Chemotherapeutic Agents

Question 1

Alkylating agents MOA

Answer 1

CCNS Nitrogen mustards ; Cross-linking (inter/intra strand) , Miscoding , DNA damage (strand breakage)

Question 2

Alkylating agents Examples

Answer 2

Cyclophosphamide and Ifosfamide , carmustine & lomustine , Melphalan , Chlorambucil , Busulfan

Question 3

Cyclophosphamide & Ifosfamide PK

Answer 3

C : Oral + IV , I: IV / Parent drugs are inactive, need biotransformation into hydroxylated intermediates (active) in liver then cytotoxic (acrolein . phosphoramide mustard)

Question 4

Cyclophosphamide & Ifosfamide MOA

Answer 4

alkylation within DNA in N7 position of guanine

Question 5

Cyclophosphamide & Ifosfamide Adverse

Answer 5

Hemorrhagic Cystitis (bladder fibrosis from acrolein NEED MESNA ) , neurotoxicity (I) , alopecia, Myelosuppression, GIT , endocrine

Question 6

Nitrosoureas

Answer 6

lipid soluble (BBB) , lomustine (oral) & carmustine (IV) (ur a must)

Question 7

Lomustine & Carmustine MOA

Answer 7

Alkylation is done on O6 (guanine)

Question 8

Lomustine & Carmustine Uses

Answer 8

Brain tumor (Gliadel wafer placement)

Question 9

Lomustine & Carmustine Adverse

Answer 9

Pulmonary toxicity + seizures , cerebral edema , depression (C) / myelosuppression , GItT

Question 10

Melphalan

Answer 10

IV+Oral ; multiple myeloma

Question 11

Chlorambucil

Answer 11

Oral ; CLL

Question 12

Busulfan

Answer 12

IV & Oral ; hematopoietic stem cell conditioning regimen

Question 13

Platinum analogs MOA

Answer 13

bind DNA with cross-links formation; N7-guanine, N3- adenine, O6-cytosine

Question 14

Platinum analogs examples

Answer 14

Cisplatin (1) , carboplatin (2) , oxaliplatin (3) all IV

Question 15

Platinum analogs Adverse

Answer 15

Cisplatin: severe myelosuppression , N V , renal toxicity , peripheral neuropathy Carboplatin has less renal & GI toxicity
Oxaliplatin peripheral acute & chronic neuropathy (colorectal & pancreatic)

Question 16

Antitumor Antibiotics

Answer 16

CCNS , Streptomyces : Anthracycline , bleomycin

Question 17

Anthracyclines PK

Answer 17

Doxorubicin , Daunorubicin = IV; eliminated by bile ; red color

Question 18

Doxorubicin , Daunorubicin MOA

Answer 18

DNA intercalation ;
Inhibition of topoisomerase II enzyme ;
Generation of free radicals

Question 19

Doxorubicin , Daunorubicin Adverse

Answer 19

Acute cardiotoxicity (reversible ↓EF) ;
Chronic cardiotoxicity (dose-dependent, dilated cardiomyopathy, irreversible ↓EF, and HF ) Liposomes spare heart
BM suppression (dose-limiting)
GIT; mucositis (dose-limiting)

Question 20

Antimetabolites

Answer 20

CCS-S ex: Antifolates (methotrexate) & pyrimidine antagonists

Question 21

Methotrexate

Answer 21

Oral , IV , IM , IT ; hydroxylated metabolite is less water soluble = crystalluria

Question 22

Methotrexate MOA

Answer 22

inhibits DHFA reductase & thymidylate synthase

Question 23

Methotrexate Adverse

Answer 23

Methotrexate-induced crystal nephropathy
Liver disease , GIT , rash , alopecia , myelosuppression

Question 24

Pyrimidine Antagonists

Answer 24

pyrimidine analog ex: 5-Flurouracil (5-FU) IV + oral

Question 25

5-FU MOA

Answer 25

inhibits thymidylate synthase + interferes in RNA processing & translation (colorectal)

Question 26

5-FU Adverse

Answer 26

Myelosuppression , GIT , neurotoxicity

Question 27

Microtubule Inhibitors

Answer 27

Vinca alkaloids (Vincristine & Vinblastine : IV) excreted in bile/stool + Taxane (VIN VIN TAXI)

Question 28

Vincristine & Vinblastine MOA

Answer 28

bind to tubulin = block MT = arrested in metaphase

Question 29

Vincristine & Vinblastine Adverse

Answer 29

Neurotoxicity (VX) ; Myelosuppression & mucositis (VBL)

Question 30

Taxanes

Answer 30

Paclitaxel , Docetaxel (IV) ; bile/stool

Question 31

Paclitaxel , Docetaxel MOA

Answer 31

promote tubulin to polymerize to form nonfunctional microtubules = cell death

Question 32

Paclitaxel , Docetaxel Adverse

Answer 32

Severe hypersensitivity reactions , myelosuppression
Peripheral neuropathy