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Cancer ChemoTheraputics
N/A
39
Pharmacology
Graduate
09/19/2009
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Term
Alkylting Agents
 Definition
Derived from Mustard Gases.
Dramatic myelosuppression, knocks out bone marrow, therefore and analog of Nitrogen Mustard gases developed to replace the severely toxic Sulfur Mustard Gas.
MOA: Bind directly to DNA, Prevent DNA unwinding, Cause DNA breaks.
Tx: used for leukemia by knocking out bone marrow.
Term
Mechlorethamine
 Definition
MOA: Bind directly to DNA of cells eith in OR out of cycle. Won't affect cells in G0 as much as others.Prevents DNA unwinding, Causes breaks in DNA - inhibits replication.
Toxicities: Bone marrow depression, N/V, & hair loss.
Term
Cyclophosphamide
 Definition
MOA: Bind directly to DNA of cells eith in OR out of cycle. Won't affect cells in G0 as much as others.Prevents DNA unwinding, Causes breaks in DNA - inhibits replication.
Toxicities: Bone marrow depression, N/V, & hair loss.
Term
Melphelan
 Definition
MOA: Bind directly to DNA of cells eith in OR out of cycle. Won't affect cells in G0 as much as others.Prevents DNA unwinding, Causes breaks in DNA - inhibits replication.
Toxicities: Bone marrow depression, N/V, & hair loss.
Term
Nitrosoureas
 Definition
MOA: Bind directly to DNA of cells eith in OR out of cycle. Won't affect cells in G0 as much as others.Prevents DNA unwinding, Causes breaks in DNA - inhibits replication.
Toxicities: Bone marrow depression, N/V, & hair loss.
Term
Cisplatin
 Definition
MOA: Bind directly to DNA of cells eith in OR out of cycle. Won't affect cells in G0 as much as others.Prevents DNA unwinding, Causes breaks in DNA - inhibits replication.
Toxicities: Renal instead of bone. Renal limiting dose. Patient has to be well hydrated b/f drug is infused.
Term
Antimetabolites
 Definition
MOA: works against metabollites. Made to look like purine/pyrimadine or folic acid to interrupt DNA.
These analogs compete w/ enzymes natural metabolites use. Interferes with DNA synthesis.
Toxicities: all inhibit cell proliferation in the bone marrow & GI epithelium.
Term
Methotrexate
 Definition
A folic acid analog.
MOA: inhibits dihydrofolate reductase.
Toxicities: all inhibit cell proliferation in the bone marrow & GI epithelium.
If give too much methotrexate can give reduced folic acid - lucovorin.
Term
Fluorouracil
 Definition
S phase specific.
MOA: inhibits thymidylate synthetase (can't make thymidine).
Toxicities: all inhibit cell proliferation in the bone marrow & GI epithelium.
Fluorouracil given with lucovorin enhances binding to thymidylate synthetase.
Term
Cytarabine (AraC)
 Definition
S phase specific.
MOA: Inhibits DNA polymerase.
Toxicities: all inhibit cell proliferation in the bone marrow & GI epithelium.
Term
6-mercaptopurine
 Definition
S phase specific.
MOA: inhibits purine anabolism.
Toxicities: all inhibit cell proliferation in the bone marrow & GI epithelium.
Term
Natural Products
 Definition
chemotheraputics derived from other life forms, i.e. plants and bacteria.
Term

A. Plants

Vincristine

 Definition

MOA: inhibits the function of the microtubules.

 

Toxicities: Bone marrow & neurological*
Term
Vinblastine
 Definition

MOA: M-phase. Inhibits the function of microtubules

 

Toxicities: Bone marrow
Term
Etoposide
 Definition

MOA: M-phase specific. Inhibits function of microtubules.

 

Toxicities: Bone marrow.
Term
Taxol
 Definition

MOA: M-phase specific. Inhibits the function of the microtubules.

 

Toxicities: bone marrow.

 

Special: taxol is the most recent drug in this class. Now synthetically made. 

Good for ovarian cancer.*
Term

B. Bacteria

 

Actinomycin

Definition

MOA: Intercalates (binds) with DNA.

 

Toxicities: Bone marrow, GI.
Term
Bleomycin
 Definition

MOA: Oxidative damage to DNA.

 

Toxicities: Lung

 

Special: causes pulmonary fibrosis, sparing on bone marrow.

Term
Adriamycin
Definition

MOA: Intercalates (binds) DNA.

 

Toxicities: bone marrow, heart*

 

Special: Adriamycin - one of the few drugs causing heart toxicity.
Term
Hormones & Hormone Antagonists
 Definition

4 Strategies:

 

1. Interfere at the hypothalamic-pituitary axis.

2. Interfere with receptors.

3. Interfere with synthesis.

4. Interfere with down-regulation.

Term
Prednisone
 Definition

MOA: Inhibits lymphocyte proliferation.

 

Toxicities: Sodium retention, osteoporosis

 

Special: anti-inflammatory, quiets macrophages & leukocytes. Used for leukemia & lymphoma.*
Term
Leuprolide
 Definition

MOA: Blocks release of gonadotropin (LH-luteinizing hormone). Interferes at the hypothalamic-pit. axis where gonadotropin is released.

 

Toxicity: Hot flashes, loss of libido.

 

Special: Used for prostate cancer, use with flutamide as medical castration to shrink the prostate.

Term
Flutamide
 Definition

MOA: blocks androgen receptor. Competing antagonist for testosterone receptor.

 

Toxicity: Diarrhea, liver toxicity.

 
Term
Tamoxifen
Definition

MOA: Blocks estrogen receptor.

 

Toxicity: Hot flashes, nausea, hypercalcemia.
Term
Letrozole/Examestane
 Definition

MOA: Blocks estrogen synthesis by inhibiting aromatase.

 

Toxicity: bone weakening - osteopenia.
Term
Breast Cancer
 Definition

Estrogen driving growth of cancer:

If remove ovaries breast cancer will start to regress. May take out uterus as well.

  • Interfere at the hypothalamic-pit. axis
  • Use tamoxifen to interfere at receptor in breast
  • Use letrozole/examestane to interfere with synthesis of estrogen.
Term

Dutasteride (Avodart)

 

Finasteride (Proscar)

 

Finasteride low dose (Propecia)

 Definition

MOA:

  • Interferes w/ synthesis of testosterone.
  • 5-alpha reductase inhibitors
  • Blocks testosterone to dihydrotestosterone.

Toxicities: Decreased libido & erectile dysfunction.

Term
Progestins
 Definition

MOA: Down-regulate estrogen receptor.

 

Toxicities: Menstrual bleeding, edema.

 

Special: estrogen is high in the follicular phase. Progesterone high in luteal phase. Progesterone down-regulates estrogen.

Used for uterine cancer - in the process of making an analog for breast cancer.

Term
Combination Chemotheraputics
 Definition
  • BVP - testicular CA
  • CMF - Breast CA
  •  FAM - Gastric CA

Drugs should:

  1. be active alone
  2. have different mechanisms of action
  3. have non-cross-reacting host toxicities - spread out the toxicity among the host but still pile it up on the tumor.
Term
BVP
 Definition

Drugs used:

  • Bleomycin
  • Vinblastine
  • Platinum

Curative regimen for testicular cancer, cured 90% of the time, even in cases of metastatic cancer, i.e. Lance armstrong had metastatic testicular CA to the brain.

Term
CMF
 Definition

Drugs used: developed in Europe, given in adjuvant setting. Use combination of drugs w/ non-cross-reacting host toxicities.

  • Cyclophosphamide
  • Methotrexate
  • 5-Fluorouracil

Used for Breast CA.

 

**Special: Adriamycin & Taxol now being used in the U.S.

Term
FAM
 Definition

Drugs used:

  • Fluorouracil
  • Adriamycin
  • Mitomycin C

Used for Gastric CA.

 

Special: stomach CA is in the top 5 in Japan & China.
Term
Drugs for Tx of N/V & Anxiety
 Definition
Term

Prochlorperazine

 

(Compazine)

 Definition

Phenothiazine

 

used to treat severe N/V and moderate to severe pain in hospitalized patients.
Term

Metoclopramide

 

(Regalan)

 Definition

Cholinergic agonist antagonizes dopamine in CNS.

 

Relieves Nausea and Vomiting
Term

Lorazepam

 

(Ativan)

 Definition

Benzodiazepine

 

anti-anxiety
Term

Dexamethasone

 

(Decadron)

 Definition

Anti-inflammatory

 

GI - CNS
Term

Ondansetron

 

(Zofran)

 Definition

Serotonin receptor antagonist.

 

Prevents Nausea & Vomiting.
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