anti NEOPLASTIC - P2

GUANINE

MOST nucleophilic

• POSITION: 7

AZIRIDINE

Nitrogen Mustards

• RING

ACROLEIN

MESNA

• 2 - Mercapto

• Ethane

• Sulfonate

• NA - sodium

CYCLOPHOSPHAMIDE

• TOXIC:

  • TO DETOXIFY USEE

CYCLOPHOSPHAMIDE

USE:

CHRONIC LYMPHOCYTIC LEUKEMIA

ACUTE LYMPHOBLASTIC LEUKEMIA

• ACTIVE PART: PHOSPHARAMIDE

AROMATIC RING

Nitrogen Mustards:

• Chlorambucil

• Melfalan

  • ADD WHAT to become available ORAL

Thiotepa

ACTIVE in BLADDER CANCER

• fatal pulmonary fibrosis, "busulfan lung

Busulfan MyleraN

• A/E

CARMUSTINE

NITROUREAS

• ACTIVE ingr. of: GLIADEL Wafer

MYELO supression

CARMUSTINE

• A/E

Triazenes

• Dacarbazines/ Procarbazine

Can inhibit MAO and aldehyde dehydrogenase (causing disulfiram-like reaction ---cannot metabolize alcohol

• ndergoes N-demethylation (liver, CYP450)

• Forms Diazomethane

MYELO supression

Antimetabolites

• a/e: is the dose-limiting toxicity for all drugs in this class.

Hypoxanthine, guanine phosphoribosyl transferase

• thioguanine

• mercaptopurine

  • will DE ACTIVATED BY

thio GUANINE monophosphate

will DE ACTIVATED BY: Hypoxanthine, guanine phosphoribosyl transferase

• thioguanine

  • convert to

thio INOSINE monophosphate

will DE ACTIVATED BY: Hypoxanthine, guanine phosphoribosyl transferase

• mercaptopurine

  • convert to

• Thiopurine-S-methyl transferase

• Xanthine Oxidase.

Mercaptopurine

• to metabolized need

AlloPURINOL

Xanthine Oxidase.

• is the enzyme INHIBITED by:

Azathioprine

a derivative of 6- Mercaptopurine,

• used as an immunosuppressive agent

  • Prevent: ORGAN TRANSPLANT REJECTION

Thymidylate synthase

Fluorouracil (5-FU)

• uridine TO thymidine

  • what enzyme

Fluorouracil (5-FU)

1ST LINE: COLON CANCER

Fluorouracil is converted into a 'fraudulent' nucleotide, fluorodeoxyuridine monophosphate (FDUMP).

• DPD (Dihydropyrimidine dehydrogenase)

Prodrugs of 5-FU

• To reduce the catabolic INACTIVATION of 5-FU by

daunorubicin

thioguanine

Cytarabine

• MIMIC: CYTOSINE

  • COMBINE TO?

    • = treatment of acute nonlymphocytic leukemia

Gemcitabine (Gemzar)

MIMIC: CYTIDINE

• 1ST LINE: LUNG CANCER