Cancer Pharmacology Flashcards
(56 cards)
1
Q
What phase does the synthesis of the components needed for DNA syntesis occur?
A
G1
2
Q
What stage does synthesis of DNA occur?
A
S
3
Q
Where are the components that are needed for mitosis made?
A
G2
4
Q
What are cell cycle specific agent examples?
A
- Antimetabolites (S)
- Epipodophyllotoxins (S-G2)
- Antitumor Ab’s (G2-M)
- Taxanes (M)
- Vinca alkaloids (M)
- Camptothecins (S)
5
Q
What are the classes of cell cycle nonspecific agents?
A
- Alkylating agents
- Antimetabolites
- Anthracyclines
- Antitumor Abx
- Platinum analogs
6
Q
What are good examples of cancers that are curable in a small subset of patients?
A
- Hodgkins
- NHL
- Choriocarcinoma
- Germ cell cancer
- AML
7
Q
What are the curable childhood cancers?
A
- Burkitt’s
- Wilms’
- Embryonal rhabdomyosarcoma
- ALL
8
Q
What is a growth fraction?
A
- ratio of proliferating cells to G0 cells
- Major determinant of responsiveness to chemotherapy
9
Q
What does a high growth fraction indicate?
A
- Very high rate of replication
10
Q
What is the log cell kill hypothesis?
A
- Antineoplastic therapy follows first order kinetics which means that a dose of a drug will destroy a constant fraction of cells
11
Q
What does PGP do? How does it relate to drug resistance?
A
- pharmacological barrier site, it “kicks” drugs out of the cell
- High baseline experssion correlates with primary inherent resistance to natural productions
- It can also be overexpressed leading to acquired drug resistance
12
Q
What are the common AE that occur with nearly all classic antineoplastic agents?
A
- Nausea
- Vomit
- Fatigue
- Stomatitis
- Alopecia
13
Q
What are three pharmacological rescue agents that decrease adverse effects of cancer treatments?
A
- Hematopoietic agents for neutropenia, thrombocytopenia, and anemia
- Serotonin receptor antagonist ((Zofran)ondansetron) and other drugs for emetogenic effects
- Bisphosphates to delay skeletal skeletal complications
14
Q
What are two ex of Nitrogen mustard alkylating agents?
A
- Cyclophosphamide
- Ifosfamide
15
Q
What are the five major types of alklyating agents?
A
- Nitrogen mustards
- cyclophosphamide
- Nitrosureas
- carmustine
- Alkyl sulfonates
- busulfan
- Methylhydrazine derivatives
- procarbazine
- Triazines
- dacarbazine
16
Q
MOA for alkylating agents?
A
forms covalent linkages with DNA
17
Q
What adverse effect does Acrolein cause and what inactivtes this drug?
A
- Hemorrhagic cystitis
- Mesna inactivates it and is used for prophylaxis of chemo iinduced cystitis
18
Q
What adverse effects does Cyclophosphamide have?
A
Hemorrhagic cystitis
19
Q
What AE does cisplatin (alkylating agent) have?
A
- Renal tubular damage
- Ototoxicity
20
Q
What AE does Busulfan (alkylating agent) have?
A
- Primalry fibrosis
21
Q
What are the main categories of antimetabolites?
A
- Folic acid analogs (methortrexate)
- Pyrimidine analogs (5-fluorouracil)
- Purine analongs ( 6-mercaptopurine)
22
Q
Antimetabolite MOA?
A
- Block pathways that lead to cell replication
- Cell cycle specific
23
Q
How does methotraxate work?
A
- Looks like folic acid and when it comes in contact with dihydrogolate reductase it blocks it so we can’t form dTMP to help make DNA
*
24
Q
Methotrexate AE? What is the rescue drug?
A
- Mucosal ulceration
- Leucovorin
- doesn’t rescue cancer cells at high does methotrexate but does rescue healthy cells
25
What is Fluorouracil?
* Prodrug
* FdUMP Covalently binds thymidylate synthetase and blocks de novo synthesis of thymidylate
26
What is Mercaptopurine?
* Metabolized by HGPRT to form monophosphate nucleotide 6-thioinosinic acid
* Inactivated by xanthine oxidase in the first pass effect
* Allopurinol inhibits xanthine oxidase, this is used as a supportive care in tx of acute leukemis to prevent hyperuricemia due to tumor cell lysis
* _This blocks the first pass effect_
* Reduce amount of 6-MP if giving Allopurinol
27
What are the common toxicities of antimetabolites?
* Diarrhea
* Myelosuppression
* N/V
* immunosuppression
* Thrombocytopenia
* Leukopenia
* Hepatotoxicity
## Footnote
*Relatively little toxicity after initial dose*
28
What are the examples of natural antineoplastic agents?
* Vinca alkaloids
* vinblastine
* vincristine
* Taxane
* paclitaxel
* Epipodophyllotoxins
* etoposide
* Abx
* doxorubicin
* Antrhacenedione
* Bleomycin
* Enzyme
* L-Asparaginase
29
How do Vinblastine and Vincristine (vinca alkaloids) work?
* Binds tubulin diners and inhibits microtubule assembly
* Cell cycle specific to M phase
30
AE of vinca alkaloids?
* Alopecia and bone marrow depression
* Vinblastine causes Myelosuppression greeater than vincristine
* Vincristine causes cumulative neuro toxicities compared to vinblastine
31
How do taxanes work?
* Bind to B tubuline and stabilze microtubule formation
* cell cycle specific to M phaase
32
What were Paclitaxel and docetaxel used for in the past? AE?
* Breast cancer tx before we knew about biologics
* Pacitaxel
* hypersens. rxn in hands and toes, change taste
* Docetaxel
* smaller dose and less side effects than pacitaxel
* hypersens. neutropenia, hair loss
33
Topoisomerase inhibitors?
* Campthothecins such as topotecan and irinotecan inhibit topoisomerase I
* Epipodophyllotoxins such as etoposide and teniposide, and the antrhacycline abx inhibit toposisomerase II
* Cell cycle specific S and G1 and G2
34
Why do anthracyclines such as doxorubicin lead to significant cardiotoxicity?
Due to production of free radicals
35
MOA of anthracycliens (doxorubicin)?
* Topoisomerase II inhibitor and DNA intercalation
* Cell cycle non specific
36
What is Bleomycin?
* Antitumor abx
* causes single and double stranded breaks
* causes minimal myelosuppression
* Causes significant **pulmonary toxicity** and presents as pneumonitis with cough dyspnea and crackles
37
How does asparaginase work?
* Hydrolyzes circulating L asparagine into aspartic acid and ammonia, inhibiting protein synthesis
* Cell cycle specific to G1
38
What can asparaginase be used to treat?
* targeted therapy for ALL
39
Asparaginase AE?
* acute hypersensitivity rxns such as
* fever
* chills
* N/V
* skin rash
* urticaria
* Delayed:
* risk of clotting and bleeding
* pancreatitis
* CNS toxicity such as lethargy confusion hallucination and coma
40
What does the suffix "nib" indicate?
* protein tyrosine kinase inhibitors that bind intracellulary
41
What is Tretinoin used to treat and how does it work? What are the AE?
* treats t(15;17) fusion protein PML-RARa which inhibits granulocytic maturation in APL
* This binds the fusion protein and antagonizes the inhibitory effect allowing the neoplastic promyelocytes to differentiate into netrioophils that rapidly die
* Vitamin A toxicity and retinoic acid syndrome are common AE
42
What is imatinib used for?
* BCR-ABL fusion protein that comes from a t(9;22) which is assoc. with CML
* Imatinib targets the ABL tyrosine kinase and blocks it
43
What is Erlotinib and gefitinib? AE and use?
* Tyrosine kinase domain inhibitorys of EGFR
* USed in non small cell lung cancer and pancreatic cancer
* Produces dermatologic toxicities
44
Ziv-aflibercept MOA?
* Recombinant fusion protein made of extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG1
* this makes it a souble receptor for VEGF-A, VEGF-B and PIGF
* Binding of VEGF ligands prevents interactions with VEGFR leading to inhibitiorn of VEGFR signaling
45
How do tyrosine kinase and growth factor receptor inhibitors work? How are they resisted? What are the AE's?
* Inhibit GF receptor signaling
* Inhibits tyrosine kinase activity
* Point mutaitonss in drug binding sites allows for resistance
* N/V and skin rash
46
What are the biological response modifiers?
* Agents that act indirectly to mediate their antitumor effects by ehancing immunologic response to neoplastic cells
* Interferons and Interleukin 2 are examples
47
How do interferons work and what are the AE?
* Inhibits cell growth alters cellular differnetiation and interferes with oncogene expression, alters cell surface Ag expression and increases phagocytic activvity of macrophages
* Bone marrow depression neutropenia, anemia, renal toxicity, ,edema, and arrhythmia
48
How does interleukin2 work and its AE?
* Increases cytotoxic killing by T and NK cells
* Capillary leak syndrome
49
Ritximab Ag, cancer, and antigen function?
* CD20
* NHL
* Proliferation and differnetiation
50
Alemtuzumab ag cancer and ag function?
* CD52
* Chronic lymphocytic leukemia
* unknown ag function
51
Gemtuzumab ag cancer and ag function?
* CD33
* AML
* unknown ag function
52
Trastuzumab ag, cancer, and ag function??
* HER2/neu
* Breast cancer
* tyrosine kinase
53
Cetuximab, ag, cancerm and ag function?
* EGFR (ErbB-1)
* Colorectal lung pancreatic and breast cancer
* Tyrosine kinase
54
Bevacizumab ag, cancer, and ag fxn?
* VEGF
* Colorectal and lung
* Angiogenesis
55
Ibritumomab and Tostiumomab ag, cancer and ag function?
* CD20
* NHL
* Proliferation and differentaition
56
What cancer are Nivolumab and pembrolizumab used to treat?
* Malignant malanoma that is unresectable or metastatic
