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Pharmacology > (2) Cancer Pharmacology and pregnancy > Flashcards

(2) Cancer Pharmacology and pregnancy Flashcards

1
Q

What is the second leading cause of death in the US

A

cancer

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2
Q

What is characteristic of cancer

A

uncontrolled cell replication of the body’s own cells

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3
Q

What is a tumor

A

an abnormal growth of new tissue arising from uncontrolled cellular proliferation that has no physiological function

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4
Q

what is a neoplasm

A

a new growth

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5
Q

What is a malignancy

A

a cancer with invasive properties, more life threatening that non-malignant cancers

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6
Q

What is benign

A

non-invasive, less life threatening than a malignancy

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7
Q

what is metastisize

A

when a tumor has pieces that break off and spread to other parts of the body

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8
Q

What is the most common type of oral cancer

A

squamous cell carcinoma (epithelial)

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9
Q

how many people per year are diagnosed with oral cancer

A

30,000

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10
Q

how many people die each year from oral cancer

A

8,000

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11
Q

What is the population at most risk for oral cancer

A 
people over 40
men 2x more likely than women
African americans more likely 
those who smoke and drink (both is higher than either alone)
people with HPV-16 and HPV-18
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12
Q

What is the link between HPV and oral cancer

A

HPV infects epithelial cells (which are prominent in the oral cavity) smoking and drinking alcohol promotes HPV invasion

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13
Q

Which is more likely to be cancerous leukoplakia or erythroplakia

A

erythroplakia

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14
Q

if a oral lesion doesn’t resolve after ________ it should be reevaluated and considered for a biopsy

A

2 weeks

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15
Q

When should a dental exam be performed in relation to cancer treatment

A

at least 1 month before the start of cancer treatment to permit adequate healing from any invasive oral procedure

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16
Q

what affect do chemotherapeutic drugs have on wound healing

A

they impair wound healing

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17
Q

do chemotherapeutic drugs cause xerostomia

A

the often do

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18
Q

What are the three main approaches to cancer treatment?

A

surgical excision
irradiation
chemotherapy

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19
Q

What is chemotherapy

A

the pharmacological approach to cancer treatment

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20
Q

what makes chemotherapy so complicated

A

the cancer cells are mammilian cells and are very similar to healthy cells

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21
Q

What are the 4 characteristics of cancer cells that differ from normal healthy cells

A

1 - uncontrolled proliferation
2 - Dedifferentiation of cells
3 - invasiveness
4 - metastisis

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22
Q

What are the two types of cells that normally prevent cells from being cancerous

A

proto-oncogenes

tumor supressing genes

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23
Q

What is an oncogene

A

a gene which has potential to cause cancer (the mutated form of a proto-oncogene)

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24
Q

What is a tumor suppressor gene

A

a gene that protects the cell from becoming cancerous (when mutated it loses that ability)

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25
Q

What are the mechanisms by which cancer cells have uncontrolled proliferation?

A
  1. resistance to apoptosis
  2. Telomerase expression
  3. Angiogenesis
  4. Loss of cell cycle stop points
  5. increased responsiveness to growth factors
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26
Q

What does dedifferentiation of cancer cells mean

A

that the cells are poorly differentiated, the cells are no longer specific to a certain function.

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27
Q

Is more differentiation or less differentiation indicative of more advanced cancer and thus a worse prognosis

A

less “poorly” differentiated cells are associated with more advanced cancers and have a worse prognosis

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28
Q

What does the cancer characteristic of invasiveness mean?

A

cancer cells lose responsiveness to region specific growth cues, this allows them to grow in other locations. They also begin secreting enzymes which break down the extracellular matrix and allow the tumor to spread

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29
Q

What is metastasis

A

when cells break off from a tumor, travel to a different location and form secondary tumors.

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30
Q

What does the TNM stand for in calculated risk in cancers

A 
T = Tumor
N = Node
M = Metastasis
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31
Q

What are the different T values in the TNM cancer staging

A

T0 = No evidence of tumor
Localized = Tumor is confined to primary site of origin
Extension (not T4) = tumor has extended beyond the site of origin but not to specified T4 locations

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32
Q

What are the locations into which if a tumor extends (in the oral region) the tumor is classified as T4a

A 
Through bone
To deep/extrinsic muscles of the tongue
Maxillary sinus
Skin of Face
Medial Pterygoid
Hard palate
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33
Q

What are the locations into which if a tumor extends (in the oral region) the tumor is classified as T4b

A 
Encases the Internal Carotid artery
skull base
pterygoid plates
massicator space
lateral pterygoid muscle
lateral nasopharynx
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34
Q

What is the relative prognosis for a T1-3 cancer and a T4 cancer

A

the higher the T value the worse the prognosis (T4 is worse than T1-3)

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35
Q

What are the different N values in the TNM cancer staging

A 
N0 = no lymph node metastasis
N1 = metastasis (<3cm) into a single ipsilateral node
N2a = Metastasis (> 3cm, < 6cm) in a single ipsilateral node
N2b = metastasis (< 6cm) in multiple ipsilateral nodes
N2c = metastasis (<6cm) in bilateral nodes
N3 = Metastasis in any node > 6 cm
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36
Q

If you have a cytotoxic cancer drugs that at a given dose is known to kill 99% of cancer cells. and you start with 100 billion cancer cells. How many cells will remain after treatment

A

1 billion

1% survives, 1% of 100 billion is 1 billion

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37
Q

why is the idea of leaving some cancerous cells (in cancer therapy) different than leaving some bacterial cells (in antibiotic therapy)

A

because leftover bacterial cells following antibiotic treatment can be cleaned up by the bodies immune system. cancer cells cannot be

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38
Q

what is the goal of cytotoxic cancer treatment drugs

A

to get the number of cancer cells as close zero as possible

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39
Q

why is early treatment of a tumor more successful

A

because early on the tumor has fewer cells so it is easier to get the total number closer to zero

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40
Q

What is adjuvant chemotherapy and why is it more successful than chemotherapy alone

A

adjuvant chemotherapy is when chemotherapy follows surgical removal of a tumor, or radiation. is it more successful because a large number of tumor cells have been removed. the smaller the number of cells remaining = easier to get close to zero cells with chemotherapy

41
Q

What is the level of detection for cancer (how many cells does the tumor have when it first becomes detectable)

A

approximately 10^9

42
Q

What happens if you stop chemotherapy when the cancer is no longer visible

A

you have left 10^9 cancer cells and they will continue to duplicate and to spread and the cancer will grow to detectable levels again

43
Q

Why are so many rounds of chemotherapy often needed to cure (approx 0 cells) cancer

A

because there is regrowth of the tumor between chemo courses (you kill two logs of cells, then 1 log regrows before the next course begins)

44
Q

What are the three types of cells typically found in a tumor

A

Group A = continuously dividing cells
Group B = not currently dividing but are capable
Group C = cells incapable of cell division

45
Q

What is important to know about Group A cells in a tumor

A

they are continuously dividing
they are the most susceptible to chemotherapy
they only make up about 5% of cells

46
Q

What is important to know about Group B cells in a tumor

A

they aren’t currently divinding, which makes them more difficult to treat with chemo, but they are capable of dividing in the future

47
Q

What is the most common target of current anticancer drugs

A

rapidly dividing cells

48
Q

what is the negative side effect of anticancer drugs attacking the rapidly dividing cells of cancer

A

they also attack the rapidly dividing cells of the body and cause

  • bone marrow toxicity
  • impaired wound healing
  • loss of hair
  • damage to GI epithelium
  • Depression of growth in children
  • sterility
  • teratogenicity in pregnant females
49
Q

What is combination therapy with anticancer drugs and why is it done

A

it is the use of several chemotherapy drugs with different mechanisms of action and thus different toxicities together. it is done because it is more effective and because it helps prevent chemotherapy resistance in the cancer

50
Q

with chemotherapy Is it better to perform high doses for a short period of time or small doses given continuously

A

high doses for short periods of time with time in between for recovery

51
Q

What are the chemotherapy drugs involved in the CHOP combination therapy

A 
C = Cyclophosphamide
H = Hydroxydaunorubicin
O = Oncovin
P = Prednisone
52
Q

What are the 8 main types of chemotherapeutic drugs

A
  1. alkylating agents
  2. antimetabolites (folate antagonists)
  3. antimetabolistes (Base analogs)
  4. cytotoxic antibodies
  5. plant derivatives
  6. hormones/antagonists
  7. kinase inhibitors
  8. Monoclonal antibodies
53
Q

What is the most commonly used alkylating agent in cancer therapy

A

cyclophosphamide

54
Q

what is the mechanism of action for anticancer alkylating drugs

A

they form intra and inter chain crosslinks with DNA bases (this doesn’t allow DNA to replicate and form a proper double stranded helix)

55
Q

What types of cells are affected by the alkylating agent cyclophosphamide

A

both rapidly proliferating and non-proliferating cells (cell cycle non-specific)

56
Q

Is cyclophosphamide a progrug

A

yes, it is activated by the p450 enzymes of the liver

57
Q

what is the major toxicity of alkylating drugs

A

myelosuppresion (suppression of bone marrow and blood cell formation)

58
Q

What is the most commonly used antimetabolite anticancer drug

A

methotrexate

59
Q

What is the function of folates in many reactions

A

it acts as a coenzyme to metabolism of amino acids and DNA

60
Q

What is methotrexate in relation to folates

A

it is a folate antagonist (prevents folates from acting as a coenzyme in metabolic reactions)

61
Q

What are the side effects of methotrexate

A
  • myelosuppression
  • GI toxicity
  • Nephrotoxicity
62
Q

What is Leucovorin

A

a drug often given in combination with methotrexate because it can rescue cells from methotrexate toxicity

63
Q

What are the antimetabolite drugs that act as base analogs

A 
5 - fluorouracil
Cytarabine
6-Mercaptopurine
6- thioguanine
pentostatin
azathioprine
64
Q

What makes base analogs good cancer treating drugs

A

they interfere with the copying of DNA

65
Q

what cells do base analogs target

A

those rapidly dividing

66
Q

What are the two most common cytotoxic antibiotics used in cancer treatment

A

Doxorubicin (Adriamycin)

Bleomycin

67
Q

What is the mechanism of action for Doxorubicin (adriamycin)

A

Topoisomerase 2 inhibitor (inhibits DNA replication and RNA synthesis)

68
Q

what are the main unwanted effects of taking the cytotoxic antiobiotic doxorubicin (adriamycin)

A 
nausea
vomiting
hair loss
myelosuppression
cardiotoxicity (high dose)
69
Q

What is the mechanism of action for bleomycin (the cytotoxic antibiotic) used in cancer treatment

A

causes single (mostly, some double) strand breaks in DNA

70
Q

what drug is commonly used to treat squamous cell cancer in the head, neck and esophagus

A

bleomycin

71
Q

What is the most common plant derivative used in cancer chemotherapy

A

Paclitaxel (taxol) (from yew tree bark)

72
Q

what is the method of action of the plan derivative paclitaxel (taxol)

A

stabilizes or freezes microtubule assembly (thus inhibiting mitosis)

73
Q

What types of cancers is the plant derivative paclitaxel (taxol) used for

A

breast and ovarian cancers

74
Q

what are the main unwanted effects of paclitaxel (taxol)

A 
myelosuppression
hair loss
GI disturbance
neurotoxicity (peripheral neuropathy)
hypersensitive reactions are fairly common
75
Q

What is the most common hormone given in the treatment of cancers

A

prednisone

76
Q

what type of hormone is prednisone

A

a glucocorticoid

77
Q

what is the method of action of prednisone in cancer treatment

A

prevents lymphocyte proliferation

78
Q

what type of cancers is prednisone used to treat

A

leukemias

also used as palliative care in other cancers, mediates nausea and vomiting

79
Q

what is the main unwanted effect of prednisone treatment for cancers

A

causes cushings syndrome

80
Q

What is the main hormone antagonist used in cancer treatment

A

tamoxifen

81
Q

what is the method of action of tamoxifen (hormone antagonist)

A

estrogen receptor antagonist

82
Q

for what types of cancers if tamoxifen used to treat

A

breast cancers that respond to estrogen

83
Q

what is the main side effect of tamoxifen treatment of cancers

A

menopause like symptoms

84
Q

What is the most commonly used monoclonal antibody used in the treatment of cancers

A

bevacizumab (avastin)

85
Q

What is the method of action for the monoclonal antibody bevacizumab (avastin)

A

binds VEGF, blocks angiogenesis

86
Q

What is the most common protein kinase inhibitor used in cancer treatment

A

Imatinib (Gleevec)

87
Q

what is the method of action for Imatinib (gleevec) as a protein kinase inhibitor of cancer treatment

A

it inhibits Bcr/Abl kinase (a product of chromosome translocation in the philidelphia chromosome)

88
Q

what type of cancer is the protein kinase inhibitor imatinib (gleevec) used to treat

A

chronic Myeloid leukemia (due to the philidelphia chromosome)

89
Q

what are the main unwanted effects of imatinib (gleevec)

A

GI effects and fatigue (minimal for chemo)

90
Q

What drug is given to manage emesis in patients receiving chemo

A

Ondansentron

91
Q

what drugs are given to manage the myelosuppression in patients receiving chemo

A

Erythropoetin - stimulates RBC development, helps recover

Filgrastim - human G-CSF, stimulates differentiation of hematopoeitic cells

92
Q

What is primary resistance in a tumor

A

when a tumor is resistant to the drug the first time that it is given

93
Q

what is acquired resistance in a tumor

A

tumor is initially susceptible to the drug but then becomes resistant

94
Q

What are the two mechanisms by which tumors become resistant to chemo drugs

A

adaptation or mutation

95
Q

What are resistance mechanisms cancer cells use to become resistant to chemo drugs

A
  • decreased drug accumulation (increase outbound transporters, decrease inbound transporters)
  • insufficient drug activation
  • increased drug inactivation
  • use of alternate metabolic pathways
  • induction of rapid cell repair mechanisms
  • mutations in the drug target
96
Q

What are the three things that must happen for a drug to be effective against cancer

A
  1. drug must reach the cell
  2. drug must enter the cell in the phase in which the drug is active
  3. tumor can’t be resistant to the drug
97
Q

what is the future of chemotherapy

A

getting the patients own immune system to attack the cancerous cells

98
Q

What is the FDA pregnancy regulation

A

no longer using pregnancy categories due to confusion. the FDA believes that a narrative structure is best

Pharmacology (8 decks)

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