Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

Trastuzumab

A
  1. monoclonal antibody against HER2/NEU R tyrosine kinase, prolonged survival
  2. combined w/ cytotoxic chemotherapy
  3. Use: specific breast cancers
  4. MOA: overexpress HEGFR2 (HER2) in primary breast CA= poor prognosis.
    Binds with high affinity to HER2 R, inhibit tumor growth.
  5. Tox: nausea & vomit, chills, fever, headaches & rahses.
    Most serious: cardiac fail w/ v dys.
    Before starting need baseline EKG & ejection fraction.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Imatinib Mesylate

A
  1. inhibits BCR-ABL tyr kinase in CML
  2. targeted prot kinase inhibitor
  3. Use: CML, GIST
  4. MOA: inhibits prot tyr kinase encoded by BCR-ABL oncogene.
    Inhibits phosphorylation of kinases. Induce apoptosis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Methotrexate

A
  1. antifolate
  2. blocks DHF reductase
  3. S phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

5 FU
Cytarabine
Floxuridine

A
  1. pyrimidine analogues
  2. Inhibit thymidylate synthase
  3. Inhibit DNA pol
  4. Block thymidylate synthase
  5. S phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Mercaptopurine

Hydroxyurea

A
  1. purine analogues
  2. inhibit purine nt. interconversions
  3. inhibit ribonucleotide reductase. Stops conversion of ribont to deoxyribont. Used in myeloproliferative disorders
  4. S phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Bleomycin

A
  1. fragments DNA

2. G2 phase

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

Vincristine

Vinblastine

A
  1. bind to tubulin & block polym of MT
  2. M phase
  3. Vinca alkaloids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Paclitaxel

A
  1. promote MT formation, prevent depol
  2. M phase
  3. Taxane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Tamoxifen

A
  1. interfere with specific gene transcription
  2. G1 phase
  3. antiestrogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Etoposide

A
  1. interfere w/ topo II
  2. Epidophyllotoxin
  3. between S & G2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Dactinomycin

A
  1. binds to DNA & inhibits DNA dep RNA synthesis by preventing transcription of DNA by RNA polym
  2. Cytotoxic antibiotic
  3. between S & G2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cyclophosphamide

Busulfan

A
  1. prodrug
  2. effective in all cells whether cycling or not
  3. alkylating agent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Doxorubicin

Daunorubicin

A
  1. Antitumor antibiotics

2. act in all cells

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

Log-Kill concept

A
  1. drug or irradiation therapy kills constant proportion of cells in pop, not fixed #
  2. 1 log kill means 90% decrease in cell pop when drug with 1 log kill is given; drug with 3 log kill means 99.9% killed
  3. smaller tumor means greater proportion of cells are killed but in between cycles will regrow faster
  4. want to achieve a selective log-kill of nepolastic cells without toxicity to bone marrow & other rapidly proliferating cells. Avoid development of resistance during chemotherapy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Dose limiting toxicity

A
  1. all cytotoxic drugs are toxic to all cells dose depending
  2. Some drugs are cumulative, irrev, toxic towards organ. (methotrexate, cisplatin, doxorubicin, bleomycin, vincristine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Resistance

A
  1. cancer cells are gene labile, can produce resistance
  2. FU inhibits thymidylate synthase: cancer cell then produces isoenzyme with reduced sensitivity to drug.
  3. mercaptopurine- nt derivative, inhibits enz in purine interconversions, cancer cell produces enz that are less sensitive.
  4. methotrexate polyglutamated form inhibits DHF reductase: cancer cell causes reduced polyglutamation effect- drug less able to inhibit DHFR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Resistance

A
  1. change R affinity: methotrexate R
  2. change in expression of drug transporter GP (Pgp) so increase transport of drug out of cell (dactinomycin, doxorubicin, etoposide, vincristine, vinblastine, paclitaxel) mdr gene
  3. modify in production of drug inactivating enz or of endogenous molecs which inactivate drug- cancer cell achieves R to drugs (cytarabine & mercaptopurine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Resistance

A
  1. Enhanced activity of enz which reseal DNA strand breaks result in increased DNA repair. Reduce (cisplatin, cyclophosphamide & other alkylating agents= mismatch repairs)
  2. Reduce drug activation cytarabine, doxorubicin, FU, mercaptopurine, methotrexate, thioguanine
  3. Alteration of p53 pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Combination Chemotherapy

A
  1. dose intensity defined as amt of chemotherapy given/unit time
  2. affected by toxicities of combos used, pharmacokinetics
  3. Broader coverage against resistant cell lines
20
Q

Guides for combo

A
  1. only use drugs w/ 1 agent activity against specific tumor
  2. drugs must have diff mech of action & diff cell cycle phase
  3. drugs can’t have overlapping toxicities
  4. all drugs in regimen should be used in theri optimal dose
21
Q

Adverse Effects

A
  1. BM- severe reduction in cell #
  2. Gonads- severe reduction in germ cell #
  3. GI- reduced in rate of renewal of cells
  4. Skin- bases of hair follicles damaged- alopecia
  5. Renal- hyperuricemia, hyperCa2+, hyperK+, destroy renal tissue
  6. CRTZ & VC- severe vomiting
  7. nerves supplying tissues may be damaged (impotence, urinary incontinence)
22
Q

Antimetabolites

A
  1. Methotrexane
  2. Oral, IV, intrathecal
  3. Use: solid tumors like: choriocarcinoma, osteogenic sarcoma, ALL.
  4. MOA: DHFR is blocked comp & reversible, can’t make DNA / RNA
  5. Methotrexate taken up by cell in same [ ] as pyrimidines Prevents FH4 forming & FH2 polyglutamate accumulates (toxic).
  6. 50% plasma portien bound but can be dispalced.
  7. Adverse: nephrotoxicity, myelosuppression (penias), pulm toxicity & hepatotoxicity, GIT issues
23
Q

Pyrimidine analgoues

A
  1. 5’FU & floxuridine
  2. Use 5FU: metastatic CA of breast, CA of GIT, ovary, bladder, prostate, pancreas, oropharyn cancer, hepatoma
  3. Use floxuridine: metastaic CA of colon, renal CA
  4. MOA: 5FU interfere w/ RNA f by misincorporation of F-uridine into RNA.
    Both 5FU & floxuridine inhibit DNA syn
    5 FU inhibits thymidylate synthas
    Floxuridine coverted into FdUMP- inhibits thymidylate synthase
  5. Toxicity: delayed; anorexia & nausea, alopecia, stomatitis & diarrhea, myelosuppression.
  6. Resist: change sensitivity of enz to anticancer drug
24
Q

Pyrimidine analogue

A
  1. Cystarabine
  2. Use: AML
  3. MOA: cytarabine incorporated into DNA, blocks elongation of DNA strand interfere w/ template & DNA syn is inhibited. RNA & prot syn, indep of DNA block, not affected.
  4. Toxicity: neurotoxic
25
Q

Purine analogue

A
  1. azathioprine, mercaptopurine
  2. Use: cancer chemotherapy, immunosuppressive, disease modifying antirheumatic drugs
  3. MOA: block de novo purine syn. Nt these purine anaogues I PRPP synthetase enz. Reduce PRPP.
    Inhibit PRPP amidotransferase.
  4. Toxicity: BM suppression, penias, hepatotoxic- cholestasis
26
Q

Alkylating agents & platinum analogs

A
  1. Cyclophosphamide
  2. Use: CLL, solid tumors, NHL, ovarian CA neuroblastoma, as immunosuppressive to prevent graft reject, SLE
  3. MOA: alkylating agents are strong electrophiles through formation of carbonium ion intermed.
    Prodrug converted in liver to active N which ends metabolism (interfere w/ transcription & translation).
  4. Oral, IV
  5. Metabolized by CYP450
  6. Toxicity: myelosuppression, amenorrhea, azoospermia, leukemogenic, cardiotox, renal & bladder tox, GIT tox, nausea & vomit, oral mucositis, pulm fibrosis
  7. Cause SIADH , water intoxication.
27
Q

Alkylating agents & platinum analogs

A
  1. Busulfan
  2. Use: CML, AML, BM transplant (prior)
  3. MOA: like cyclophosphamide
  4. Tox: lung pulm fibrosis, hyperpigmentation, adrenal suppression, cataracts, thrombocytopenia
28
Q

Alkylating agents & platinum analogs

A
  1. Nitrosures: carmustine
  2. MOA: bif alkylating agent, lipophilic so cross BBB
  3. Use: malignant astrocytoma & metastatic tumors of brain
    Melanomas
    GI tumors
  4. Toxicity: CNS tox
  5. uptake into cell by active transport or passive uptake.
    Covalent bind of alkyl grps to certain molecs= form reactive electrophilic intermeds with + charge.
    Enter 2x helix & distrupt. Get abnormal base pairing & strand breakage.
29
Q

Alkylating agents & platinum analogs

A
  1. Platinum coordination complex= cisplatin, carboplatin, oxaliplatin
  2. Use: urogen cancer, testicular, ovarian, bladder, oxaliplatin in colorectal cancer
  3. MOA: cisplatin enter cells by diffusion, Cl- replaced by H2O. React with DNA & inhibit replication & transcription. Works specificially.
  4. IV w/o aluminum.
  5. Tox: nephrotoxic, vigorous hydration prior. Ototoxic, marked nausea & vomit. Periph neuropathy. Pro inflamm.
30
Q

Cytotoxic antibiotics

A
  1. doxorubicin
  2. use: solid tumors of breast, endometrium, testes & lung.
    ABVD in HL, CHOP in NHL, sarcomas, osteogenic, Ewing’s, soft tissue SA, metastatic CA of thyroid.
  3. MOA: intercalates w/ DNA & binds helical groove. Topo II poison (prevents resealing helical breaks). Strand breaks.
    Cause ROS formation
  4. Resist: deve abnormal transport proteins, mdr gene overexpress gp= pump out.
  5. IV
  6. Hepatic metabolism. bile
  7. Tox: serious cardiomyopathy, supraventricular arrhythmia.
    Erythematous streaking @ infusion site
    Myelosuppression, stomatitis, GI prob, alopecia, mutagenic & carcinogenic.
31
Q

Cytotoxic antibiotics

A
  1. Daunorubicin
  2. Use: Leukemia
  3. Similar to doxorubicin- hematuria
32
Q

Cytotoxic antibiotics

A
  1. Dactinomycin
  2. Use: rhabdomyosarcoma, Wilm’s, Ewing’s, Kaposi’s
  3. MOA: bind to DNA helix preventing transcription of DNA by RNA pol. Cause single DNA breaks= ROS form.
  4. IV
  5. Tox: hematopoietic suppresion
    pancytopenia
    proctisis, diarrhea, glossitis
    Cheilitis, ulcer in oral mucosa
    alopecia, anorexia, nause & vomit
33
Q

Cytotoxic antibiotics

A
  1. Bleomycins
  2. Use: part of combo therapy for testicular cancer
    Squamous CA of head, neck , lungs
    Lymphomas
  3. MOA: fragmentation of DNA, due to ROS. Cells accumulate in G2 phase of cell cycle.
  4. Tox: very little myelosuppression, pulm toxicity (dry cough), pulm fibrosis, hyperthermia, skin blisters, pigmentation, hyperkeratosis
34
Q

Natural Products: Vinca alkaloids

A
  1. Vincristine

2. Use: pediatric leukemia, solid tumors, HL, rhabdomyosarcoma, lymphomas, neuroblastomas

35
Q

Vinca alkaloids

A
  1. Vinblastine
  2. Use: HL, testicular CA
  3. MOA: vincristine & vinblastine are spindle poisions. Bind to tubulin & prevent assembly of MT. Block M phase of cell cycle.
  4. Resistance: associated w/ multiple drug resistence mdr gene mut
36
Q

Toxic Effects of Vinblastine & Vincristine

A

Vincristine: relatively BM sparing, peripheral neuropathy, sensory & motor paresthesias, autonomic neuropathy
Vinblastine: reversible myelosuppression, less neurotoxic, dose-limit neutropenia, leucopenia, alopecia

37
Q

Natural Products

A
  1. Epidophyllotoxins: etoposide (myelotoxic)
  2. Use: testicular CA as component of combo therapy.
    Diffuse lymphomas
    HL
    Oat cell CA of lung
  3. MOA: stabilize topo II- DNA complex causing 2x strand breaks in DNA during repl.
    Specific for late S, early G2
  4. Tox: dose limit leukopenia
    hypersensitivity rxn
    Hepatic & renal toxicity @ high doses
    Neuromuscular & skeletal toxicities.
    Unusual: may cause AML
38
Q

Natural products

A
  1. Camptothecins: Topotecan
  2. Use: colorectal, ovarian, small cell cancers
  3. MOA: topo I inhibitor, Topo I involved in DNA uncoiling for replication & transcription.
    Causes single strand DNA breaks but get repaired. Topo I inhibitors stabilize breaks leading to DNA fragment & cell death.
  4. Tox: neutropenia: dose-limit
    In pts w/ hemat malignancies: GI side effects like mucositis & diarrhea
    Nausea, vomit, liver transaminase increase, fever, fatigue, rash
39
Q

Taxanes

A
  1. Paclitaxel & Docetaxel
  2. use: primary treatment of advanced ovarian cancer.
    Metastatic ovarian cancer
    Metastatic CA of breast
    lung, esoph, bladder, head & neck cancers
    Docetaxel used for metastatic non-small cell lung cancer!
  3. Give prior: corticosteroid, antihis, H2 antagonist
  4. MOA: inhibit MT dis assembly, MT plates accum in cells causing abnorm & dysf spindles. Bind B tubulin units w/in MT polymer.
  5. Tox: hypersensitivity rxns
    severe neutropenia
    cardiac conduction defect w/ arrhythmia
    alopecia
    nausea & vomit
    Paclitaxel: periph neuropathy & m. pain, Cisplatin reduces clearance!
    Dacetaxel: nail damage & skin. Cumulative toxicity!
40
Q

Antiestrogens

A
  1. Tamoxifen
  2. SERM, selective estrogen R modulator
  3. Use: Breast cancer treatment & prophylaxis.
    After surgery, older women with inoperable tumors, in healthy women with increased risk of breast cancer
  4. MOA: blocks binding of estrogen to estrogen R in estrogen + breast CA
  5. Prodrug, metabolized by CYP2D6.
  6. Tox: nausea & vomit, hot flashes, vaginal bleeding, disease flare, hyperCa2+, ocular dysf, periph edema
41
Q

Antiestrogens

A
  1. Fulvestrant- pure ER antagonist
  2. Use: breast cancer resist to Tamoxifen. ONLY FOR POSTMENOPAUSAL women
  3. IM
42
Q

Aromatase Inhibitors

A
  1. Anastrozole
  2. inhibits estrogen syn by preventing testosterone & androstenedione to estradiol & estrone.
  3. Aromatase I not used in premonopausal women
  4. Use: adjuvent of breast cancer.
43
Q

Antiandrogens

A
  1. Flutamide

2. Non steroidal androgen antagonist, Inhibits translocation of steroid R to nucleus

44
Q

GnRH analogues

A
  1. Leuprolide, goserelin, naferelin
  2. Partial agonist at GnRH R
  3. When not pulsated= inhibit LH & FSH release
  4. Use: prostatic CA
  5. Tox: hypogonadism
    bone pain & back pain
    gynecomastia
    hematuria
    impotence
    testicular atrophy
45
Q

Glucocorticoids

A
  1. Prednisone
46
Q

Antibodies

A
  1. rituximab
  2. monoclonal antibody
  3. unconjugated chimeric anti CD-20 antibody that binds to CD20 on follicular B cells in NHL
    Facilitate complement mediated cell death
47
Q

Asparaginase

A
  1. Enzyme isolated from E. coli or Erwinia carotovora.
  2. Immune sys recognizes this as foreign so use m-PEG instead
  3. Antibodies can be raised agains PEG in some children.”silent inactivation”
  4. Use: ALL
  5. MOA: ALL cell can’t make L-asparagine & need external source like from plasma. Asparaginase hydrolyze asparagine to aspartic acid & NH4 so deprive cancer cell of aa asparagine for prot syn! Apoptosis!
  6. IV or IM
  7. Toxicity: fever, nausea
    Hypersensitivity rxns reported in up to 75% of paitents.
    Severe allergic acute rxns in 24-29% of children.
    Potential for infusion related rxns- anaphylaxis
    Hypotension, bronchospasm, rash
    Acute Pancreatitis , rare but raised plasma a-amylase levels.
    Reduced prot syn
    Can be CNS toxic (coma)
    Intra cranial hemorrhage.
    Delay tox: hepatotox, raised liver enz. Increase bleeding & clotting risk due to reduced prot syn!

Pharmacology (3 decks)

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