Brainscape's Knowledge GenomeTM

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


See full index

SBL 2 > Cancer Pharm (Liz P.) > Flashcards

Cancer Pharm (Liz P.) Flashcards

1
Q

Major MOA of alkylating agents and causes arrest where in cell cycle?

A
  • Transfer of alkyl group to DNA –> DNA cross-linking

- Arrest occurs in late G1, early S phase

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

What are 3 mechanisms to resistance of Alkylating agents?

A
  • ↑ capability to repair DNA lesion –> ↑ expression MGMT
  • ↓ cellular transport of the alkylating drug
  • ↑ expression of glutathione
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the most widely used alkylating agent that has a high oral bioavailability and can be given IV?

A

Cyclophosphamide

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

Which toxic metabolite of Cyclophosphamide is responsible for the antitumor effects?

A

Phosphoramide mustard

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

Which toxic metabolite of Cyclophosphamide is associated with hemorrhagic cystitis?

A

Acrolein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What should patients receive when on high doses of Cyclophosphamide?

A

Vigorous IV hydration

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

Complete remissions and presumed cures have been seen with Cyclophosphamide when given as a single agent for what type of cancer?

A

Burkitt Lymphoma

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

Which 2 alkylating agents are lipid soluble nitrosoureas allowing them to cross BBB and be effective in treating brain tumors?

A

Carmustine and Streptozocin

  • Generate both alkylating and carbamylating moieties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the clinical use of Carmustine and what makes this drug so effective in these tumors?

A
  • Malignant Glimoas (implantable Carmustine wafer)
  • Methylation of the MGMT promter inhibits MGMT expression in 30% of primary gliomas
  • Assoc. w/ sensitivity to carmustine and other nitrosureas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the AE’s associated with the alkylsulfonate, Busulfan, at high doses?

A

ulmonary fibrosis** + GI mucosal damage + hepatic VOD

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

What alkylatingn agen can be used to treat malignant melanoma?

A

Dacarbazing and Cisplatin however the response to them is low

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

What is the MOA of Methotrexate?

A
  • Inhibits synthesis of THF

- Interferes w/ formation of DNA, RNA, and key cellular proteins

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

What are 4 mechanisms by which resistance to Methotrexate may develop?↓

A
  • ↓ drug transport via the reduced folate carrier or folate receptor protein
  • ↓ formation of cytotoxic methotrexate polyglutamines
  • ↑ levels of the target enzyme DHFR thru gene amplification, etc.
  • Altered DHFR protein with reduced affinity for methotrexate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are 4 drug-drug interactions that you must be aware of when giving Methotrexate?

A

Aspirin, NSAIDs, penicillin, and cephalosporins all inhibit its renal excretion —> ↑ toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Aspirin, NSAIDs, penicillin, and cephalosporins all inhibit its renal excretion —> ↑ toxicity

A

Aspirin, NSAIDs, penicillin, and cephalosporins all inhibit its renal excretion —> ↑ toxicity

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

What are the 3 active metabolites of 5-FU and what is the MOA of each?

A
  • FdUMP —> inhibition of DNA synthesis thru “thymineless death”
  • FUTP –> incorporated in RNA; interferes w/ RNA processing and mRNA translation
  • FdUTP –> incorporated into DNA resulting in inhibition of DNA synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are 4 AE’s of the antimetabolite, 5-FU; which is unique?

A
  • GI toxicity (diarrhea/mucositis) = unique
  • Myelosuppression
  • Skin toxicity (hand-foot syndrome) = unique
  • Neurotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

5-FU is the most widely used drug in the tx of which cancer?

A

Colorectal cancer

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

6-mercaptopurine (6-MP) is inactive in parent form and becomes active when metabolized to what?

A

Metabolized by HGPRT –> monophosphate nucleotide 6-thioinosinic acid

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

What is the MOA of the active metabolite of 6-MP, mono- and triphosphate nucleotide 6-thioinosinic acid?

A

Monophosphate acts to inhibit several enzymes of de novo purine nucleotide synthesis

  • Triphosphate form incorporated into both DNA and RNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How is the active form of 6-mercaptopurine (6-MP) inactivated and what clinical implication does this have?

A
  • Converted to inactive metabolite by xanthine oxidase
  • Allopurinol (xanthine oxidase inhibitor) is commonly used in tx of acute leukemia for prevention of hyperuricemia
  • If allopurinol is used w/ 6-MP, would result in ↑ levels of 6-MP and excessive toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

6-mercaptopurine is used in the tx of what?

A

Childhood acute leukemia

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

List the 5 MOA of 6-thioguanine?

A
  • Inhibits several enzymes in de novo purine nucleotide synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

6-thioguanine synergizes with what drug in the tx of adult acute leukemia?

A

Cytarabine

25
Q

What is the MOA of the vinca alkaloids, vinblastine, vincristine, and vinorelbine; specific to which phase?

A
  • Inhibit tubulin polymerization by DISRUPTING assembly of microtubules; especially those involved in mitotic spindle
  • M-phase specific: results in mitotic arrest in metaphase
26
Q

AE’s of vinblastine and Vincristine?

A

Hair loss, local cellulitis

  • Myelosuppression to greater extent with VinBlastine
  • VinCristine causes neurological toxicities
27
Q

Vinblastine is used for what cancers?

A

Hodgkin’s and NHL’s, breast, and germ cell cancer

28
Q

How does drug resistance to Vinca alkaloids occur?

A

Membrane efflux pump P glycoprotein

29
Q

What is the dose-limiting AE’s of Vincristine?

A
  • Neurotoxicity –> Peripheral sensory neuropathy manifesting as:
  • ANS dysfunction w/ orthostatic hypotension; urinary retention; paralytic ileus or constipation; CN palsies; ataxia; seizures; coma
30
Q

Which 2 vinca alkaloids are associated with SIADH as potential AE’s?

A
  • Vincristine

- Vinorelbine

31
Q

Which vinca alkaloid can be used for pediatric tumors, rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma, and Wilms tumor?

A

Vincristine

32
Q

Which 3 natural products work by binding to microtubules and enhancing tubulin polymerization causing cell death; which phase do they work in?

A
  • Paclitaxel, Docetaxel, and Cabazitaxel (Taxanes)

- Work in the M phase

33
Q

Which 2 natural products are associated with hypersensitivity reactions as AE’s?

A
  • Paclitaxel

- Docetaxel

34
Q

What are acute vs. delayed dose limiting toxicities associated with Paclitaxel?

A
  • Acute = N/V, hypotension, arrhythmias, hypersensitivity

- Delayed = myelosuppression, peripheral sensory neuropathy

35
Q

What is the MOA of the epipodophyllotoxin, Etoposide?

A

Forms complex w/ and inhibits activity of topoisomerase II and DNA

36
Q

What is the MOA of the camptothecins, Topotecan and Irinotecan?

A

Inhibit activity of topoisomerase I, the key enzyme for cutting and religating single DNA strands –> DNA damage

37
Q

What are 2 forms of diarrhea which may arise as AE of camptothecins, Topotecan and Irinotecan?

A
  • Early form = occurs within 24-hrs of tx; cholinergic event; tx w/ atropine
  • Late form = occurs 2-10 days after tx; can be severe and leads to electrolyte imbalances and dehydration
38
Q

What are the major MOA of the anthracyclines?

A
  • Inhibition of topoisomerase II
  • Generation of free radicals
  • DNA intercalation –> blocking of DNA and RNA synthesis
39
Q

What is a major AE associated with anthracyclines?

A

Cardiotoxicity; both an acute and chronic form

40
Q

What is the MOA of bleomycin; arrests cells in which phase?

A

ells accumulate in G2 phase Think ‘B’leomycin = bi- = 2

41
Q

What is the dose limiting toxicity associated with bleomycin?

A

Pulmonary toxicity –> pneumonitis w/ cough, dyspnea, dry crackles on PE and infiltrates on CXR

42
Q

Tyrosine kinase inhibitors are metabolized by what CYP?

A

CYP3A4

43
Q

The tyrosine kinase inhibitor, Imatinib, specifically inhibits what?

A
  • BCR-ABL fusion protein

- Inhibits RTK’s for PDGFR and c-kit

44
Q

What are some of the delayed toxicities associated w/ the tyrosine kinase inhibitor, Imatinib?

A
  • Fluid retention w/ ankle and periorbital edema
  • Myalgias
  • CHF
  • Diarrhea
45
Q

What is the clinical use for the tyrosine kinase inhibitor, Imatinib?

A

1st line for chronic phase CML, in blast crisis, and as 2nd line for chronic phase CML that has progressed on prior IFN-α tx

  • GI stromal tumors expressing c-kit
46
Q

What is the MOA for the tyrosine kinase inhibitors, Dasatinib and Nilotinib; how do they differ from Imatinib?

A
  • Inhibitor of BCR-ABL, c-kit, and PDGFR-β tyrosine kinases
  • Dasatinib binds active and inactive conformations of ABL kinase; while Nilotinib has higher binding affinity for ABL kinase
  • Overcomes imatinib resistance from mutations in BCR-ABL kinase
47
Q

What is the clinical use for Dasatinib and Nilotinib?

A

1st line therapy of chronic phase CML

48
Q

What are 3 unique AE’s of the GF receptor inhibitor, Cetuximab?

A
  • Acneiform skin rash
  • Hypersensitivity infusion rxn
  • Hypomagnesemia
49
Q

The activity of the GF receptor inhibitor, Cetuximab, is restricted to patients with tumors expressing what?

A

Wild-type RAS, including KRAS and NRAS

50
Q

What is the MOA of the GF receptor inhibitor, Erlotinib; who responds best to this drug?

A
  • Inhibitor of the tyrosine kinase domaine assoc. w/ EGFR

- Pt’s who are non-smokers are more responsive

51
Q

AE’s associated w/ the GF receptor inhibitor, Erlotinib and Gefitinib?

A

Skin rash and diarrhea

52
Q

What are the 5 unique AE’s of the GF receptor inhibitor, Bevacizumab, Ziv-afibercept, and Ramucirumab?

A

HTN

  • ↑ incidence of arterial thromboembolic events (TIA, stroke, angina, MI)
  • Wound healing complications
  • GI perforations
  • Proteinuria
53
Q

What is the unique MOA of the GF receptor inhibitor, Ziv-aflibercept?

A

Soluble receptor to VEGF-A, VEGF-B, and PIGF; binds ligands of VEGF and prevents their interactions with VEGFR

54
Q

What is the MOA of the GF receptor inhibitor, Sorafenib?

A

Inhibits multiple RTK’s, including VEGF-R2 and R3, PDGFR-β, and raf kinase

55
Q

What are the AE’s associated with the GF receptor inhibitor Sorafenib and Sunitinib?

A 
Vascular toxicities
fatigue
Nausea
Diarrhea
Anorexia
56
Q

MOA for Dasatinib, a RTK inhibitor?

A

Kinase inhibitor that inhibits BCR-Abl, Src, C-KIT, and PDGFR-B

57
Q

Nilotinib MOA?

A

Kinase inhibitor that inhibits BCR-Abl, Src, C-KIT, and PDGFR-B

Higher binding affinity for Abl compared with imatinib, it overcomes imatinib resistance

58
Q

What is the MOA for the proteasome inhibitor Bortezomib?

What is it approved for?

A

Inhibits proteasomes activating signaling cascade that leads to cell cycle arrest and apoptosis

Approved for multiple myeloma or mantle cell

SBL 2 (9 decks)

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