E3: Cancer Drugs Flashcards
What are the 3 main steps of cancer growth?
1.Transformation 2.Proliferation 3.Metastasis
________: When a cell with normal growth changes into a cell with dysregulated growth (malignancy)
Transformation
Transformation is mainly attributed to ______ damage: inherited, gene mutations, alterations/loss in regulatory proteins
GENETIC damage
________: Growth of transformed cells into a tumor
Proliferation
Proliferation of a tumor is an increase in the ______ of cells
NUMBER of cells (not their size)
Proliferation: Critical cell cycle events include the synthesis of DNA (__ phase) and the division of the parent cell into 2 daughter cells (__ phase = ______)
synthesis (S phase)….M phase mitosis
Most antineoplastic drugs target _______ cells
DIVIDING
Original tumor may respond well to chemotherapy, but _______ lesions may be less responsive = poor prognosis
metastatic
Most chemotherapy agents interfere with cell _______
proliferation
What is the critical gene that can asses of a cell can be repaired or not? If the damage can not be repaired what happens in a normal situation?
p53 gene….apoptosis
The p53 gene is a _______ that functions as a tumor _______
transcription factor…tumor supressor
p53 is _______ after many different stressors: UV radiation, oncogenes, DNA damaging drugs
INDUCED
If _____ gene is damaged, tumor suppression is severely reduced
p53
Cancers that express p53 (leukemias, lymphomas, testicular cancer) = highly _______ to chemotherapy
RESPONSIVE
Cancers that acquire a mutation in p53 are _______ responsive or resistant to DNA- damaging chemotherapy drugs
minimally
Chemo drugs act under ______ kinetics.
First-order
______ tumors DO NOT respond well to chemotherapy and often require _______ and/or ______ as well
SOLID… radiation… surgery
Current emphasis on cancer chemotherapy is use of drug _________ therapy
combination
G0 = ______ phase
resting
G1 = ____ phase; occurs after ______; genes for replication are activated
gap…mitosis
S = DNA _______
synthesis
G2 = second gap phase; “_______”; DNA REPAIR progresses
premitosis
Which phase does DNA repair progress?
G2
Cell-cycle ______ (drugs affects one phase)….Cell-cycle ________ (drug affects any/all phases)
specific…non-specific
Which cycles are considered interphase?
G0/G1–>S–>G2 (M is only one not in interphase)
Perspective: What are the 7 classes of Chemo Drugs?
1.Alkylating Agents 2.AntiMetabolites 3.Platinum Complexes 4.Vinca Alkyloids 5.Hormonal Agents 6.Antibiotics 7.Thalomide
Oral Manifestations of Chemo: Concern is that complications pose __________ risk and/or may dictate the need to temporarily discontinue treatment
econdary infection
Oral complications of Chemo pose great ________ to the patient
discomfort
Mgmt of Oral Complications during Chemo: Good _____ control…Pain control with ________
plaque…topical anesthetics
Mgmt of Oral Complications during Chemo: Salivary replacement for _________
xerostomia
Mgmt of Oral Complications during Chemo: _____ due to caries risk…Antifungals… Antivirals… Antimicrobial _______ or dentifrices
Fluorides… mouthrinses
What is the extremely painful oral condition when on chemo that is best treated with ICE CHIPS?
Oral Mucositis
What are the 4 major oral manifestations of Chemo tx?
1.Oral Mucositis 2.Candidiasis 3.Black Hairy Tongue (antibiotics) 4.Viral Lesions
All chemo drugs have a ___ therapeutic index.
LOW
What are 3 major areas/ signs of the toxicity of chemo drugs?
1.BLOOD dyscrasias 2.Ulcerations of ORAL mucosa/GI tract 3.Nausea/Vomiting
Alkylating agents transfer alkyl groups to important cell constituents. When alkylating DNA, which nucleotide is it most likely alkylating to start cell death?
GUANINE
DO alkylating agents target a specific part of the cell cycle?
NO, Alkylating agents are cell-cycle NON-specific (drugs combine with cells in any phase of the cycle)
For Alkylating agents, __________ is common outcome of treatment
Susceptibility to infection
What is the most common example of an alkylating agent?
Cyclo-phosph-AMIDE
Antimetabolites are __ phase specific
S phase
Nitrogen mustard is a class of _________
alkylating agents
The 3 classes of antimetabolites are all antagonists, which antagonists are they?
1.Folic Acid Antagonists 2.Purine Antagonists 3.Pyrimidine Antagonists
What is an example of a folic acid antagonist?
meth-o-trex-ATE
Folic Acid antagonists inhibit DNA/Nucleic acid synthesis by blocking the enzyme ____________.
Di-Hydro-Folate Reductase
______ antagonists inhibit enzymes that convert hypoxanthine ribonucleotide to adenine and xanthine ribonucleotide
Purine
What is an example of a PURINE Antagoinist? Inhibits ____ AND ____ synthesis.
MER-CAP-TO-PURINE
What are the two Pyrimidine antagonists that “really kick people’s buts”?
Fluoro-Uracil “5-FU” and CYT-ARA-BINE “Ara-C”
Which cell cycle phase do Pyrimidine antagonists target?
Since they are antimetabolites- they target S phase
In Platinum complex drugs they inhibit ____ synthesis and repair, which induces cell death.
DNA
Platinum complex drugs are platinum ions surrounded by _______ ions.
chloride
What is an example of a Platinum Complex drug? (Hint what do they all have in their name?)
they all have “Plat” in their name…CARBO-PLATIN
What is ALMOST always a toxicity associated with Platinum derived meds?
OTOTOXICITY—Hearing loss
VINCA alkyloids-is this a cell cycle-specific drug? If so, what cycle(s) does this affect?
Yes, M and S phases
VINCA alkyloids-Inhibit mitotic division by interfering with ________ proteins involved in the formation of mitotic spindles.
microtubular
What are the two examples of Vinca Alkyloids? (you better not get this wrong)
VIN-BLAST-INE and VIN-CRIST-INE
What is a common side effect of the Vinca Alkyloids?
NeuroToxicty—Hearing loss specifically
Melissa is on Vinca Alkyloids for lymphoma, but what is the one indication Dr. S pointed out in lecture?
Kaposi’s Sarcoma
Which cell cycle phase do Hormonal Agents interfere with?
Hormones interrupt cells in G phase
What are the 5 hormonal agents used in Chemo therapy?
1.Estrogens 2.Androgens 3.Progestins 4.Glucocorticoids 5.TAM-OX-IF-EN
What are the two main Cancers indicated for the use of Estrogens? What is the form of Estrogen administered?
1.PROSTATE!!!! 2.Mammary…Ethinyl EstraDiol
Who would you give ANDROGENS to for Cancer therapy?
POSTmenopausal women with Mammary Cancer
Testosterone propionate and FLU-OXY-mesterone are drugs in the ______ family. What are they used for?
ANDROGEN….POSTmenopausal women with Mammary Cancer
What are the two main indications for Progestin chemotheraputics?
1.RENAL 2.Endometrial cancers
What are the two Progestin drugs?
1.MED-ROXY-PROGESTERONE 2.MEG-ES-TROL
What is the hormone of choice for these indications? hematologic; lymphomas; bone metastases; immunosuppression for organ transplantation
GLucoCorticoids
What is the only drug Dr. S gave us for the Glucocorticoid family?
PRED-NIS-ONE
The anti tumor effects of PRED-NIS-ONE may be related to inhibition of _______ transport, phosphorylation, or induction of cell death in immature ________
glucose…. lymphocytes
What is the hormonal agent that competitively binds to ESTROGEN receptors on tumors and other target tissues?…What cancer is it indicated for?
TAM-OX-IFEN…breast cancer
TAM-OX-IFEN Decreases ______ synthesis and inhibits _______ effects
DNA… estrogen
Which phases of the cell cycle does TAM-OX-IFEN act on? Is this cytostatic or cytosidal?
G0 and G1…cytostatic
uterine cancer, stroke, pulmonary emboli, liver problems, osteoporosis are the adverse effects of what hormonal drug?
TAM-OX-IFEN
Mech of Action for Antibiotics: ________ bind with DNA to inhibit cell division
Cytotoxins
What phase do antibiotics attack cells?
haha TRICK question…non-cell cycle specific AND Cell cycle specific!!
What type of tumors are ANTIBIOTICS most effective for?
Solid mass tumors
What is the ONE Antibiotic drug Dr. S said TO KNOW?! What is is indicated for?
DAUN-O-RUB-ICIN CITRATE (DaunoXome)….HIV-assoc Kaposi’s sarcoma
What do MOST, if not all the Antibiotic Chemo Agents end in?
“-CIN”
What is the Angiogenesis inhibitor, immunosuppressant, TNF blocking agent used in multiple myeloma, AIDS-related pathos ulcers?
THAL-ID-O-MIDE
What drug did we talk about that is the CLASSIC model drug for Teratogens?
THAL-ID-O-MIDE
WHAT ARE THE 8, yes 8 Systmemic Effects of Chemotherapy?
1.Bone Marrow Suppression 2.GI Disturbances 3.Dermatological Reactions 4.HepatoToxicity 5.NeuroToxicity 6.NephroToxicity 7.Immune Deficiency 8.Infertility
What are 2 signs of bone marrow suppression in systemic effects of Chemo?
1.Fatigue 2.ImmunoSuppression
What are two major signs of GI disturbances in Chemo effects?
1.Nausea/Vomiting/Diarrhea 2.Change in Gut Flora
What are 2 examples of Dermatological reactions to Chemo therapy?
- Skin lesions/ ulcerations 2.AloPecia
What is the systemic effect of Chemo tx on Hepatotoxicity?
Enzymatic INDUCTION or INHIBITION via P450 enzymes
What is the main NeuroToxicity from Chemo Therapy that we discussed?
Hearing Disorders
In the Nephrotoxicity assoc with Chemo, there is _________ from excess cell destruction and byproducts. This is Treated with _________ to inhibit Uric Acid production and resultant Urema.
HYPERuremia…ALLOpurINOL
In the immune deficiency consequence of Chemo, what are the two possible outcomes?
1.Susceptible to infection 2.Secondary Malignancy
Chemo can cause infertility because it inhibits _________ and ________
spermatogenesis and oogenesis