antigen.
Problem is cancer cells mutate and antigen changes.
Strategy 4 for antineoplastic drug treatment
Rounds of treatment:
therapy_recovery_therapy…
often 8 rounds.
Cancer Immunotherapy
Highly selective, perhaps permanent, less toxic.
Only a fraction of patients respond on a subset of cancers.
Much research ongoing.
Monoclonal antibodies
Synthetic immune proteins that can be designed to attack a specific component of a cancer cell
Cancer vaccines
substances designed to trigger an immune response against a disease.
“Dream” for fighting cancer
Non-specific immunotherapy
General immune system stimulation to increase anti cancer activity.
Cytokines like interleukins and interferons
Categories of antineoplastic drugs
- Cytotoxic
2. Non-cytotoxic
Cytotoxic Drugs
Cause cellular injury.
Often called chemotherapy.
Administered in cycles.
Non-cytotoxic Drugs
Drugs that don’t cause cellular injury.
Immunotherapy, hormone therapy…
How does endocrine manipulation help to fight cancer?
20% male cancer and 40% female cancers grow in response to sex steroids.
One strategy is to interfere with hormones that control cell growth.
Leuprolide
A long-acting gonadotropin releasing hormone (GnRH) receptor agonist.
Suppresses release of LH and FSH, reducing production of estrogens and androgens.
Treats hormone-dependent prostate and breast CA
Anastrozole
aromatase inhibitor;
used to treat estrogen-positive breast CA in post menopausal patients;
Blocks synthesis of estradiol
Estradiol
Active sex steroid produced by ovaries (small amount by testes)
Exemestane (Aromasin)
aromatase inhibitor (new); Prevents development of breast CA in select risk groups; Prophylactic
Cholesterol
Precursor for all steroid hormones
Aromatase Inhibitor
Blocks production of estradiol in ovaries, controlling hormone dependent CA growth.
Hormone Receptor Antagonists
- Tamoxifen
2. Flutamide
Tamoxifen
an estrogen receptor antagonist in mammary tissue
Flutamide
an androgen receptor antagonist (testosterone)
Hormone Receptor Agonist
Prednisone
Prednisone
A cortisol receptor agonist that induces leukocyte apoptosis; activates an inhibitory pathway that prevents DNA replication
Inhibition of DNA Replication
- Cyclophosamide
- Cisplatin
Both bind to DNA and inhibit replication.
Both are Cytotoxic
Cyclophosamide
Bind to DNA and inhibit replication.
Cytotoxic
Cisplatin
Bind to DNA and inhibit replication.
Cytotoxic;
Renal toxic.
Inhibition of RNA and Protein Synthesis
Actinomycin D (an antibiotic) binds to DNA and inhibits the catalytic activity of RNA polymerase. Cytotoxic
Actinomycin D
An antibiotic that binds to DNA and inhibits the catalytic activity of RNA polymerase.
Cytotoxic
Asparaginase
catalyzes conversion of asparagine to aspartate; reduces blood levels of AA asparagine, essential for some leukemias.
Not Cytotoxic.
Antimetabolites
Inhibit enzymes that produce intermediates needed for CA cell division Cytotoxic. 1. Methotrexate 2. Mercaptopurine 3. 5-flurouracil (5-FU)
Methotrexate
an antimetabolite.
inhibits the enzyme that catalyzes production of folic acid
Mercaptopurine
An antimetabolite.
Inhibits enzymes used in the production of purines
5-flurouracil (5-FU)
An antimetabolite.
Inhibits enzymes used in production of pyrimidines
Inhibitors of spindle fiber formation
Cytotoxic
Blocks mitosis
1. Vincristine/vinblastine
2. Taxol
Vincristine/Vinblastine
Inhibitors of Spindle fiber formation.
Cytotoxic
They inhibit microtubule polymerization
Taxol
Inhibitor of spindle fiber formation.
Cytotoxic
Stimulates uncontrolled polymerization of microtubules
Oncogenes
Control CA cell growth;
- Control localized production of growth factors (GF) and cytokines; EGF, IGF
- Signal transduction events triggered by GF receptors; Tyrosine Kinase (TK)
- angiogenesis
- DNA Repair
Herceptin
Interferes with production of local Growth factors.
Treats breast CA
TK inhibitors
blocks signal transduction
Treats some myelogenous leukemia
VEGF (Vascular endothelial GF) inhibitors
Monoclonal antibody inhibiting angiogenesis
Treats colorectal CA
PARP (Poly ADP-ribose polymerase) Inhibitors
Prevent repair of DNA repair mechanisms.
Treats Non-small cell lung carcinoma
Combination chemotherapy
CMF: cyclophosamide, methotrexate, and fluorouracil.
Advantages:
1. Each drug’s dose is reduced, thus reducing organ-specific toxicity
2. Inhibits cell division at more than one site making them more effective.
3. Helps prevents resistance.
Pharmacotoxicology
Nonselective on cell division
Therapeutic index is near 1
Toxic effects of chemotherapeutic agents
Bone marrow suppression causes:
- anemia. Treated with EPO.
- Leukopenia (low WBCs). Treated with a growth hormone, GMCSF.
2nd Toxic effect of Chemotherapeutic agents
Suppression of GI tract cell division; walls become thin, causing ulcers, N/V.
Treated with Ondansetron, a serotonin receptor antagonist and Cimetidine, a H2 receptor antagonist.
3rd Toxic effect of Chemotherapeutic agents
alopecia (temporary)
4th Toxic effect of Chemotherapeutic agents
Sterility;
Reduces sperm counts and can induce premature menopause
How do CA cells develop drug resistance?
- Increased production of conjugation enzymes, increasing metabolism and elimination
- Increased production of p-glycoproteins to transport drugs out of cells. (Vincristine)
- Gene amplification: Increase the production of the inhibited enzyme. Increase folic acid production in response to methotrexate.
