First Aid for the USMLE Step 1 2021, Thirty first edition
Learning cancer chemotherapy can be difficult, especially for USMLE step 1. I made this drug char that includes all step 1 cancer drugs and their combinations. An important component of USMLE step 1 cancer drugs is to know the specific side effects which I have included with helpful mnemonics. The ...
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USMLE STEP 1 PATHOLOGY QUESTION BANK 3
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University of Central Lancashire Preston (UClan)
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MedSchoolNotez
Category Cell cycle target Mechanism of action Side Effect Resistance
• Bone marrow suppression (most
dose limiting) • Cancer cell ability to repair DNA
• Alkylation of DNA bases causes • ↑ risk of infections lesions
strands to cross link. • Vesicant properties • ↓ Permeability of alkylating drug
Alkylating Agents Non-specific
• Cross links cause DNA damage • Hemorrhagic Cystitis • ↑ production of glutathione/
and prevent replication • Nausea/Vomiting glutathione S-transferase (catalyzes
• Alopecia conjugation of drug to glutathione
• Secondary Malignancies
Antifolates (Methotrexate)
• ↓ Cellular uptake
• ↓ Polyglutamate formation
• Analogs to molecules required
• ↑DHFR synthesis
for normal function interfere
Pyrimidine analogs (5-Fluorouracil)
with utilization of essential
Antimetabolites S phase • Myelosuppression • ↑ expression or mutations of
molecules
thymidylate synthase
• Inhibits DNA, RNA, and protein
Purine analogs (6-MP,6-TG)
synthesis
• Mutations or ↓ affinity of HGPRT
• ↑Drug degradation (xanthine
oxidase)
Topoisomerase • Causse DNA breaks by • Myelosuppression • Mutation or overexpression of
G1 & S phase
Inhibitors inhibiting topoisomerases • GI track issues topoisomerase I
• Myelosuppression
Microtubule • Interfere with microtubules
M phase • Neuropathy • MDR (p-glycoprotein mediated)
Inhibitors causing inhibition of mitosis
• Constipation (vinca drugs)
Non-specific
• Myelosuppression
Antitumor except • Intercalate between DNA and
• Cardiotoxicity -
Antibiotics Bleomycin (G2 produce free radicals
• Pulmonary toxicity
specific)
Signal • Inhibit kinases and second
Transduction Non-specific messengers preventing DNA • Vary -
Inhibitors synthesis
• Target hormones and its
Anti-Hormonals Non-Specific • Vary -
receptors
,MedSchoolNotez
• Make cancer cells more
susceptible to immune
system (CD20, PD1,PD-L1
Monoclonal targets)
Antibodies Non-specific • Block growth signals (EGFR • Infusion reactions -
(MOABs) targets)
• Stop blood vessels from
forming (VEGF target)
•
Others Non-specific • Varied • Varied • Varied
, MedSchoolNotez
Alkylating Agents
• Alkyl group: CnH2n+1
• Alkylating agents add alkyl group (e.g., methyl, ethyl, propyl) to nucleotide base in DNA (mainly N7 of guanine).
• Addition causes strands to cross link which cause DNA damage and prevent replication.
• Cell cycle non-specific
• Subtypes:
1. Nitrogen Mustards: Cyclophosphamide, Ifosfamide
2. Nitrosoureas: Carmustine (BCNU), Lomustine (CCNU)
3. Other: Temozolomide, Busulfan
Subgroup Drug Indication/Use Pharmacokinetics Side Effect/Toxicity Antidote
• Cross-link DNA
• Require liver bioactivation
(CP450)
• Broad spectrum
• Acrolein metabolite • Hemorrhagic cystitis
Cyclophosphamide anticancer • MESNA
Nitrogen damages bladder epithelium • Bladder cancer
• Autoimmune disorders
Mustard • Resistance: Aldehyde
oxidase produced by cancer
cells
• Acrolein metabolite • Hemorrhagic cystitis
Ifosfamide • Broad spectrum • MESNA
damages bladder epithelium • Nephrotoxicity
Carmustine • Fat soluble (cross BBB)
• Brain Tumors • Bone marrow suppression
Nitrosourea (BCNU), Lomustine • Require liver bioactivation •
• Metastases • Carmustine pulmonary toxicity
(CCNU) (CP450)
• Fat soluble (cross BBB)
Temozolomide • Glioblastoma multiforme • Myelosuppression •
• Methylates DNA
Other • Immunosuppressant for • Severe myelosuppression
Busulfan bone marrow transplants • Crosses BBB • Pulmonary fibrosis •
(e.g., CML) • Seizures
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