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pharm 411/412 > Antineoplastic agents > Flashcards

Antineoplastic agents Flashcards

1
Q

What is cancer?

A

Its characterized by uncontrolled growth thro uncontrolled cell division

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2
Q

What are the types of cancer

A

There are many types of cancer and they are all named for the places in which they are located
Lung, breast, colon and so on

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3
Q

Where does cancer sit on the list of most likely to kill Americans?

A

its number two but by the year 2025 its projected to be the number one

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4
Q

What are the differences between normal cells and cancer cells?

A

Cancer has uncontrolled cell division
They do not go thro apoptosis (programmed cell death)
Causes more angiogenesis
The cells metastasize

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5
Q

What is apoptosis?

A

Process of programmed cell death (PCD) biochemical events lead to cell death

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6
Q

What is angiogenesis?

A

formation of new blood vessels

** it gives blood supply to the tumor which allows it to grow rapidly

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7
Q

What does it mean by metastasize?

A

Its the spread of cancer cells to nearby and other tissues frequently using blood vessels and or lymphatic system
**ex is prostate cancer, very low people die from prostate cancer it is more likely it will metastasize and infect somewhere else

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8
Q

What is the most effective way to treat cancer?

A

surgery, 70% are cured this way, best thing to to do is cut it out

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9
Q

What is radiation?

A

Its next best option to treat cancer is usually given along with surgery to shrink before you have the surgery or after to help eliminate anything left over

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10
Q

What are anti-neoplastic agents?

A

They are used to treat cancer by stopping one of the areas which cause cancer
Chemotherapy
Targeted Therapy

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11
Q

What is adjuvant chemotherapy?

A

Its a chemo treatment given AFTER primary therapy (usually surgery) this will increase the chance of long-term disease-free survival
**Even tho it might have been cut out the cancer could have metastazied elsewhere which doesnt show up on a scan so it best to just try and treat it

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12
Q

What is a Neo-adjuvant chemotherapy?

A

Its chemo given prior to primary treatment (usually surgery) to shrink the tumor
**minimize organ dmg

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13
Q

What is a biologic drug (biologics)

A

A product from living organisms or contain components of living organisms that change the manner of operation of natural bio intracellular and cellular actions

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14
Q

What are the anti-Neoplastic drug classes?

A

Chemotherapy

Targeted Therapy

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15
Q

What are the Chemotherapy anti neoplastics

A 
Antimetabolits (Block DNA/RNA synthesis)
Mitotic Inhibitors (Block microtubules)
Topoisomerase Inhibitors 
Alkylating agents 
Anti-tumor antibiotics
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16
Q

What are the targeted therapy Anti-Neoplastic drugs

A

Tyrosine kinase inhibitors
Monoclonal antibodies
Hormone regulators
Others

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17
Q

Where do chemotherapy drugs work and why is it an issue for patients?

A

They target rapidly dividing cells by inhibiting the cell-cycle
This is a problem because it also inhibits normal cells with rapidly divide
Hair follicles
Digestive tract (mucositis)
Myelosuppression (blood cells such as WBC and RBC, leads to anemia)

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18
Q

What is the interphase of the cell cycle and how long does it take?

A

G1, S, and G2

Its the longest part of the cell cycle

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19
Q

What happens during mitosis?

A 
This is where actual cell division occurs in 4 phases
Prophase (longest, Puppy)
Metaphase (Mayva)
Anaphase (Ate)
Telophase (Tarantula)
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20
Q

What is the G0 phase?

A

Its the stage of a cell who is not ready for division (usually starvation)
**NOT part of interphase

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21
Q

What happens during G1 phase?

A

Cell synthesizes enzymes and proteins needed for division

**RNR to create dNTPs

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22
Q

What happens during S phase?

A

In this phase DNA replication occurs, now cell have two sets of chromosomes (prelude to 4n condition)

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23
Q

What happens during the G2 phase?

A

Phase during which proteins and enzymes need for mitosis are produced
**microtubules are produced to aid in mitosis, centrosome divides

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24
Q

What is the M phase?

A

Mitosis phase

When cell division occurs

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25
Q

What regulates the cell cycle?

A

Cyclins (DEAB)
Cyclin-dependent Kinases (CDKs)
**these work together as positive regulator of cell cycle
CDK inhibitor proteins (CKI) and or cyclin inhibitors
**these are known as tumor suppressors

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26
Q

What happens in cancer cells in regulates to what cyclins and CDKs do?

A

They upregulate the expression of CDKs and cyclins to force cell division to move forward
this leads to uncontrolled cell proliferation and growth

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27
Q

What happens to CKIs and cyclin inhibitors in cancer cells?

A

They are often mutated and dont work which leads to uninhibited/unchecked cell division
**often time both CDK and cyclins as well as CKI and cyclin inhibitors are messed up

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28
Q

What are the two main tumor suppressor proteins?

A 
P class of proteins (p53) 
P stands for peptide and the number just means how long it is

Retinoblastoma (Rb)
*they block CDKs or cyclins

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29
Q

What controls the cell from going from G0 to G1?

A

It requires growth signaling from cell surface
Controlled by cyclin D/ cdk4,6

**cyclin D is a big influencer in cancer

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30
Q

What controls going from G1 to S in the cell cycle?

A

If no DNA dmg is found (proof reading, role of p53)

Cyclin E/cdk2 controls if it moves forward

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31
Q

What causes the cell cycle to go from S to G2?

A

If no DNA dmg (second proof reading by p53)

Cyclin A/cdk2 controls the movement

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32
Q

What controls the cell cycle to go G2 to M?

A

No DNA dmg

CyclinB/cdk1 controls the movement

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33
Q

How does p53 work when it comes to controlling the cell cycle?

A

p53 looks for DNA dmg and then from there it will release other peptides which can block cyclin D (G0 to G1) as well as blocking cyclin E (G1 to S)
Guardian of the cell genome

**retinoblastoma (Rb) can block cyclin E (G1 to S)

***They lead the cell to go thro apoptosis!!

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34
Q

What can a mutation in p53 lead to?

A

It can lead to mutation of other proteins including oncogenes (like activation of RAS or inhibition of tumor suppressor genes like p21)

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35
Q

What are microtubules made of?

A

the proteins alpha and beta tublin

*they pull apart the chromosomes

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36
Q

What is prophase?

A 
Longest phase 40 min
Chromosomes condense 
Nuclear envelope disappears
Centrosomes move to opposite poles 
Spindle apparatus is assembled
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37
Q

What happens during Metaphase

A

14 min
Short resting period where the chromosomes line up along the equator of the cell and the spindle fibers attached to the centromeres

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38
Q

What happens during Anaphase?

A

2 minutes
The centromeres divide, at this point, each individual chromosome goes from 1 chromsome with 2 chromatids to 2 chromosomes with on chromatid each

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39
Q

What happens during telophase?

A

4 minutes
The cell actually divides
Goes thro cytokinesis and the cytoplasm is divided into 2 separate cells

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40
Q

What happens during cytokinesis?

A

The organelles get divided into 2 daughter cells.

It uses actin fibers (microfilaments composed of actin) forms around the equator and contracts pinching it in half

41
Q

What is process of nuclear division and the division of the cytoplasm called?

A

Mitosis and cytokinesis

42
Q

What are the different categorizes of antineoplastic drugs?

A 
Cell cycle specific (CCS) 
*only goes after 1 specific phase
Cell cycle non-specific (CCNS)
**goes after many areas of the cell cycle, often more side effects 
Others AKA targeted therapy
43
Q

What are the cell cycle specific (CCS) antineoplasic drugs

A 
Antimetabolites (DNA/RNA synthesis, S-phase)
Vinca Alkaloids (formation of microtubles, M-phase)
Taxanes (effects breaking down mircotubles, M-phase)
Topoisomerase inhibitors (required in DNA replication, S-phase)
44
Q

What are the cell cycle non-specific (CCNS) antineoplasic drugs

A 
Alkylating agents
Cytotoxic antibodies (anthracyclines)
45
Q

What are the targeted therapy antineoplasic drugs?

A

Monoclonal antibodies
Tyrosine kinase inhibitors
Hormone modulators
Immunotherapy

46
Q

How do antimetabolites work to prevent cancer?

A

They are anti-folic acid pathway, pyrimidine or purine analogues
They induce cell death during S phase by getting incorporating into RNA and DNA or inhibiting enzymes needed for nucleic acid production

47
Q

What are the types of antimetabolites?

A

Anitpyrimidines (uracil and cytosine analogs)
Antipurines (adenine and guanine analogs)
Antifolates

48
Q

How does methotrexate and premetrexed work?

A

Inhibits dTTP: deoxythymidine triphosphate synthesis
They bind to the active site of DHFR which interferes with synthesis of tetrahydrofolate (THF)
Used for cancer and inflammation (rheumatoid arthritis)
**inhibits cell cycle in S-phase

49
Q

Whats something you would want to give to a patient after they take methotrexate or premetrexed?

A

This is because you want to try and repair the cells other than the cancer because by blocking DHFR you stopped the production of THF and the folic acid will help to produce more THF

50
Q

What is 5-Flourouracil (5-FU) and capecitabine?

A

They are anitmetabolites of uracil and inactivate thymidylate synthase (TS) in the s-phase

51
Q

What is the difference between capecitabine and 5-FU?

A

5-FU must be given thro IV and you must give folic acid with it where capecitabine is the prodrug of 5-FU and is more potent as well as taken by oral route (doesnt need to be taken with folic acid)

52
Q

How does 5-FU and capecitabine work?

A

they get metabolized into FdUMP
FdUMP binds to thymidylate synthase (TS) and so does THF to form a ternary complex
**the binding of these break TS
Its important to note that 5-FU must be given with luecovorin (folic acid) this is because you need it go thro DHFR and produce THF
***works in S-phase

53
Q

What is the cytosine antimetabolite?

A

Gemcitabine, works in S-phase

54
Q

What is the gaunine antimetabolite?

A

6-mercaptopurine

Works in S-phase by becoming incorporated into DNA and RNA

55
Q

What is the adenine antimetabolite?

A

Cladribine

**works in S-phase

56
Q

What are vinca alkaloids?

A

Antimitotic drug
Blocks spindle fiber formation (interacts with B-tubulin and disrupts microtuble formation)
Happens in Metaphase
Causes Neurotoxicity
Examples: VINcristine, VINblastine, VINorelbine
**all start with vin

57
Q

What are Taxanes?

A

Antimitotic drug
Binds B-tubulin stabilizes microtubules, and prevents breakdown
Prevent anaphase to telophase
Side effects: Hypersensitivity, myelosupression
Examples: PacliTAXEL, doceTAXEL
**have TAX in the name

58
Q

What does a pt need to take while also taking a taxane?

A

Since a side effect is hypersensitivity patients need take a steroid (dexamethasone, anti-inflammation)
They also should take diphenhydramine (anti-histamine) and ranitidine (antacid)

59
Q

What are topoisomerase inhibitors?

A

Its a CCS which works in the S-phase, it causes kinks in the DNA and causes it to break and then not be able to be recreated

60
Q

What are the topoisomerase I inhibitor?

A

IrinoTECAN
TopoTECAN
**end in tecan

Common side effect
Myelosuppression (remember each chemo drug causes this)
comes from bark of camptotheca acuminata

61
Q

What is the topoisomerase II inhibitors?

A 
etopOSIDE
tenipOSIDE
**end in OSIDE
common side effect myelosuppression
comes from american mayapple plant
62
Q

What are anthracyclines?

A 
CCNS, known as cytotocic antibiotics
Block cell cycle at various stages
Side effects Cardiotoxicity
Examples: DoxoRUBICIN, daunoRUBICIN
**end in RUBICIN
63
Q

How do alkylating and intercalating agents work to prevent cancer?

A

They cause DNA dmg by the formation of cross-bridges, bonds between atoms this keeps DNA from being separated fro synthesis
**run the risk of getting leukemia 5 to 10 years after being treated with one

64
Q

What are the alkylating agents?

A 
CCNS, given as last resort usually
Create A-G or G-G crosslinking
Side effects: N/V Myelosuppression
Examples: Busulfan, Cyclophosphamide
AABC
All, Aminals, Become, Cute
65
Q

What are platinum based intercalating agents?

A 
Alkylating-like
Binds guanine resides of DNA and creates crosslinking
Side effects: Nephrotoxicity
Ex: cisPLATIN, carboPLATIN, oxaliPLATIN
**ends in PLATIN
66
Q

What does it mean to use a combination therapy?

A

We must give combos of drugs in order to fight the cancer and stop it at as many places as possible

67
Q

What does FOL stand for in a combo drug?

A

Leucovorin (folic acid)

68
Q

What does F stand for in combo drug?

A

5-FU

69
Q

What does iri stand for in a combo drug

A

irinotecan

70
Q

what does ox stand for in a combo drug?

A

oxaliplatin

71
Q

What something important to note about the use of FOL in a combo drug?

A

It must also have F with it because it would be needed in order to treat the pt effectively

72
Q

what is R in an R-CHOP combo drug?

A

Rituximab

73
Q

What is C in an R-CHOP combo?

A

cyclophosphamine

74
Q

what is H in an R-CHOP combo?

A

Doxorubicin hydrochloride (Hydroxydaunomycin)

75
Q

What is O in an R-CHOP combo?

A

Vincristine sulfate (Oncovin)

76
Q

What is the P in an R-CHOP combo?

A

Prednisone

77
Q

What are tyrosine kinase inhibitors?

A

Things like cytokines (IL-6) and growth factors (EGF) signal to-regulate cell cycle using protein tyrosine kinases
They inhibit these kinases and growth factors to block tumor growth, metastasis and induce apoptosis
EX: imatiNIB, sorafeNIB and sunitiNIB
** they end in NIB

78
Q

Whats important to note about imatinib

A

Brand name: gleevec
Tyrosine kinase (BCR-ABL) inhibitor, was called “magical bullet”
works by binding to BCR-ABL and keeping it from signaling and prevents cancer from growing

79
Q

Whats important to note about Sorafenib and Sunitinib?

A

They block many different TKR and stop cancer at cell cycle, thro angiogenesis and stops metastasis

80
Q

What are monoclonal antibodies?

A

Created thro biotech. and are very targeted towards what they treat
They are given thro IV (since its a protein and oral would cause it to break down)

81
Q

Whats the biggest ADR (adverse drug reaction) when giving a monclonal antibody?

A

An immune rxn at the site of infusion called infusion rxn

82
Q

What is Avastin (bevacizumab)

A

Its an anti VEGF

**this prevent angeogensis meaning blocking blood supply to the tumor

83
Q

What is herceptin (trastuzumab)

A

Treats HER2+ breast cancer

Its an anti HER2 drug (stops it from over signaling and helps stop tumor growth)

84
Q

What is Erbitux (cetuximab)

A

Its an Anti EGFR which means it stops signaling of the tumor so it doesnt grow

85
Q

What is yervoy (Ipilimumab)

A

Its an antitumor T-cell activator

86
Q

What are cytotoxic T-cells?

A

They are natural defense mech against cancer. They detect mutated protein which are expressed in cancer cells and kill them

87
Q

What is cancer Immunotherapy?

A

Its using drugs to find a way to get out T-cells to become active and attack the mutated cancer cells

88
Q

What is PD1?

A

PD1 is a receptor on a T-cell which can be bound to inactivate the T-cell or keep it dormant

89
Q

What is PDL1?

A

This is something found on our cells and some cancer cells that bind to PD1 of T-cells and cause them to become inactive and not attack the cancer cells

90
Q

What is a PD1 inhibitor?

A

Pembrolizumab (keytruda) and Nivolumab (Opdivo)

91
Q

What is a PDL1 inhibitor?

A

Atezolizumab (texentriq)

Good for treating bladder cancer

92
Q

What something you need to worry about when using PD1 and PDL1 inhibitors?

A

They can lead to autoimmunity because it can cause the body to attack itself which can lead to harm to organs and tissues

93
Q

What is CTLA-4?

A

Think of it like a gun without bullets, its a T-cell that has a lot of these which means it wont go and attack cells.

94
Q

What is a CTLA-4 inhibitor?

A

Ipilimumab (Yervoy)
This binds to CTLA-4 and can motivate cytotoxic T-cells to attack cancer cells

*can have ADR of autoimmunity related organ dmg

95
Q

What are Hormone Modulators?

A

Tamoxifen (soltamox)

It blocks the actions of estrogen by binding estrogen receptor (ER) which shuts off the signaling it produces

96
Q

What are rescue Therapy-symptom relievers?

A

They dont treat cancer but they are given because they treat related side effects of taking cancer meds

97
Q

What is Denosumab?

A

Its used for osteoporosis but it often given with cancer meds because they can create brittleness and pain in bones
**activates osteoclast which is for bone resorption

98
Q

What is Neulasta (pegfilgrastim) or Neupogen (filgrastim)

A

Used when giving chemo to mobilize neutrophils from bone marrow. used for treatment of neutropenia

pharm 411/412 (11 decks)

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