DSA antineoplastic agents, Linger, Part II Flashcards
What are the 5 major types of alkylating agents
nitrogen mustards, methylhydrazines, alkyl sulfonates, nitrosoureas, triazenes
and dNA platinum compounds
MOA alkylating agents
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
which cells are most susceptible to alkylating agents
cells that are replicating
alkylating agents
cell cycle specific or non?
nonspecific
though late G1 and S phase most susceptible
Which drug group has direct vesicant effects that can dmaage tissue at sits of injection
alkylating agents
systemic toxicities of alkylating agents
dose related and occur in rapidly growing tissues like bone marrow, GI tract and repro system
what are acute toxicity Sx of alkylating agents and preTx to avoid the Sx?
nausea and vomiting within 30-60 min IV administration
pretreat with odansetron
what are the delayed toxicities of alkylating agents
BM depression with leukopenia, thrombocytopenia, nephrotoxicity, alopecia, mucosal ulceration and intestinal denudation
what must you do if administering alkylating agent
monitoring blood counts to watch for leukopenia and thrombocytopenia
alkylating agents increase risk for what
secondary malignancies
AML
adverse effects cyclophosphamide
hemorrhagic cystitis from accumulation of acrolein
Tx for adverse effects of cyclophasphamide
mesna, sulfhydryl compound that reacts and neutralizes acrolein in acid environment in urinary tract
what are adverse effects of cisplatin
nephrotoxicity
ototoxicity- tinnitus and hearing loss of high freq range, unilateral or bilaterl
nausea and vomiting
how do we overcome nephrotoxicity from cisplatin administration
routine hydration and diuresis
adverse effect busulfan
hyperpigmentation, pulmonary fibrosis and adrenal insufficiency
Main categories of antimetabolites
folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors
What is the main folic acid analog
methotrexate
MOA methotrexate
inhibits dihydrogolate reductase and blocks conversion folic acid to tetrahydrofolic acid which is needed to make thymidylate, purines, serine and methionin
low dose methotrexate is common Tx for what
RA colitis, psoriasis, some cancers
high dose methotrexate therapy enters cells how
healthy cells via diffusion across concentration gradient causing injury to healthy tissues
what is the resuce drug for methotrexate
leucovorin because allows thymidylate synthesis to continue
is methotrexate cell cycle spceific or non
cell cycle specific S phase
adverse effects methotrexate
mucositis, diarrhea, myelosuppression with neutropenia dn thrombocytopenia, nausea, vomiting, immunosuppression, hepatotoxicity, fatigue
What drugs are pyrimidine analogs
Fluorouracil (5-FU)
cytarabine (Ara-C)
MOA fluorouracil
covalently binds to thymidylate synthestase and blocks synthesis
also incorporated into DNA and RNA interfering with synthesisis, function , processing and mRNA translation
most widley used in colorectal cancer
5-FU
is 5-FU cell cycle specific or non
cell cycle specific S phase
adverse effects 5-FU
anorexia, nausea, stomatitis, diarrhea
MOA cytarabine
competetively inhibits DNA polymerase alpha and beta blocking synthesis and repair
is cytarabine cell cycle specific or non
cell cycle specific S phase
What do we use cytarabine for
hematologic malignancies
main adverse effects cytarabine
myelosuppression, mucositis, nausea, vomiting and neurotoxicity at high doses
What are the purine analogs and MOA
Mercaptopurine
inhibits purine NT synthesis and DNA and RNA synthesis because if triphosphate incorporation
is mercaptopurine cell cycle spcific or non
cell cycle specific S phase
what drug should you not use with allopurinol because increased toxicity
mercaptopurine
adverse effects mercaptopurine
myelosuppression, immunosuppression, hepatotoxicity
MOA thioguanine
inhibits NT synthesis and DNA and RNA synthesis due to triphophate incorporation
what drug CAN you use will full dose allopurinol that still inhibits DNA
thioguanine
What are the antimitotic drugs
vinca alkaloids and taxanes
what are the vinca alkaloids
vinblastine and vincristine
MOA of the drug derived form madagascar periwinkle plant
bind to beta tubulin and inhibit microtubule assembly
(inhibits mitosis)
vinblastine and vincristine
Drug resistance to vinca alkaloids
from membrane efflux pump P glycoprotein
adverse effects of the vinca alkaloids
hair loss, local cellulitis if extravasated
myelosuppresion- vinblastine
which vincalkaloid causes more neurological toxicities
vincristine
numbness and tingling of the extremities and loss of DTR followed by motor weakness
what are the taxanes
paclitaxel and docetaxel
MOA of drug derived from western yew tree
binda beta tubulin and promotes microtubule formation and stabilization (prevents mitosis)
taxanes
adverse effects paclitaxel
bone marrow depression and peripheral sensory neuropathy
docetaxel
neurotoxicity, fluid retention, neutropenia
what are the epipdophyllotoxins
etoposide and teniposide
MOA epipodophyllotoxins
inhibit topoisomerase II leading to DNA damage through strand breakage induced by formation of drug complex with DNA and enzyme
What are the camptothecin analogs
topotecan andirinotecan
MOa camptothecin analogs
inhibit activity of topoisomerase I resulting in DNA damage and blockade of DNA replication and trascription
are camptothecin analogs cell cycle specific or non
cell cycle specific
adverse effects camptothecin analongs
bone marrow depression, diarrhea, nausea and vomiting
Tx for early diarrhea from captothecin analogs? late diarrhea Tx?
early- atropine
late- need electrolyte and fluid replacement
What are the tyeps of antitumor Ab
anthracyclines, dactinomycin, bleomycin and mitomycin
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
how do anthracyclines lead to cardiotoxicity
release of O2 species
are antrhacyclines cell specific or non
non because intercalation of DNA
Adverse effects anthracyclines
nausea, red urine!, alopecia, myelosuppression, stomatitis, cardiotoxicity
MOA bloemycin and is it cell specific?
binds DNA causing single and ds breaks
inhibits DNA biosynthesis
cell cycle specific G2
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
MOS dactinomycin
binds to ds DNA and intercates between guanine-cytosine base pairs which prevents DNA dependent RNA polymerase from transcribing RNA
adverse effects dactinomycin
anorexia, nausea, vomiting
long term: alopecia, BM depression, stomatitis, increased inflammation and pigmentation in areas previously subjected to Xray radiation
what are the groups of natural antineoplastic agents
antimitotic epipodophyllotoxins camptothecin analogs antitumor Ab enzymes
what enzymes are natural antineoplastic agents
asparaginase and pegaspargase
MOA asparaginase and pegaspargase
hydrolyzes circulating L asparagine to aspoartic acid and ammonia
(inhibits protein synthesis)
what has longer half life
asparaginase and pegaspargase
pegaspargase
are asparaginase and pegaspargase cell cycle specific
yes G1
Which tumors are vulnerable to asparaginase and pegaspargase
ALL tumor cells because lack asparagine synthetase and need exogenous source L asparagine
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
what are the steroids used forcancer and why
antilymphocytic effects
oral: prednisone, hydrocortisone, dexamethasone
topical: clobetasol, diflorasone, halobetasol, betamethasone
MOA hydroxyurea
inhibits ribonucleoside diphosphate reductase
S cell cycle specific
What drug is used for acute promyelocytic leukemia
tretinoin because induces clonal proliferation or granulocytic differentiation
adverse effects tretinoin
Vit A toxicity, retinoic acid syndrome, increased cholesterol and TGs
CNS toxicity
GI disturbances
What is used to treat progressive persistent or reccurent cutaneous T cell lymphoma
vorinostat
MOA imatinib
inhibits tyrosine kinase domain of Bcr-Abl and prevents phosphorylation
also inhibits kinases PDGFR, stem cell factor and c-kit
what is imatinib used to Tx
CML
GI stromal tumors with c-kit
which protein tyrosine kinase inhibitor should be used with caution with drugs that interact with CYP3A4
imatinib
adverse effects imatinib
myelosuppression, fluid retention with ankle and periorbital edema, diarrhea, myalgias
MOA dasatinib
kinase inhibitor Bcr-Abl, c-kit and PDGFR-beta
MOA Nilotinib
inhibits Bcr-Abl, c kit and PDGFR-beta with higher affinity for Abl
Imatinib resistance
What are the inhibitors of Epidermal EGFR
erlotinib and gefitinib
MOA sorafenib and sunitinib
multikinase inhibitor
inhbits intracell Rag kinases and surface kinases R like VEGFR
drug used to inhibit Her2/neu that is less cardiotoxic than trastuzumab
lapatinib
MOA bortezomib
inhibits proteosomes, activating signaling cascades that lead to cell cycle arres and apoptosis
what is bortezomib used for
multiple myeloma
or refractory mantle cell lymphoma
What is IL-2 used for
stimulate proliferation activated T cells and secretion NK cytokines to increse cytotoxic killing
What are first line drugs in post-transplant immunsuppression? and MOA
temsirolimus and everolimus
inhibit mTOR R causing immunosuppression
MOA rituximab
against CD20 on normal and malignant B lymphocytes causing C’mediated lysis and Ab-dependent cellular cytotoxicity and induction apoptosis
What is rituximab used to Tx
low grade follicular CD20+, B cell non-hodgkin lymphoma and Tx DLBCL20+
RA with methotrexate
adverse effects rituximab
cytopenia, HS reactions
What monoclonal Ab is approbed for Tx B cell CLL?
alemtuzumab
gemtuzumab used to Tx?
AML
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
adverse effects trastuzumab
cardiotoxicity, ventricular dysfunction- should be discontinued if dec in L ventricular function
what is used to Tx refractory or relapsed low grade NHL or follicular B cell NHL
ibritumomab
Gardasil prevents what
HPV 16 and 18 strains
and 6 and 11– genital warts