University:
University of North Carolina at Chapel Hill
Course:
NURS 312 | Pharmacology
Academic year:

2020
Views:

298

Pages:

1
Author:

Shyanne Johnson

2.1 – “Alkylat “Alkylating ing Odyssey”: Cyc Cyclophosphamide, lophosphamide, Ifo Ifosfamide, sfamide, Busulfan, Nitr Nitrosoureas osoureas • Recall that an alkyl group is a molecular group with the formula -CnH2n+1. Alkylating agents add an alkyl group to nucleotide bases, most commonly to the guanine N7. This leads to the cross-linking of DNA strands, which causes DNA damage, interferes with DNA replication, and ultimately results in apoptosis. • Alkylating agents can act any point during the cell cycle. • Cyclophosphamide o The most commonly used alkylating agent (Cyclops Polyphemus). Like all of the alkylating agents, cross-links DNA (ankle chains). Once activated, forms a nitrogen mustard (similar to mustard gas). o Related agents are ifosfamide, melphalan, chlorambucil, mechlorethamine. o Activated by CYP450 in the liver (chariot with the CYP450 tag plate). o Indications ▪ variety of different cancers, both hematologic & solid tumors (sail torn through the image of a crab). ▪ Uniquely among the alkylating agents, used for autoimmune conditions (red lanterns look like immunoglobulins and are closer to the Cyclops than any of the other pharm avatars). o Toxicities ▪ Myelosuppression (bone club) ▪ An alternative metabolism pathway results in the toxic metabolite acrolein, responsible for several of the adverse effects of this drug ▪ Hemorrhagic cystitis caused by acrolein (red Greco-Roman fountain). Can preventatively administer mesna (“Maze”-na), the sulfhydryl group of which will bind acrolein and prevent the damage. ▪ ↑risk of bladder cancer (gold crab at the level of the bladder) ▪ SIADH & consequent hyponatremia (ADH bucket on cyclops head). Resultant encephalopathy in 10-30% of patients if not controlled. Worsened with hyperhydration during chemo, for unknown reasons. ▪ Infertility (M & F) & premature menopause (F) (dried up ovarian tree) ▪ Ifosfamide: Fanconi syndrome • Busulfan o Used for bone marrow ablation to prepare for BM transplant (beautiful sirens surrounded by cracked bones with bloody marrow exposed). Does not require bioactivation. o Toxicities ▪ Nigh universal severe myelosuppression (hence use as ablative) ▪ Lung toxicity, including acute ling injury, interstitial fibrosis, alveolar hemorrhage (sirens wearing golden chest plates with lung outlines) ▪ Hyperpigmentation – “busulfan tan” (dark-skinned sirens) • Nitrosoureas o include Carmustine, Lomustine, Streptozocin (mustang centaurs – sounds like -mustine; zebra striped centaur for streptozotocin). o Cross BBB, enabling treatment of CNS tumors including glioblastoma multiforme. o Toxicities ▪ CNS toxicities, including convulsions, dizziness, ataxia (centaur stumbling around clutching head) ▪ Myelosuppression ▪ Rarely, pulmonary fibrosis