Harvey's Garden

Chemotherapeutic agents

5 min read

Microtubule 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

Cell‑cycle independent agents

  • Alkylating agents
    • Busulfan
    • Nitrogen mustards
      • Cyclophosphamide
      • Ifosfamide
    • Nitrosoureas
      • Carmustine
      • Lomustine
    • Procarbazine
  • Platinum compounds
    • Cisplatin
    • Carboplatin
    • Oxaliplatin
  • Dactinomycin (an antibiotic)

“G1 inhibitors” is incorrect

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
      • When taken together, allopurinol inhibits the metabolism of azathioprine, leading to increased levels of 6-mercaptopurine. This can result in potentially severe side effects such as bone marrow suppression, leading to leukopenia, thrombocytopenia, or anemia. Therefore, when used together, azathioprine dose typically needs to be reduced by 50-75%.
      • See Treatment, Lesch-Nyhan syndrome
  • Antifolates

Topoisomerase inhibitors (G2 phase)

Mnemonic

  • Eight (Etoposide) + II = Ten (Teniposide)
  • I (Irinotecan) + I = Two (Topotecan)
  • Topoisomerase I
    • Cleaves only one of both DNA strands
    • Has nuclease activity to cut DNA strands
    • And has ligase activity to reseal the ligated strand
    • Does not require ATP
  • Topoisomerase II
    • Cleaves both DNA strands for larger structural alterations of DNA
    • Requires ATP

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
  • Side effects
    • Pulmonary toxicity (e.g., pneumonitis)

Proteasome inhibitor

  • Mechamism
    • The ubiquitin-proteasome pathway (UPP) is responsible for degrading damaged or unnecessary ubiquitinated proteins within cells.
    • Cancer cells, particularly multiple myeloma (MM) plasma cells, produce large quantities of monoclonal proteins and have a high protein turnover, making them highly dependent on the proteasome.
    • Proteasome inhibitors (PIs) block the function of proteasomes, leading to an accumulation of misfolded or unfolded proteins. This buildup causes endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR) and ultimately triggers apoptosis (programmed cell death).
    • PIs also work by inhibiting the NF-κB pathway, which is crucial for the growth and survival of myeloma cells.

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.

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