Cell cycle non-specific drugs:
• Alkylating agents (FMGE Dec 2020)
• Platinum compounds
Alkylating agents | Drugs |
Nitrogen mustard | • Mechlorethamine (Mustin chloride) • Cyclophosphamide • Melphalan • Cholrambucil • Busulfan |
Nitrosoureas | Bifunctional alkylating agents |
Miscellaneous | • Temozolomide • Dacarbazine • Procarbazine • Thiotepa • Altretamine • Trabectedin • Lubinectedin |
Platinum compounds-
• Cisplatin
• Carboplatin
• Oxaliplatin
• Nedaplatin
Platinum-induced nephropathy:
• Platinum compounds cause direct toxicity to proximal tubule (S3 segment), leads to acute tubular necrosis (ATN).
Platinum drugs are filtered and actively taken up by proximal tubular cells
↓
High intracellular concentration
↓
Attach to the N7 guanine position on DNA
↓
Crosslinking of DNA
↓
DNA damage
Lab findings-
• Persistent hypomagnesemia (very characteristic)
• ± Hypokalemia
• Mild proteinuria
• ↑ Creatinine
Antidote: Amifostine (It’s a nephroprotector)
