Download chemo drugs 2 (Sarah)

Class and Name
MOA
Clinical uses
Adverse effects
Antimetabolites
Inhibition of DHFR leading to
partial depletion of reduced
folates
Gestational carcinoma,
hydatidiform mole, ALL
(prevents meningeal
leukemia & combo tx), br
ca, epidermoid ca’s of
head & neck, adv’d
mycosis fungoides, lung
ca (esp sq & sm cell),
advance NHL
N/V, photosensitivity,
myelosuppression –IV (nadir 7 -10 d,
recover by 14-20d)
-renal : direct to renal tubular cells &
intratubular precipitation of
methotrexate and metabolites (high
dose IV)
-hepatic: ↑ed transaminase (oral, esp
daily dose)
-mucositis (3-7d): IV
-CNS: (intrathecal, iv sometimes)
1. Acute chem. Arachnoiditis, arises
imm after admin – severe HA, nuchal
rigidity, vomiting, fever, and inflame
cells in CSF
2. subacute: ~10%, usu 3-4th course, m
common in those w/ active meningeal
leukemia – motor paralysis, CN palsies,
seizure, coma; cont’d intrathecal tx may
->death
3.chronic demyelinating
encephalopathy: usu in kids mo-yrs
after receiving intrathecal MTX
-diarrhea
diminish toxicity &
counteract effects of
impaired MTX elimination
and of inadvertent
overdosage of folic acid
antagonists
After high dose MTX tx in
osteosarcoma & in adv’d
colorectal ca
Allergic sensitization, including
anaphylactoid reactions and
urticaria
Met: liver
Elim: urine(90%) & feces
Inhibits dihydrofolate
reductase and thymidine
synthetase
-solid tumors: malignant
mesothelioma, breast,
pancreatic, head & neck,
non-sm cell lung, colon,
gastric, cervical, bladder
-myelosuppression (ANC nadir btwn 89.6 d w/ return to baseline 4.2-7.5 d
later)
-mucositis
-GI toxicity
Excreted 90% unchanged in
urine
1. methotrexate
(MTX)
2.
Leukovorin (LV)
3. Premetrexed
-admin folic acid & B12
Mechs of drug resistance &
metabolism
-defective transport common
(ALL & osteosarcoma)
-glutamic acid residue 45
-drug efflux pumps: multi
resistant-asstd protein family
(MRP -1,2,3, &4); 1 is primary
route; overexp of efflux
pump
-↓ ability to form MTX
polyglutamates
Pyrimidine Antagonists
1. Azacitidine
(5 –Aza)
2. Decitabine
supplements 2 wks prior tx
ca’s
-skin rash/desquamatn(40%)
-hepatotoxicity: reversible
transaminasemia
-anorexia
-N/V (84%/58%)
-infusion rxn: shivering
Pyrimidine nucleoside analog
of cydidine
-hypomethylation of DNA &
direct cytotoxicity on abn
hematopoietic cells in BM
MDS, CMML
-direct incorporation into DNA
and inhibition of DNA
methyltransferase, causing
hypomethylation of DNA and
cellular differentiation or
apoptosis
MDS
nonFDA: CMML
Pro-drug of 5-FU; converted in
tumor cell to 5-FU
Met breast, met colon
-as pass thru S phase,
incorporates into cell & blocks
polymerization of DNA by
inhibiting DNA polymerase &
leads to shortened DNA
strands
AML, ALL, CML, CNS
leukemia, HD, NHL
Myelosuppression (dose limiting
toxicity),
- IV: ↑ed serum Cr, reanl failure,
renal tubular acidosis, hypokalemia,
hepatic coma
-subQ: N/V, pancytopenia, pyrexia, ,
diarrhea, fatigue, injection site
erythema, constipation, ecchymosis
Myelosuppression is dose limiting,
fatigue, pyrexia, nausea, cough,
petechiae, constipation, diarrhea,
hyperglycemia
-uncommon: A fib, cardiac arrest,
HF, cerebreal hemorrhage, MI,
intracranial hemorrhage,
pneumonia, pulm edema
Myelosup (lymphonenia in 94%);
diarrhea, N/V, stomatitis, hand-foot
syndrome (45%) – pain, redness,
scaling of skin of palms/soles;
faigue, anorexia, paraesthesia, HA,
cardiotoxicity in 3% can be fatal –
MI, angina, dysrythmias, arrest,
failure, ECG changes
Myelosuppression (14-21d),
hepatic-jaundice and elevations in
serum bilirubin, transaminases & alk
phosphatase, alopecia, GI-diarrhea,
anorexia, derm –marcopap rash,
erythema, blistering/peeling of skin,
esp on hands and feet), hand-ft
syndrome
3. Capecitabine
(oral 5-FU)
4. Cytarabine
(Ara-C, Cytosine,
Arabosinide,
Arabinosylcytosin
)
Met by liver and excreted in
urine
->
-High dose Ara-C toxicity:
Cerebellar dysfxn (20%), usu
w/in 2-8 days, accumulation
of ara-U or ara-CTP causes
nerve damage AND
conjunctivitis/corneal toxicity
(use steroid eye drops)
5. Flurorouracil
(5-FU, 5fluorouracil)
6. Gemcitabine
(difluorodeoxyCytidine, dFdC)
Purine Antagonists
1. .Adenosine Analogs
-general
Analog of pyrimidine uracil
-inhibits thymidylate synthase
(TS) by FdUTP ->affects DNA
synthesis
Incorporation into cell DNA
and RNA
-incorporation into DNA
strands, inhibiting replication
and repair blocking nucleotide
production
-Inhibition of DNA repair &
synthesis
-Inhibition of RNA fxn
-inhibiting synthesis of
substrates needed for DNA
synhthesis
-cell-cycle specific for S phase
Colorectal, gastric,
pancreatic, breast, basal
cell carcinoma
nonFDA: liver, head &
neck, ovarian, cervical
-myelosuppression (7-14 d nadir w/
rapid recovery), possibility of febrile
neutropenia
- mucositis
-diarrhea/nausea
-skin: alopecia, maculopap rash of
extremities
-DPD deficiency:
-> -cardiac: myocardial ischemia &
rare, inherited disorder of angina in 2%
pyrimidine degredation
-CNS: somnolence & cerebellar
d/t low/deficien DPD in
ataxia in ~1%
caucasion (~5%) and AA
-ocular: conjunctivitis, lacrimation,
(~.1%); pts; no evidence
blepharitis, photophobia
of fluorouracil
-beware those w/ dihydrodegredation in these pts
pryrimidine DH deficiency!- tx w/ 5--toxicities: diarrhea,
FU can be life threatening for even
stomatitis,
partial deficiencies
myelopsuppression, N/V,
rectal bleeding, vol
depletion, skin changes,
neurologic!
Met pancreatic, NSCLC
Myelosuppression (anemia 68%,
nonFDA: bladder, breast, leucopenia 62%, thrombocytopenia
ovarian, malignant
24%)
mesothelioma, NSCLC
-N/V, Diarrhea, stomatitis, ↑es in
serum transaminases, mild
protein/hematuria ->can lead to
irreversible renal failure (manifests
as HUS), rash, fever/fluish sxs,
dyspnea, peripheral edema
Excreted in urine
a. Fludarabine
b. Cladribine
a. 6-mercaptopurine
(6-MP)
-heme: myelosuppression (severe
immunosuppression -> opp
infections (OI’s) d/t ↓CD4’s ->
herpes zoster, candida, PCP
-CV: edema, chest pain, hypotension
-fever (flu-like sxs in 25%)
-derm: alopecia, rash
Hariy cell leukemia, CLL,
AML, NHL,
Waldenstrom’s
macroglobinemia
Myelosuppression, CD4 & 8↓ 6 mo,
OI’s, candida /aspergillosis (use px
abx)
-fever
-rash
-fatigue/HA
-mild nausea
Myelosuppression (esp T & B
lymphocytes (esp CD4) – recovery
prolonged & incomplete, fever &
OI’s in 2nd and 3rd course)
-dry skin, rash
-fatigue, seizures
-mild N/V
-renal: tubular toxicity (↑ Sr CR) –
use hydration
Hairy cell leukemia, NHL,
CLL, T-cell
leukemia/lymphoma
c. Pentostatin
2.Guanine Analogs
(Thiopurines)
CLL, low grade NHL, AML,
Waldenstrom’s
macroglobinemia,
cutaneous T-cell
lymphoma, BM transplant
-inhibit de novo purine
synthesis & purine
interconversion rxns by falsely
incorporating into RNA/DNA
-cell specic for S phase
Met in liver and excreted in urine
->
CNS:peripheral neuropathy,
blindness, coma, death
-GI: diarrhea, N/V
-pulm: pna, pulm
hypersensitivity, interstitial
pneumonitis
-Results from decreased ability to
form cytotoxic nuncleotide
metabolites
-resistant cells express either
complete or partial deficiency of
HGPRT (or altered affinity)
ALL, CML, AML, NHL
Pancytopenia
-hepatic: jaundice, cholestasis,
ascites, hepatic encephalopathy, ↑
liver enzymes
-GI: N/V/D, abd pain
-derm; necrosis, rash, HA
ALL, AML, CML, NHL
Myelosuppression (leucopenia,
thrombocytopenia m com), ↑liver
enzymes, VOD, jaundice, N/V/anrxa,
stomatitis, severe diarrhea,
rash/dermatitis, tumor lysis
syndrome
AML (blast crisis), sickle
cell
Myelosuppression, skin: rash,
hyperpigmentation, pruritis,
radiation recall
b.6-thioguanine (6TG)
Hydroxyurea
S phase dep
Enzyme that inhibits
ribonucleotide reductase (nec
for DNA synthesis)
Microtubule Targeting
Agents:
1. Vinca Alkyloids
Naturally occurring nitrogenous
base in periwinkle plant
-inhibit microtubule assembly
-rapidly/reversibly binds
alternative sites on tubulin &
disrupts microtubule fxn leading
to metaphase arrest
a. Vincristine
50% met in liver and 50%
excreted unchanged in urine
-Pleitropic or multidrug
resistance (MDR) -> results in
decreased drug accumulation &
retention
-alteration in α & β tubulins:
leads to ↓ed drug binding or
↑ed resistance to microtubule
disassembly
ALL, HD, NHL, MM
Testicular Ca, CLL, Aid’srelated Kaposi’s sarcoma,
Ewing’s sarcoma,
rhabdomyosarcoma,
SCLC, medulloblastoma,
cervical CA, CML
-Neuro: peripheral neuropathy,
parasthesia, ↓DTR’s, gait changes,
pharyngeal/paratid pain
(esp cristine/relbine)
-adynamic ileus: mimics surgical abd
-fatal ascending paralysis post
intrathecal admin-> leads to resp
failure/death
b. Vinblastine
Met testicular ca,
bladder, prostate, HL,
NHL, Kaposi’s sarcoma,
breast ca, mycosis
fungoides,
choriocarcinoma, CML,
cutaneous T-cell
lymphoma, head & neck,
lung, melanoma,
neuroblastoma, ovarian
c. Vinorelbine
-GI: abd cramps, wt loss, N/V/D, oral
ulcerations, paralytic ileus, int
necrosis, anorexcia
-mucositis, pharyngitis, stomatitis
-constipation (esp vinorelbine)
-heme:
.vincristine: mild anemia,
leucopenia, thrombocytp
.vinblastine: myelosup. (esp
neutropenia)
.vinorelbine: neutropenia
-derm: alopecia, photosentivity
-CV: chest pain, htn, MI
NSCLC, met br ca,
hormone refractory
prostate ca, cervical,
ovarian
2. Taxanes
a. Paclitaxel
Promotes assembly of
microtubules from tubulin
diamers, and stabilizes
microtubules by preventing
depolymerization resulting in
inhibition
Abraxane: (alb bound
paclitasel)-facilitates the
admin of water insoluble
contents
Ovarian ca, br. Ca, NSCLC,
Aids related Kaposi’s
sarcoma, bladder, head &
neck
-hypersensitivity rxn (HSR)
-neutropenia
-derm: alopecia
-onycholyosis, hand-ft/palm-plantar
dysesthesia syndrome, urticaria,
alopecia
-fluid retention (↑ed cap
permeability allows leakage of fluid)
-peripheral neuropathy
-transient myalgia, myopathy
-cardiac: hypotension, bradycardia,
Docetaxel more water
soluble (more potent) than
paclitaxel
Hypersensitivity: major in 25% and
minor in 40% ->bronchospasm,
urticaria, hypotension, rash, flush
-N/V, mucositis
- arrhythmias
-neurotoxicity
Excreted in bile
-met: p450
-resistance: same as vinca
alkyloids
b. Docetaxel
-Epothalone A has similar
3. Epothilones
a. Ixabepilone
(Azaepothilone B)
Breast ca, NSCLC,
Prostate Ca, Gastric adenocarcinoma, head and
neck
Maj and minor HSR’s in 31%
-D/N/V
-erythematous, prurtic maculopap
rash of forearms and hands in 75%
Excreted in feces
Met breast cancer
-neutropenia, HSR’s, cardia (LV
dysfxn or supraventric arrhythmia)
-sensory neuropathy, CN palsy,
ocular/visual changes, athralgia,
myalgia, increased transaminases,
N/V/A/D, abd pain, alopecia, rash
Not as susceptible to
resistance
tubular polymerization as
paclitaxel
-Epothalone B more potenet
than A or paclitaxel
-binds β-tubulin subunit of
microtulbules
-promotes prolif and resists
breakdown of mitotic spindles
-binds multiple sites on
microtubules
G1 specific agents:
1. Asaparaginase
hydrolyzes circulating Lasparagine to aspartic acid
and ammonia resulting in
inhibition of protein
synthesis
G2 Specific Agents:
1. Topoisomerase
Ihibitors
Topoisomerases are nuclear
enzymes which make transient
breaks in DNA allowing the cell
to manipulate its topology
•Functions:
DNA replication,
DNA transcription,
Chromosomal segregation,
DNA repair
ALL
->-topoisomeraseI:
acts on one strand of
DNA, removes negative
supercoils, no
involvement in DNA
replication, expression
continuous during G2
phase of the cell cycle &
in quiescent cells, ATP
Met by liver; excreted in
urine and feces
HSR, ↓clotting factors (IX, XI, PC,
PS, antithrombin III, fibrinogen;
pancreatitis, neurologic toxicity,
fever, chills, N/V
->
Topoisomerase II:
Acts on both strands of DNA,
Removes positive supercoils
Involved in DNA replication
Expression increases during S
phase of cylcle ~absent in
quiescent cells
ATP dependent
-alterations in topoisomeras I
-inadequate accumulation of
drug in tumor
-P-glycoproteins and MDR
efflux pumps
independent
a. Camptothecin
analogs
(inhibit topoisomerase I)
-Topotecan
b. Epipodophyll
otoxins
(inhibit topoisomerase I)
-Irinotecan
c. Etoposide
(VePeside,
VP-16)
-topoisomerase II
inhibitor
d. ANthracyclines
-MOA: stabilizes cleavable
complex where topoisom. I
covalently bound to DNA at a
single-stranded break site
-conversion to lethal DNA
damage follows when a DNA
replication fork encounters
these cleavable complexes
Ovarian ca, SCLC
-first converted by
carbosylesterase to active
metabolite SN-38, same
mech as above
Met colon ca
topoisomerase II inhibitor
-single strand breaks in
DNAand inhibits topoisom II
-late S phase/early G II
-production of free radicals
-disrupt membrane transport
SCLC, testicular ca
(refractory), ALL, AML,
BMT, MM, MDS,
lymphoma, gastric
Myelosuppression (esp
neutropenia), N/V, stomatitis,
diarrhea, transient ↑s in liver
enzymes, skin rash and alopecia
Myelosuppression, neutropenic
fever, diarrhea –acute cholinergic
-> like sxs, D/N/V/A, chills, malaise,
Can lead to dev of AML dizzy, visual disturbance, salivation,
lacrimation, asx bradycardia,
delayed-onset diarrhea, N/V,
alopecia, fatigue, skin toxicity,
increased liver transaminases
Myelosuppression, N/V, alopecia,
CHF, MI, stomatitis, 2˚ AML (<5yrs)
pH conversion to active
form; minimal liver
metabolism
–Excreted in urine
–metabolized by the liver
and intestinal mucosa
–Excreted in feces
S phase specific
-inihibit topoisomerase II
which leads to apoptosis
-intercalation into DNA
leading to inhibited synthesis
Myelosuppression (can lead to AML)
Neutropenia
–GI toxicity: mucositis, diarrhea,
delayed vomitting
–Cardiotoxicity:
•Acute: arrhythmias, pericarditis,
myocarditis
breast, soft tissue
sarcomas, ovarian, NHL,
HD, ovarian,
1. Doxorubicin
ALL, AML (and a million
other things)
ALL, AML,
2. Daunorubicin
Breast
3. Epirubici
n
ALL, AML
4. Idarubici
n
Breast
5. Mitroxan
trone
6. Lipsomal
Doxrbicin
Slightly dif MOA, ↓ed free
radical production, DNAreactive agent that
intercalates into DNA thru
hydrogen bonding causing
cross links and strand breaks
AML, ALL, Prostate Ca –
hormone refractory
phase,AML
•Chronic: CHF, dilated
cardiomyopathy
–Red-orange urine discoloration
–Radiation recall skin reaction,
hand-foot syndrome
*Dexrazoxane:
-indicated for the reduction of
cardiomyopathy asst’d w/
doxorubicin admin in women w/
met breast ca w/ high dose
-may add to myelosuppression
Presence of efflux pumps, Pglycoprotein and multipleresistance associated protein,
which belongs to the ATP
binding cassette family of
transporters
-pt mutations to binding site
of DNA topoisomerase gen
-increased inactivation of
superoxide free radicals
evades detection and
destruction by the immune
system
–increases the time the drug
is in the body
Kaposi’s sarcoma, ovarian
ca
Bluish discoloration of sclera,
urine, and finger nails; Less
cardiotoxicity and N/V than,
doxorubicin, HSR, Hand/foot
syndrome
–majority of the drug stays
inside the liposome while in
the blood (at least 90%)
Cell Cyle Specific Drugs:
1. Platinums
Cell cycle nonspecific
-form DNA intrastrand
adducts as opposed to DNA
interstrand cross links
HSR
Altered cell accumulation of
drug d/t impaired influx or
enhanced efflux
-cytosolic inactivation of drug
-increased DNA repair
-altered apoptotic process:
drug induced apoptosis may
be altered in cells that have
MMR defects ->results in
enhanced tumor cell survival
and ↑ed resistance
-widely distributed thru body
and excreted in urine
a. Cisplatin
b. Carboplatin
carboplatin induces same
adduct formation as cispllatin,
but must use 10x higher
concentration
cervical, esophageal,
gastric, head/neck, lung,
testicular, ovarian,
bladder, breast, NHL
Breast, lung, ovarian,
NHL, bladder, testicular,
head/neck
Peripheral neuropathy,
nephrotoxicity, tinnitus, delayed
N/V, myelosuppression
Anemia > thrombocytopenia,
delayed N/V
c. Oxaloplatin
2. Alkylating Agents
Colorectal, ovarian,
gastric
-Alkylator attatches to alkyl
groups to DNA bases resulting
in the DNA being fragmented
by repair enzymes preventing
DNA synthesis and RNA
transcription
-Crosslinks w/ DNA resulting
in inhibition of DNA synthesis
Increased risk of 2˚malignancies
Nitrogen mustard
Breast, ovarian, NHL,
sarcomas, endometrial,
CLL
Nitrogen mustard
Nitrogen mustard
Germ cell tumors,
sarcomas, lymphoma,
lung
MM
Nitrogen mustard
CLL, HD, NHL, MM
Uricaria, myelosup, pulm fibrosis,
neurotoxicity
Nitrosurea
Brain tumors, HD, NHL
Myelosup, pulm fibrosis, N/V, renal
and hepatotoxicity
Alkyl sulfonates
BM transplant
Myelosuppression, N/V, hepatotox,
VOD, electrolyte abn’s, interstitial
pneumonitis
a. Cyclphosphamide
b. Ifosphamide
c. Melphalan
d. Chlorambucil
e. Carmustine
f.
Busulfan
Acute-neuropathy (parasthesia,
dsysthesia, of hands, ft, throat),
chronic, cumulative neurotoxicity,
N/V
Myelosuppression(risk of MDS),
hemorrhagic cycstitis, SIADH,
hyperpigmentation, delayed
vomiting ,
Myelosuppresion(risk of MDS)
,delayed N/V, dysuria, neurotox,
SIADH, hemorrhagic cystitis
Myelosup, N/V/D, mucositis, HSR
3. Non classic
alkylating agent
Antitumor Abx
1. Bleomycin
2. Mitomycin
non-classice alkylating agent
–Methylation of guanine
residues in DNA which
inhibit DNA, RNA, and
protein synthesis
Leukopenia, thrombocytopenia
–N/V, anorexia
–Headache, and dizziness
–Elevated LFTs (40%)
–Skin: rash, itching, photosensitive
–Increased incidence of PCP
(prophylactic treatment with
Bactrim)
From fungus
-activation by oxidized iron
to form oxygen free radicals
resulting in DNA breaks
Testicular, HD
subacute and chronic pulmonary
fibrosis, mucositis, skin
(erythema/ hyperpig), HSR, vascul
events: MI/ CVA/ Raynauds
Intracell met; excreted in
urine
Antitumor antibiotic –
isolated from Streptomyces
caespitosus
Anal cancer & gastiric ca
Leucopenia, N/V, mucositis, HUS,
interstitial pneumonitis, HSR
Met by liver, spleen, kidney,
heart; excreted in bile
Apoptosis of APL cells
–Degradation of the fusion
protein PML/RAR-a
Acute promyelocytic
leukemia
CV: Prolonged QT interval
–GI: N/V/D/C
–HA, myalgias, and bone pain
–Leukocytosis (50% of pts)
–neuropathy, tremors, insomnia
–cough, sob, pleural effusions
–Electrolyte abnormalities
induces maturation of
promyelocytes to myelocyte;
thus decreasing proliferation
APL
Vitamin A toxicity symptoms: HA,
fever, bone pain, nausea, vomiting,
sweating, dry skin, mucositis, rash
–Cross-link DNA resulting in
inhibition of synthesis
–Inhibits transcription by
targeting RNA polymerase
3. Arsenic Trioxide
4. Trentinoin (ALLtransretinoic
acid)
–abdominal pain
–Neuro: dizziness, confusion,
depression
–Increasing leukocyte count
Hormonal Agents:
1. Tamoxifen
2. Aromatase
Inhibitors
-Anastrozole,
Letrozole, etc
3. Fulvestrant
Completely binds ER,
inhibiting transcriptional
processes
-SERM: selective E receptor
modulator
Premenopausal breast ca
pts
Menopausal sxs, vaginal bleeds,
peripheral edema, DVT/PE,
endometrial hyperplasia/ca (2%)
Inactivates aromatase and
blocks the conversion of
adrenal androgens to estrogn
Post menopausal br ca
Hot flashes, arthralgias, HA, flu-like
sxs
ER antagonits and downreg ER
expression
Met br ca
Asthenia, hot flashes, flu-like sxs, HA
Br/prostate ca
Hot flashes, impotence, decreased
libido, tumor flare – increasing bone
pain, urinary retention, back pain
Prostate ca
Hot flashes, decreased libido,
gynecomastia, myalgias,
hepatotoxicity
4. LHRH Agonists
-Leuprolide,
Goserelin
5. Anti-Androgens
-bicalutimide,
nilutamide,
flutamide
Binds androgen receptor and
inhibits androgen uptake
Strong inhibitors of CYP2D6
SSRI’s:
Paxil>Prozac>Zoloft>>Effexor
*monoclonal Ab’s(traztusumab): HSR
*Gleevec: Imatinib
*procarbazine: an alkylating agent used for HL (part of MOPP) inhibits monamine oxidase so avoid cheese, wine, smoked meat) food and drug interactions
*MOPP and ABVD (tx’s for HL): can lead to MDS
*ABVD: tx for HL: Adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine
*MOPP for HL: nitrogen mustard(cyclophosphamide), vincristine, procarbazine, prednisone
*R-CHOP: tx for NHL: Rituximab+ cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone
Common acute toxicities:
1. Myelosupression: leucopenia, thrombocytopenia, and anemia (lowest portion (nadir) is usu 7-10 d)
2. Febrile Neutropenia:
a. Neutropenia: <0.5 *10^9 cell/L and <1 *10^9 cells/L w/ predicted decrease in 48 hr
b. Fever: >101 F (38.3C), and sustained tem >100 F (38 C)
c. Infection risk correlates w/ depth and duration of neutropenia
3. N/V: stimulation of chemoreceptor trigger zone (CTZ) in medulla; stimulation excites dopaminergic paths which converge on adjacent emetic center
a. Other paths also converge on this center including cortical and peripheral cholinergic neurons and vestibular serotonin and histaminergic
neurons
4. Chemotherapy induced diarrhea:
a. GI epithelial lining replace Q 3-5 d
b. Toxicity to epith cells leads to inflame and secretory diarrhea
c. Chemo most implicated:
i. 5-FU, methotrexate, cytarabine, HD chemo
ii. Irinotecan causes dose limiting diarrhea
d. Early onset: cholinergic-mediate
e. Late-onset: resistant to antidiarrheal tx and may be life threatening