Mitotic inhibitors (M phase)

Mnemonic

两颗长杉树，围成一个门。门里有个蛋，从此不合成：两颗长杉树-长春碱、长春新碱、紫杉醇，门-门冬酰胺酶氨，蛋&合成-干扰蛋白质合成。

• Chris Christie closed lanes at George Washington Bridge
  • He is toxic
• Need to take taxi
• People boo

Alkylating agents (G1 phase)

Mnemonic

两安两素一铂金，破坏结构真闹心：两安-环磷酰胺、白消安（Busulfan），两素-丝裂霉素、博来霉素，一铂金-顺铂，破坏结构-直接破坏DNA 结构和功能药。

Detoxifying agents for antineoplastic treatment

• Platinum-based agents
  • Prevent Nephrotoxicity
  • Amifostine: free radical scavenger
  • IV saline: induces chloride diuresis → ↑ urine chloride concentration → ↓ cisplatin reactivity
• Oxazaphosphorines
  • Prevent Bladder toxicity
    • Hemorrhagic cystitis
    • Bladder carcinoma
  • Mesna (2-MErcaptoethane Sulfonate Na) and fluids
• Antifolates
  • Prevent
    • Myelosuppression
    • Mucositis
    • Hepatotoxicity
    • Pulmonary fibrosis
  • Leucovorin (folinic acid)
    • Precursor of tetrahydrofolate
    • Application 24 h after the administration of antifolates
• Anthracyclines
  • Prevent Cardiotoxicity
  • Dexrazoxane: iron chelating agent

Antimetabolites (S phase)

Mnemonic

1. 嘌呤核苷酸合成抑制剂：巯嘌呤（Azathioprine），嫖娼者，二流子
2. 胸苷酸合成酶抑制剂：氟尿嘧啶，胸前戴座佛
3. 二氢叶酸还原酶抑制剂：甲氨蝶呤，二甲
4. 核苷酸还原酶抑制剂：羟基脲（Hydroxyurea），核战争，还用抢?
5. DNA 多聚酶抑制剂：阿糖胞苷，多聚聚，才甜蜜。

• See De novo pyrimidine and purine synthesis
• Purine antagonists
  • Azathioprine is the prodrug of 6-MP
    • Azathioprine and 6-MP are purine analogs, so they are metabolized to inactivate forms by xanthine oxidase like purines
    • See Gout > Treatment, Lesch-Nyhan syndrome
• Antifolates
  • Methotrexate
    • Adverse effects
      • Myelosuppression, anemia
      • Hepatotoxicity, hepatic fibrosis
      • Pulmonary fibrosis, pneumonitis
      • Nephrotoxicity
      • Mucositis (e.g., oral ulcerations)
      • Birth defects (due to folate deficiency), e.g., neural tube defects

Topoisomerase inhibitors (G2 phase)

Mnemonic

• Eight (Etoposide) + II = Ten (Teniposide)
• I (Irinotecan) + I = Two (Topotecan)

Antitumor antibiotics

Mnemonic

• 多么温柔，令人放心啊：温柔-多柔比星，放心-放线菌素D，啊-干扰RNA合成。
• Mnemo I use for Doxorubicin /Daunorubicin:
  • They both end in -rubicin → ruby (= red) → the heart is red → cardiotoxicity
  • Dilated cardiomyopathy because it starts with D like Doxorubicin
  • Dexrazoxane used to prevent it → also starts with D and sounds like Roxane (‘Roxane, you don’t have to put on the red light’, song by the police) → again red for RUBYcin and heart.
• Bleomycin: bleo → fibro

Protein kinase inhibitors

CDK inhibitors

• Palbociclib
• Inhibition of cyclin-dependent kinase 4 and 6 → inhibition of cancer cell growth and induction of apoptosis
• Indications
  • Metastatic breast cancer
  • Myelosuppression
• Side effects
  • Pulmonary toxicity (e.g., pneumonitis)

Anticancer treatment-related complications

Chemotherapy-induced nausea and vomiting (CINV)

• Acute-phase CINV (<24 hours after chemotherapy) is mediated primarily by the release of serotonin from intestinal enterochromaffin cells that have been damaged by chemotherapy. Serotonin stimulates vagal afferent fibers (5-HT3 receptors) in the bowel wall, which project to the brainstem and stimulate the vomiting reflex. Therefore, serotonin receptor antagonists (eg, ondansetron) can be used for treatment.
• Delayed-phase CINV (1-5 days after chemotherapy) is mediated primarily by increased levels of substance P in the brainstem due to chemotherapy-associated emetic stimuli in the cerebrospinal fluid and bloodstream. Substance P binds to and activates the neurokinin-1 (NK1) receptor in areas of the brainstem that mediate vomiting (eg, nucleus tractus solitarius, area postrema). Therefore, NK1 receptor antagonists (eg, aprepitant, fosaprepitant) are often used for treatment.