med chem III test IV cancer

epithelial origin

connective or muscle origin

lymphatic tissue

hematopoetic origin

muscle tissue

solid tumor; adrenal gland

skin pigment cells

2 STD risk factors linked to cancer

most common disease related problem encountered with antineoplasics

alkylating agent
nitrogen mustard
least toxic 
use contraception
bifunctional

alkylating agent
nitrogen mustard
uses 17-beta-estradiol for delivery
phosphate group solubilizes the agent for rapid hydrolyzation
do not take with calcium containing drugs

alkylating agent
nitrogen mustard
prodrug - CYP 450 mediated
cardiotoxic
SE due to acrolein (bladder inflamm)

alkylating agent
nitrogen mustard
nephrotoxic

alkylatig agent
nitrogen mustard
extravasation a problem
injection only

alkylating agent
nitrogen mustard
analog of DNA
adjust dose to BUN
known to cause chromosome abnormalities

alkylating agent
nitrosourea
ind - hodgkins and non-hodgkins
injection or wafer
bifunctional

alkylating agent
nitrosourea
ind - brain tumors
highly lipid soluble
monofunctional

alkylating agent
nitrosourea
highly renal toxic
no known antidote

how do you treat extravasation of a ziradinium

alkylating agent
palliative treatment
used for bone marrow ablation (infuse and it migrates)
can cause hyperuricemia (allopurinol)

alkylating agent
palliative
oral based on body surface area
prodrug

alkylating agent
IV only (oral - eradicate absorption)

compounds that prevent the biosynthesis or use of normal cellular metabolites

3 naturally occuring purines

antimetabolite
folic acid antagonist
MOA - inhibit dihydrofolate reductase & thymidylate synthase 
do not take with food
yellow skin

methotrexate overdose therapy

antimetabolite
folic acid anatagonist
no back diffusion = decreased toxicity

antimetabolite
folic acid antagonist
fast tracked - new for 2009
injection
racemic

reduces anemia in ppl taking dapsone
decreases bone marrow tox used in combo with trimetrexate
combo in chemotherapy with methotrexate

3 naturally occuring pyrimidine

MOA of pyrimidine analogs

antimetabolite
pyrimidine analog
MOA - inhibts thymidylate synthetase
suicide substrate
IV only
metabed by DPD

antimetabolite
pyrimidine analog
prodrug converted to 5-FU
SE hand and foot painful swellig
DI with warfarin

antimetabolite
analogue of 2' deoxycytidie
prodrug
ind - myelodysplasitc syndrome

antimetabolite
purine analog
MOA - competes with hypoxanthine and guanine
tablet
many many drug interactions = increase tox
long term use can increase risk of cancer

how is 6-mercaptopurine inactivated

mitotic inhibitor
MOA - inhibits tubulin causing random chromosome distribution
SE - peripheral neuropathy

antimitotic
forms spiral aggregates
most active of two
metabolized by 3A4

antimitotic
forms spiral aggregates
irreversible inhibition of mitosis
metabolized by 3A4

MOA  and metab of taxoids

antimitotic
taxoid
derived from pacific yew tree
24 hour infusion
SE hypersensitivity

antimitotic
taxoid
derived from pacific yew tree
24 hour infusion
SE hypersensitivity
second line in metastatic breast cancer
combo with 5-FU and cisplatin
metab by CYP3A4
monitor bilirubin levels

antimitotic
semi-synthetic analog of Epothilone B
special diluent, contains ethanol
cardiotoxic
moa similar to taxoids
IV dosing based on skin surface area

antimitotic
semisynthetic marine sponge
IV drug 
moa - inhibition of growth phase w/o affecting the shortening phase

intracalating agent
anti-malaral agent

anti-tumor antibiotics MOA

5 types of antitumor antibiotics

antibiotic
anthracycline
pee and sweat will turn dark red
cardiotoxic
IV only
not bioequivalent forms

liposomal form of doxorubicin with less toxicity

what can be added to anthracyclines to plug the pumps

antibiotic
Cu chelating peptide
minimal myelosupression - good one to add to decrease infection
SE - pulmonary fibrosis
off label - plantar warts

antibiotic
prodrug
crosslinks guanine and cytosine
IV only
natural product

antibiotic
extremely corrosive to soft tissue
natural product
ind - wilm's tumor, ewing's sarcoma

antibiotic
anthracenedione
also used in the Tx of MS
urine will be a blue-green color
IV only

platinum complexes
prodrugs
non cycle specific
potentcy is a function of hydration
don't use with Al
sever vomitting

substituted methylhydrazine
ind - hodgkins
moa - inhibits transmethylation by methionine
initial Tx should be in hospital

imidazotetrazine
prodrug producing MTIC
ind - refractory anaplastic (brain) astrocytoma

ribonucleotide reductase inhibitor
very underprescribed for sickle cell disease

topoisomerase II inhibitor
epipodophylotoxin 
G2 specific
isolated form podophyllum peltatum
CYP3A4 to active form
ind - refractory testicular & small cell lung

topoisomerase II inhibitor
epipodophylotoxin 
G2 & S specific
isolated form podophyllum peltatum
CYP3A4 to active form
ind - refractory testicular & small cell lung

topoisomerase I inhibitor
isolated from bark of camptothecal acuminata
pentacyclic quinoline alkaloid
  high cytotoxic
  poor solubility
  subject to hydrolysis

topoisomerase I inhibitor
combo with 5-FU and leucovorin for colon/rectal refractory cancer
hepatic metab to a 2000X more active metabolite
polymorphism UGT1A1*28 = increased risk of neutropenia

anti-androgen 
moa - non-steroidal competitive inhibitor
must be taken in combo with LHRH
racemic - R active
SE - gynecomastia
ind - advanced prostate cancer

anit-androgen 
moa - inhibits cellular uptake to testosterone and inhibits muclear binding to receptors
ind - surgical castration of prostate

progestin 
moa - anti-leutinizing effect mediated by the pituitary gland
off label - appetite stimulant in HIV
ind - pallitive Tx, carcinoma of breast or endometrium

progestin
moa - inhibits secretion of pituitary gonadotropin
ind - adjunct and pallative of inoperable endometrial cancer
long acting contraceptive via IM injection

GnRH analog
moa - decrease androgen production in testes ind - advanced prostate cancer when estrogen dependent

polymeric matrix formulation of lupron for injection dosing
every 3 months for sex offenders

GnRH analog
moa - receptor antagonist
sub Q only
prolongs QT interval
new for 2009

anti-estrogen
DOC for breast cancer
moa - non-steroidal that competes with estradiol for receptors
hepatic metab by CYP2D6
resistance develops

anti-estrogen
IM once monthly
steroidal estrogen antagonist
moa - down regulates estrogen receptor
ind - use for tolerance to tamoxifen

aromatase inhibitor
DOC for advanced breast cancer not responding to tamoxifen
reversible competitive inhibitors
postmenopausal women
no endometrial cancer connection

aromatase inhibitor
DOC for advanced breast cancer not responding to tamoxifen
suicide substrate
postmenopausal women
no endometrial cancer connection

radiopharmaceutical
ind - selected cases of thyroid cancer or Tx of hyperthyroidism
moa - 90% beta and 10% gamma

radiopharmacetical
ind - thyroid evaluation, short acting imaging
moa - electron capture decay

radiopharmaceutical
ind - painful skeletal metastatic disease
IV only
moa - beta particle emission
warning - use a normal toilet to prevent spread of radiation the first week following therapy

brachytherapy
implants
contains either iodine 125 or palladium 103

cytoprotective
ind - reduction of cumulative renal toxicity associated with 1) platinum based drugs 2) reduction of xerostomia due to irradiation 3) protects lung fibroblasts from taxol toxicity
moa - scavenger prodrug

cytoprotective agent
ind - reduction of cardiomyopathy associated with doxorubicin therapy, extravasation
moa - prodrug of EDTA that prevents ferric iron free radicalization
use only with anthracycline type anti-neoplastic agents

cytoprotective agent
ind - ifosfamide and cyclophosphamide induced hemorrhagic cystitis
moa - thiol group scavenges the reactive urotoxic metabolit (acrolein)

retinoid
ind - induction of remission of acute leukemia containing the PML/RARa gene
moa - induces maturation of promyelocytes

retinoid
ind - cutaneous T-cell lymphoma
moa - promotes cellular differentiation and proliferation

protein -tyrosine kinase inhibitor
ind - most effective in chronic myeloid leukemia
metab - CYP3A4
SE - fluid retention and edema,
CI - breast feeding

protein synthesis inhibitor
ind - Tx of adults with chronic or accelerated phase chronic myeloid leukemia (CML)
SE - myelosuppression, hyperglycemia, embryo-fetal toxicity

protein serine/threonine kinase inhibitor
ind - advanced renal cell carcinoma
moa - mTOR kinase inhibitor, arrests G1 phase and decreases expression of VEGF
infusion only agent
pretreat with anti-histamines

protein serine/threonine kinase inhibitor
ind - advanced renal cell carcinoma
moa - mTOR kinase inhibitor, arrests G1 phase and decreases expression of VEGF
DI - p glyco p pumps inhibitors
no live virus immunizations
monitor for oral ulcers, infections
tablet

moa - PML-RARa inhibitor
ind - refractory acute promyelocytic leukemia (APL)
orphan drug
monitor ECG

ind - multiple myeloma pts who have failed at least 2 prior therapies
moa - reversible inhibitor of the  26s proteosome

moa - tetrapeptide epoxyketone proteasome inhibitor
ind - multiple myeloma

moa - hedge hog pathway inhibitor
ind - metastic basal cell carcinoma
BBW - both sexes tetratogenic
do not donate blood for at least 7 months after last dose

histone deacytylase inhibitor
capsule
contains hydroxamic acid
 
ind - cutaneous manifestations of T-cell lymphoma (CTCL)
metab - beta oxidation and glucoronidation
DI - coumarin derivatives
SE - GI, QT prolongaton

histone deacytylase inhibitor
IV
cyclic depsipeptide

ind - cutaneous manifestations of T-cell lymphoma (CTCL)
metab - beta oxidation and glucoronidation
DI - coumarin derivatives
SE - GI, QT prolongaton
IV agent, cyclic depsipeptide

oxidative stress inducer
orphan drug
ind - metastatic melanoma

moa - inhibitor of CYP17
ind - prevention of testosterone who have failed docetaxel therapy

ind - esophageal cancer
photodynamic therapy
moa - superoxide and hydroxide radical causing tissue and tumor death
last resort drug for palliative Tx

ind - Tx inoperable adrenocortical carcinoma
moa - suppresses adrenal function and production of adrenal steroids
palliative Tx and last resort because of brain damage and depression

ind - ALL
moa - hydrolysis of L-asparagine
increases half life to increase metabolism

moa - increases the proliferation of fast growing cells
SE - white fuzzy tongue growth