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Pharmacology > Antineoplastics > Flashcards

Antineoplastics Flashcards

1
Q

What are the specific checkpoints that cells need to pass for…
G1/S?
G2/M?
metaphase/anaphase?

A

G1/S: Prepare for synthesis. Are Cell nutrition, size, environment favorable? is all DNA intact?
G2/M: Is DNA completely replicated?
Metaphase/Anaphase: Is all DNA intact? all chromosomes attached to mitotic spindle?

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2
Q

Describe 3 mechanisms of oncogene formation

A

Start as Proto-oncogene - mut - become oncogene
Point mutation; one amino acid
Gene amplification: extra copies of the mutated gene
Chromosomal Translocations: Proto-oncogene getting fused with another gene that is active.

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3
Q

Describe the hallmarks of cancer

A 
Sustained Proliferative signal
evade growth suppressor
avoid immune system
inducing angiogenesis
resisting cell death
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4
Q

Define the 4 goals of cancer drug therapy

A
  1. Primary chemo/curative
    • ALL, Testicular, AML, Hodgkins
  2. Primary chemo/control
  3. Adjuvant therapy. after sx
  4. Neoadjuvant therapy. b4 sx
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5
Q

What are the general mechanisms of drug resistance to chemotherapeutic agents?

A

Epigenetics, Drug efflux, DNA damage repair, Cell death inhibition, Epithelial-Mesencymal Transition, Drug target alteration, Drug inactivation

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6
Q

MOA: 6-Mercaptopurine

A

Converted to Thio-IMP by HGPRT = blocks AMP prod and other stuff with DNA synthesis

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7
Q

MOA: Fludarabine

What cancer tx?

A

Incorporated into DNA and blocks transcription.

CLL

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8
Q

MOA: Cytarabine

What cancer tx?

A

Gets incorporated into DNA, messes up DNA polymerase

AML

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9
Q

MOA: 5-fluorouracil

A

Inhibit Thymidilate synthase, incorporated into DNA/RNA and stops

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10
Q

MOA: capecitabine

A

Inhibits Thymidylate synthase, incorporated into DNA/RNA stops

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11
Q

MOA: Methotrexate

A

blocks dihydrofolate reductase. decreased DTTP and purines in DNA/RNA

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12
Q

MOA: Cyclophosphamide

A

Cause DNA crosslinking, breaks, abnormal base pairs

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13
Q

MOA: Carmustine (BCNU)

What cancer?

A

Cause DNA crosslinking, breaks, abnormal base pairing

Brain, GI Tumor, Hodgkins Lymphoma

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14
Q

MOA:
Cisplatin
Carboplatin

A

No alkyl group, but leads to DNA crosslinking

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15
Q

MOA: Doxorubicin

A

Inhib Topo II, intercalated DNA and changes shape

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16
Q

MOA: Bleomycin

A

Chelates Iron and Copper and causes DNA breaks

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17
Q

MOA: Paclitaxel

A

Prevent disassembly of microtubules

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18
Q

MOA:
Vinblastine
Vincristine

A

Mitotic arrest in metaphase - Prevent microtubule formation

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19
Q

MOA:
Irinotecan
Topotecan

A

Inhibiting Topo I - no strand repair

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20
Q

MOA: etoposide

A

Class II Topo inhibitor, double strand DNA breaks

21
Q

MOA:
Prednisone
Dexamethasone

A

Decrease Lymphocyte Proliferation

22
Q

MOA: tamoxifen

What cancer?

A

Selective Estrogen Receptor Modulator, competetive inhibitor

Breast

23
Q

MOA: Flutamide

What cancer?

A

Competetively inhibits testosterone from androgen receptor

Prostate

24
Q

MOA: Anastrozole
What cancer?
*****

A

aromatase inhibitor - limits peripheral estrogen production

Breast

25
Q

MOA: Imatinib

What cancer?

A

Binds to ABL and causes conformational change - limits ATP binding
CML

26
Q

MOA: Erlotinib
What cancer?
*****

A

Binds and inhibits EGFR receptor - limit proliferation

NSCLC, mut on chrom 19,21

27
Q

MOA: Vemurafenib

What cancer?

A

BRAF inhibitor, for when it is mutated and always active

Lots of Cancers

28
Q

MOA: Bevacizumab

A

Binds VEGF, inhibits angiogenesis

29
Q

MOA: Trastuzumab

What cancer?

A 
Binds HER2 (EGFR) on extracellular surface.
Breast
30
Q

MOA: Cetuximab

A

Binds EGFR and stops signaling

31
Q

MOA: Ipilimumab
What cancer?
*****

A

Blocks activation of T cells to save for cancer attack.

Blocks CTLA-4 binding B7

32
Q

MOA: Nivolumab

What cancer?

A

PD-1 inhibitor

Melanoma

33
Q

MOA: Asparaginase
What cancer?
*****

A

Hydrolyzes plasma L asparagine into aspartate, starving cancer cells
Childhood ALL

34
Q

MOA: Leucovorin

A

Reduced Folic acid

Used with MTX to reduce toxicity

35
Q

MOA: Mesna

A

Used to reduce damages caused by toxic metabolites of cyclophosphamide

36
Q

MOA: Filgrastin

A

Prevents myelosuppression when used with Paclitaxel

37
Q 
What are the mechanisms by which cancer cells become resistant to:
Methotrexate?
Cyclophosphamide?
6-Mercaptopurine?
5-Fluorouracil?
Vinblastine?
Vincristine?
Doxorubicin?
Topotecan?
Irinotecan?
Cytarabine?
Fludarabine?
Alkylating Agents?
Imatinib?
Cetuximab?
A

Methotrexate: Duplication of DHFR, reduced transport
Cyclophosphamide: p53 mut, Inc MGMT, accel DNA repair, reduced uptake
6-MP: acquired deficiency in HGPRT
5-FU: amplification of Thymidylate synthase
Vinblastine: causes myelosuppression
Vincristine: less myelosuppression, more neurotoxicity
Doxorubicin: ?
Topotecan: ?
Irinotecan: ?
Cytarabine: Lose Deoxycytadine kinase, reduced transport, cytadine deaminase
Fludarabine: Decreased activity of Deoxycytadine Kinase, drug efflux
Alkylating Agent: p53 mut, inc MGMT, accel DNA repair, reduced uptake
Imatinib: Pt mutation in ABL
Cetuximab: mut in RAS

38
Q 
What drugs lead to the following adverse effects:
Neuropathy
hypersensitivity reaction
caridac toxicity
nephrotoxicity
Pulmonary toxicity
bladder toxicity 
cerebellar syndrome
endometrial cancer
A

Neuropathy: Vincristine, Cytarabine, Cisplatin, Paclitaxel
Hypersensitivity rxn: asparaginase, paclitael, cisplatin, carboplatin
Cardiac toxicity: Doxorubicin, trastuzumab
Nephrotoxicity: cisplatin, methotrexate
Pulmonary Toxicity: MTX, bleomycin
Bladder toxicity: Cyclophosphamide
Cerebellar syndrome: Cytarabine
Endometrial Ca: Tamoxifen

39
Q 
what agents/tx are used to mitigate use of...
Methotrexate
cisplatin
doxorubicin
paclitaxel
cyclophosphamide
A

MTX: Leucovorin
Cisplatin: water and saline
Doxorubicin: Epirubicin has less cardiotoxicity
Paclitaxel: Filgrastim for myelosuppression
Cyclophosphamide: Mesna

40
Q

What drugs used in curative chemo for Testicular Cancer?

A

BEP: Bleomycin, Etoposide, Cisplatin

41
Q

What drugs used in curative chemo for Hodgkins lymphoma?

A

MOPP: Mechlorethamine, Vincristine, Procarbazine, Prednisone
ABVD: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine

42
Q

What are the drugs in the Antimetabolite category?

A

6-MP, Fludarabine, Cytarabine, 5-FU, Capecitabine, MTX

43
Q

What are the drugs in the Alkylating agents category?

A

Cyclophosphamide, Carmustine

Cisplatin, carboplatin (both non classical)

44
Q

What are the drugs in the Cytotoxic antibiotic category?

A

Doxorubicin, Bleomycin

45
Q

What are the drugs in the Natural product agents category?

A

Paclitaxel, vinbalstine, Vincristine, Irinotecan, Topotecan, Etoposide

46
Q

What are the drugs in teh Hormone agonists/antag category?

A

Prednisone, Dexamethasone, Tamoxifen, Flutamide, anastrozole

47
Q

What drugs are in teh small molecule tyrosine kinase inhibitors category?

A

Imatinib, erlotinib, vemurafenib

48
Q

What drugs are in teh Monoclonal antibodies category?

A

Bevacizumab, trastuzumab, cetuximab, ipilimumab, nivolumab

Pharmacology (10 decks)

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