Anticancer Drugs II Flashcards
what are the alkylating agents
MANNT
Methylhydrazines Alkyl Sulfonates Nitrogen Mustards Nitrosoureas Triazenes
mechanism of action of alkylating agents
-transfer of alkyl groups to DNA sites such as N7 position of guanine (there are other sites)
what is an additional mechanism that occurs with alkylation agents Nitrosoureas
carbamoylation of lysine residues of proteins through formation of isocyanates
what are the nitrogen mustards
CIMM
Cyclophosphamide
Ifosfamide
Mechlorethamine
Melphalan
what is cyclophosphamide converted to and by what enzyme
converted to 4 hydroxycyclophosphamide by CYP2B6, which has the most 4 hydroxylase activity
adverse effect of cyclophosphamide
Hemorrhage Cystitis
what is responsible for the hemorrhage cystitis seen with cyclophosphamide and how can it be prevented
Acrolein, metabolite of cyclophosphamide, is responsible
-prevented by parenteral administration of Mesna, sulfhydryl compound, that reacts with acrolein in the bladder
what is Ifosfamide
it is an analogue of cyclophoshamide hence needs Mesna to prevent hemorrhagic cystitis as well
what is Mechlorethamine
an alkylating agent that is also a powerful vesicant (blistering agent)
what is Melphalan used for
Multiple Myeloma
what are the Nitrosoureas
Carmustine (IV)
Lomustine (orally)
types of activity do nitrosoureas have (name them)
carmustine and lomustine
they have both alkylating activity and carbamoylating activity
clinical application of nitrosoureas (name them)
carmustine and lomustine
they are highly lipid soluble and can cross the BBB so used for brain tumors
what is the alkyl sulfonates
Busulfan
what is the methylhydrazines
Procarbazine
adverse effect of methylhydrazines
- MOA inhibitor and can be potentiated if given with sympathomimetic agents and tyramine containing foods
- carcinogenic: increased risk of secondary cancers as compared to other alkylating agent
name the triazenes
dacarbazine
what are the two potent vesicant
Triazene: Dacarbazine
Nitrogen mustard: Mechlorethamine
what are the platinum complexes
Cisplatin
Carboplatin
mechanism of the platinum complexes (name them)
Cisplatin and Carboplatin
inhibits DNA synthesis and binds DNA through formation of cross links
Cisplatin is used in combination with what drugs and to treat what
combination with Vinblastin and Bleomycin to treat nonseminomatous testicular cancer
adverse effects of platinum complexes (name them)
Cisplatin and Carboplatin
Ototoxicity
Nephrotoxicity
Peripheral Neuropathy
what can be used to prevent the Cisplatin induced nephrotoxicity
hydration and diuresis
Amifostine - thiophosphate cytoprotective agent
what the anticancer hormonal agents
HORMONAL AGE
Androgen Inhibitors
Glucocorticoids
Estrogen Inhibitors
what glucocorticoids is used in treatment of cancer and its mechanism
Prednisone: induces lymphocyte apoptosis
name the estrogen inhibitors according to class
- Selective Estrogen Receptor Modulators (SERMs): Tamoxifen and Raloxifene
- Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant
- Aromatase Inhibitors: Anastrozole, Letrozole, Exemestane
what are the selective estrogen receptor modulators (SERMs)
Tamoxifen
Raloxifene
mechanism of tamoxifen and clinical application
anti estrogen effect at the breast but estrogen receptor agonist in the endometrium and bone
used to treat breast cancer
adverse effect of tamoxifen
Endometrial Hyperplasia
Hot flashes
Thromboembolic Events
mechanism of Raloxifene
estrogen antagonist in the breast and endometrium
estrogen agonist in the bone (prevent osteoporosis in post menopausal women)
what is the selective estrogen receptor downregulators (SERDs)
Fulvestrant
mechanism of selective estrogen receptor downregulator (name it) and when used
fulvestrant
pure estrogen antagonist with no agonist activity
-used in tamoxifen resistant breast cancer
what are the aromatase inhibitors
Anastrozole
Letrozole
Exemestane
mechanism of the aromatase inhibitors
Anastrozole and Letrozole are nonsteroidal competitive inhibitors of aromatase
Exemestane is a steroidal non competitive inhibitor of aromatase
what are the androgen inhibitors
Androgen inhibitor: Goserelin and Leuprolide
Androgen Receptor Inhibitor: Flutamide
name the androgen receptor inhibitor and its mechanism
Flutamide: non steroid competitive antagonist of the androgen receptor used for prostatic carcinoma
adverse of flutamide
mild gynecomastia since it is blocking androgen receptor
mechanism of Goserelin and Leuprolide
androgen inhibitors
- gonadotropin releasing (GnRH) analogues that stimulate the release of gonadal hormones
- Initially: 7-10 days, they increase gonadal hormone production which can be inhibited by flutamide
- delayed: with continued GnRH analogues, there becomes an inhibitory action to reduce gonadal hormone release
