Anti-neoplastic Drugs: Module 15

Question 1

Anti-neoplastic Drugs to learn:

Answer 1

• Alkylating drugs
• Anti-metabolite drugs
• Antibiotic anti-neoplastic drugs
• Hormonal anti-neoplastic drugs, hormone modulators
• Natural anti-neoplastic drugs
• Monoclonal antibodies
• Topoisomerase I inhibitors
• Targeted therapies
• Unclassified anti-neoplastic drugs

Question 2

Alkylating drugs:

• Produce:
• Are cell cycle-phase:
  - Bifunctional alkylation:
  - Monofunctional alkylation:

Answer 2

• Produce anti-neoplastic effects by damaging DNA so DNA replication halted
• Are cell cycle-phase non-specific (actions take place at any phase of cell cycle)
• Bifunctional alkylation: drug inserted between two base pairs
• Monofunctional alkylation: drug separates one part of a pair from its partner.

Question 3

Anti-metabolite Drugs

-Structurally resemble:

     Folic acid analogues:
     Pyrimidine analogues:
     Purine analogues:

Answer 3

• Structurally resemble DNA base pairs; synthesize nucleic acids, proteins; are cell cycle-specific, affect cells actively synthesizing DNA (S phase-specific)
• Folic acid analogues: methotrexate
• Pyrimidine analogues: floxuridine
• Purine analogues: mercaptopurine

Question 4

Anti-metabolite drugs adverse effects

• Methotrexate adverse effects include:
• Kidney toxicity with?

Seizures, paralysis, and death with?

Answer 4

Bone marrow suppression, stomatitis, pulmonary toxicity, skin reactions.

• Kidney toxicity with high doses
• Seizures, paralysis, and death with intrathecal administration (through dura into subarachnoid space)

Question 5

Antibiotic Anti-neoplastics:

• Anti-microbial products that produce tumoricidal (tumor-destroying) effects by?
• Mechanism:
• Adverse effects:

Answer 5

• Anti-microbial products that produce tumoricidal (tumor-destroying) effects by binding DNA; inhibit cellular processes of normal, malignant cells [doxorubicin, dactinomycin]
• Mechanism: physically separate adjacent base pairs of DNA molecule —-results in mutant DNA molecule.
• Adverse effects: primarily bone marrow suppression.

Question 6

Hormonal Anti-neoplastics & Modulators

-Prescribed to:

-Effective against:
=Aromatase inhibitors

=Anti-estrogens:

=Androgens:

=Anti-androgens:

=Progestins:

=Gonadotropin-releasing hormone analogues:

Answer 6

• Prescribed to alter growth of malignant neoplasms, or manage;treat physiologic effects
• Effective against hormone-dependent tumors

=Aromatase inhibitors: prevent androgens—estrogen in post-menopausal women, thereby blocking estrogen activating cancer cells; induce estrogen deprivation, bone thinning, osteoporosis.

=Anti-estrogens: bind estrogen receptors, blocking estrogen action [tamoxifen]

=Androgens: synthetic drivatives of testosterone; can reduce prolactin receptors or bind competitively

=Anti-adrogens: inhibit androgen uptake or prevent androgen binding [flutamide]

=Progestins: cytostatic (keep cells from multiplying)

=Gonadotropin-releasing hormone analogues: to treat prostate cancer; increase luteinizing hormone—-increases testosterone.

Question 7

Natural Anti-neoplastics:

• Vinca alkaloids:
• Podophyllotoxins:
• Adverse effects:

Answer 7

• natural products
• Vinca alkaloids: nitrogenous bases from periwinkle plant; cell cycle-specific for M phase (mitosis); disrupt microtubule function [vinblastine, vincristine, vinorelbine]
• Podophyllotoxins: glycosides; cell cycle-specific (G2 and late S phases) [etoposide]
• Adverse Effects: nausea, vomiting, stomatitis, bone marrow suppression, hair loss.

Question 8

.Monoclonal Antibodies are:

Cause tumor death:

• Induce:
• Recruit:
• Deliver:

Adverse effects:

Answer 8

Large protein structures; bind target receptors, cancer cells [gemtuzumab ozogamicin, rituxmab, alemtuzumab]

• Induce programmed cell death
• Recruit immune system to attack cancer cells
• Deliver toxic chemotherapy drugs or radiation to tumor site.

Adverse effects: infusion-related reactions that are occasionally fatal (fever, chills, shortness of breath, low blood pressure, anaphylaxis)

Question 9

Topoisomerase I Inhibitors

• Inhibit ___________ that mediates relaxation of _______ DNA —–prevents _________—-causes DNA strand ______——DNA ______ impaired [irinotecan, topotecan]
• Adverse effects:

Answer 9

• Inhibit topoisomerase I enzyme that mediates relaxation of supercoiled DNA—- prevents DNA resealing—-causes DNA strand breaks—-DNA synthesis impaired [irinotecan, topotecan]
• Adverse effects: diarrhea, abdominal cramps, hair loss, increased sweating/saliva, nausea, vomiting, loss of appetite.

Question 10

Targeted therapies:

Adverse effects:

Answer 10

• Target proteins associated with growth patterns of specific types of cancers [bortezomib, gefitinib, imatinib]
• Adverse effects: avoid becoming pregnant as can cause fetal harm/death.

Question 11

Unclassified Anti-neoplastics

• Arsenic trioxide:
• Asparaginases:
• Procarbazine:
• Hydroxyurea:
• Interferons:
• Paclitaxel, docetaxel:

Answer 11

• Arsenic trioxide: causes DNA fragmentation
• Asparaginases: degrade asparagine—tumor cells die
• Procarbazine: causes chromosomal damage; suppresses mitosis; inhibits DNA, RNA, protein synthesis
• Hydroxyurea: inhibits enzyme for DNA synthesis
• Interferons: bind receptors initiating intracellular events
• Paclitaxel, docetaxel: disrupt microtubule network essential for mitosis and cellular function.