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Pharmacology: Exam 3 > Lecture 6: Cancer Chemotherapy II > Flashcards

Lecture 6: Cancer Chemotherapy II Flashcards

1
Q

What is Multiple Myeloma?

A

A malignancy of plasma cells

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2
Q

What are 6 characteristics of multiple myeloma?

A
  • Skull x-ray- “punched-out lesions”
  • Very painful and usually older patients
  • Monoclonal gammopathy
  • Bence-Jones proteins in urine (Ab light chains) leading to renal insufficiency
  • Bacterial infections due to low IgG production;
  • Hypercalcemia
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3
Q

What are 4 key disposing factors of Hepatocellular carcinoma?

A
  • Chronic Hepatitis B
  • Chronic Hepatitis C
  • Alcoholism
  • Aflatoxin exposure (Mold)
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4
Q

What is the environmental cause of Mesothelioma and what can this increase the risk of?

A
  • Asbestos induces mesothelioma directly
  • increases the risk of Squamous cell carcinoma in conjunction with cigarette smoking

Mesothelial lining = Outside lining of the lung

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5
Q

Does smoking increase the risk of Mesothelioma?

A

NO

if you smoke and you get squamous cell carcinoma it does not increase your chance of getting mesothelioma

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6
Q

What are 2 antibiotics used as Chemotherapeutic agents?

A

Doxorubicin
DNA-bleomycin

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7
Q

What do antibiotics do to act as a chemotherapeutic agent?

A

Interacts with DNA and disruption of function, intercalates into DNA, inhibits topoisomerases, and generates free radicals to induce their effect

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8
Q

MOA of Doxorubicin as a chemotherapeutic agent (3)

A

Induces cytotoxicity due to:

  • Membrane lipid peroxidation
  • DNA-strand breaks
  • Direct oxidation of purines and pyrimidines

uses CP450 to create free radicals and cause DNA break

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9
Q

What is a major side effect of doxorubicin/ daunorubicin?

A

Cardiotoxicity

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10
Q

MOA for bleomycin as a chemotherapeutic agent

A

causes DNA breaks, used to treat Hodgkin’s disease and testicular cancer, bleomycin-Fe3+ interacts with DNA to cause strand breaks.

creates a complex with oxidized Fe and creates free radicals which causes DNA break

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11
Q

What is a major side effect of Bleomycin?

A

Pulmonary fibrosis

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12
Q

Which drugs (5) are alkylating agents used as chemotherapeutic agents?

A

Cyclophosphamide
Carmustine and Lomustine
Decarbazine
Temoxolomide

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13
Q

How do Alkylating agents work as a chemotherapeutic agent? What is a major side effect that they can cause?

A
  • Through Covalent interactions with key cellular component such as DNA, frequently used in combination with other drugs to treat cancers
  • They are mutagenic and cause other cancers such as acute leukemia
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14
Q

Cyclophosphamide
1. Therapeutic use
2. MOA
3. Major toxicity

A
  1. Therapeutic use: non-Hodgkin’s lymphoma, breast cancer, and sarcomas
  2. MOA: its modification in the liver via CytochromeP450, to phosphoramide mustard is the major alkylating agent for DNA that is cytotoxic
  3. Major toxicity: hemorrhagic cystitis
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15
Q

Which alkylating agent(s) crosses the BBB?

A

Carmustine, Lomustine, Temozolomide

!!CLT CROSSES BBB!!

all used for treatment for brain tumors
temozolomide can also be used for melanoma therapies

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16
Q

Which 2 drugs are nitrosoureas?

A

Carmustine and Lomustine

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17
Q

Temozolomide is related to ____ and is metabolized into ____

A

Dacarbazine, MTIC

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18
Q

Dacarbazine
MOA?
Theraputic use?
Cross BBB?

A

MOA: (MTIC) which induces DNA methylation of guanine residues
Therapeutic use: Melanoma and Hodgkin’s lymphoma
Cross BBB: NOOO

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19
Q

Alkylating agents

What are the therapeutic uses for each?
Mechlororethamine
Melphalan
Busulfan
Chlorambucil

LY

A

Mechlorethamine- lymphoma treatment
Melphalan- multiple myeloma treatment
Busulfan- CML treatment
Chlorambucil- CLL treatment

LY

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20
Q

What are the microtubule inhibitors used as chemotherapeutic agents?

A
  • Vincristine and Vinblastine
  • Paclitaxel and Docetaxel
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21
Q

Vincristine and Vinblastine
–MOA?
–Vincristine therapeutic use
–Vinblastin therapeutic use

A

–MOA: microtubule depolymerizing drugs that block tumor cell proliferation by interfering with the cell cycle at the M phase.
–Vincristine: ALL, Wilm’s tumor, Ewing’s sarcoma, Hodgkin’s and Non-Hodgkin’s lymphoma
–Vinblastine: Hodgkin’s and Non-Hodgkin’s lymphoma

-stine=depoly

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22
Q

Paclitaxel and Docetaxel
–MOA?
–Paclitaxel therapeutic use (3)
–Docetaxel therapeutic use (4)

A

–MOA: microtubule stabilizing drugs that block tumor cell proliferation by interfering with the M phase of the cell cycle.
–Paclitaxel: ovarian, breast, and non-small cell lung cancer
–Docetaxel: prostate, breast, GI, and non-small cell lung cancers

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23
Q

Which drug(s) are platinum coordination complexes?

A

Cisplatin

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24
Q

Cisplatin
MOA?
Therapeutic use?
Side effects?

A

MOA: binds to guanine in DNA forming inter- and intra strand cross-links, these modifications block both DNA and RNA synthesis
Therapeutic use: used synergistically with radiation and other drugs to treat: ovarian, testicular, and bladder cancer
Side effects: severe nausea and vomiting, nephrotoxicity, ototoxicity

cross-links with strand and outside strand

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25
Q

Which drugs are Topoisomerase Inhibitors?

A

Topotecan
Etoposide

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26
Q

Topotecan and Etoposide MOA

A

Topoisomerase Inhibitors
Topoisomerases reduce torsional strain during DNA replication (S PHASE),
Blockade leads to double-strand breaks in DNA, inhibiting DNA replication

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27
Q

Theraputic use for
A. Topotecan
B. Etoposide

A

A. Topotecan- used to treat ovarian and small cell lung cancer, inhibits DNA replication
B. Etoposide- used to treat lung and testicular cancer

28
Q

Which drugs are steroid hormones and their antagonists? These drugs are impt for which type of cancers?

A
  • Tamoxifen
  • Anastrozole and Letrozole
  • Leuprolide

important in the therapy of breast and prostate cancer

29
Q

What is Tamoxifen?

A

estrogen antagonist, and inhibits estrogen-dependent growth of breast cancer (in ER+ tumors)

30
Q

What is Anastrozole and letrozole?

A

Aromatase inhibitors that block extra-adrenal synthesis of estrogen
Use: postmenopausal women with breast cancer

31
Q

What is Leuprolide?

A

A GnRH analog which inhibits FSH and LH release, which reduce estrogen and testosterone levels (Prostate Cancer)

32
Q

4 characteristics of Acute lymphoblastic leukemia (ALL)

A
  1. young patients
  2. Big cells=Leukemia blasts
  3. Cells are early in development
  4. Can rapidly kill pt (Survival has increased to 90% due to effective tx)
33
Q

3 characteristics of Chronic lymphocytic leukemia (CLL)

A
  1. Elderly patients
  2. Cells stuck in late development
  3. Not as rapid-chronic and slow
34
Q

Prostatic Adenocarcinoma
SX?
Lab?

A

Sx: Low back pain
Lab: Elevated PSA

35
Q

3 Key Genetic Changes in Leukemias/ Lymphomas

A

MYC trabslocation->progrowth by incr cell division warburg metabolusm
MLL translocation and PML-RARA fusion gene->incr self-renewal
BCL2 translocation-> Prosurvival by decr apoptosis

36
Q

What is Hodgkin’s Lymphoma?

A

spread contiguity with no extra nodal presentation
Has a big success With tx

37
Q

What is Non-Hodgkin’s lymphoma?

A

spread noncontiguous, through multiple nodes, with Waldeyers ring, and Extra nodal presentation.
Tx more difficult

spreading crazy in lymph nodes=harder to treat

38
Q

What is Burkitt’s Lymphoma?

A

Myc amplification
Lymphoma cells are latently infected with Epstein-Barr virus (EBV)

39
Q

What is Follicular lymphoma?

A

Amplified expression of the anti-apoptotic gene, Bcl-2

40
Q

What is Diffuse Large B-Cell Lymphoma?

A

Highly aggressive tumor with a marked growth rate; must be treated right away with chemotherapeutic regimens
Most cases show increased expression of !! Bcl6 !!, Bcl2 or Myc expression

41
Q

What are the subtyes of Acute Myeloid Leukemia (AML)?

A

M3 and M5

42
Q

What is the M3 subtype of AML?

A

M3 subtype: Promyelocytic leukemia
Stuck as Pro-myelocyte
Auer Rods
APC

43
Q

What is the M5 subtype of AML?

A

M5 subtype: Monocytic leukemia
Stuck as Pro-MONOcyte

44
Q

What is Acute Promyelocytic Leukemia (APL) caused by?

A

Chromosome 15-17 translocation causing RARα/PML fusion.

PML is related to cell death, when translocated it will disrupts self renewal
And they cannot differentiate (no seld-renewal)-> Grow Leukemic Blasts

45
Q

What can treat (therapeutics) RARα/PML fusion?

A

All trans retinoic acid and arsenic trioxide
Trans retinoic Acid leads to differentiation (May not last)
Trans Retinoic Acid + Arsenic Trioxide = better chance

46
Q

Hodgkin’s Disease plays a key role for what and induces what?

A

key role for malignant Reed-Sternberg cells and inducing
a proinflammatory and tissue injury environment

47
Q

Why are malignant lymph nodes growing in Hodgkin’s disease?

A

because the accumulation of non-malignant cell types ( the environment creates mass that is similar to cancer mass aka, acts like a malignant mass but isn’t one)
Pro Inflammation + Mass that grows like a Cancer (Very unusual)

malignant cells are NOT causing damage

48
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

What is R-CHOP?
Treats?

A

Rituximab
Cyclophosphamide
(H) Doxorubicin
(O) Vincristine
Prednisone
Treats: non-Hodgkin’s lymphoma- B-cell lineage

49
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

What is MOPP?
Treats?

A

Mechlorethamine
(O) Vincristine
Procarbazine
Prednisone
Treats: Hodgkin’s disease

50
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

What is ABVD?
Treats?

A

(A) Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
Treats: Hodgkin’s disease

51
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

What is BEACOPP?
Treats?

A

Bleomycin
Etoposide
(A) Doxorubicin
Cyclophosphamide
(O)Vincristine
Procarbazine
Prednisone
Treats: Advanced or recurrent Hodgkin’s disease

52
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

What is Hyper-CVAD?
Treats?

A

Cyclophosphamide
Vincristine
(A) Doxorubicin
Dexamethasone
Methotrexate and Cytarabine also used in alternating cycles
Treats: pediatric ALL, administered into the CNS to prevent lymphoma spread there

53
Q

What treats ALL of the B-Cell lineage?

A

Monoclonal antibodies directed to CD22

B-cell surface marker

54
Q

Key Multidrug Combinations that are effective Chemotherapeutic Regimens

Which drugs are AC-T?
Treats?

A

(A) Doxorubicin
Cyclophosphamide
(T) Paclitaxel
administered in a sequential manner
Treats: early-stage breast cancer

55
Q

What is malignant melanoma?

A

Local invasion and lymph node metastasis
Mutations in controlling cell proliferation and survival
Sometimes people regress and they wonder if it is due to the immune system

56
Q

What is the treatment for Malignant melanoma?

A

Immunomodulatory antibodies- a developing therapy for solid tumors including melanoma
(ANTI PDLI is Tx)

57
Q

Renal Cell Carcinoma/Clear Cell Carcinoma
SX?
Path?
Hx?

A

Sx: Flank pain and mass, hematuria
Path: Renal vein invasion
Hx: Von-Hippel Lindau syndrome

58
Q

What are genetic alterations that cause the development of pancreatic adenocarcinoma

A

telomere shortening
Activation of: KRAS mutation
inactivation of: CDKN2A, TP53, SMAD4, BRAC2

59
Q

What is Glioblastoma multiforme?

A

Can spread along white matter tracks and cross the midline through the corpus callosum

60
Q

Explain Pulmonary and bone metastasis

A

It’s a metastasic carcinoma

  • Renal cell CA goes to the lung
  • Metastatic Breast CA goes to the bone
61
Q

Doxorubucin falls under which class of chemotheraputics?
A. Alkylating agents
B. Anti-metabolites
C. Antibiotics
D. Microtubule inhibitors

A

C. Antibiotics

62
Q

Which of the following drugs depolarize the microtubules?
A. Paclitaxel
B. Vinblastine
C. Docetaxel
D. None of the abive

A

B. Vinblastine

63
Q

Which of the following cancers presents with cells latently infected with Epstein-Barr virus?
A. Multiple Myeloma
B. Follicular Lymphoma
C. Burkitt’s Lymphoma
D. Hodgkin’s Disease

A

C. Burkitt’s Lymphoma

64
Q

Which of the following cannot cross the BBB to treat cancers finding sancturary in the CNS?
A. Carnustine
B. Lomustine
C. Temozolomide
D. Darcabazine

A

D. Darcabazine

65
Q

Which of the following drugs is not part of the MOPP multi-drug therapy of Hodgkin’s?
A. Mechloroethamine
B. Vincristine
C. Procarbazine
D. Doxorubicin

A

D. Doxorubicin

Pharmacology: Exam 3 (8 decks)

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