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24 Cards in this Set
- Front
- Back
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What is the difference between CCS and CCNS?
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Cell Cycle Specific - Cell is undergoing cycling.
Cell Cycle Non-Specific |
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What are the three main mechanisms that anti-cancer agents work through?
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Action on mitotic spindle (microtubule inhibitors)
Hormonal agents (Agonists, Antagonists) Action on DNA (Damage DNA, Inhibit synthesis) |
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Give an example of a hormonal agent agonist and an antagonist.
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Agonist = Prednisone
Antagonist = Tamoxifen |
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Give an example of a microtubule inhibitor.
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Vincristine
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What are two ways you can damage DNA. Give an example of a drug for each.
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Alkylation = Cyclophosphamide
Free Radical Formation = Doxorubicin |
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What are two ways you can inhibit the synthesis or function of DNA? Give an example of a drug for each method.
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You can create anti-metabolites (Methotrexate)
You can inhibit Topoisomerase (Etoposide) |
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What is the primary target of DNA alkylators?
What is chemically characteristic of these compounds? |
They primarily target the DNA itself
They are very electrophilic. The nucleophilic DNA attacks and forms a bond forming an irreversible alkylation. (Cross linking) |
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How do Nitrogen mustards destroy DNA?
What are Nitrogen mustards commonly called? |
Alkylation of DNA via a highly electrophilic Aziridine intermediate.
Bis-beta-haloalkylamine |
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Describe the 5 steps of Azirdine mediated Alkylation and destruction of DNA.
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Step 1 = Unionized nitrogen attacks beta carbon, displaces Cl creating Aziridine intermediate. Very electrophilic
Step 2 = The DNA nucleophilically attacks the Aziridine intermidate and is alkylated. When Step 3/4 = Repeats steps 1 and 2 with second arm of mustard and second DNA molecule. Step 5 = Hydrolytic depurination. DNA is released damaged. |
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Why is the ring closing in step two so important?
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The lone pair of electrons on the N is regenerated.
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Draw the Bis-beta-haloalkylamine.
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Bis-beta-haloalkylamine
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What portion of these compounds are altered to change the actions of the compound?
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The 3rd R group attached to the N.
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What effect does an aliphatic R group such at CH3 on the N have on the compounds action?
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It pushes the electrons to the amine, making it more nucleophilic and therefore inceases the rate of step 1 where the aziridine intermediate is formed.
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What effect would an aromatic N substituent have on the compounds action?
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Will stabilize the lone pair on the N decreasing nucleophilicity and slowing the rate of nucleophilic attack
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What does this property confer clinically?
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Their reactivity is controlled enough to allow oral administration.
It also gives the compound enough time to reach malignant tissue before the aziridine imtermediate forms which increases tissue specificity. |
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How are Nitrogen mustards decomposed?
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Water is added which forms an inactive dehalogenated diol.
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What decreases their rate of decomposition?
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Protonation
Buffering solutions to be slightly acidic can stabilize the compound. |
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Name the 5 main Aziridine mediated alkylators?
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Mechlorethamine HCl
Melphanlan Chlorambucil Estramustine phosphate sodium Cyclophosphamide |
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What is each drug used for?
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Mechlorethamine HCl - Cancers of the blood (aliphatic)
Melphanlan - Myeloma (aromatic) Chlorambucil - CLL, Lymphoma, Hodgekin's disease (aromatic) Estramustine phosphate sodium - prostate cancer (tetracyclic) Cyclophosphamide - treats a wide variety of neoplasms (contains phosphorus, nitrogen) |
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What 3 drugs are Nitrosoureas?
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camustine
lomustine streptozocin |
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By what 2 pathways are these compound decomposed?
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Pathway A = cyclization resultant anion to unstable oxazoladine. Then a second decomposition. Both release cytoxic electrophiles capable of alkylating DNA
Pathway B = Carbocation produces that is capable DNA alkylation at Guanine. |
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What 2 drug types O-methylate DNA also, but by a different mechanism
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Triazines and Procarbazine
Free radical mechanism |
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Name two Triazines.
What is each used to treat? |
Decarbazine - Malignant myeloma
Temozolomide - Glioblastoma CYP11A1 metabolizes |
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What are organoplatinum complexes?
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They are compounds that contain an electro-deficient metal atom that acts like a magnet for DNA nucleophiles. DNA repair mechanisms are unable to correct damage.
Used in testicular cancer, bladder, lung, ovary |
