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3028PHM > Cancer 2.0 > Flashcards

Cancer 2.0 Flashcards

1
Q

Explain the cell cycle and involved drug classes

A

Go= resting phase (dormant, hidden cancer cells)

Growth factors between G1 and G0

Temsirolimus works on G1

Checkpoint 1 between G1 and S

DNA synthesis inhibitors work on S phase

G2 = bleomycin, etoposide, and teniposide

Checkpoint 2 between G2 and M

M= mitotic inhibitors

Nonspecific= all DNA alkylating and most DNA intercalating

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2
Q

Explain tumour hypoxia

A

Limits chemo ability
Further from capillary = less oxygen
Less vasculature to get chemo

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3
Q

Explain clonal selection

A

Increased resistance from second round of chemo, increases w/ more rounds.
Commensalism

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4
Q

Explain tumour initiation and metastasis

A
  1. Initiation of growth of tumour
  2. metastasis initiation = invasion, angiogenesis
  3. metastasis progression = remodelling, immune evasion
    Leads to metastasis virulence= organ specific function

Simply, blood vessel breaks and primary tumour spreads. No pattern in brain. Bone pattern= prostate.

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5
Q

Explain tumour staging

A

TNM method to provide informed plan

T= size of primary tumour (0-3)
N= extent of lymph node spread (0-3)
M= distant metastasis (organ specific)

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6
Q

Principles of chemotherapy

A

Treat blood cancers that cannot be surgically removed
Combined w/ surgery or radiation to treat solid tumours
Palliative therapy

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7
Q

Limitations of chemo

A

Drug resistance:
- abnormal gene mutations/expression
- proapoptotic expression changes

Multidrug-resistance protein (MRP) and P-glycogprotein (Pgp)

Drug toxicity:
- myelosuppression (RBC, WBC)
- N/V
- Alopecia
- Tumour lysis syndrome
- Secondary cancers

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8
Q

Methotrexate class and MOA

A

DNA synthesis inhibitor / folate antagonist

Inhibit dihydrofolate reductase (DHFR) to prevent conversion of dihydrofolate to tetrahydrofolate. Stop DNA synthesis.

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9
Q

Pemetrexed class and MOA

A

DNA synthesis inhibitor / folate antagonist

Inhibit DHFR, TS, and GARFT to prevent conversion of dihydrofolate to tetrahydrofolate. Stop DNA synthesis. Tetra=DNA synthesis.

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10
Q

Methotrexate PK

A

Oral or intrathecal
Does not penetrate CNS, intrathecal only
Renal excretion

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11
Q

DNA synthesis inhibitor indications

A

Methotrexate- trophoblastic (repro), blood, and solid.
Pemetrexed- solid

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12
Q

DNA synthesis inhibitor ADR

A
  • Myelosuppression (RBC and WBC- bone marrow suppression, anaemia, fatigue, low O2, immunocompromise, febrile neutropenia)
  • GI toxicity - N/V
  • Stomatitis
  • Hepatotoxicity
  • Renal toxicity

Toxicitiy can be reduced w/ folinic acid supplements. Leucovorin.

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13
Q

Mercaptopurine class and MOA

A

Purine analogue (A and G)

Inhibit purine biosynthesis to interfere w/ DNA synthesis.

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14
Q

Thioguanine class and MOA

A

Purine Analogue (A and G)

Inhibit purine biosynthesis to interfere w/ DNA synthesis.

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15
Q

Purine analogue ADRs

A

Dose-limiting myelosuppression w/ thioguanine. Mild w/ mercaptopurine.

Hepatotoxicity w/ mercaptopurine.

2nd cancers from both

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16
Q

Allopurinol in purine analogues

A

Mercaptopurine dose must be reduced in allopurinol

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17
Q

Purine analogue indications

A

Blood cancers
Cladribine for hairy cell leukaemia

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18
Q

Fludarabine class and MOA

A

Purine analogue

DNA chain termination. Incorporates itself into developing DNA to disrupt DNA synthesis.

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19
Q

Cladribine class and MOA

A

Purine analogue

DNA chain termination. Incorporates itself into developing DNA to disrupt DNA synthesis.

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20
Q

Cytarabine class and MOA

A

Pyrimidine antagonist (CTU)

Cytarabine active metabolites (di and triphosphates) block DNA synthesis. Inhibit DNA polymerase. Incorporate drug into growing chain to cause DNA chain termination.

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21
Q

Fluorouracil class and MOA

A

Pyrimidine antagonist (prodrug)

Converted to 5dUMP and 5dUTP. 5dUMP inhibits TS to stop thymidine synthesis.
5dUTP incorporated into RNA by RNApolymerase.

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22
Q

Gemcitabine class and MOA

A

Pyrimidine antagonist

Converted from mono to di and triphosphate (RNA integrity). Inhibits DNA synthesis during S phase.

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23
Q

Explain use of leucovorin w/ fluorouracil

A

Synergy.
Counter effects.
Synergy at receptor to bind more effectively.
Synergy w/ DUMP of fluorouracil.

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24
Q

Pyrimidine antagonist indications

A

Cytrabine IV or SC combined w/ daunorubicin

Fluorouracil IV for solid tumours. Topical for actinic keratosis.

Gemcitabine for pancreatic carcinoma w/ cisplatin for inoperable solids.

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25
Q

Pyrimidine antagonist ADRs

A

N/V usually mild

Myelosuppression

GIT and oral ulcers

Fluorouracil bolus injection (IV push) = myelosuppression

Mucosal damage = continuous IV

High doses= liver, heart, and organ damage

Rapid tumour lysis syndrome

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26
Q

Cyclophosphamide class and MOA

A

DNA alkylating drug

Converted to phosporamide mustard. Cross-link DNA strands by forming covalent bonds between alkyl groups and guanine bases. DNA synthesis disrupted. Partly converted to acrolein.

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27
Q

DNA alkylating drug ADRs

A

Alopecia
N/V - severe w/ IV
Myelosuppression - dose-limiting
Tumour lysis syndrome

Hemorrhagic cystitis (caused from acrolein, depletes thiol groups. Protect by mesna to replenish thiol groups).

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28
Q

Platinum compound drug example and MOA

A

Cisplatin and carboplatin.

Cross-link DNA by forming intra and interstrand covalent bonds w/ DNA bases. DNA synthesis disrupted.

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29
Q

Platinum compounds indications and ADR

A

IV- testicular, ovarian, cervical, bladder, melanoma.

ADR= significant N/V and nephrotoxicity. Mild myelosuppression.

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30
Q

Mitomycin C class and MOA

A

DNA alkylating drug

Alkylates DNA to break strand and inhibit DNA synthesis.

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31
Q

Mitomycin C indication and PK

A

Parenteral = activated by hepatic reduction

Indicated for salvage therapy for breast cancer in combination w/ vincristine.

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32
Q

DNA intercalating drugs/anthracyclines example and MOA

A

Daunorubicin, doxorubicin, and dactinomycin.

  1. Intercalate DNA.
  2. Inhibit topoisomerase.
  3. Produce free radicals
33
Q

Bleomycin class and MOA

A

DNA intercalating drug

Intercalate DNA and produce free radicals.
G2 cell cycle specific.

34
Q

DNA intercalating drugs / anthracyclines PK

A

IV= rapidly distributed to all tissues except CNS
Long half-lives. Bind to tissues. Large Vd. Liver metabolised.

35
Q

DNA intercalating drug / anthracyclines ADR

A

Myelosuppression and cardiac damage (dose limiting)
NV dose related
Alopecia
Mucosal ulcerations
Tumor lysis syndrome
IV infusion can lead to severe localised tissue ulceration and necrosis (shai’s example)

36
Q

Advantages of PEG liposomal doxorubicin

A

Pegylated liposomal coating allows drug to evade detection and destruction by immune system.
Increase blood circulation time.
Remain stable in blood.
increase delivery to tumour.
Less systemic side effects.
Drug stays encapsulated within liposome during circulation.

Coat and stability = better delivery, safer. Less cardiovascular events and less toxicity.

37
Q

Bleomycin / DNA intercalating drug ADR

A

Very little myelosuppression
Often combined w/ myelosuppressive drugs
Pulmonary and mucocutaneous reactions (no aminohydrolase in skin)

Pneumonitis that progresses to interstitial fibrosis (lose elastic), hypoxia, and death.

Mild stomatitis, skin hyperpigmentation, erythema, and edema.

38
Q

Why do you see hyperpigmentation w/ bleomycin use

A

Aminohydralase inactivates drug.
Not a high conc in skin or lungs
Drug build up = toxicity

39
Q

Vinca alkaloids / mitotic inhibitor examples and MOA

A

Vincristine and vinblastine

Inhibit mitosis by blocking microtubule assembly. = Continued disassembly.

40
Q

Vinca alkaloid / mitotic inhibitor PK

A

IV administration only, intrathecal will kill.
Does not enter CNS.
Biliary excretion, extensive metabolism.

41
Q

Vinca alkaloids indications

A

Blood.
Solid= small-cell lung cancer and neuroblastoma

42
Q

Vincristine and vinblastine ADR

A

Dose-limiting neurotoxicity (peripheral neuropathy)
Suppress deep tendon reflexes.
Parasthesia.
Cranial nerve damage= hoarse, facial palsies, jaw pain.
Autonomic neuropathies= orthostatic hypotension, abdominal pain, and constipation.

Vinblastine= dose-limiting myelosuppression. Little neurotoxicity.

43
Q

Taxanes / mitotic inhibitor drug examples and MOA

A

Paclitaxel and docetaxel

Inhibit mitosis by blocking microtubule disassembly. = Continued assembly.

44
Q

Taxane PK and indications

A

Given IV.
Eliminated via metabolism and biliary excretion.

Paclitaxel indicated for metastatic ovarian/breast cancer in combination w/ cisplatin or if unresponsive to first-line therapy.

Docetaxel indicated for castrate-resistant prostate cancer.

45
Q

Taxanes ADR

A

Dose-limiting myelosuppression.
Alopecia.
Neurotoxicity.
Hypersensitivity reactions at site of infusion.

46
Q

Explain nAB paclitaxel

A

Albumin-bound paclitaxel = better delivery and less toxicity

47
Q

Etoposide class and MOA

A

Topoisomerase inhibitor / podophyllotoxin

Cause double stranded DNA breaks by inhibiting topoisomerase 2.

48
Q

Camptothecin analogue / topoisomerase inhibitor examples and MOA

A

Topotecan and irinotecan.

Cause single stranded DNA breaks by inhibiting topoisomerase 1.

49
Q

Etoposide (T2) PK and indications

A

TDM important- oral bioavailability varies between patients, so check for over/underdosing.

Unchanged in urine.

Synergy w/ platinum compounds.

Indicated for preoperative treatment for bone marrow transplant

50
Q

Etoposide ADR

A

Well tolerated.

Alopecia, mild N/V, dose-limiting myelosuppression.

Low incidence of secondary nonlymphocytic leukemias.

51
Q

Camptothecin analogue (topotecan and irineotecan) PK and indications

A

IV. Prodrugs.

Indicated for colorectal cancer that has recurred or progressed following fluorouracil therapy.

52
Q

Camptothecin analogue ADRs

A

Myelosuppression - dose-limiting - both.

Irinotecan = diarrhoea
Both = alopecia and mild N/V

53
Q

Imatinib class and MOA

A

Protein kinase inhibitor

Inhibit BCR-ABL tyrosine kinase that decreases transformation and proliferation. Increases apoptosis.

54
Q

Erlotinib class and MOA

A

Protein kinase inhibitor

Inhibit epidermal growth factor (EGFR), which decreases proliferation, metastasis, and angiogenesis.
Increases apoptosis.

55
Q

Abemaciclib class and MOA

A

Protein kinase inhibitor

Inhibit CDK4 and 6. Prevents transition from G1 to S phase.
Arrests cell in G1 phase to prevent DNA synthesis.

56
Q

Encorafenib class and MOA

A

Protein kinase inhibitor

Inhibit BRAF gene. Prevent activation of RAF/MEK/ERK signalling pathway to prevent tumour proliferation.

57
Q

Venetoclax class and MOA

A

Monoclonal antibody.

Inhibit BCL-2 and promote apoptosis.

58
Q

Sunitinib class and MOA

A

Protein kinase inhibitor

Inhibit VEGFR to decrease angiogenesis.

59
Q

Rituximab class and MOA

A

Monoclonal antibody.

Bind to CD20 antigen on surface of non-Hodgkins lymphoma cell to prevent cell cycle initiation.

60
Q

Cetuximab class and MOA

A

Monoclonal antibody.

Antobody to EGFR. Decrease proliferation, metastasis, and angiogenesis.
increase apoptosis.

61
Q

Bevacizumab class and MOA

A

Monoclonal antibody

Antibody binds to VEGF that inhibits angiogenesis.

62
Q

Trastuzumab class and MOA

A

Monoclonal antibody

MAB binds to HER2/neu receptor which inhibits cell proliferation.

63
Q

Ipilimumab class and MOA

A

MAB / immunomodulator

Antibody binds to CTLA-4 and leads to T-cell activation.

64
Q

Pembrolizumab and nivolumab class and MOA

A

MAB / immunomodulator

MAB binds to PD1 receptor. Blocks interactions between ligands, PD1, PDL1 and 2. = Increase T cell activation.

65
Q

Trastuzumab ADRs

A

Chills, fever, N/V, chest pain, and dyspnoea.

66
Q

Ipilimumab (Yervoy) ADR

A

Immune-related
- colitis
- hepatitis
- dermatitis
- neuropathies

67
Q

Pembrolizumab (Keytruda) ADR

A

Pneumonitis
Colitis
Hepatitis (and autoimmune)
Hypophysitis

If SE, stop drug forever.

68
Q

Abemaciclib indication

A

HR+ve or HER2-ve
metastatic breast cancer

69
Q

Tamoxifen class, MOA, and use.

A

Oestrogen antagonist. Starve tumour of hormones. Prevent breast cancer. Combination w/ surgery to treat.

70
Q

Aromatase inhibitors examples and MOA

A

Anastrozole and letrozole.
- prevent oestrogen synthesis

71
Q

Gonadotropin-releasing hormone agonist example and MOA

A

Leuprorelin

Increase testosterone levels, increase DHT, then hypothalamus stops production of T.
Bad SE at first because tumour size increases for 2-3weeks at start

72
Q

Gonadotropin-releasing hormone receptor antagonist example and MOA

A

Degarelix

Block GNRH on testes. Androgens release T from testes.

73
Q

Corticosteroid MOA in cancer

A

switch off hypothalamus androgen production. Block ACTH.

74
Q

5a-reductase inhibitor example and MOA

A

Finasteride

Decrease DHT = stop tumour proliferation.

75
Q

ADT side effects

A

Sexual - erectile dysfunction, libido loss, genital shrinkage
Physical - weight gain, gynaecomastia, muscle atrophy
Metabolic - osteoporosis, anaemia, hypertension, diabetes, heart disease, dyslipidemia
Emotional
Systemic - fatigue
Tumour “flare” - GnRH agonist

76
Q

Principles of radiotherapy

A

Direct= radiation->DNA damage-> cell death

Indirect= radiation-> free radicals-> DNA damage-> cell death. (increase cytokine production)

77
Q

External vs internal radiotherapy

A

External= x-ray, gamma, proton beams
Internal= brachytherapy.

78
Q

ADR of radiation

A

Psychological= depression
Fatigue
Skin= dermatitis.
Cardio/pulm= CVD. Pneumonitis.
GIT= dry mouth, esophagitis, diarrhea, N/V.

Genitourinary= erectile dysfunction, dry vagina, infertile, cystitis, teratogenic.

Radiation recall= skin necrosis, inflammatory response. Only problem if radiation+chemo.

3028PHM (9 decks)

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