Conventional cytotoxic drugs Flashcards
What are the key characteristics of cancer cells?
1.Growth not subject to normal 2.spatial restrictions.
3.Local invasiveness.
4.Tendency to metastasize.
5.Telomerase expression.
6.Less differentiated morphology.
7.Tendency to retain some 8.characteristics of the tissue of origin.
What are the different classifications of tumors by tissue type?
- Carcinomas: Malignant growths from epithelial cells.
- Sarcomas: Malignant growths from muscle or connective tissue.
3.Carcinoma in situ: Pre invasive stage limited to epithelial cells of origin. - Hematologic malignancies: Leukemias and lymphomas.
What are the main cancer treatment options?
*Surgery and Radiotherapy
*Cytotoxic chemotherapy
*Endocrine therapy
*Immunotherapy
*Biological or targeted therapy
What is adjuvant therapy in cancer treatment?
Treatment administered after the main treatment to lower the risk of cancer recurrence, such as chemotherapy, radiation, or hormone therapy.
What is neo-adjuvant therapy?
Treatment given before the main treatment to reduce tumor mass, such as chemotherapy before surgery or radiation.
What is the role of alkylating agents in chemotherapy?
Alkylating agents prevent cell division and replication by damaging DNA. They are cell cycle phase non-specific.
Alkylating Agents: MOA
*Attach an alkyl group to DNA, primarily at the 7 nitrogen (N7) group of guanine.
*Cross-linking DNA strands, mispairing nucleotides, and causing strand breakage.
*Results in cytotoxic effects, preventing cell replication and transcription.
Alkylating Agents: Side Effects?
*Myelosuppression
*Hemorrhagic cystitis (e.g., cyclophosphamide)
*Gastrointestinal toxicity (nausea, vomiting, diarrhea)
*Alopecia
*Cardiotoxicity (at high doses)
*Reproductive toxicity (infertility, premature menopause)
*Secondary malignancies
Cyclophosphamide: MOA
*Pro-drug activated by P450 into 4-hydroxycyclophosphamide and aldophosphamide, which convert into phosphoramide mustard and acrolein.
*Phosphoramide mustard forms cross-links with DNA, particularly at the N7 position of guanine, leading to DNA strand breakage and apoptosis.
*Acrolein causes toxic side effects, particularly hemorrhagic cystitis.
Cisplatin: MOA
*Forms cross-links with purine bases on DNA, preventing DNA repair and leading to apoptosis.
*Platinum atom binds to DNA forming intrastrand and interstrand cross-links, causing DNA damage that inhibits replication and transcription.
Cisplatin: Side Effects
*Nephrotoxicity (mitigated by hydration and diuretics)
*Ototoxicity (permanent hearing loss)
*Neurotoxicity (peripheral neuropathy)
*Gastrointestinal toxicity (high emetic potential)
*Myelosuppression
*Electrolyte imbalance (low magnesium and potassium)
Antimetabolites: MOA
*Interfere with DNA and RNA synthesis by substituting normal building blocks.
*Target the S-phase of the cell cycle where DNA synthesis occurs.
Antimetabolites: Side Effects
*Myelosuppression
*Gastrointestinal toxicity
*Hepatotoxicity
*Mucositis
*Dermatologic reactions
Methotrexate (MTX): MOA
*Folic acid analog that inhibits dihydrofolate reductase.
*Prevents formation of tetrahydrofolate, essential for DNA synthesis.
*Leads to inhibition of purine and thymidylate synthesis, causing cell death.
Methotrexate (MTX): Side Effects
Myelosuppression
Gastrointestinal toxicity
Hepatotoxicity
Mucositis
Renal toxicity
