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Pharm Midterm - Oncology
for CRNA students
58
Health Care
Graduate
08/22/2006

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Cards

Term
cancer cells are...
Definition
mutant, rapidly dividing cells with no proliferation restriction
Term
the goal in treating cancer is to...
Definition
eradicate 100% of the tumors
Term
DNA synthesis happens in which phase?
Definition
S-phase
Term
Mitosis happens in what phase?
Definition
M-phase
Term
cancer protocol includes:
Definition
intermittent infusions of multiple agents in order to affect diff. growth stages or mech. of actions WITHOUT overly suppressing the bone marrow
Term
Tumors are not visible on X-Ray until...
Definition
it reaches 100 million cells
Term
Tumors are not palpable until...
Definition
it reaches about 1 billion cells
Term
Death occurs when...
Definition
there are 1-100 trillion cancer cells
Term
Log-kill hypothesis
Definition
If cancer tx doesn't fully eradicate the cancerous cell, it is possible to leave only one cell and have a relapse of cancer.

You can plot data (# of cancer cells on a log scale vs. time) to find of the tx is killing enough C cells each round

Term
Rapidly growing tumor cells spend a large amt. of time in which phase(s)?
Definition
S & M phases. "Growth fraction"
Term
Cell cycle specific (CCS) means what?
Definition
They are schedule-dependent and only work in their respective phases (i.e M or S phase)
Term
In slower growing tumors, most cells are in which phase?
Definition
G1 phase
Term
Cell cycle non-specific (CCNS) means what?
Definition
They will be effective regardless of cell cycle or phase.

Their efficacy is limited only by dose, and therefore are dose-dependent

Term
Alkylating Agents - properties/SE
Definition
*CCNS (works on DNA)
*highly emetogenic
*Vesicant
*Mutagenic (rare)
*Myelosuppressive
*Given on intermittent schedule to all WBC count to rebound. Dose/therapy limiting.
Term
What to do if drug is emetogenic?
Definition
Premedicate with Zofran, Kytril, Ativan, or Reglan
Term
What can happen with drugs that are vesicants?
Definition
It is a blistering agent. If extravasation occurs, they cause blistering and killing of the tissue.
Term
Why would an alkylating agent be mutagenic?
Definition
They chemically modify the DNA to destroy the cancer. This can happen in normal cells as well, and cause a different kind of cancer after tx.
Term
What are two types of Alkylating agents?
Definition
Nitrosureas & Nitrogen mustards
Term
Name three Nitrosurea drugs
Definition
1. Carmustine (BCNU)
2. Lomustine (CCNU)
3. Semustine (methyl-CCNU)
Term
Name two types of Nitrogen Mustard drugs
Definition
1. Cyclophosphamide (Cytoxin)
2. Ifosfamide
Term
What does it mean when a drug is myelosuppressive?
Definition
All anti-neoplastic drugs kill some amount of bone marrow b/c it is composed of fast growing cells - each drug varies in its degree, however.

Because of this, a pt will have leukopenia, neutropenia, and/or thrombocytopenia

Term
What is one of the main advantages of Carmustine?
Definition
It's CNS concentration is 50% of plasma levels.

So, it can be made into wafer form (Gliadel) and implanted into the the cavity made when a brain tumor is removed.

The wafers degrade slowly, distributing Carmustine over 2-3 weeks.

Gliadel is approved for tx of malignant brain cancers (ex: glioblastoma).

Term
What is the main side effect of Nitrogen Mustard drugs, and how can it be prevented?
Definition
Both Cytoxin and Ifosfamide have to be activated by CYP450, but in doing so acrolein, which is v. toxic to kidney/bladder, is formed and can cause hemorrhagic cystitis.

Prevention:
*Vigorous hydration: Infuse 1L NS before and during chemo tx.
*Mesna is a cpd. that neutralizes acrolein. Give scheduled does before and several times after infusion.

Term
Toxicities specific to Nit. Mustards:

(besides the ones shared with all alkylating agents)
Definition
alopecia, mucosal ulcerations (i.e. mouth, GI
Term
What are three types of Platinum Coordination Complexes?
Definition
1. Cisplatin
2. Carboplastin
3. Oxilliplatin
Term
Name three of the Platinum Coordination Complexes
Definition
1. Cisplatin
2. Carboplastin
3. Oxiliplatin
Term
Platinum Coordination Complexes major toxicities
Definition
1. Renal toxicity
2. Ototoxicity
3. PROFOUND nausea & vomiting
4. Electrolyte disturbances
Term
What makes Oxiliplating preferred over the other PCC drugs?
Definition
It's a third gen. of Cisplatin and has fewer adverse effects
Term
PCC Pharmacokinetics
Definition
1. Highly protein bound (esp. Cisplatin)
2. It's renally excreted, accumulation causes toxicity so be sure to adequately hydrate
3. Oxiliplatin has a v. lrg. Vd so it can cross membranes easily and reach more tumors
Term
In Cisplatin gel, what is the role of epi & collagen?
Definition
This gel is being developed for direct injection into solid tumors. The epi provides local vasoconstriction (to dec. sys. response) and the collagen keeps all the material together.
Term
Antimetabolites work on what phase of the cell cycle?
Definition
S-phase, CCS agents
Term
What is the relationship btwn Methotrexate (MTX) and Leucovorin?
Definition
MTX is cytotoxic to all rapidly dividing cells.

Leucovorin is given at timed intervals during MTX therapy so that normal cell will take it up (instead of the MTX?) and 'side-step' toxicity.

Term
MTX mj. toxicities
Definition
1. Myelosuppresion/thrombocytopenia
2. GI tract ulcerations
Term
MTX PK:
Definition
1. 90% renal excretion (this is why pts are susceptible to renal fail.)
2. 'Saturable absorption from GI tract' - there is a ceiling to how much drug is absorbed b/c there is a finite amt of transporters in the body
Term
Name the drugs in 4 subcategories of the Antimetabolites
Definition
1. Methotrexate (MTX)
2. Fluorouracil & Capecitabine
3. Cytarabine, Fludarabine, & Gemcitabine
4. 6-Mercaptopurine (6-MP) & 6-Thioguanine (6-TG)
Term
Fluorouracil & Capecitabine mj toxicities:
Definition
1. myelosuppression/thrombocytopenia
2. alopecia
Term
Capecitabine PK:
Definition
*It is a prodrug of fluorouracil
*80% bioavailability and can be administered as a tablet
*Required enzyme for bioactivation to fluorouracil is expressed very high in the cells of solid tumors (compared to NL cells) *Fun fact: Fluorouracil is used as a topical cream for psoriasis
Term
Cytarabine, Fludarabine, & Gemcitabine mj. toxicities:
Definition
1. leucopenia
2. thrombocytopenia
3. anemia
4. GI problems
Term
Cytarabine (Ara-C) PK:
Definition
Activated to AraCTP by nucleotide kinases (adds phosphates).

AraCTP then competes with dCTP for incorporation into DNA, where it will inhibit DNA polymerase.

AraC is *highly* S-phase specific and should be run in by continuous IV infusion for max exposure

Term
6-Mercaptopurine PK
Definition
6-MP is metabolized by xanthine oxidase, therefore *major* drug interaction with xanthine oxidase inhibitor (ex: allopurinol - a chemo pt would be on this to decrease the uric acid burden post tumor kill)
Term
Name four sub-categories of the Plant Alkaloids & Antitumor Abxs.
Definition
1. Vinca Alkaloids (Vincristine, vinblastine, vindesine, vinorelbine)

2. Epipodophyllotoxins (Etoposide/VP16, Teniposide)

3. Camptothecin Analogs (Topotecan, Irinotecan)

4. Taxanes (Paclitaxel, Docetaxel)

Term
Vinca alkaloids mj toxicities:
Definition
1. Myelosuppresion
2. Neurotoxicity = perpheral/central neuropathy and cognitive decline (neurotx stems from axonal transport, wh. interferes w/microtubule formation)
Term
Vinca alkaloids are CCS for...
Definition
M phase
Term
Epipodophyllotoxins are primarily CCS for...
Definition
the S phase
Term
Etoposide & Teniposide mj toxicity:
Definition
myelosuppression
Term
Etoposide & Teniposide mech. of resistance
Definition
*P-glycoprotein
*mutations in Topo-II that don't allow the drug to bind
Term
Etoposide & Teniposide PK:
Definition
these agents are highly protein bound... what is the influence of plasma albumin levels?

(?) less albumin, more free drug
Term
Topotecan & Irinotecan are CCS for...
Definition
S phase
Term
Topotecan & Irinotecan mj. toxicities
Definition
1. myelosuppression
2. SEVERE GI complications (dose-limiting) - profound loss GI epithelial cells cause diarrhea, etc.
Term
Taxanes (Paclitaxel, Docetaxel) are CCS to...
Definition
M phase
Term
Paclitaxel & Docetaxel PK
Definition
Have limited solubility and must be delivered in an ethanol/castor oil vehicle = high sensitivity rxns.

Pretx w/ dexamethasone and antihistamines

Term
Paclitaxel & Docetaxel mj. toxicities:
Definition
1. myelosuppression
2. peripheral neuropathy (r/t altered microtubules, like with the vinca alkaloids)
3. hypersensitivity rxns (from the ethanol/castor oil)
Term
Anthracycline Abx (5 types)
Definition
1. doxorubicin (adriamycin)
2. daunorubicin
3. valrubicin
4. epirubicin
5. Idarubicin
Term
Anthracycline Abx mj. toxicities
Definition
1. myelosuppression
2. GI ulcerations
3. Cardiotoxicity*
4. Radiation recall rxn

*Cardiotoxicity is assoc. w/ cumulative doses (550mg/m2). Causes CHF unresponsive to Dig therapy.

Term
Anthracycline Abx produce ROS, why is this important?
Definition
Reactive Oxygen Species (ROS) is a free radical.

Any cell w/ inc. mitochondria (i.e. inc. heme & iron- like the HEART) will throw off free radicals. This is the cause of cardiotoxicity.

Term
With the Anthracycline Abx agents, what can be done to prevent ROS induced cardiotoxicity?
Definition
*Tx with the iron-chelating agent, dexrazoxane. It 'cages' iron, making it inactive so it can't participate in redox (free radical) rxns.

*Dexrazoxane is primarily used in breast CA pts who have met cumulative dose. (Will need baseline EKG & Echo)

*Dexrazoxane does NOT decrease efficacy of doxorubicin

Term
Bleomycin PK
Definition
Bleomycin is inactivated by bleomycin hydrolase, which is found in liver, spleen, and bone marrow = reduced toxicity in these areas.

HOWEVER, the hydrolase is NOT present in skin & lung, which is where the Bleomycin toxicity manifests.

Term
Bleomycin toxicities
Definition
1. VERY LITTLE myelosuppression 2. Cutaneous toxicity 3. Pulm toxicity*

*O2 will form ROS, so do not exceed 30% FiO2 b/c it will potentiate toxicity

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