Cancer Drugs

Question 1

Cyclophosphamide

Answer 1

• most commonly used alkylating agent
• Oral / IV admin
• non reactive prodrug
• treat lyphomas, leukemias, neruoblastomas and breat ovarian carcinomas
• Resistance
  
  • inc DNA repair, dec drug permeability, rxn w/ other cell constinuents = cross resistance
• Adverse Effects
  
  • nausea and vomiting
  • bone marrow, immunosupression and alopecia
  • hemorrhagic cystitis, sterility, menopause and veno occulsive disease of liver
    
    • stop adverse effects by stop taking drug, platelet RBC transfusion

Question 2

Cisplatin

Answer 2

• covalently binds N7 of guanine, also interacts with cystine and adenine
• kills cells in all stages of cell cycle
• IV or locally
• testicular, ovarian and bladder
• Adverse Effects
  
  • neuseaa, vomiting, nephrotoxicity and neurotoxicity
• Resistance
  
  • inc DNA repair, reaction w/ other cellular constituents and dec cell uptake

Question 3

Bleomycin

Answer 3

• non covalent dna binding agent
• forms dna-bleomycin-Fe(II) complex
• oxidation -> free radicals -> DNA strand breakage (cells stay in G2 phase)
• treat squamous cell carcinomas, lymphomas and testicular tumours
• **Adverse Effects: **
  
  • pulmonary fibrosis, pyrexia, anaphylaxis
• Resistance:
  
  • inc DNA repair, inc drug efflux, inc expression of antioxidant enzymes or bleomycin hydrolase

Question 4

methotrexate

Answer 4

• enters cell active transport
• Folic Acid Inhibitor binding to dihydrofolate reductase (DHF)
• reduce purine + pyrimidine synthesis -> affect RNA, DNA , protein synthesis
• methotrexate polyglutamates: retained in cancer cells further inhibit RNA/DNA synthesis
• treat leukemias, lymphomas and carcinomas
• IV/oral
• Adverse Effects
  
  • myelosuppresion, GI distress, alopecia, teratogenic, renal damage (high dose), liver damage (long term)
• Resistance
  
  • Non proliferating cell, inc DHF reductase, dec binding to DHF, dec cell uptake

Question 5

Fluorouracil

Answer 5

• carrier mediated transport
• covnerted to ribosyl and deoxyrybosyl nucleotide metabolites
• inhibit thymidylate synthetase -> dec thymidine -> dec DNA synthesis
• primary use for breast and GI carcinomas
• IV or topically
• Adverse Effects
  
  • bone marrow, nausea, vomitting, diarrhea, oral and GI ulceration, anorexia, alopecia
• Resistance:
  
  • inc fluorouracil metabolism, dec conversion nucleotide metabolite, inc thymidylate synthase activity.

Question 6

Topotecan

Answer 6

• targets cells in S phase
• binds to Topoisomerase I-DNA complex to prevent annealing of DNA breaks
  
  • Topoisomerase I assists w/ DNA replication and transcription
• IV administration
• ovarian cancers

Adverse Effects

• bone marrow suppression
• nausea
• vomiting
• diarrhea
• alopecia
• headache

Resistance

• increase transport of drug out of cell
• dec expression or a mutation in topoisomerase I

Question 7

Vincristine

(periwinkle plant)

Answer 7

• Microtubule Inhibitors
  
  • decreases microtubule half-life -> spindle dissolves -> cell divides
• block tubulin polymerization -> dysfunctional spindle
• kills cell in M stage
• IV admin
• treat leukemias, lymphomas , rapid proliferating tumours

Adverse Effects

• nausea, vomiting, alopecia, perhipheral neuropathy. antifungals slow metabolism. anticonvulsants accelerate metab

Resistance

• altered tubulin structure, eeflux via P-glycoprotein in cell membrane

Question 8

Paclitaxel

Answer 8

• microtubule inhibitor
  
  • decrease microtubule half-life -> spindle dissolves -> cell divides
• promotes tubulin polymerization -> microtubules too stable = no dividing
• advanced ovarian cancer, metastatic breast cancer - w/ cisplatin

Adverse Effects

• nausea, vomiting, hypersensitivity, alopecia, myelosuppresion, peripheral neuropathy, pulmonary toxicity, heaptic function (CYP450)

Resistance

• altered tubulin structure
• eeflux via P-glycoprotein in cell membrane

Question 9

Prednisone

Answer 9

• steroid sensitive tumours
  
  • mediating cell growth/proliferation
• induce apoptosis of leukemia and lymphoid
• for immune and inflammatory suppression - primarily lymphomas and leukemias

Adverse Effects

• immunosuppression, hyperglycemia, ulcers, pancreatistis, weakening, osteoporosis, hypertension, mood swings

Resistance

• absence or mutation of receptor

Question 10

Tamoxifen

Answer 10

• ER partial agonist
• estrogen sensitive tumour cells, bind ER mediating gene expression -> tumour growth
• for estrogen dependent breast cancer
• oral admin

Adverse Effects

• hot flashes, nausea vomiting, irregular periods, blood clots, cataracts, uterine cancer

Resistance

• absence or mutation of receptor