Anticancer Drugs II

Question 1

what are the alkylating agents

Answer 1

MANNT

Methylhydrazines
Alkyl Sulfonates
Nitrogen Mustards
Nitrosoureas
Triazenes

Question 2

mechanism of action of alkylating agents

Answer 2

-transfer of alkyl groups to DNA sites such as N7 position of guanine (there are other sites)

Question 3

what is an additional mechanism that occurs with alkylation agents Nitrosoureas

Answer 3

carbamoylation of lysine residues of proteins through formation of isocyanates

Question 4

what are the nitrogen mustards

Answer 4

CIMM

Cyclophosphamide
Ifosfamide
Mechlorethamine
Melphalan

Question 5

what is cyclophosphamide converted to and by what enzyme

Answer 5

converted to 4 hydroxycyclophosphamide by CYP2B6, which has the most 4 hydroxylase activity

Question 6

adverse effect of cyclophosphamide

Answer 6

Hemorrhage Cystitis

Question 7

what is responsible for the hemorrhage cystitis seen with cyclophosphamide and how can it be prevented

Answer 7

Acrolein, metabolite of cyclophosphamide, is responsible

-prevented by parenteral administration of Mesna, sulfhydryl compound, that reacts with acrolein in the bladder

Question 8

what is Ifosfamide

Answer 8

it is an analogue of cyclophoshamide hence needs Mesna to prevent hemorrhagic cystitis as well

Question 9

what is Mechlorethamine

Answer 9

an alkylating agent that is also a powerful vesicant (blistering agent)

Question 10

what is Melphalan used for

Answer 10

Multiple Myeloma

Question 11

what are the Nitrosoureas

Answer 11

Carmustine (IV)

Lomustine (orally)

Question 12

types of activity do nitrosoureas have (name them)

Answer 12

carmustine and lomustine

they have both alkylating activity and carbamoylating activity

Question 13

clinical application of nitrosoureas (name them)

Answer 13

carmustine and lomustine

they are highly lipid soluble and can cross the BBB so used for brain tumors

Question 14

what is the alkyl sulfonates

Answer 14

Busulfan

Question 15

what is the methylhydrazines

Answer 15

Procarbazine

Question 16

adverse effect of methylhydrazines

Answer 16

• 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

Question 17

name the triazenes

Answer 17

dacarbazine

Question 18

what are the two potent vesicant

Answer 18

Triazene: Dacarbazine

Nitrogen mustard: Mechlorethamine

Question 19

what are the platinum complexes

Answer 19

Cisplatin

Carboplatin

Question 20

mechanism of the platinum complexes (name them)

Answer 20

Cisplatin and Carboplatin

inhibits DNA synthesis and binds DNA through formation of cross links

Question 21

Cisplatin is used in combination with what drugs and to treat what

Answer 21

combination with Vinblastin and Bleomycin to treat nonseminomatous testicular cancer

Question 22

adverse effects of platinum complexes (name them)

Answer 22

Cisplatin and Carboplatin

Ototoxicity
Nephrotoxicity
Peripheral Neuropathy

Question 23

what can be used to prevent the Cisplatin induced nephrotoxicity

Answer 23

hydration and diuresis

Amifostine - thiophosphate cytoprotective agent

Question 24

what the anticancer hormonal agents

Answer 24

HORMONAL AGE

Androgen Inhibitors
Glucocorticoids
Estrogen Inhibitors

Question 25

what glucocorticoids is used in treatment of cancer and its mechanism

Answer 25

Prednisone: induces lymphocyte apoptosis

Question 26

name the estrogen inhibitors according to class

Answer 26

• Selective Estrogen Receptor Modulators (SERMs): Tamoxifen and Raloxifene
• Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant
• Aromatase Inhibitors: Anastrozole, Letrozole, Exemestane

Question 27

what are the selective estrogen receptor modulators (SERMs)

Answer 27

Tamoxifen

Raloxifene

Question 28

mechanism of tamoxifen and clinical application

Answer 28

anti estrogen effect at the breast but estrogen receptor agonist in the endometrium and bone

used to treat breast cancer

Question 29

adverse effect of tamoxifen

Answer 29

Endometrial Hyperplasia
Hot flashes
Thromboembolic Events

Question 30

mechanism of Raloxifene

Answer 30

estrogen antagonist in the breast and endometrium

estrogen agonist in the bone (prevent osteoporosis in post menopausal women)

Question 31

what is the selective estrogen receptor downregulators (SERDs)

Answer 31

Fulvestrant

Question 32

mechanism of selective estrogen receptor downregulator (name it) and when used

Answer 32

fulvestrant

pure estrogen antagonist with no agonist activity
-used in tamoxifen resistant breast cancer

Question 33

what are the aromatase inhibitors

Answer 33

Anastrozole
Letrozole
Exemestane

Question 34

mechanism of the aromatase inhibitors

Answer 34

Anastrozole and Letrozole are nonsteroidal competitive inhibitors of aromatase

Exemestane is a steroidal non competitive inhibitor of aromatase

Question 35

what are the androgen inhibitors

Answer 35

Androgen inhibitor: Goserelin and Leuprolide

Androgen Receptor Inhibitor: Flutamide

Question 36

name the androgen receptor inhibitor and its mechanism

Answer 36

Flutamide: non steroid competitive antagonist of the androgen receptor used for prostatic carcinoma

Question 37

adverse of flutamide

Answer 37

mild gynecomastia since it is blocking androgen receptor

Question 38

mechanism of Goserelin and Leuprolide

Answer 38

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