Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Fundamentals of Pathology > Anti-Neoplastics Drugs > Flashcards

Anti-Neoplastics Drugs Flashcards

1
Q

What are the three alkylating agents?

A

Mechlorethamine
Cyclophosphamide
Carmustine
Procarbazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do the alkylating agents work and what do they target?

A

Introduce alkyl-groups into DNA (+ other various targets)

causing DNA cross-linking and strand breaks.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the alkylating agents that is cell-cycle nonspecific?

A

Mechlorethamine
Carmustine
Target any tumor cells in any phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What alkylating agent is cell-cycle specific, phase nonspecific?

A

Cyclophosphamide - targets any dividing cell, not G0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do the myelosuppression of the alylating agents compare?

A 
Cyclophosphamide = Limited suppression
Carmustine = Delayed suppression
Mechlorethamine = Most suppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What alkylating agent can pass the blood-brain barrier?

A

Carmustine, due to high lipophilicity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What alkylating agent is used in combination Hodgkin’s Lymphoma and has a very short half-life?

A

Mechlorethamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What alkylating agent is a pro-drug and what is a unique side effect?

A

Cyclophosphamide. Must be activated by cytochrome.
Produces phosphoramide (active) and Acrolein (toxic).
Acrolein can cause bladder toxicity, sterile hemorrhagic cystitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What alkylating agent has the widest spectrum of treatment?

A

Cyclophosphamide, cycle-specific, phase nonspecific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What kind of cancers does Carmustine treat?

A

Brain tumors
Multiple myeloma
–Only one that can cross the blood-brain barrier quickly–

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What class of anti-neoplastics specifically target cells that are in the S-phase?

A

Anti-metabolites, analogs of compounds required for metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What drug prevents the recycling of tetrahydrofolate for thymidine synthesis?

A

Methotrexate, inhibits DHFR, preventing reduction of folate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is Methotrexate used and how are normal cells spared?

A

Methotrexate can be used in large doses, then given Leucovorin to “rescue” normal cells, due to their ability to import the Leucovorin inside more easily.
(fully reduced folate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What should be watched when treating a patient with Methotrexate?

A
  • bone marrow suppression
  • renal tubular necrosis
  • *Other drugs that can displace Methotrexate from Albumin (how it’s transported)**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What kind of cancers is Methotrexate typically used for?

A

Acute Lymphocytic Leukemia

Choriocarcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What anti-metabolite is a uracil analog and what are it’s effects?

A

Fluorouracil (5FU)
- becomes activated in the cell, converted to:
5UTP = inhibits RNA synthesis
FdUMP = interferes with thymidine synthesis, preventing DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What kind of cancers is 5FU most commonly used for?

A

GI Cancers, stomach, colon, pancreas

Breast and Basal cell carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a cytidine analog used to treat acute leukemias, especially myelocytic leukemia?

A

Cytarabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the common side effects of 5FU?

A
  • n/v/d + anorexia

- Myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does Cytarabine work in preventing cell division?

A

Competes with Cytidine for phosphorylation and incorporation into DNA causing chain terminations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How are the side effects of Cytarabine different than 5FU?

A
  • more significant myleosuppression, limits dosing

- neurotoxicity (not a side effect of 5FU)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is a common purine analog used to prevent DNA synthesis?

A

Mercaptopurine, inhibits DNA/RNA synthesis by being converted to a ribonucleotide 6MP, becoming incorporated into the strands and disrupting.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the biggest concern when treating a patient with Mercaptopurine for ACUTE LEUKEMIAS?

A

There are populations of patients who have deficient TPMT that breaks down 6MP, which can cause severe bone marrow suppression. Patients should be tested for the defect prior to starting treatment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What therapeutic is used to prevent the conversion of NTP to dNTP for integration into DNA?

A

Hydroxyurea - inhibits ribonucleotide reductase

causing the blocking of DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does hydroxyurea effect the cell cycle and what is commonly used with this treatment?

A

S-specific treatment, arrests the cell in S-G1 interface. Used in conjugation with radiation therapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is hydroxyurea commonly used to treat and what is the biggest concern of side effects?

A

Granulocytic Leukemia

Side effect: Hematopoietic Depression ( + GI symptoms)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do the vinca alkaloids effect cancer cells?

A

M-phase specific, bind tubulin, inhibiting formation of microtubules and the mitotic spindle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How are the side effects of Vinblastine and Vincristine different?

A

Vinblastine, STRONG bone marrow suppression and epithelial ulcerations
Vincristine, hairloss, neuromuscular abnormalities and neuropathy, LESS bone marrow suppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Which Vinca alkaloid would be best for treating Hodgkin’s and Non-Hodgkin’s lymphoma?

A

Vinblastine, also treats Breast Cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What type of cancer is most commonly treated by Vincristine?

A

Acute Lymphocytic Leukemia

+ Wilms Tumor, Neuroblastoma, Lymphomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the mechanism of action of taxanes and what phase do they work?

A

Taxanes enhance the stability of microtubules by binding the B-subunit, which blocks transition into M-phase. G2-M transition.

32
Q

What drug can be used to sensitize cancer cells to be more susceptible to radiation?

A

Paclitaxel. This blocks transition into M-phase, which is when the cancer cells are most susceptible to radiation therapy.

33
Q

Paclitaxel can be used with what other drugs for an additive effect?

A

Paclitaxel can interfere with DNA repair intensifying the effects of DNA damage caused by cisplatin / cyclophosphamide.

34
Q

When are taxanes (Paclitaxel) typically used to treat cancers and what are the side effects?

A

Refractory ovarian and breast cancer.

Dose-Limiting leukopenia, peripheral neuropathy / myalgias

35
Q

What are the various mechanisms of action of Doxorubicin?

A
  • intercalating between DNA base pairs
  • lipd peroxidation / free radical generation
  • binds to DNA and topoisomerase
36
Q

What kind of cells does Doxorubicin target and types of cancer?

A

Cycle-specific, phase nonspecific

  • Hodgkins/Non-Lymphoma
  • Breast/Ovarian
  • Small-cell lung
37
Q

What is a unique attribute of Doxorubicin that is uncommon among many anti-neoplastics?

A

Has anti-angiogenic properties

38
Q

What is the biggest drawback of using Doxorubicin?

A

Cardiomyopathy, cumulative dose effect

+bone marrow suppression and GI

39
Q

What is the key to the functionality to Bleomycin?

A

Iron activates the glycopeptides that bind DNA causing oxidative damage and double stranded breaks

40
Q

What type of cells are targeted by Bleomycin?

A

Cells in G2 phase, Bleomycin = phase specific

Used to treat: Germ Cell Tumors of testes/ovaries

41
Q

What is a unique side effect of Bleomycin?

A

Dose-related Pulmonary Toxicity, possibly fetal
Vesiculation of the skin
Skin Hyperpigmentation
*Minimal bone marrow and immune suppression

42
Q

Which natural antibiotics selectively target cells in the G2 phase?

A

Bleomycin

Etoposide

43
Q

What is the mechanism of Etoposide?

A

Stabilizes topoisomerase complexes, causing double stranded breaks

44
Q

What are typical side effects and usages for Etoposide?

A

Wide range = Lymphomas, Acute leukemia, testicular

Side effects: Dose-limiting Leukopenia

45
Q

What can be used to help limit neutropenia from cancer therapy?

A

Filgrastim - G-CSF, promotes progenitors of neutraphils to be released and expands the population.
Faster recovery from bone marrow suppression.

46
Q

What is the antibody used to selectively target metastatic breast cancer cells? How?

A

20-30% of breast cancer cells overexpress the HER2 receptor, Trastuzumab binds the receptor preventing its function of promoting proliferation.

47
Q

What are the adverse effects of using the Trastazumab antibodies?

A

Cardiomyopathy
Hypersensitivity
Infusion reactions, fever/chills, etc

48
Q

What chemotherapy drugs use platinum complex to cross-link DNA?

A

Cisplatin - cycle specific, phase nonspecific
Carboplatin
Oxaliplatin

49
Q

What is Cisplatin primarily used for treating?

A

Testicular and Ovarian cancers (in combination)

50
Q

What are the main toxicities associated with Cisplatin?

A
  • Nephrotoxicity
  • Ototoxicity
  • Neuropathy + Electrolyte imbalance
  • Mild-Mod Myleosuppression
51
Q

How are Carboplatin and Oxaliplatin different from Cisplatin?

A

Lower chance of the serious side effects from Cisplatin, but they have a more narrow spectrum.
Oxaliplatin is best at Colon Ca of the group

52
Q

How does Procarbazine work at killing tumor cells?

A

Atypical alkylating agent, activated in vivo into a methylating agent damaging chromosomes. Does not cross react with other alkylating agents.

53
Q

What does Procarbazine typically target?

A

Best for cells in G1 and S-phase
–Hodgkin’s Lymphoma
Side effects, myleosuppression + n/v

54
Q

When are hormones used as chemotherapy agents?

A

When the cancers are dependent upon steroids for growth signals.

55
Q

What are the various approaches to battling steroid dependent cancers?

A
  • Opposite Steroid compounds

- Anti-Hormon compounds

56
Q

What is a possible consequence of using hormonal therapy?

A

The tumor cells can stop responding to the hormones and switch to G0 making it more difficult to kill them.

57
Q

When and how is prednisone used to treat cancers?

A

Binds to steroid receptors, depresses expression of growth factor genes inducing nucleases which can modulate lysis of the cell.
Primarily: Lymphomas and Leukemias + Breast Cancer

58
Q

What are added effects of Prednisone?

A
  • Anti-emetic
  • Stimulates appetite
  • Anti-inflammatory
    Can cause: Immunosuppression, limited myleosuppression
59
Q

How does Tamoxifen block breast cancer from growing?

A

Nonsteroidal anti-estrogen activated in vivo that competitively blocks estrogen receptors, typically preventing the cancer from growing, but once treatment stops they continue growing again.

60
Q

Who can Tamoxifen be used in most effectively?

A

Advanced Post-Menopausal breast Cancer
Pre-menopausal metastatic breast cancer
–Prophylaxis for high risk patients–

61
Q

What are the side effects from Tamoxifen?

A

Hot flashes
Fatigue
Muscle pain
N/V

62
Q

How does the mechanism of Letrozole compare to Tamoxifen?

A

Letrozole is an irreversible aromatase inhibitor, preventing estrogen from being produced
Tamoxifen blocks the estrogen receptor.
Same side effects*

63
Q

What kind of patients is Letrozole used for?

A

1st line treatment with post-menopausal advanced or metastatic breast cancer

64
Q

How is the effectiveness of Letrozole compared to Tamoxifen?

A

Letrozole has a longer survival rate and longer time for the cancer to progress

65
Q

How does Leuprolide lower the amount of testosterone?

A

Analog of GnRH, which stimulates LH/FSH causing testosterone to PEAK, then after 2-4 weeks lowers it to very low amount due to desensitizing the cells to GnRH

66
Q

What and When is Leuprolide used to treat?

A

Advanced Hormonal responsive prostate cancer, usually 1st line therapy.
Side effects: Impotence and Hot flashes

67
Q

What drug is typically used to treat metastatic prostate cancer?

A

Flutamide

68
Q

How does Flutamide function in treating prostate cancer?

A

Anti-Androgen that blocks the androgen receptor, nonsteroidal.

69
Q

What are unwanted side effects of Flutamide?

A

Gynecomastia
Hepatotoxicity
Impotency

70
Q

What are ways in which resistance can occur against cancer therapies?

A
  • Resting Cells, G0
  • Toxic side effects, lowered doses
  • Normal apoptosis triggers not functional
  • Spontaneous mutations
  • SELECTION
  • Multi-Drug Resistance
71
Q

How do therapies unknowingly select for resistant cells?

A

Tumors that are overgrown have many variations and when a chemotherapy drug is introduced there WILL be cells that are not effected and they are the only ones that continue to grow as the rest die from therapy.

72
Q

How do strains develop that are multidrug resistant?

A

Mediated by ATP-pumps that prevent the influx of the toxic therapy drugs.
Problematic with: Vineristine, Doxorubicin, Bleomycin, Paclitaxel, and Etoposide

73
Q

How can resistance be prevented?

A

Increasing doses of drug
Multidrug therapies
Co-administration to prevent resistance mechanisms
Recruit cells out of G0

74
Q

Which common drugs lack bone marrow suppression?

A

Prednisone
Vincristine
Bleomycin

75
Q

What are methods of combo therapies?

A

Sequential Blockage - same pathway multi targets
Concurrent inhibition - both paths
Complementary inhibition - product and synthesis inhibit
Rescue Cells - Leucovorin
Synchonization - get cells in one phase
Recruitment - entice cells to divide, then attack

Fundamentals of Pathology (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions