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1. Introduction and Alkylating Agents
Oncology
49
Pharmacology
Pre-School
01/08/2011

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Term
Autonomous
Definition
-Cancer cells fail to respond to molecular signals from either within or without
- due to genetic mutations
- Reprogram for uncontrolled growth
Term
Tumor suppression genes
Definition
normally protect against effects of malignant changes due to oncogenes
Term
Oncogenes
Definition
Mutated genes that have become autonomous
Term
Apoptosis
Definition
-Programmed cell death
-Cancer cells evade this, and become immortalized
Term
Angiogenesis
Definition
Formation of new blood vessels
- Cancer cells do this to satisfy increased O2 and nutrient requirement of tumor
Term
Cancer cells and immune system
Definition
- Cancer cells avoid detection by body's immune system
Term
Metastasize
Definition
Cells break loose from site of origin and implant in other tissues
Term
Alkylating agents
Definition
-Activated to reactive intermediates capable of forming adducts with DNA
Term
Mustard Gas
Definition
-First use of chemical agents to treat cancer from it
-WWI
-Extremely vesicant low boiling liquid that causes severe blistering of the skin
- two chloroethyl groups each attached to a S atom
Term
Bari, Italy
Definition
US ship John Harvey blew up killing a lot of people b/c tons of mustard gas was on it.
Term
Mechlorethamine (Mustargen, Nitrogen Mustard)
Definition
First drug for chemo of cancer in 1946
Term
Mechlorethamine
Definition
Acts as an alkylating agent, thru the intermediacy of the highly reactive three membered aziridinium ion
Term
Warhead
Definition
Alkylating Group: CH2CH2Cl
Term
Alkylating Agent Mechanism
Definition
-Disrupt DNA structure and function
-Enhanced in cells that undergo mitosis
Term
p53 Tummor suppressor gene
Definition
-Causes activation of DNA repair enzymes
-Controls transition of cell from G1 phase to the S Phase
-initiates apoptosis
-mutations may lead to resistance
Term
Cytotoxic Agents
Definition
React with and damage DNA
Term
Cell Cycle non specific drugs
Definition
Do not target any one phase of the cell cycle.
Term
Sodium Thiosulfate
Definition
Antidote for Mechlorethamine extravasation
Term
Extravasation
Definition
IV drugs leak out cause problems
Term
Melphalan and Chlorambucil
Definition
Have a benzene ring that acts as an electron sink
Term
Chlorambucil (leukeran)
Definition

For chronic lymphocytic leukemia

 

nitrogen mustard alkylating agent

Term
Melphalan (Phenylalanine mustard, Alkeran)
Definition
For multiple myeloma
Term
Cyclophosphamide (Cytoxan)
Definition
-Breast, ovarian, non-Hodgkin's Lymphoma, Burkitt's Lymphoma
-Oxidized by Cytochrome P450
Term
Acrolein
Definition
Causes hemorrhagic cystitis
Term
Isofamide (Ifex)
Definition
-alkylating agent
-Testicular tumors, can cause hemorrhagic cystitis via acrolein formation
Term
Mesna (Sodium 2-mercaptoethane sulfonate)
Definition
Treats Hemorrhagic cystitis
Term
N-acetylcysteine
Definition
-Treats hemorrhagic cystitis
-Acetaminophen Overdose
Term
Adequate Hydration
Definition
Treats hemorrhagic cystitis
Term
Bendamustine (Treanda)
Definition
Bifunctional Alkylating agent
-treats chronic lymphocytic leukemia and Hodgkin's disease
Term
Estramustine (Emcyt)
Definition
Interacts with microtubules, causing disassembly
- Mitotic inhibitor
Term
Nitrosoureas
Definition
Carmustine (BCNU) and Lomustine (CCNU)
-Highly lipophilic, can cross BBB
-Important to treat brain tumors
Term
Gliadel
Definition
Biodegradable wafer, direct application, and it dissolves following surgery
Term
Streptozocin (Zanosar)
Definition
Naturally occurring antibiotic for treatment of islet cell carcinoma (insulinoma)
Term
Nitrosoureas Mech
Definition
-Undergo spontaneous degradation
-Can cause interstrand or intrastrand DNA crosslinks
-Cytotoxicity
Term
Guanine O6alkyl transferase
Definition
-DNA repair enzyme
-Major DNA adducts formed with nitrosourea degradation
Term
O6-benzylguanine
Definition
Inhibits guanine O6alkyl transferase
Term
Dacarbazine (5-dimethyltriazinyl-4imidazolecarboxamide; DTIC-Dome)
Definition
-Combo therapy for Hodgkin's disease and malignant melanoma
-must be given IV
-Penetrates CNS poorly
Term
Temozolomide (Temodar)
Definition
-Rapid oral absorb
-Crosses BBB
-Standard drug in Tx of Gliomas in combo with radiation
Term
Cisplatin
Definition
-MSU
- Metastatic testicular and ovarian tumors
-Advanced bladder cancer
-Renal damage, peripheral neuropathy, ototoxicity, and N/V (more than carboplatinum)
Term
Aquation
Definition
Cl atoms of cisplatin are displaced by water, yields a + molecule to react with nucleophiles
Term
Carboplatin (Paraplatin)
Definition
approved only in advanced ovarian cancer
Term
Oxaliplatin (Eloxatin)
Definition
approved for use in combo with fluorouracil and leucovorin for the Tx of colorectal cancer
-Cold induced neuropathies (avoid cold temps)
Term
Amifostine (Ethyol)
Definition
Cytoprotective drug
-Reduce renal toxicities w/Cisplatin
Term
Altretamine (Hexalen)
Definition
advanced ovarian cancer after failure of front line Tx
-activity b/c formaldehyde is released
Term
Triethylenethiophosphoramide (ThioTEPA, Thioplex)
Definition
3 aziridine rings
-used to control intracavitary effusions secondary to diffuse or localised neoplastic dz of serosal cavities
-Superficial papillary carcinoma of urinary bladder
Term
Busulfan (Myleran)
Definition
Bifunctional alkylating agent, has a mesylate group at each end
-used orally in the Tx of the chronic phase of chronic myelogenous leukemia
Term
Imatinib (Gleevec)
Definition
Chronic phase of chronic myelogenous leukemia
Term
Mitomycin C
Definition
ABX first isolated from Strep caespitosus
-IV use in desseminated adenocarcinoma of the stomach or pancreas
Term
Procarbazine (Matulane)
Definition
-Hydrazine derivative, first was a MAO-I
-Used in combo to Tx Hodgkin's Disease
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