Chemotherapeutic Agents

1. Chemotherapeutic Agents Munir Gharaibeh, MD, PhD, MHPE School of Medicine The University of Jordan mgharaib@ju.edu.jo Munir Gharaibeh MD, PhD, MHPE

2. Antifungal Agents Nystatin • Binds to the wall of the fungus (Candida). • Poorly absorbed, very toxic if given IV. • Given to work locally: • GIT: tablets, not absorbed. • Oral cavity: solution. • Vaginal: cream or suppository Munir Gharaibeh MD, PhD, MHPE

3. Antifungal Agents Miconazole Ketokonazole Itraconazole • Modern drugs for fungal infections, widely used. • Good for Candida and other fungi. • Given locally and systemically. • Can cause liver damage. Munir Gharaibeh MD, PhD, MHPE

4. Antifungal Agents Griseofulvin • Used for chronic nail and skin infections. • Slow acting and usually used for long periods. • Can cause GIT upset and drug interactions. Munir Gharaibeh MD, PhD, MHPE

5. Antifungal Agents Amphotericin B • Used for systemic serious fungal infections, after cancer chemotherapy. • Given by slow IV infusion, should be closely monitored. • Very toxic immediate reactions: N, V, Fever, Renal damage. Munir Gharaibeh MD, PhD, MHPE

6. Metronidazole • Very important antimicrobial, widely used. • Amebiasis: Entameba histolytica. • Trichomoliasis: caused by T. vaginalis. • Giardiasis: caused by G. lamblia. • Anaerobic bacterial infection: dental infections, prophylaxis before surgery. • Can be used by all routes of administration, and by all ages, except by pregnant ladies. • Toxicity: • Nausea, metallic taste. • Headache. • Skin rashes. • Teratogenic. Munir Gharaibeh MD, PhD, MHPE

7. Antiviral Agents • Viral disease are self limiting, so no need for Rx. • Viruses live intracellular, so drugs should be able to enter the human cells. Aciclovir • Wide spectrum antiviral agent. • Herpes virus. • Available as oral tablets, IV injections, eye drops and ointment, or as a cream. • In Varicella= Chicken Pox, use is restricted to immunocompromised patients. • Side Effects: N, V, Skin rashes. Munir Gharaibeh MD, PhD, MHPE

8. Anti HIV Agents Zidovudine • Inhibits viral DNA production. • Causes N, V, muscle pain, and bone marrow suppression. Indinavir • Protease inhibitor. • Causes N, V, Diarrhea, Renal stone formation. Munir Gharaibeh MD, PhD, MHPE

9. Interferones • Viral infection gives immunity for variable duration. • Natural substances produced by virally infected cells. • Modify the immune response to increase resistance to viral infection, and control growth of the virus. • Obtained in small amounts form donor WBCs. • Nowadays, obtained commercially by recombinant DNA technology. • Used in Hepatitis C, and some leukemias. • Can cause nausea, fever, and malaise (flu-like symptoms). Munir Gharaibeh MD, PhD, MHPE

10. Life Cycle of Malaria Parasites Munir Gharaibeh MD, PhD, MHPE

11. Antimalarial Drugs • Chloroquine • Most useful agent to terminate an acute attack. • Available as oral, IV, and IM preparation. • Resistance develops. • Causes N, headache, and is teratogenic. • Quinine: • Oldest drug, from Cinchona tree. • Many actions • Toxic • Still used, no resistance to its action. Munir Gharaibeh MD, PhD, MHPE

12. Antimalarial Drugs • Chloroquine • Quinine: • Artemisinin: • New drug, from Sweet wormwood, الشيح • Doxycycline • Pyrimethamine Munir Gharaibeh MD, PhD, MHPE

13. Anthelmintics • Mebendazole”Vermox”: • Widely used, wide spectrum, safe drug. • Threadworm: Enterobius vermicularis, simple teratment: single dose, can be repeated after 3 weeks. • Hockworm: Ankylostomiasis: 2tablets*3days. • Roundworm: Ascaris lumbricoidis • Piperazine: • Prolonged treatment and might need a purgative. • Niclosomide: • Tapeworm: two doses on an empty stomach, also followed by a purgative. Munir Gharaibeh MD, PhD, MHPE

14. Cancer Chemotherapy • Cells, normal and cancerous, pass through a series of phases during its life. • Cancer cells in the Go will be in the resting phase, and they will be least sensitive to chemotherapy. • Cytotoxic drugs interfere with DNA or RNA and thus have profound effects on cells, normal and malignant. Munir Gharaibeh MD, PhD, MHPE

15. Munir Gharaibeh MD, PhD, MHPE

16. The Cell Cycle and Cancer Many of the effective anticancer drugs exert their action on cells traversing the cell cycle and are called cell cycle–specific (CCS) drugs. A second group of agents called cell cycle–nonspecific (CCNS) drugs can kill tumor cells whether they are cycling or resting in the G0 compartment. CCNS drugs can kill both G0 and cycling cells (although cycling cells are more sensitive). Munir Gharaibeh MD, PhD, MHPE

17. Cancer Chemotherapy • “Magic bullet” drug, is a dream that did not materialize yet. • Cytotoxic drugs are given in repeated courses arranged so that the recovery of normal cells can occur, but little recovery of cancer cells is possible. Munir Gharaibeh MD, PhD, MHPE

18. The log-kill hypothesis. Relationship of tumor cell number to time of diagnosis, symptoms, treatment, and survival Munir Gharaibeh MD, PhD, MHPE

19. Toxicity of Cancer Chemotherapy • Cells of the bone marrow, the lymphatic system, and the lining of the intestinal tract are very sensitive to cytotoxic drug effects. • Almost all anticancer drugs cause toxicity, e.g. : • Bone marrow suppression: Nitrogen mustard. • Immunosuppression: Methotrexate. • Neuropathy: Vincristine. • Cardiotoxicity: Doxorubicin(Adriamycin). Munir Gharaibeh MD, PhD, MHPE

20. Combination Therapy • Anticancer drugs are usually given in combinations to: • Increase effectiveness. • Reduce the toxicity. Munir Gharaibeh MD, PhD, MHPE

21. Adjuvant(مساعد) Therapy • Although surgery can theoretically eradicate many well circumscribed tumors, cancer chemotherapy is given as an adjuvant to surgery, even if there is no evidence of metastasis. Munir Gharaibeh MD, PhD, MHPE

22. Palliative(مسكن) Therapy • Includes the non anticancer drugs given to cancer patients only to relieve the symptoms and prolong life, not to cure the cancer. Munir Gharaibeh MD, PhD, MHPE

23. Classes of Anticancer Drugs • Cytoxic drugs: • Alkylating Agents • Cytotoxic Antibiotics • Antimetabolites • Plant and Animal derived drugs • Sex Hormonse and Hormone Antagonists. • Immunomodulator drugs. Munir Gharaibeh MD, PhD, MHPE

24. Special Problems/Practical Points • Storage . • Preparation. • Administration. • Extravasation of injection. • Vomiting: • Lorazepam for anxiety. • Dexamethasone, Domperidone. • Ondansetron: 5HT3 antagonist. • Teratogenesis. • Bone Marrow suppression. • Immunosuppression leading to severe infection. Munir Gharaibeh MD, PhD, MHPE