Alkylating Cytostatics

Question 1

General characteristics

Answer 1

• Non phase specific. Covalent bonds with nucleophilic substances (esp. Guanine) -> crosslinks -> inhib. Replication & transcription.
• Leukemia’s, Lymphomas, Multiple myelomas, Sarcomas.
• AE: BM suppression, Alopecia, GIT disturbances, Impaired gametogenesis.
• Cytotoxic & mutagenic -> risk of Acute Leukemia

Question 2

Melphalan

Answer 2

• Nitrogen Mustard.
• Releases 2 Cl- to form reactive compound
• Multiple Myeloma. Po/IV.
• AE: Nausea, vomiting, Oral ulcers, BM suppression.

Question 3

Cyclophosphamide, Ifosfamide

Answer 3

• Prodrugs -> CYP450 -> phosphoramide mustard that interact with DNA.
• Broad spectrum: Burkitts lymphoma, NHL, Breast cancer. Also in Nephrotic syndrome and RA.
• AE: Myelosuppression, Hemorrhagic cystitis, Neurotoxicity

Question 4

Lomustine, Carmustine

Answer 4

• Can cross BBB -> Brain & meningeal tumors.

- AE: Severe cumulative myelosuppression

Question 5

Busulfan

Answer 5

• BM selective. Decreases granulocytes+thrombocytes in low doses, RBC in high doses.
• Chronic granulocytic leukemia
• AE: Pulmonary fibrosis