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Year 2 Heme lymph > DSA antineoplastic agents, Linger, Part II > Flashcards

DSA antineoplastic agents, Linger, Part II Flashcards

1
Q

What are the 5 major types of alkylating agents

A

nitrogen mustards, methylhydrazines, alkyl sulfonates, nitrosoureas, triazenes
and dNA platinum compounds

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2
Q

MOA alkylating agents

A

form covalent bonds with DNA and alkylate it leading to intra and inter-strand corss lnking to prevent tumor from unwiding DNA for mRNA production

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3
Q

which cells are most susceptible to alkylating agents

A

cells that are replicating

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4
Q

alkylating agents

cell cycle specific or non?

A

nonspecific

though late G1 and S phase most susceptible

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5
Q

Which drug group has direct vesicant effects that can dmaage tissue at sits of injection

A

alkylating agents

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6
Q

systemic toxicities of alkylating agents

A

dose related and occur in rapidly growing tissues like bone marrow, GI tract and repro system

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7
Q

what are acute toxicity Sx of alkylating agents and preTx to avoid the Sx?

A

nausea and vomiting within 30-60 min IV administration

pretreat with odansetron

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8
Q

what are the delayed toxicities of alkylating agents

A

BM depression with leukopenia, thrombocytopenia, nephrotoxicity, alopecia, mucosal ulceration and intestinal denudation

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9
Q

what must you do if administering alkylating agent

A

monitoring blood counts to watch for leukopenia and thrombocytopenia

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10
Q

alkylating agents increase risk for what

A

secondary malignancies

AML

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11
Q

adverse effects cyclophosphamide

A

hemorrhagic cystitis from accumulation of acrolein

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12
Q

Tx for adverse effects of cyclophasphamide

A

mesna, sulfhydryl compound that reacts and neutralizes acrolein in acid environment in urinary tract

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13
Q

what are adverse effects of cisplatin

A

nephrotoxicity
ototoxicity- tinnitus and hearing loss of high freq range, unilateral or bilaterl
nausea and vomiting

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14
Q

how do we overcome nephrotoxicity from cisplatin administration

A

routine hydration and diuresis

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15
Q

adverse effect busulfan

A

hyperpigmentation, pulmonary fibrosis and adrenal insufficiency

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16
Q

Main categories of antimetabolites

A

folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors

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17
Q

What is the main folic acid analog

A

methotrexate

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18
Q

MOA methotrexate

A

inhibits dihydrogolate reductase and blocks conversion folic acid to tetrahydrofolic acid which is needed to make thymidylate, purines, serine and methionin

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19
Q

low dose methotrexate is common Tx for what

A

RA colitis, psoriasis, some cancers

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20
Q

high dose methotrexate therapy enters cells how

A

healthy cells via diffusion across concentration gradient causing injury to healthy tissues

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21
Q

what is the resuce drug for methotrexate

A

leucovorin because allows thymidylate synthesis to continue

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22
Q

is methotrexate cell cycle spceific or non

A

cell cycle specific S phase

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23
Q

adverse effects methotrexate

A

mucositis, diarrhea, myelosuppression with neutropenia dn thrombocytopenia, nausea, vomiting, immunosuppression, hepatotoxicity, fatigue

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24
Q

What drugs are pyrimidine analogs

A

Fluorouracil (5-FU)

cytarabine (Ara-C)

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25
MOA fluorouracil
covalently binds to thymidylate synthestase and blocks synthesis also incorporated into DNA and RNA interfering with synthesisis, function , processing and mRNA translation
26
most widley used in colorectal cancer
5-FU
27
is 5-FU cell cycle specific or non
cell cycle specific S phase
28
adverse effects 5-FU
anorexia, nausea, stomatitis, diarrhea
29
MOA cytarabine
competetively inhibits DNA polymerase alpha and beta blocking synthesis and repair
30
is cytarabine cell cycle specific or non
cell cycle specific S phase
31
What do we use cytarabine for
hematologic malignancies
32
main adverse effects cytarabine
myelosuppression, mucositis, nausea, vomiting and neurotoxicity at high doses
33
What are the purine analogs and MOA
Mercaptopurine | inhibits purine NT synthesis and DNA and RNA synthesis because if triphosphate incorporation
34
is mercaptopurine cell cycle spcific or non
cell cycle specific S phase
35
what drug should you not use with allopurinol because increased toxicity
mercaptopurine
36
adverse effects mercaptopurine
myelosuppression, immunosuppression, hepatotoxicity
37
MOA thioguanine
inhibits NT synthesis and DNA and RNA synthesis due to triphophate incorporation
38
what drug CAN you use will full dose allopurinol that still inhibits DNA
thioguanine
39
What are the antimitotic drugs
vinca alkaloids and taxanes
40
what are the vinca alkaloids
vinblastine and vincristine
41
MOA of the drug derived form madagascar periwinkle plant
bind to beta tubulin and inhibit microtubule assembly (inhibits mitosis) vinblastine and vincristine
42
Drug resistance to vinca alkaloids
from membrane efflux pump P glycoprotein
43
adverse effects of the vinca alkaloids
hair loss, local cellulitis if extravasated | myelosuppresion- vinblastine
44
which vincalkaloid causes more neurological toxicities
vincristine | numbness and tingling of the extremities and loss of DTR followed by motor weakness
45
what are the taxanes
paclitaxel and docetaxel
46
MOA of drug derived from western yew tree
binda beta tubulin and promotes microtubule formation and stabilization (prevents mitosis) taxanes
47
adverse effects paclitaxel
bone marrow depression and peripheral sensory neuropathy
48
docetaxel
neurotoxicity, fluid retention, neutropenia
49
what are the epipdophyllotoxins
etoposide and teniposide
50
MOA epipodophyllotoxins
inhibit topoisomerase II leading to DNA damage through strand breakage induced by formation of drug complex with DNA and enzyme
51
What are the camptothecin analogs
topotecan andirinotecan
52
MOa camptothecin analogs
inhibit activity of topoisomerase I resulting in DNA damage and blockade of DNA replication and trascription
53
are camptothecin analogs cell cycle specific or non
cell cycle specific
54
adverse effects camptothecin analongs
bone marrow depression, diarrhea, nausea and vomiting
55
Tx for early diarrhea from captothecin analogs? late diarrhea Tx?
early- atropine | late- need electrolyte and fluid replacement
56
What are the tyeps of antitumor Ab
anthracyclines, dactinomycin, bleomycin and mitomycin
57
what are the anthracyclines and MOA
doxorubicin daunorubicin -inhibit topoisomerase II -intercalate DNA and block synthesis of DNA and RNA and blocks DNA strand scission -generates semiquinone and ROS -binds to cellular membranes to alter fluidity and ion transport
58
how do anthracyclines lead to cardiotoxicity
release of O2 species
59
are antrhacyclines cell specific or non
non because intercalation of DNA
60
Adverse effects anthracyclines
nausea, red urine!, alopecia, myelosuppression, stomatitis, cardiotoxicity
61
MOA bloemycin and is it cell specific?
binds DNA causing single and ds breaks inhibits DNA biosynthesis cell cycle specific G2
62
adverse effects belomycin
pulmonary toxicity dose limited pneumonitis, cough, dyspnea, dry inspiratory crackles, infiltrates on CXR allergic rxns fever, hypotension, skin toxicity, mucositis and alopecia
63
MOS dactinomycin
binds to ds DNA and intercates between guanine-cytosine base pairs which prevents DNA dependent RNA polymerase from transcribing RNA
64
adverse effects dactinomycin
anorexia, nausea, vomiting long term: alopecia, BM depression, stomatitis, increased inflammation and pigmentation in areas previously subjected to Xray radiation
65
what are the groups of natural antineoplastic agents
``` antimitotic epipodophyllotoxins camptothecin analogs antitumor Ab enzymes ```
66
what enzymes are natural antineoplastic agents
asparaginase and pegaspargase
67
MOA asparaginase and pegaspargase
hydrolyzes circulating L asparagine to aspoartic acid and ammonia (inhibits protein synthesis)
68
what has longer half life | asparaginase and pegaspargase
pegaspargase
69
are asparaginase and pegaspargase cell cycle specific
yes G1
70
Which tumors are vulnerable to asparaginase and pegaspargase
ALL tumor cells because lack asparagine synthetase and need exogenous source L asparagine
71
adverse effects asparaginase and pegaspargase
acute HS reaction: fever, chills, nausea, vomiting, skin rash, urticaria delayed toxicities:inc risk clotting and bleeding, pancreatitis and CNS toxicity:lethargy, confusion, hallucinations and coma
72
what are the steroids used forcancer and why
antilymphocytic effects oral: prednisone, hydrocortisone, dexamethasone topical: clobetasol, diflorasone, halobetasol, betamethasone
73
MOA hydroxyurea
inhibits ribonucleoside diphosphate reductase | S cell cycle specific
74
What drug is used for acute promyelocytic leukemia
tretinoin because induces clonal proliferation or granulocytic differentiation
75
adverse effects tretinoin
Vit A toxicity, retinoic acid syndrome, increased cholesterol and TGs CNS toxicity GI disturbances
76
What is used to treat progressive persistent or reccurent cutaneous T cell lymphoma
vorinostat
77
MOA imatinib
inhibits tyrosine kinase domain of Bcr-Abl and prevents phosphorylation also inhibits kinases PDGFR, stem cell factor and c-kit
78
what is imatinib used to Tx
CML | GI stromal tumors with c-kit
79
which protein tyrosine kinase inhibitor should be used with caution with drugs that interact with CYP3A4
imatinib
80
adverse effects imatinib
myelosuppression, fluid retention with ankle and periorbital edema, diarrhea, myalgias
81
MOA dasatinib
kinase inhibitor Bcr-Abl, c-kit and PDGFR-beta
82
MOA Nilotinib
inhibits Bcr-Abl, c kit and PDGFR-beta with higher affinity for Abl Imatinib resistance
83
What are the inhibitors of Epidermal EGFR
erlotinib and gefitinib
84
MOA sorafenib and sunitinib
multikinase inhibitor | inhbits intracell Rag kinases and surface kinases R like VEGFR
85
drug used to inhibit Her2/neu that is less cardiotoxic than trastuzumab
lapatinib
86
MOA bortezomib
inhibits proteosomes, activating signaling cascades that lead to cell cycle arres and apoptosis
87
what is bortezomib used for
multiple myeloma | or refractory mantle cell lymphoma
88
What is IL-2 used for
stimulate proliferation activated T cells and secretion NK cytokines to increse cytotoxic killing
89
What are first line drugs in post-transplant immunsuppression? and MOA
temsirolimus and everolimus | inhibit mTOR R causing immunosuppression
90
MOA rituximab
against CD20 on normal and malignant B lymphocytes causing C'mediated lysis and Ab-dependent cellular cytotoxicity and induction apoptosis
91
What is rituximab used to Tx
low grade follicular CD20+, B cell non-hodgkin lymphoma and Tx DLBCL20+ RA with methotrexate
92
adverse effects rituximab
cytopenia, HS reactions
93
What monoclonal Ab is approbed for Tx B cell CLL?
alemtuzumab
94
gemtuzumab used to Tx?
AML
95
MOA trastuzumab and what is it used to Tx
binds Her2/neu R that is on 25-30% breast cancers and inhibits intracell signaling events and neoplastic prliferation
96
adverse effects trastuzumab
cardiotoxicity, ventricular dysfunction- should be discontinued if dec in L ventricular function
97
what is used to Tx refractory or relapsed low grade NHL or follicular B cell NHL
ibritumomab
98
Gardasil prevents what
HPV 16 and 18 strains | and 6 and 11-- genital warts

Year 2 Heme lymph (28 decks)

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