Anticancer Flashcards
1
Q
cancer drugs overview
A
2
Q
describe primary, adjuvent, and neoadjuvent chemotherapy
A
- Primary: when neoplasms are disseminated and not amenable to surgery
- Adjuvent: used to attack micrometastases following surgery and radiation
- Neoadjuvent: Given prior to surgery to shrink the cancer
3
Q
which cells are most sensitive to anticancer drugs?
A
- rapidly dividing cells
- buccal mucosa (stomatitis)
- bone marrow (myelosuppression)
- GI mucosa (nausea vomit)
- hair cells (alopecia)
4
Q
describe cell-cycle specific drugs
A
- Exert action on cells traversing cell cycle, most effecting in hematologic malignancies, useful in high growth-fraction tumours
- Antimetaboites (S-phase)
- Bleomycin (G2-phase)
- Camptothecins
- Epipodophyllotoxins (late S-G2 phase)
- Microtubule inhibitors (metaphase arrest)
5
Q
describe cell-cycle nonspecific drugs
A
- kill tumour cells whether they are cycling (more sensitive) or in Go resting phase, useful in low and high growth-fraction solid tumours
- Alkylating agents (can cause treatment induced neoplasms)
- Platinum coordination complexes
- Antitumour antibiotics
6
Q
list high, medium, and low myelosuppression drugs
A
- High
- Cytarabine
- Alkylating Agents
- Doxorubucin and Daunorubucin (antitumour anitbiotic)
- Vinblastine (vinca alkaloid)
- Medium
- Carboplatin
- Methotrexate (antimetabolite)
- 5-fluorouracil (antimetabolite)
- Low
- Bleomycin (antitumour anitbiotic)
- Vincristine (vinca alkaloid)
- Asparaginase
7
Q
doxorubicin toxicity
A
cardiotoxicity - anticancer antibiotic
8
Q
cyclophosphamide toxicity
A
hemorrhagic cystitis
9
Q
bleomycin toxicity
A
pulmonary fibrosis
10
Q
vincristine and paclitaxel toxicity
A
peripheral neuropathy
11
Q
rescues bone marrow from methotrexate (methotrexate antidote)
A
Leucovorin
12
Q
reduces hemorrhagic cystitis from cyclophosphamide
A
Mesna
13
Q
reduces anthracycline-induced cardiotoxicity (ex. from doxorubicin)
A
Dexrazoxane
14
Q
reduces renal toxicity caused by cisplatin
A
Amifostine
15
Q
list antimetabolites and the phase it acts on
A
- S-phase
- folate analog: Methotrexate
- purine analogs: 6-mercaptopurine (6-MP), 6-thioguanine (6-TG)
- pyrimidine analogs: 5-fluorouracil (5-FU), Capecitabine, Cytarabine
16
Q
Methotrexate MOA
A
Inhibits DHF reductase → deprives cells of folate → dTMP and purine nucleotide synthesis decreases → RNA/DNA/protein synthesis decreases → cell death
Undergoes conversation to a series of polyglutamates (MTX-PGs)
17
Q
methotrexate AEs
A
- Renal damage (from high-dose)
- Hepatic fibrosis
- Cirrhosis, pneumonitis, neurologic toxicities (IT administration)
- Common: stomatitis, mucositis, myelosuppression, alopecia, nausea, vomiting
18
Q
Leucovorin MOA
A
- N5-formyl-THF
- antidote for drugs that decrease folic acid (like methotrexate)
- rescues bone marrow
- provides normal tissues with reduced folate, circumventing the inhibition of DFHR
19
Q
Clinical use of Leucovorin
A
- Rescues bone marrow suppression from MTX
- Potentiates effect of 5-FU
20
Q
effects of Allopurinol
A
Potentiates 6-MP
No effect on 6-TG
21
Q
6-Thioguanine treats which cancer specifically?
A
Acute nonlymphocytic leukemia
22
Q
6-Mercaptopurine MOA
A
Converted to thio-IMP by HGPRT (purine salvage pathway) → inhibits 1st step of de novo purine synthesis
Thio-IMP also blocks formation of AMP and GMP
Dysfunctional RNA and DNA result from incorporation of guanylate analogs
23
Q
xanthine oxidase
A
Metabolizes 6-MP to thioruic acid
24
Q
If ___ is given to reduce ___, dose of 6-MP must be DECREASED to avoid accumulation
A
If allopurinol is given to reduce hyperuricemia, dose of 6-MP must be DECREASED to avoid accumulation
25
6-MP and 6-TG AEs
* Nausea, vomiting, diarrhea
* bone marrow suppression,
* hepatotoxicity (6-MP)
26
6-thioguanine (6-TG) MOA
converted to nucleotide → inhibits purine synthesis and phosphorylation of GMP to GDP, can be incorporated into RNA and DNA
27
5-FU inhibits ___ resulting in \_\_\_\_.
5-FU inhibits **thymidylate synthase** resulting in **'thymineless death'.**
28
Combination chemotherapy used for colorectal cancer
**5-FU and LEUCOVORIN**
*Leucovorin increases N5,N10-methylene-THF, potentiating 5-FU (which inhibits thymidylate synthase)*
29
5-FU and Capecitabine AEs
* **HAND-FOOT SYNDROME:** erythematous desquamation of the palms and soles seen after extended infusions
30
Cytarabine (ARA-C) MOA
*(deoxycytidine analog)*
phosphorylated to triphosphate → incorporated into DNA → **inhibits DNA polymerase**
*"tara takes double penetration"*
31
Antitumour Antibiotics MOA
* Bind to DNA through **INTERCALATION** between bases and block synthesis of new RNA or DNA
* causes DNA strand breakage and interferes with cell replication
* Cell-Cycle NON specific agents
* _Bleomycin, Doxorubicin, Daunorubicin_
32
Doxorubicin & Daunorubicin MOA
1. Inhibition of **topoisomerase II**
2. **intercalation** in DNA with consequent blockade of DNA & RNA synthesis and strand breakage
3. Binding to **cell membrane** to alter fluidity and ion transport
4. Generation of **free radicals** (cause of cardiac toxicity)
33
\_\_\_ is an iron-chelating agent educing cardiotoxicity from \_\_\_\_
**Dexrazoxane** is an iron-chelating agent educing cardiotoxicity from **Doxorubicin**
34
Bleomycin cell specific phase it acts on
**G2 phase**
35
Alkylating Agents MOA
* Cytotoxic effects via transfer of their alkyl groups to various cellular constituents leading to cell death
* can occur on **single strand or both strands** through **cross-linking**
* _Nitrogen mustards, Nitrosoureas, Platinum coordination complexes, Busulfan, Dacarbazine, Procarbazine_
36
Alkylating Agents AEs
* **MUTAGENIC + CARCINOGENIC**
* particularly in rapidly growing tissues
37
list the Nitrogen Mustards
mechlorethamine, cyclophosphamide, melphalan
("MCM = Mel Phalan")
38
\_\_\_\_ is a metabolite of cyclophosphamide, responsible for \_\_\_\_\_.
**Acrolein** is a metabolite of cyclophosphamide, responsible for **hemorrhagic cystitis**.
39
list ways of preventing hemorrhagic cystitis
* adequate fluid intake
* mesna
* acrolein
40
list Nitrosoureas and its properties
* Carmustine, Lomustine
* very lipophilic, can cross BBB
* useful treatment for **BRAIN tumours**
41
Busulfan toxicity
Pulmonary fibrosis, myelosuppression
42
\_\_\_\_ is converted by liver P450 enzymes to alkylating metabolites
**Procarbazine** is converted by liver P450 enzymes to alkylating metabolites
43
Procarbazine AEs
* BONE MARROW DEPRESSION, nausea, vomiting
* WEAK MAO INHIBITOR: hypertensive reactions may result if given with sympathomimetic agents, or tyramine-containing foods (cheese and wine)
* **DISULFIRAM-LIKE REACTIONS**
* mutagenic + teratogenic
44
Cisplatin, Carboplatin MOA
treatment for which cancers?
* Platinum drugs
* Do **not** alkylate DNA
* Covalently bind to DNA and **CROSS-LINKS DNA**
* Broad antineoplastic activity
* Treats: testicular cancer, ovarian cancer, and cancers of the head and neck, bladder, esophagus, lung and colon
45
Cisplatin AEs
* **Nephrotoxicity, ototoxicity**
* **Peripheral neuropathy**
* Mild/Moderate Myelosuppresion
46
Carboplatin AEs
* less nausea, neurotoxicity, ototoxicity, nephrotoxicity than cisplatin
* dose-limiting toxicity is myelosuppression
47
Vinca alkaloids/mictotubule inhibitors
Vicristine, vinblastine
48
Vicristine, vinblastine (Vinca alkaloids) MOA
* bind to B-tubulin and **inhibits** **polymerization** of microtubules
* Arrest in **M phase**
* Cell division stops → apoptosis
49
Vinca Alkaloids AE
* Vincristine: **peripheral neuropathy**
* Vinblastine: **dose-limiting myelosuppresion**
50
list the taxanes and their MOA
* Paclitaxel, Docetaxel
* Bind to B-tubulin of microtubules and **promote microtubule polymerization**
* stabilization of microtubules arrests cells in **mitosis** → apoptosis
51
Paclitaxel AEs
* Hypersensitivity
* peripheral neuropathy
52
Hypersensitivity from Paclitaxel is reduced by premedication with...
Dexamethason, Diphenydramine, H2 blocker
53
Docetaxel Adverse Effects
* **fluid retention**
* peripheral neuropathy (not as frequently as paclitaxel)
* Myelosuppression is dose-limiting
54
pretreatment with ____ is required to prevent fluid retention from docetaxel
pretreatment with **Dexamethasone** is required to prevent fluid retention from docetaxel
55
Camptothecins and MOA
* **Topotecan, Irinotecan**
* Inhibit Topoisomerase I
* DNA damage → fragments of single stranded DNA
56
Etoposide MOA
* Inhibits Topoisomerase **II** (E-two-poside)
* DNA damage
* through strand breakage → fragments of double stranded DNA
* Blocks cell in **late S-G2 phase**
57
Prednisone
* glucocorticoid
* lympholytic → suppresses **mitosis** in **lymphocytes**
* Used for acute leukemia and malignant lymphomas, "lymphocyte PRED-ator"
58
Selective Estrogen-Receptor Modulators (SERMs)
Selective Estrogen-Receptor Downregulators (SERDs)
SERMs: Tamoxifen, Raloxifene
SERDs: Fulvestrant
59
Tamoxifen vs. Raloxifene
* Tamoxifen:
* **antagonist** @ breast
* **agonist** @ bone & uterus
* treatment for receptor-positive breast cancer
* increased risk of endometrial cancer
* Raloxifene:
* **antagonist** @ breast & uterus
* **agonist** @ bone
* increased risk for thromboembolic events
* NO increased risk for endometrial cancer
* Prevention of postmenopausal osteoporosis
* prophylaxis of breast cancer in high risk postmenopausal women
60
Fulvestrant
* **Devoid** of all estrogen **agonist** activity
* binds to estrogen inhibitor and inhibits dimerization
* increasing its degradation
* ER-mediated transcription abolished
61
Aromatase inhibitors (AI)
Nonsteroidal reversible competitive inhibitors:
**Anastrozole, Letrozole**
Steroidal irreversible competitive inhibitors:
**Exemestane**
62
\_\_\_\_ converts androstenedione to estrone
* *Aromatase** converts androstenedione to estrone
* (primary source of circulating estrogens in postmenopausal women)*
therefore, **aromatase inhibitors** are standard care of adjacent treatment of postmenopausal women with **hormone receptor-positive breast cancer**
63
Androgen Inhibitors
Gonadotropin-Releasing Hormone Agonists:
**Goserelin, Leuprolide**
Androgen receptor blockers: **Flutamide**
64
GnRH Agonists MOA
* Cause initial surge in LH + FSH (1-2 weeks), followed by inhibition of gonadrotropin release
* testosterone falls to 10% of initial values after 1 month
* FLUTAMIDE for 2-4 weeks to prevent surge
65
