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Pharm Week 14

Terms in this set (21)

Etiology of Cancer: Carcinogens, Oncogenes,
-Carcinogens can act as initiators and promoters. They include chemical, physical/radiation or biological/viral agents.
- Oncogenes: non-random chromosomal changes in genes that normally are involved in regulation of cellular function, such as tumor suppressor genes.
Etiology of Cancer: Controllable causes, Uncontrollable causes, Tumor development,
- Controllable causes: environmental, predisposing disease.
- Uncontrollable causes: familial traits, unidentified causes.
- Tumor development: initiation, promotion, progression, metastasis.
Tumor Burden - the numbers that count
detectable is about 1 g in mass = 109 cells. about 30 doublings from 1 cell. lethal tumor is about 1 kg in mass = 1012 cells. That is only another 10 doublings. A drug that kills 99.9% of the cells in a tumor leaving only 1 in a 1000 cells alive only reduces exponent by 3
Tumor Burden - the numbers that count: Resistance
primary and acquired. Some do not respond at all, showing primary resistance. Many are heterogeneous. Once mutation begins, process continues. Cells w/ resistance mutations are selected and continue to X. These tumors respond initially then later fail, showing acquired resistance.
The Cell Cycle Order
G0,
G1,
S,
G2,
M,
The Cell Cycle: GO, G1, S,
G0 - resting phase of the cell. Most normal cells live the majority of their lives in this phase.
G1 - the cells prepares for DNA synthesis by preparing the enzymes and necessary substrates for DNA synthesis. (40%)*
S - DNA synthesis takes place. (39%)*
The Cell Cycle: G2, M, portion of growth phase,
G2 - the cells produce RNA, specialized enzymes and the mitotic spindle apparatus. (19%)*
M - the cells splits (mitosis). (2%)*
*portion of the growth phase only (G1- M)
Cell Cycle MOA
The cell cycle is normally regulated by lymphokines, hormones and growth factors.
Some agents attack the cell during a specific phase of growth. They are known as cell cycle specific (CCS) agents. Others attack without regard to the phase. They are known as cell cycle nonspecific (CCNS).
Cell Cycle Specific Agents: MOA
tend to be more effective with tumors with a high percentage growth fraction such as hematologic malignancies. CCNS agents are useful in low growth fraction malignancies such as solid tumors.
Cell Cycle Specific Agents
CCS agents include the antimetabolites, the podophyllin alkaloids, the vinca alkaloids and bleomycin. CCNS agents include the alkylating agents, antibiotics, nitrosoureas and cisplatinum and related compounds.
Nucleic Acid Chemistry: DNA
- DNA: zipper, coded by nucleotide sequence,
- each nucleotide; made of sugar, phosphate, and base,
- DNA: 4 bases, Adenine, Thymine, Guanine, Cytosine,
- T and C = pyrimidines,
- A and G = purines,
- transcripted by enzyme unzipping,
- RNA makes mirror image,
- rezips by enzyme,
Nucleic Acid Chemistry: RNA
- sugar/ribose, phosphate, and 4 bases,
- Uracil substituted for Thymine,
- messenger, transfer, and ribosomal types,
- product of DNA transcription, read during protein synthesis,
- tRNA retrieves amino acid for ribosome during protein synthesis,
Alkylating Agents and related compounds: MOA
- act by forming chemical bridges between the two sides of the DNA zipper. zipper becomes stuck. can occur during any phase of cell cycle, but cell death occurs when the cell enters or is in one of the growth phases.
- vesicant, Cyclophosphamide when activated,
- CCNS mostly,
Classic alkylating agents 1
- Mechlorethamine(Mustargen): Vesicant, Bone marrow depression
- Bendamustine (Treanda): Same,
- Chlorambucil (Leukeran)
[po only]: Same + pulmonary fibrosis,
- Melphalan (Alkeran) [po]: irritant, same,
- Busulfan (Myleran, Busulfex) [po]: irritant, same + pulmonary fibrosis, skin pigmentation, adrenal insufficiency,
Classic alkylating agents 2
- Cyclophosphamide (Cytoxan) [po]: irritant, same + alopecia, hemorrhagic cystitis ,
- Nitrosoureas (alkylators): ,
- Carmustine
(BiCNU, Gliadel Wafer) [po]: irritant, Leukopenia, thrombocytopenia, secondary malignancies ,
- Lomustine (CeeNU) [po only]: same,
Classic Alkylating Analogs: Platinum Analogs
- Cisplatin (Platinol): vesicant, bone marrow depression + renal + acoustic nerve damage,
- Carboplatin (Paraplatin): irritant, same but less renal and nerve damage,
- Oxaliplatin (Eloxatin): irritant nearly vesicant, bone marrow depressions + neuropathy,
Alkylating Analogs: Nonnclassic
- Dacarbazine (DTIC): irritant, bone marrow depression,
- Procarbazine (Matulane): P.O. only, bone marrow depression + MAOI substrate,
Antimetabolites
- structural analogs to many compounds important to nucleic acid synthesis,
- mess with various enzyme systems in nucleic acid synthesis, provide false substrate,
- = inhibition of nucleic acid synthesis or defective product,
- many S phase specific,
Antimetabolites: Folic Acid Analogues
- Methotrexate (MTX): PO, Folic acid analogue, enteric mucosal ulceration, bone marrow depression,
- Pemetrexed (Alimta), folic acid analogue, same,
- Prlatrexate (Folotyn), folic acid analogue, same,
- Fluorouracil (5- FU, Adrucil): Pyrimidine analogue, saame,
Antimetabolites: Pyrimidine Analogues
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Antimetabolites; Purine Analogues
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