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  1. Anti-folates
    1. DHFR inhibitor
    2. Resistance results from mutation in DHFR gene or amplification
    3. Well absorbed orally but has no metabolism or entry into blood brain barrier. Therefore the drug is given intrathecally
    4. Uses
      1. Ectopic pregnancy
      2. CNS prophylaxis of leukemia
      3. DMARD
      4. Choriocarcinoma (Curative)
      5. Psoriasis – Pustular, Arthropathy 
  1. Antipurine
  1. Azathioprine is converted to 6-MP in human body
  2. Metabolized by XAnthine oxidase
  3. Dose of Azathioprine should be reduced when combined with allopurinol(xanthine oxidase inhibitor)
  4. Azathioprine is nephrotoxic
  5. Pentostatin is another purine inhibitor which is Adenosine deaminase inhibitor
  6. Useful for the treatment of Hairy cell leukemia although DOC is Cladarabine (another antipurine drug) 

C. Antipyrimidines

  1. 5-FU
    1. Prodrug
    2. Inhibits S-phase of cell division so cell cycle specific
    3. Requires metabolic conversion in tumor cells into 5-flurodeoxyuridinemonophosphate(5-fdUMP)
    4. Inhibits THYMIDYLATE SYNTHETASE enzyme,required for thymidine formation
    5. Leads to Thymine less cancer cell death
    6. Uses: front line drug for Colorectal Ca
    7. Other uses
      1. Solar keratosis              
      2. BCC                      
      3. Mycosis fungoides        
      4. Liver Ca              
      5. Stomach Ca

P/K: short half life=5-15 min, Best give IV infusion

  • S/E
  1. GI Upset

2. Capecitabine

  1. Prodrug of 5-FU
  2. Also causes HAND FOOT disease
  3. Use: breast & colorectal Ca
  4. Other S/E: Bone marrow depression

3. Decitabine  and Azacitidine

  1. Useful for myelodysplastic syndromes(MDS)
  2. Act by Hypomethylation of DNA  

4. Gemcitabine

  1. Useful for Ca Pancreas
  2. Side effect is Bone suppression

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