Cancer Flashcards
Goal of chemo
Goal is to cause a lethal cytotoxic event or apoptosis in the cancer cell.
Dose response curve and TI for cancer drugs
Steep dose response curve and small TI
What cells are usually more susceptible to cancer drugs?
Rapidly dividing cells. Cells in G0 may survive.
When are cell cycle specific drugs effective?
For high growth fraction malignancies
When are cell cycle non specific drugs effective?
For low and high growth fraction malignancies
How does the growth rate of tumors change over time
Growth rate is initially rapid, but slows as it increases in size due to decrease in resources. Surgery/radiation can shift remaining cells to become active and then chemo can be more effective.
How can cancer drugs cause toxicity to normal cells undergoing rapid proliferation
Cheek and mouth ulcers
Bone marrow depression
GI mucosa
Hair follicles
Tx induced tumor
Most are mutagenic. Neoplasms can arise 10 or more years after original cancer was cured.
Especially probable with alkylating agents
What cancer drug class is most likely to cause a future tumor
Alkylating agents.
Antimetabolites MOA
Structurally related to normal compounds in the cell. Interferes with availability of normal purine or pyrimidine nucleotides. Causes inhibition of synthesis.
Maximal effects during S phase.
Cytarabine
MOA
Admin
Adverse effects
Enters cell and inhibits DNA pol.
Not effective oral. Give IV. Penetrates CNS.
GI, myelosuppression, hepatic disfunction, chemical conjunctivitis at high doses
5-FU
MOA
Given along with?
MOA: Enters cell through carrier medicated system.
Forms molecular complex that deprives cell of thymidine. DNA synthesis stops.
Given along with leucovorin. Booster. Helps 5-FU work longer
Given IV typically bc GI toxicity. Also given topically for skin cancer and prevention of scar tissue. Used in some ocular surgeries. Penetrates CNS
What drug can be given topically to prevent scar tissue formation and used in some ocular surgeries.
5-FU
Adverse effects of 5-FU (Systemic vs topical)
Systemic: Gi probs, alopecia, ulceration, BM depression, anorexia
Topical: not many
Mercaptopurine MOA
3 prong:
Nucleotide formation. Pretends to be purine base.
Incorporated into nucleic acid
Inhibit protein synthesis
**Thioguanine has similar
Which two antimetabolites have a 3 prong MOA
Mercaptopurine and thioguanine
Mercaptopurine
pharmacokinetics
adverse effects
Incomplete absorption on oral admin. Low bioavailability due to 1st pass. But still given orally lol weird
BM depression, jaundice, GI probs.
Thioguanine MOA
3 prong:
Nucleotide formation. Pretends to be purine base.
Incorporated into nucleic acid
Inhibit protein synthesis
Same as mercaptopurine
Adverse effects of thioguanine
Dose related BM depression. Risk of liver toxicity with long term use. Not used for maintenance therapy.
methotrexate MOA
Antagonist for an enzyme that creates folic acid. Required for cell response. Results can be reversed by thousand fold by dihydrofolate or leucovorin (similar structure to folic acid)
What cells are resistant to Methotrexate
Non proliferating cells are resistant.
Methotrexate results can be reversed thousand fold by
dihydrofolate or leucovorin (similar structure to folic acid)
other than cancer, what could you take methotrexate for?
Low doses to treat some inflammation diseases. RA, chrons, psoriasis
Methotrexate admin
Oral, IM, and IV.
Pt must remain hydrated to prevent renal toxicity: crystalluria.
Methotrexate adverse effects
GI, toxicities in renewing tissues, renal damage if unhydrated, liver
Pulmonary toxicity in children
Avoid in pregnancy= abortion.
What antimetabolite should you avoid in pregnancy
Methotrexate
MOA of anti-tumor antibiotics
Binds DNA and prevents mRNA synthesis. Leads to free radicals that are cytotoxic.
Dactinomycin MOA Admin Excretion Adverse effects
MOA: interferes with RNA pol
Pharmacokinetics: IV admin. No CNS penetration.
Bile excretion.
adverse effects: BM suppression, immunosuppression, GI, sensitizes pt to radiation (inflammation may occur)
Doxorubican pharmacokinestics
MUST be given by IV. Inactivated by GI tract.
Extravasation of drug may cause necrosis.
Extensive liver metabolism
Excreted by bile. Dose adjust in people with liver probs
Veins near IV may be dark red and red urine.
Doxorubican adverse effects
Cardiotoxicity- irreversible. Dose dependent.
BM depression
GI
Severe alopecia.
Bleomycin primarily used to tx __ cancer. Not used for ____ cancer
Testicular
Not used for liver or spleen tumors (enzymes there will inactivate drug)
Bleomycin admin and adverse effects
Admin: Sub q, IM, IV
Adverse: pulmonary toxicity, alopecia, hypertrophic and hyperpigmentation of skin.
Alkylating agents MOA
Adds carbon chains to DNA to alter structure and function.
*** ALL are mutagenic and carcinogenic. May cause secondary malignancies in the future.
Alkylating agents for slow or fast growing tumors
Slow growing tumors. Not effective against fast.
Admin of mAbs
Injection only.
MOA of mAbs
Bind and induce apoptosis, inhibit growth, or interfere with cellular function.
Could also deliver toxin
Rituxumab tx
Lymphomas and leukemias. Binds to sites on B lymphocytes and recruits immune effectors to kill.
Trastuzumab tx
Breast cancer Tx. Arrests cells in GI. Reduces rate of relapse by 50% in the first year.
Bevacizumab tx
Anti VEGF
Decreases O2 in tumor cells. Also used in retinal neovascular disease.
MOA and admin of cisplatin, carboplatin, and oxiplatin
Similar to alkylating agents= cross linking DNA
IV admin
Side effects of cisplatin
Cisplatin: Vomiting, nephrotoxicity, ototoxicity
Side effects of carboplatin and oxiplatin
Mild nausea and myelosuppression (decreased blood cell formation)
3 interferon types
Alpha: Leukocytic
Beta: produced by connective tissue fibroblasts
Gamma: produced by T cells
Interferon alpha 2a and 2b used to tx
MOA and admin
Neoplastic disease.
MOA: binding of interferons produces intracellular reactions. Increases immune response of macrophage, T and B cells. Suppresses growth and tumor proliferation,
IM or subQ injection. Minimal liver met.
