This document discusses various groups of anticancer drugs used in pharmacotherapy. It describes several classes of drugs including antibiotics like doxorubicin and bleomycin that work by damaging DNA. Other drug classes discussed are alkylating agents like cyclophosphamide that modify DNA, antimetabolites like methotrexate and gemcitabine that interfere with DNA synthesis, taxanes and vinca alkaloids that affect microtubule function during cell division, and hormonal therapies like tamoxifen and aromatase inhibitors. For each drug, a brief overview of mechanism of action, administration route, and common side effects is provided.

1. GROUP 8
PHARMACOTHERAPY OF ANTICANCER
DRUGS
MEMBERS
KACHONGIL LILIAN: BCM/K/0014/2021
JOHN KIBET CHERUIYOT: BCM/K/0504/2021
WICLIFF YEKO AMAYA: BCM/K/0019/2021
GATERU JOSEPH WAIHENYA: BCM/K/0010/2021

2. ANTIBIOTICS
• Antitumor antibiotics used to treat cancer.
• Examples: Dactinomycin, Doxorubicin, Daunorubicin, Bleomycin,
Mitomycin C.
• Produced by Streptomyces bacteria.
• Given intravenously or intramuscularly.
• Treats leukemia, lymphoma, sarcoma, breast cancer.

3. Dactinomycin
• Pharmacodynamics and Pharmacokinetics:
• Dactinomycin binds DNA, blocks RNA polymerase.
• Nonspecific to cell cycle.
• Poorly absorbed, given intravenously.
• Rapidly distributed, high concentrations in tissues.
• Crosses placenta, half-life of 36 hours.

4. Doxorubicin
• Derived from Streptomyces peucetius.
• Treats various cancers.
• Interferes with DNA and RNA synthesis.
• Administered intravenously in intervals.
• Adverse reactions include fatigue, nausea, vomiting.
• Extravasation can result in severe tissue damage.

5. Bleomycin
• Mechanism: DNA damage via metallobleomycin complexes.
• DNA damage: causes cell cycle arrest.
• DNA damage halts cell replication.
• Hydrolase: inhibits cytotoxicity in normal tissues.
• Pharmacokinetics: parenteral administration, high elimination rate.
• Adverse effects: pulmonary toxicity, hypersensitivity reactions.

6. Mitomycin C
• Is an antibiotic for cancer therapy.
• Cross-links DNA by CpG sequence.
• Non-specific for cell cycle phase.
• Administered via IV or intravesical.
• Bone marrow toxicity is common.
• May cause haemolytic uremic syndrome.

7. CAMPOTHECIN ANALOGUES
• Topotecan:
• It is derived from campothecin.
• Inhibits topoisomerase I to treat tumors.
• Halts cancer cell growth.
• IV administration, 2-3 hour half-life.
• Effects: nausea, vomiting, hair loss, diarrhea.

8. SERD
• Fulvestrant:
• Steroidal anti-estrogen for metastatic breast cancer.
• Synthetic estrogen receptor antagonist with SERD.
• Binds to estrogen receptor, makes it unstable.
• Low affinity agonist of estrogen receptor.
• Rapidly cleared by hepatobiliary route.
• Metabolism involves biotransformation pathways.

9. Alkylating Agents
• Alkylating agents modify DNA guanine base.
• DNA breakage leads to cell death.
• Alkylation of DNA is major interaction.
• Other cellular nucleophiles also affected.
• Long duration of action on DNA.
• Adverse effects affect rapidly growing tissues.

10. Examples;
• Mechlorethamine: Forms DNA crosslinks, inhibits synthesis.
• Indications: Hodgkin's & non-Hodgkin's Lymphoma.
• Adverse effects: Nausea, vomiting, depression of blood count.
• Chlorambucil: Forms DNA crosslinks, inhibits synthesis.
• Indications: Chronic Lymphocytic Leukemia & non-Hodgkin's
lymphoma.
• Adverse effects: Fever, chills, cough, hematuria.

11. Glucocorticoids
• Glucocorticoids induce haematological apoptosis.
• Anti-inflammatory effects manage cancer-related symptoms.
• Prophylaxis against anti-cancer therapy side effects.
• Counters immune-mediated effects in immunotherapy.
• Efficacious with cytotoxic chemotherapy for malignancies.
• Reduces pain, opioid use, and nausea.

12. Examples;
• Prednisone: reduces inflammation and immune response.
• Used to treat various types of cancer.
• Also used to treat cancer-related conditions.
• Dexamethasone: prevents chemotherapy side effects.
• Increases anti-tumor activity, inhibits tumor growth.
• Produces effects in anti-inflammation, anti-angiogenesis.

13. Miscellaneous compounds
• Hydroxyurea (HU): Acts as anti-leukemic and radiation sensitizer.
• HU inhibits enzyme for DNA biosynthesis.
• HU is specific to S phase.
• HU and irradiation cause synergistic antitumor effects.
• L-Asparaginase: Has dramatic antitumor activity.
• L-Asparaginase is purified from E. coli.

14. Mechanism of Action
• Normal tissues synthesize asparagine adequately.
• L-ASP hydrolyzes asparagine, leading to death.
• L-ASP are used with other agents.
• L-ASP deprives malignant cells of asparagine.
• Treats ALL and high-grade lymphomas.
• Other agents; methotrexate, doxorubicin, vincristine.

15. Aromatase Inhibitors
• Aromatase inhibitors block enzyme function.
• Enzyme converts androgens to estrogens.
• AIso suppress peripheral aromatase activity.
• AIso cause estrogen deprivation in women.
• Used to treat ER+ breast cancer.
• Effective in preventing tumor growth.

16. Anti-Androgens
• Anti-androgens inhibit binding to ARs.
• Nonsteroidal antiandrogens are taken orally.
• They inhibit ligand binding and AR translocation.
• Testosterone and dihydrotestosterone are affected.
• Anti-androgen monotherapy not first-line treatment.
• Not indicated for advanced prostate cancer.

17. Taxanes
Mechanism of Action
• Paclitaxel, docetaxel interfere with mitotic spindle.
• Prevent microtubule disassembly into tubulin monomers.
• They enhance polymerization of tubulin.
• Microtubules are stabilized and depolymerization prevented.
• Abnormal bundles of microtubles are produced.

18. Vinca alkaloids
Mechanism of action:
• Vinca alkaloids block mitotic spindle formation.
• Prevent assembly of tubulin dimers into microtubules.
• They act primarily in the M phase.
• Bind to ß-tubulin, inhibit tubulin polymerization.
• Leads to depolymerization of existing microtubules.
• Vincristine and Vinblastine for various cancers.

19. Antimetabolites
• Antimetabolites treat cancer with chemotherapy.
• They disrupt DNA and RNA synthesis.
• Antimetabolites mimic natural molecules.
• They substitute and disrupt synthesis.
• Faulty DNA and RNA lead to cell death.
• Antimetabolites selectively target cancer cells.

20. Methotrexate
• Methotrexate is a chemotherapy drug.
• It inhibits the DHFR enzyme.
• Methotrexate disrupts DNA and RNA synthesis.
• Methotrexate is given orally or injection.
• Side effects include anemia and fatigue.
• Also used to treat autoimmune diseases.

21. Gemcitabine
• Gemcitabine is a chemotherapy drug.
• It interferes with DNA synthesis process.
• Gemcitabine is given through injection.
• It mimics naturally occurring nucleotides.
• Side effects include fatigue, nausea, vomiting.
• May be used in combination therapy.

22. Cytarabine
• Cytarabine is a chemotherapy drug.
• It interferes with DNA synthesis process.
• Cytarabine is given through injection.
• It mimics naturally occurring nucleotides.
• Side effects include nausea and vomiting.
• May be used in combination therapy.

23. SERMs
• SERMs block estrogen receptors in cancer.
• They selectively bind to estrogen receptors.
• SERMs prevent growth of cancer cells.
• They may also benefit bone health.
• SERMs are taken orally.
• They may cause side effects.

24. Tamoxifen
• Tamoxifen is a SERM drug.
• It treats hormone receptor-positive breast cancer.
• Tamoxifen blocks estrogen receptors.
• It prevents growth and spread.
• Side effects may include hot flashes.
• Tamoxifen reduces cancer recurrence risk.

25. Raloxifene
• Raloxifene is a SERM drug.
• It treats and prevents osteoporosis.
• Raloxifene blocks estrogen receptors.
• It may reduce risk of breast cancer.
• Side effects include hot flashes.
• May be used with other treatments.

26. Toremifene
• Toremifene is a SERM drug.
• It treats and prevents breast cancer.
• Toremifene blocks estrogen receptors.
• It reduces the risk of recurrence.
• Side effects include hot flashes.
• It may be used with other treatments.

27. References
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biotherapy: Principles and practice. Wolters Kluwer Health.
• DeVita Jr, V. T., Lawrence, T. S., & Rosenberg, S. A. (2019). DeVita,
Hellman, and Rosenberg's cancer: principles & practice of oncology.
Wolters Kluwer.
• Katzung, B. G., Trevor, A. J., & Kruidering-Hall, M. (Eds.). (2020). Basic
& clinical pharmacology. McGraw Hill Professional.
• Grahame-Smith, D. G., & Aronson, J. K. (Eds.). (2020). Oxford textbook
of clinical pharmacology and drug therapy. Oxford University Press.