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Pharmacology > Antineoplastics > Flashcards

Antineoplastics Flashcards

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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

Study These Flashcards
A

Class II Topo inhibitor, double strand DNA breaks

21
Q

MOA:
Prednisone
Dexamethasone

Study These Flashcards
A

Decrease Lymphocyte Proliferation

22
Q

MOA: tamoxifen

What cancer?

Study These Flashcards
A

Selective Estrogen Receptor Modulator, competetive inhibitor

Breast

23
Q

MOA: Flutamide

What cancer?

Study These Flashcards
A

Competetively inhibits testosterone from androgen receptor

Prostate

24
Q

MOA: Anastrozole
What cancer?
*****

Study These Flashcards
A

aromatase inhibitor - limits peripheral estrogen production

Breast

25
MOA: Imatinib | What cancer?
Binds to ABL and causes conformational change - limits ATP binding CML
26
MOA: Erlotinib What cancer? *****
Binds and inhibits EGFR receptor - limit proliferation | NSCLC, mut on chrom 19,21
27
MOA: Vemurafenib | What cancer?
BRAF inhibitor, for when it is mutated and always active | Lots of Cancers
28
MOA: Bevacizumab
Binds VEGF, inhibits angiogenesis
29
MOA: Trastuzumab | What cancer?
``` Binds HER2 (EGFR) on extracellular surface. Breast ```
30
MOA: Cetuximab
Binds EGFR and stops signaling
31
MOA: Ipilimumab What cancer? *****
Blocks activation of T cells to save for cancer attack. | Blocks CTLA-4 binding B7
32
MOA: Nivolumab | What cancer?
PD-1 inhibitor | Melanoma
33
MOA: Asparaginase What cancer? *****
Hydrolyzes plasma L asparagine into aspartate, starving cancer cells Childhood ALL
34
MOA: Leucovorin
Reduced Folic acid | Used with MTX to reduce toxicity
35
MOA: Mesna
Used to reduce damages caused by toxic metabolites of cyclophosphamide
36
MOA: Filgrastin
Prevents myelosuppression when used with Paclitaxel
37
``` 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? ```
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
``` What drugs lead to the following adverse effects: Neuropathy hypersensitivity reaction caridac toxicity nephrotoxicity Pulmonary toxicity bladder toxicity cerebellar syndrome endometrial cancer ```
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
``` what agents/tx are used to mitigate use of... Methotrexate cisplatin doxorubicin paclitaxel cyclophosphamide ```
MTX: Leucovorin Cisplatin: water and saline Doxorubicin: Epirubicin has less cardiotoxicity Paclitaxel: Filgrastim for myelosuppression Cyclophosphamide: Mesna
40
What drugs used in curative chemo for Testicular Cancer?
BEP: Bleomycin, Etoposide, Cisplatin
41
What drugs used in curative chemo for Hodgkins lymphoma?
MOPP: Mechlorethamine, Vincristine, Procarbazine, Prednisone ABVD: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine
42
What are the drugs in the Antimetabolite category?
6-MP, Fludarabine, Cytarabine, 5-FU, Capecitabine, MTX
43
What are the drugs in the Alkylating agents category?
Cyclophosphamide, Carmustine | Cisplatin, carboplatin (both non classical)
44
What are the drugs in the Cytotoxic antibiotic category?
Doxorubicin, Bleomycin
45
What are the drugs in the Natural product agents category?
Paclitaxel, vinbalstine, Vincristine, Irinotecan, Topotecan, Etoposide
46
What are the drugs in teh Hormone agonists/antag category?
Prednisone, Dexamethasone, Tamoxifen, Flutamide, anastrozole
47
What drugs are in teh small molecule tyrosine kinase inhibitors category?
Imatinib, erlotinib, vemurafenib
48
What drugs are in teh Monoclonal antibodies category?
Bevacizumab, trastuzumab, cetuximab, ipilimumab, nivolumab

Pharmacology (10 decks)

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