Pharmacology Third Year

1. ANTICANCER DRUGS

2. Introduction
Cancer
Disease of cells characterized by progressive, abnormal &
uncontrolled proliferation of tissues.
Both normal as well as cancerous cells must pass through the
following phases of cell cycle.
1. G1 phase: Synthesis of enzymes and other cellular components
needed for DNA synthesis.
2. Synthetic phase: DNA synthesis takes place
3. G2 phase: Synthesis of cellular components for mitosis
(proteins and RNA synthesis)
4. M phase: Mitotic cell division takes place
5. G0 phase: Cells stop dividing temporarily or permanently.

4. Anticancer drugs
Cell cycle-specific drugs : act mainly on dividing cells
• Antimetabolites: Methotrexate, 5 Fluorouracil
• Antibiotic: Bleomycin
• Vinca alkaloids: Vinblastine, vincristine
Cell cycle non-specific drugs: act on dividing as well as resting
cells
• Alkylating agents: Cyclophosphamide, Busulphan
• Antibiotics: Doxorubicin, daunorubicin,
• Metal complexes: Cisplatin
Hormonal agents
• Glucocorticoids – Prednisone
• Gonadal hormone antagonists – Tamoxifen, Flutamide

5. METHOTREXATE
Mech of action:
• Inhibits dihydrofolate reductase ↓ nucleic acid synthesis.
Uses:
• Acute leukemias, Non-Hodgkin’s lymphoma, Breast cancer,
• As Immunosuppresant - Rheumatoid arthritis, Inflammatory
bowel diseases
Adv effects
• Mucositis, Myelotoxicity, hepatotoxicity & pulmonary fibrosis
- prevented by Leucovorin (folinic acid)

6. FLUOROURACIL (5-FU)
Mech of action:
• Converted in cells to 5 fluoro-2-deoxyuridine-5’-
monophosphate (5-dUMP) which inhibits thymidylate
synthase and leads to ‘thymineless’ death of cells.
Uses:
• Bladder, breast, colon cancers.
Adv effects: GI distress, myelotoxicity, Alopecia

7. Uses:
• Non Hodgkin’s lymphoma, breast & ovarian cancers
• As immunosuppressant - Rheumatoid arthritis, nephrotic
syndrome & organ transplantation
Adv effects:
• Hemorrhagic cystitis
– prevented by vigorous hydration & MESNA –Sodium mercaptoethane
sulfonate
• Myelosuppression
CYCLOPHOSPHAMIDE

8. CISPLATIN
Uses: Testicular CA & cancers of bladder, lung and ovary
Adv effects
• Nephrotoxicity,
• Vomiting ( prevented by Ondansetron),
• Myelotoxicity
Carboplatin is less nephrotoxic, has greater myelotoxicity.

9. Vinca alkaloids
Mech of action :
• Bind to tubulin & prevent its polymerization into microtubules
thereby block the formation of mitotic spindles
Uses:
• Vincristine: Acute leukemias, lymphomas, Wilm’s tumour,
• Vinblastine: Testicular CA, lymphomas, neuroblastoma,
Adv effects :
• Myelotoxicity (Vinblastine)
• Neurotoxicity (Vincristine )

10. ANTIBIOTICS
DOXORUBICIN & DAUNORUBICIN
– Inhibit topoisomerase II & generate free radicals causing DNA damage.
Uses :
• Doxorubicin -Hodgkin’s
lymphoma, breast, endometrial, lung, ovarian, & thyroid
cancers.
• Daunorubicin – Acute leukemias
Toxicity :
• Cardiotoxicity (prevented by Dexrazoxane)
• Myelotoxicity,

11. HORMONAL AGENTS
TAMOXIFEN
• Antiestrogenic action
Uses : Breast carcinoma
Adv effects:
• Endometrial hyperplasia
• Thromboembolism,
FLUTAMIDE
• Androgen receptor antagonist
Use: Prostatic cancer
Adv effects: Gynecomastia, hot flushes

12. Specific toxicities
• Haemorrhagic cystitis : Cyclophosphamide
• Megaloblastic anaemia : Methotrexate
• Nephrotoxicity : Cisplatin
• Neuropathy : Vincristine
• Pulmonary fibrosis & pigmentation of skin : Busulphan &
Bleomycin
• Cardiotoxicity : Doxorubicin & Daunorubicin
• Severe vomiting : Cisplatin, Doxorubicin
• Extravasation : vesicant drugs like Doxorubicin, Vinblastine

13. Management of Cancer Chemotherapy induced
Adverse drug reactions
• Nausea & Vomiting : Ondansetron
• Bone marrow Suppression: Filgrastim (CSF)
• Methotrexate toxicity: Leucovorin
• Cyclophosphamide toxicity : MESNa
• Cisplatin toxicity : Amifostine
• Doxorubicin toxicity: Dexrazoxane
• Hyperuricemia (rapid tumor cell lysis): Allopurinol