B.33. Cancer Chemotherapy ll (Alkylating agents) Flashcards
list the alkylating agents
cyclophosphamide cisplatin oxaliplatin dacarbazine temozolomide bleomycin dactinomycin
which alkylating agent is cell cycle specific (ccs)?
bleomycin
*all the others are CCNS
how do alkylating agents exert their cytotoxic effects?
they covalently bind to nucleophilic groups on cell constituents (e.g: DNA alkylation)
most toxic to rapidly dividing cells, but do not discriminate between cycling and resting cells.
what alkylating agents cause lung fibrosis?
cyclophosphamide
bleomycin
what prevents nephrotoxicity in Cisplatin?
Amifostine and saline infusions
what kind of regimen is Oxaliplatin part of?
FOLFOX regimen (colon cancer)
a side effect of oxaliplatin
neurotoxicity
which alkylating agent causes SIADH and Hemorrhagic cystitis?
cyclophosphamide
what is given as an antidote to reduce the incidence of hemorrhagic cystitis when giving cyclophosphamide?
Mesna
what is the name of the metabolic product from cyclophosphamide that causes hemorrhagic cystitis?
acrolein
contraindications of alkylating gents
gravidity, nursing, and general disability
which alkylating agents require hepatic P450 activation
cyclophosphamide
dacarbazine
which alkylating agents are platinum-based?
Cisplatin
Oxaliplatin
what does cyclophosphamide do?
it attacks guanine N7–> dysfunctional DNA
how is cyclophosphamide given?
partnteral/ oral
how is cyclophosphamide classified chemically?
as nitrogen mustard
how does cisplatin/oxaliplatin work?
cross-links DNA strands
indications for dacarbazine
H&M
Hodgkin lymphoma
Melanoma
which drugs are usually used in combination with Dacarbazine?
Vinblastine
Bleomycin
doxorubicin
side effects of dacarbazine
nausea, vomiting alopecia skin rash photosensitivity myelosuppression
which alkylating agents cause myelosuppression
cyclophosphamide
dacarbazine
dactinomycin
which alkylating agent is activated in physiologic pH?
temozolomide
what is temozolomide used for?
CNS tumors (e.g: glioblastoma)
side effects of temozolomide
nausea, vomiting
myelosuppression
indications for cyclophosphamide
breast cancer ovarian cancer testicular cancer non- Hodgkin lymphoma CLL, ALL (children) neuroblastoma immunosuppressive therapy
SE of cyclophosphamide
nausea, vomiting, myelosuppression alopecia hemorrhagic cystitis, bladder cancer SIADH lung fibrosis
indications for cisplatin
lung cancer!
testicular cancer
bladder cancer
ovarian cancer
SE of cisplatin
nausea, vomiting (severe)
nephrotoxicity
neurotoxicity (ototoxicity, peripheral)
mechanism of bleomycin
complexes with Fe and O₂–> free radicals formation–> DNA strand termination
indications of bleomycin
Hodgkin lymphoma
lymphoma
testicular cancer
squamous cell carcinoma
indications of Dactinomycin (actinomycin-D)
Wilms tumor
Ewings sarcoma
Rhabdomyosarcoma
gestational choriocarcinoma
what is the mechanism of action of Dactinomycin?
inhibits DNA-dependent RNA polymerase–> at high doses inhibit DNA synthesis
side effects of dactinomycin
nausea, vomiting
Myelosuppression
alopecia
side effects of bleomycin
pulmonary fibrosis
pneumonitis
HS reaction
Mucocutaneous reactions (alopecia, hyperpigmentation, blisters, hyperkeratosis)
