Alkylating

agents
Nitrogen mustards:

Methane Sulfonic Acid Esters

p
Nitrosoureas:

Triazenes

Resistance:

Antimetabolites
Folic Acid Analogues

Purine Analogues

Pyrimidine Analogues

Leukovorin Rescue

Resistance to
Antimetabolites:

Antibiotics
Intercalators/Topo II

p
p
Noncovalent-bonding
intercalators
Alkylators
Strand scission

p
Plant alkaloids

Vinca alkaloids

p
Podophyllotoxins
Topoisomerase II inhibitors:
Taxanes

Topoisomerase I inhibitors

Miscellaneous
Procarbazine

Hydroxyurea

Platinum Comounds

Enzymes
Steroids

Biologic
response
modifiers
Monoclonal
antibodies
Targeted agents

all renal except methchlorethamine and

ifosphamide (metabolized also)
Cyclophosphamide

renal elimination

Ifosfamide

encephalopathy, as well as acquired

Fanconi's syndrome which can lead to
renal failure

mechlorethamine, melphalan,
chlorambucil

(chart in notes)

Busulfan

BCNU (Bischloroethyl nitrosourea)

CCNU
DTIC (Dicarbazine)
Temozolamide

terrible
prodrug that becomes DTIC when
metabolized

binding to GT, increaesd DNA

repair, excission repair
(All Renal clearance)
Methotrexate

renal toxicity from precipitation in Renal

tubule (so must have 3 accompanying
tx: fluids, alkalinize urine, leukovorin)

trimetrexate, piritrexim,
pemetrexed (alimta)
6-MP, 6-thioguanine

old, 6-mp used in peds

Fludarabine,

modified BASE; phosphorylates

intracellularly forming triphosphate, then
gets incorperated into genome forming
dysfunctional DNA;

2-deoxycofomycin (Pentostatin)
2-CdA (Cladribine)
5-Fluorouracil,

Modified Base (F added)

Xeloda = capecitabine

Tx: GI malignancy

FUdR (floxuridine)
cytosine Arabinoside (Ara-C)
(cytarabine)

Gemcitabine, azacytidine
(vidaza)

modified Sugar (OH added)

modified sugar (2 F's aded)

amplify enzyme (DHFR,

thymidylate snthetase),
change enzyme structure
- drug transport
- balance of
metabolism Ara-C, gemcitabine
(deamination vs. kinase
activation)

Actinomycin D
Adriamycin/Daunorubicin

Mithramycin
Mitomycin
Bleomycin

crazy molecule

Vinblastine
Vincristine

from periwinkle plant; disrupt MT fxn

(binds tubulin--> self-assoc into
non-tubes); causes metaphase arrest.
biliary
biliary

eTOPOside

Paclitaxel (Taxol)

from bark of yew tree; reversible binding

to tubulin --> STABILIZATION of MT's

Docetaxel

from needles of yew tree

Camptothecin analogues:
Topotecan
Irinotecan

ribonucleide reductase inhibitor,

so don't get deoxyribonucleotides
(make DNA adducts, preventing
nucleotide complementation;
similar to alkylation)

cisplatin

nephro-, neuro-, oto-toxicity

carboplatin
oxaliplatin

nephro-, neuro-, oto-toxicity

cold induced neuropathy

all myelosuppression
Myelosuppression side effect if you see
a fever 7-10 days after drug
administration = NEUTROPENIC FEVER

good for SLOW GROWING tumors

(apopstosis--???)

SFx: hand/foot syndrome;

diarrhea/mucositis
Tx: ALL
Mech:
KINASE: deoxycytidine analogue;
inhibits ribonucleotide reductase,
thereby inhibits pyrimadine synthesis.
-Deaminated: exported from cell

biliary/renal clearance
biliary

renal
extensively metabolized
renal clearance

Resistance: MDR Efflux

myelosuppression
neurotoxicity

radiosensitizer

conjugated to glucoronide; the less

your liver can conjugate it, the more
diarrhea you get.

ANEMIA

TP, leukopenia
mild leukopenia

CHOP

Tx: CLL, NHL recurring after treatment

(Indolent--too slowly growing to respond to Tx)

resistance from MDR (efflux)

SFx: Thrombpcytopenia (TP), fever rash

local necrosis; cardio toxicity

pulomary fibrosis

works on ovarian, breast, lung, H&N cancer

SFx: myelosuppression, diarrhea

resistance from decreased uptake,

-inactivated by
glutathione/metallothioneins,
-increased DNA repair;
DNA damage TOLERANCE

SFx: chills, fever, opportunistic infection

(PCP), myelosuppression

If deaminated more quickly than kinase, then

cell is resistant

toxicity: neuropathy b/c of long axons

affected by MT dysfxn (especially feet b/c
longest axons
-peripheral neuropathy worsened with
short infusion schedules (
capillary leak syndrome (reversible if stopped
right away)