Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FTCM > L21, L23, L25- Chemotherapy and Neoplastic Diseases > Flashcards

L21, L23, L25- Chemotherapy and Neoplastic Diseases Flashcards

1
Q

in general chemotherapies aim to attack (1) or (2)

A
  • DNA

- metabolic sites essential to cell replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q
  • (1) chemotherapy is used to attack micrometastases following surgery and radiation
  • (2) chemotherapy is given prior to surgery to shrink the cancer
  • (3) chemotherapy is indicated when neoplasms are disseminated (spread) and surgery is not possible
A

1- Adjuvant
2- Neoadjuvant
3- Primary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

destruction of cancer cells by drugs follows (1) kinetics, and is this phenomenon is termed (2)

A

1- first order (a given dose destroys a constant fraction of cells)
2- log kill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Diagnosis of leukemia requires (1) leukemic cells present. (2) log kills by treatment eliminates 99.999% of cancer cells to induce clinical remission. However, in the case of leukemia, (3) cells would remain, therefore (4) is required. In contrast, drugs for bacterial infections only require (5) log kills, as the body readily eliminates residual bacterial cells- not the case for cancer cells.

A 
1- 10^9
2- 5 log kills
3- 10^4 cells (0.001%)
4- additional Tx (tumor cells aren't as readily eliminated as bacterial cells)
5- 3 log kills
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

describe the effects of combination chemotherapy

A
  • multiple chemotherapy drugs used, each with different mechanism of action (standard approach)
  • synergism can be reached
  • used to prevent/slow down development of resistance to anticancer drugs
  • maximal kill, tolerated toxicity: each drug has its own log kill and can destroy tumor cells that are resistant to the other drugs
  • given intermittently to allow normal tissue to recover (ex. immune system to reduce chance of serious infection)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

anticancer drugs are more effective on (rapid/slow) growing neoplasms, especially those with (large/small) growth fractions

A

1- rapid growth

2- large growth fraction (more cells in cell cycle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

list the two types of chemotherapy drugs and their subtypes

A

Cell Cycle-Specific agents: antimetabolites (S), bleomycin (G2), microtubule inhibitors (M), epipodophyllotoxins (S-G2), camptothecins (S-G2)

Cell Cycle-Nonspecific agents: alkylating agents, platinum coordination complexes, antitumor antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cell cycle-specific drugs are most effective on (1) malignancies and other tumors with (2) as they target (3).
Cell cycle-nonspecific drugs are most useful for (4) tumors, as well as other tumors with (5) as they target (6).

A

1- hematologic
2- large growth fraction
3- cell cycle (S to M phases)

4- solid
5- large growth fraction
6- cells in Go phase or in cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

primary drug resistance is defined as….

A

no response to a drug upon first exposure (naturally resistant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

acquired drug resistance can be either (1) due to (2) OR (3) because (4) occurs

A

1- single drug resistance
2- inc expression/amplification of one or more genes
3- multi-drug resistance (MDR)
4- resistance to several drugs after exposure to single agent (very difficult to Tx)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

MDR mainly occurs as a result of…..

A

(multi-drug resistance)

  • overexpression of membrane efflux pumps
  • MOST importantly P-Glycoprotein (most responsible)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

(T/F) chemotherapy drugs have a narrower therapeutic window compared to other drugs

A

T- usually higher dose needed for min therapeutic effects and lower dose needed for min toxic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

chemotherapy drugs that target rapidly proliferating cells will also affect the following types of normal cells, (1), causing the following adverse effects, (2)

A

1- buccal mucosa, GI mucosa, bone marrow, hair cells

2- severe vomiting (GI), stomatitis (buccal- mouth/lip inflammation), bone marrow suppression, alopecia (hair)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

the following drugs have high myelosuppression….

A
  • cytarabine
  • alkylating agents
  • doxorubicin
  • daunorubicin
  • vinblastine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

the following drugs have medium myelosuppression….

A
  • carboplatin
  • methotrexate (MTX)
  • 5-FU (fluorouracil)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

the following drugs have low myelosuppression….

A
  • bleomycin
  • vincristine
  • asparaginase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name the drug related to the following specific adverse effect:

(1) cardiotoxicity
(2) hemorrhagic cystitis
(3) peripheral neuropathy
(4) pulmonary fibrosis

A

1- doxorubicin
2- cyclophosphamide
3- vincristine, paclitaxel
4- bleomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

_______ drugs are used to manage chemotherapy induced emesis (vomiting)

A
  • 5-HT3 (serotonin) receptor blockers

- NK-1 (neurokinin) inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

_______ drugs are used to prevent and treat chemotherapy induced neutropenia (from myelosuppression)

A
  • filgrastim

- sargramostim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

_______ drugs rescue bone marrow from MTX

A

leucovorin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

(1) binds the metabolite of (2) drug- (3) - to prevent hemorrhagic cystitis

A

1- mesna
2- cyclophosphamide
3- acroleine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

(1) drugs reduce anthracycline induced cardiotoxicity, usually from (2) drugs

A

1- dexrazoxane

2- doxorubicin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

_______ drugs reduce renal toxicity of cisplatin

A

amifostine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

because most antineoplastic agents are (1), (2) may arise 10 or more years after curing cancer; this is the biggest problem after therapy with (3)

A

1- mutagenic
2- neoplasms
3- alkylating agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Antimetabolite chemotherapy drugs mostly target (1) related pathways, they are cycle-(non-/specific) affecting the (3) phase most. The three types of antimetabolites include: (4).

A

1- nucleotide or nuclei acid synthesis
2- cycle-specific
3- S phase (DNA replication)
4- folate analogs, purine analogs, pyrimidine analogs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

The main folate analog of the antimetabolite drugs is (1), which functions to inhibit (2). This deprives the cell of folate and therefore decreases the synthesis of (3) specifically and (4) overall.

A

1- MTX (methotrexate)
2- dihydrofolate reductase
3- dTMP (from dUMP) and purine synthesis
4- DNA, RNA, proteins => cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

describe the mechanism of action of MTX in detail

A
  • inhibits dihydrofolate reductase
  • catalyzes folate –> DHF and DHF –> THF
  • THF (tetrahydrofolate) is methylates to Me-THF
  • Me-THF is needed for thymidylate synthase to convert dUMP –> dTMP AND for adenine/guanine synthesis
  • => incomplete and disrupted DNA(/RNA) synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

MTX metabolism is defined as the conversion to (1) by (2) enzyme

A

1- polyglutamates (MTX-PGs)

2- folylpolyglutamate synthase (FPGS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

list the adverse effects on MTX

A
  • Common: stomatitis, mucositis, myelosuppression (medium), alopecia, nausea/vomiting
  • Uncommon is renal damage if high dose is given
  • hepatic fibrosis, cirrhosis
  • pneumonitis
  • neurological toxicities with IT administration (intrathecal, administration into CSF for brain tumors as MTX won’t cross BBB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Leucovorin is also called (1), and is an antidote to (2) drugs in order to rescue (3) as it provides normal tissue with (4).

A

1- N(5)-formyl-THF (replaces Me-THF)
2- folate analogs / MTX / drugs that reduce folate
3- bone marrow
4- reduced folate (bypassing DHFR inhibition by MTX)

[basically used so normal cells (bone marrow) can produce dTMP, purines (adenine/guanine) for DNA/RNA synthesis during chemotherapy, although too much would cancel the effects of MTX]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

list the two main purine analogs

A
  • 6-MP (6-mercaptopurine)

- 6-TG (6-thioguanine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

6-MP is an analog of (1), and is converted to (2) by (3) enzyme. (2) will inhibit (4) and block the formation of (5). Lastly, dysfunctional (6) will result from incorporated (7) analogs.

A 
(6-mercaptopurine)
1- (thiol analog of) hypoxanthine
2- thiol-IMP
3- HGPRT (salvage pathway)
4- 1st step of de novo purine ring biosynthesis
5- AMP/GMP from IMP
6- DNA, RNA
7- guanylate analogs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

6-MP is metabolized into (1) by (2) enzyme. 6-MP should not be given to patients taking (3) drug as it inhibits (2).

A

(6-mercaptopurine)
1- thiouric acid
2- xanthine oxidase
3- allopurinol (–> oxypurinol by xanthine oxidase is the effector)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

list the adverse effects of 6-MP

A

(6-mercaptopurine)

  • n/v/d
  • myelosuppression
  • hepatotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

list the cell cycle-specific agents and the associated phases they affect

A
  • antimetabolites (S phase)
  • bleomycin (G2 phase)
  • MT inhibitors (M phase)
  • epipodophyllotoxins (S-G2 phase)
  • camptothecins (S-G2 phase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

list the cell cycle-nonspecific agents

A

alkylating agents, platinum coordination complexes, antitumor antibiotics (except bleomycin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

P-glycoprotein can lead to MDR to the following anticancer drugs: (1)

They cannot transfer the following cancer drugs: (2)

A

1- doxorubicin, daunorubicin, dactinomycin, vincristine, vinblastine, etoposide

2- alkylating agents, antimetabolites, cisplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what are the contraindications of using MTX

A

MTX is teratogenic and abortifacient – avoid in pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

6-MP is mostly used in (1) cancer.

It has resistance based on the following: (2), (3), (4)

A

(6-mercaptopurine)
1- acute lymphatic leukemia

2- HGPRT deficiency / Lesch-Nyhan syndrome: cannot bio-transform 6-MP

  • inc dephosphorylation
  • inc metabolism of drug to thiouric acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

After administration of 6-thioguanine, it is converted to (1) in order to (2) and (3). It is mainly used for (4) cancers. Its toxic adverse effects include: (5).

A

1- nucleotide / TGMP
2- inhibit purine synthesis / phosphorylation of GMP –> GDP
3- incorporate into DNA, RNA –> dysfunctional strands
4- acute nonlymphocytic leukemias
5- -n/v/d, myelosuppression, hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

6-MP and 6-TG are secondarily metabolized by….

A

TPMT- thiopurine methyltransferase: if it has weak activity then they cause inc risk of severe toxicities (myelosuppression)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

list the pyrimidine analogs

A
  • 5-FU (5-fluorouracil)
  • capecitabine
  • cytarabine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

5-FU is converted to (1) in order to inhibit (2) and therefore (3). (4) will result as a consequence. 5-FU can also be converted to (5) to disrupt (6).

A 
(5-fluorouracil)
1- 5-FdUMP
2- thymidylate synthase (dec dTMP)
3- DNA synthesis
4- thymineless cell death
5- 5-FUTP
6- RNA processing and function due to incorporation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

5-FU is metabolized by (1) enzyme, which is deficient in (2)% of cancer patients who will suffer with (3)

A

(5-fluorouracil)
1- DPD (dihydropyrimidine dehydrogenase)
2- 5% Pts
3- severe toxicity: myelosuppression, neurotoxicity, life-threatening diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

traditional adverse effects of 5-FU are…

A

(5-fluorouracil)

  • n/v, alopecia, myelosuppression
  • erythematous desquamation of hands/soles (‘hand-foot’ syndrome) after extended infusions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

5-FU is commonly combined with (1) in (2) cancer. A (3) complex formation results, since (1) increases the levels of (4). In essence (1) potentiates the activity of 5-FU.

A 
(5-fluorouracil)
1- leucovorin (N5-formyl-THF)
2- colorectal cancer
3- thymidylate synthase-5F-dUMP-N5,N10-methylene-THF complex
4- N5,N10-methylene-THF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q
  • 5-FU is commonly used to treat (1) cancers

- Resistance to 5-FU results from (2)

A

(5-fluorouracil)
1- breast, GI CAs + topically for keratoses/BCC
2- inability to convert 5-FU to 5-FdUMP

48
Q

(1) is a oral prodrug of 5-fluorouracil and is converted to 5-FU through (2). It is used for (3) cancers.

A

1- capecitabine
2- series of 3 enzymatic reactions
3- metastatic breast and GI CAs
(same mechanism of action and adverse effects as 5-FU)

49
Q

T/F- MTX has much higher affinity for DHF reductase than folate

A

T- 1000 times more affinity then folate

50
Q

ARA-C, aka (1), is an analog of (2). It functions by the following mechanism: (3).

A

1- cytarabine
2- deoxycytidine
3- phosphorylation x3 –> triphosphate form (ara-CTP) –> incorporated into DNA –> inhibits DNA polymerase (dec DNA synthesis)

51
Q

ARA-C is used for (1) cancers in combination with (2) and (3). It is administered in (4) fashion. Adverse effects include: (5).

A 
(cytarabine)
1- acute non-lymphocytic leukemia
2- 6-TG
3- daunorubicin
4- IV or IT if necessary
5- n/v/d, severe myelosuppression, hepatic dysfunction (+ seizures/altered mental state if high dose given IT)
52
Q

describe antitumor antibiotics mechanism

A
  • binds DNA via intercalation between bases
  • blocks synthesis of DNA/RNA
  • causes DNA strand breakage
  • interferes with cell replication
53
Q

list the types/subtypes of antitumor antibiotics

A
  • Anthracyclines: doxorubicin, daunorubicin

- Bleomycin

54
Q

(1) are the most important type of antitumor antibiotics, and (2) is the most widely used, and (3) is also a popular drug

A

1- anthracyclines antibiotics
2- doxorubicin
3- daunorubicin

55
Q

list the 4 major mechanisms of action for anthracyclines

A
  • inhibit topoisomerase II (gyrase)
  • intercalate in DNA –> blocks DNA/RNA synthesis + strand breakage
  • bind cell membrane –> alter fluidity + ion transport
  • generate free radicals via Fe-dep enzyme mediated process
56
Q

(1) is a major toxicity of anthracyclines, caused by its (2) mechanism

A

1- cardiac toxicity

2- generation of free radicals

57
Q

list the 4 mechanisms of resistance to anthracyclines

A
  • inc efflux via P-glycoprotein (MDR1)
  • inc glutathione peroxidase activity => inc free radical scavenging
  • dec activity or mutation of topoisomerase II (gyrase)
  • enhanced ability of cancer cells to repair breaks in DNA strand
58
Q

list the adverse effects of anthracyclines [include an agent given to reduce its unique adverse effect]

A
  • myelosuppression
  • cardiotoxicity: via free radicals, dose dependent dilated cardiomyopathy w/ associated HF
  • *dexrazoxane** is an Fe-chelating agent to reduce cardiotoxicity
59
Q

anthracyclines are always given by (1) administration because of (2); (3) is the main method of excretion

A

1/2- IV, deactivated in GIT

3- bile excretion (some renal)

60
Q

doxorubicin is used for the following CAs: (1)

daunorubicin is used for the following CAs: (2)

A

1- lymphoblastic leukemia, acute myoblastic leukemia, Wilm’s tumor, neuroblastoma, sarcomas, breast / ovarian / transitional cell bladde / thyroid / gastric / bronchogenic CA, Hodgkin’s disease, malignant lymphoma

2- acute nonlymphocytic leukemia (adults), acute lymphocytic leukemia (adults + children)

61
Q

bleomycin is made up of (1) and caused (2) by (3) process, resulting in cells being (4)

A

1- glycoprotein mixture
2- breakage of DNA
3- oxidative processes
4- arrested in G2 phase

62
Q

bleomycin forms a (1) complex which is converted to (2) via oxidation; (3) released from this reaction reacts with (4) to cause (5)

A

1- DNA-bleomycin-Fe2+
2- DNA-bleomycin-Fe3+
3- electrons (liberated)
4- O2 –> free radicals (superoxide, hydroxyl radicals)
5- DNA strand breakage (attacks phospho-diester bond)

63
Q

list the adverse effects of bleomycin

A

-minimal myelosuppression
-**pulmonary toxicity: pneumonitis, fibrosis (low levels of bleomycin hydroxylase)
-cutaneous rxns: hyperpigmentation, hyperkeratosis, erythema, ulceration (absent bleo. hyd. enzy.)
-hyperthermia, HA, n/v
(dose limiting)

64
Q

bleomycin is given by (1) administration, metabolized by (2) enzyme, and is used for (3) CAs

A

1- IV, SC, IM, intracavitary
2- bleomycin hydrolase (levels differ based on tissue- low in lungs and skin)
3- testicular CA, lymphomas

65
Q

alkylating agents general mechanism of action

A
  • transfer alkyl group to various cell molecules
  • DNA alkylation => cell death
  • alkylation of one DNA strand OR both thru cross-linking (most are bi-functional)
66
Q
  • (1) is the most widely used alkylating agent
  • toxicities occur in (2) tissues
  • (3) are the most common adverse effects
  • alkylating agents are also dangerous due to their (4) properties
A

1- cyclophosphamide
2- rapidly growing tissues: bone marrow, GIT, gonads
3- n/v
4- mutagenic, carcinogenic

67
Q

list the alkylating agents

A
  • nitrogen mustards
  • nitrosoureas
  • others
  • platinum coordination complexes
68
Q

list the nitrogen mustards

A
  • mechlorethamine
  • cyclophosphamide
  • melphalan
69
Q

list the major characteristics and adverse effects of mechlorethamine

A
  • very unstable; soln made just before administration
  • powerful vesicant (causes blistering), given IV

adverse effects: severe n/v, severe myelosuppression, alopecia, immunos`uppression

70
Q

Cyclophosphamide is given by (1) route of administration and is converted to (2) by (3) into an active drug. It is used for (4) cancers.

A

1- oral/IV (prodrug)
2- 4-OH-cyclophosphamide
3- CYP2B
4- broadly, its apart of most combination chemotherapies

71
Q

list the adverse effects of cyclophosphamide

A
  • n/v
  • myelosuppression
  • alopecia
  • sterility
  • hemorrhagic cystitis (acrolein metabolite)
72
Q

(1) is the metabolite of cyclophosphamide that causes (2). (2) can be prevented by (3) and (4).

A

1- acrolein
2- hemorrhagic cystitis
3- adequate fluid intake
4- mesna (drug binds acrolein in bladder)

73
Q

(1) is an analog of cyclophosphamide with (2) as an additional adverse effect which can be treated with (3) [if it doesn’t respond spontaneously to discontinued treatment)

A

1- ifosfamide (same mechanism as cyclophosphamide)
2- neurotoxicity: encephalitis with ranging Sx severity (onset takes hrs-days)
3- methylene blue, thiamine

74
Q

melphalan is a (1) type of chemotherapy drug; its mechanism of action is (2) and has (3) adverse effects

A

1- alkylating agent, nitrogen mustard
2- bi-functional DNA alkylation (cross-linking of DNA strands) => cell death
3- myelosuppression

75
Q

The nitrosoureas drugs are (1). The are useful in treating (2) because of their (3) property.

A

(alkylating agents)
1- carmustine, lomustine
2- brain tumors
3- highly lipophilic => crosses BBB

76
Q

list the other alkylating agents

A
  • busulfan
  • dacarbazine
  • procarbazine
77
Q

busulfan is a (1) type chemotherapy drug, mainly used for (2) cancers, and has (3) as its adverse effects

A

1- alkylating agent (other)
2- CML (chronic myeloid leukemia)
3- myelosuppression, pulmonary fibrosis

78
Q

Dacarbazine is a (1) type chemotherapy drug that is activated by (2) and has a (3) mechanism of action. It is mainly used for (4) cancers, and has (5) as its adverse effects.

A 
1- alkylating agent (other)
2- CYP450 isoforms
3- methylating agent
4- malignant melanoma, Hodgkin's lymphoma
5- n/v, low/moderate myelosuppression
(IV administration)
79
Q

Procarbazine is a (1) type chemotherapy drug that is activated by (2) and has a (3) mechanism of action. It is mainly used for (4) cancers, and has (5) as its adverse effects.

A

1- alkylating agent (other)
2- CYP450 isoforms
3- methylating agent of DNA, RNA, protein
4- Hodgkin’s disease
5- n/v, myelosuppression, weak MAO inhibitor (=> HTN rxns w/ SNS agents, tyramine foods), disulfiram-like rxn, mutagenic, teratogenic
(oral administration)

80
Q

The platinum coordination complexes include (1) and (2). They act by (3). They are used for (4) cancers and are administered by (5).

A

1- cisplatin
2- carboplatin
3- covalent DNA binding => cross-linking => dec DNA synthesis
4- broadly for many CAs (testicular, ovarian CA)
5- IV

81
Q

list the adverse effects of cisplatin [include drug to reduce one particular effect]

A
  • mild/moderate myelosuppression
  • n/v
  • ototoxicity (hearing/vestibular issues)
  • peripheral neuropathy
  • nephrotoxicity (tx by hydration/diuresis OR Amifostine to reduce renal toxicity)
82
Q

list the adverse effects of carboplatin

A

include the following, but less severity than cisplatin: dose-limiting myelosuppression, n/v, ototoxicity (hearing/vestibular issues), neurotoxicity, nephrotoxicity

83
Q

describe the general mechanism of action of MT inhibitors

A

disrupts mitotic spindle essential for DNA partitioning –> arrests the cell in Metaphase of mitosis

84
Q

list the MT inhibitors (include subtypes)

A
  • Vinca alkaloids: vincristine, vinblastine

- Taxanes: paclitaxel, docetaxel

85
Q

describe vinca alkaloids mechanism of action

A

(vincristine, vinblastine)

  • binds β-tubulin –> prevents MT polymerization
  • cells arrested in metaphase –> stops cell division –> apoptosis
86
Q

list the adverse effects for vinca alkaloids

A

Vincristine: peripheral neuropathy, mild myelosuppression, alopecia

Vinblastine: dose-limiting myelosuppression, alopecia, peripheral neuropathy

87
Q

describe taxanes mechanism of action

A

(paclitaxel, docetaxel)

  • binds β-tubulin –> promotes MT polymerization
  • MT stabilization arrests cell in mitosis –> apoptosis
88
Q

list the adverse effects of taxanes

A

Paclitaxel: myelosuppression, alopecia, peripheral neuropathy, hypersensitivty (reduced with meds)

Docetaxel: dose-limiting myelosuppression, alopecia, peripheral neuropathy (less than paclitaxel), fluid retention, mucositis

89
Q

taxanes can be pretreated with _____ to avoid _____

A

Paclitaxel: dexamethasone / diphenhydramine / H2 blocker to prevent hypersensitivity

Docetaxel: dexamethasone to prevent fluid retention

90
Q

Etoposide is a (1) type chemotherapy drug. Its mechanism is to inhibit (2) resulting in (3) and causing (4). It has the following adverse effects: (5).

A 
1- epipodophyllotoxins
2- topoisomerase II (gyrase)
3- DNA strand breakage
4- cell arrest in late S to G2
5- myelosuppression, alopecia, n/v
91
Q

The main camptothecins are (1) and (2) which function to (3) to cause (4).

A

1/2- topotecan, irinothecan
3- inhibit topoisomerase I
4- DNA damage (breakage) in S phase => G2 arrest => cell death

92
Q

list the types of hormonal chemotherapeutic agents

A
  • glucocorticoids
  • estrogen inhibitors
  • androgen inhibitors
93
Q

The main glucocorticoid is (1) which has a (2) property in order to have (3) function. It is used to treat (4) cancers.

A

1- prednisone
2- lypholytic
3- suppress mitosis in lymphocytes (cell death)
4- acute leukemia, malignant lymphomas

94
Q

list the types of estrogen inhibitors

A
  • SERMs: selective estrogen receptor modulators
  • SERDs: selective estrogen receptor downregulators
  • AIs: aromatase inhibitors
95
Q

describe the function of each SERM

A

(selective estrogen receptor modulator)
Tamoxifen: antagonist in breast tissue/cancer (agonist for nonbreast tissues); Tx for receptor-pos. BC (tumor growth in response to hormone) and to chemopreventive for BC (of people at risk)

Raloxifene: antiestrogen in uterus/breast (inhibits bone resorption - a proestrogen effect; Tx for osteoporosis and BC prevention

96
Q

The main SERD is (1) which has the following mechanism of action: (2). It is used for (3) treatment.

A

1- fulvestrant
2- binds estrogen receptor –> prevents dimerization + promotes degradation (note it has NO estrogen agonist activity)
3- receptor-pos. metastatic BC

97
Q

Aromatase functions to complete (1), which is vital in (2), therefore inhibitors are adjuvant treatments for (3)

A

1- androstenedione to estrone conversion
2- post-menopausal women, the only source of estrogens
3- receptor-pos. BC

98
Q

(1) and (2) are nonsteroidal aromatase inhibitors through a (3) mechanism
(4) is steroidal, and inhibits through (5) mechanism

A

1/2- anastrozole, letrozole
3- reversible competitive inhibitor

4- exemestane
5- irreversible inhibitor

99
Q

list the types of androgen inhibitors and indicate the preferred type

A

-GnRH agonists (PREFERRED- alone or in combination)
-androgen receptor blockers
(for prostate cancer)

100
Q

list the GnRH agonists

A

leuprolide, goserelin

for prostate cancer

101
Q

describe GnRH agonists mechanism of action [include drug often used concurrently]

A

-initial surge of LH/FSH
-followed by inhibition of gonadotropin release
-=> 10% of normal testosterone levels after 1 mo.
(note- for prostate cancer & GnRH usually has pulsatile excretion)

Flutamide given to counteract initial surge

102
Q

The main androgen receptor blocker is (1) which is metabolized into (2) and acts as a (3) type androgen receptor blocker.

A

1- flutamide (nonsteroidal, synthetic)
2- hydroxylated metabolite
3- competitive antagonist (–> prevents translocation to nucleus)
(given in first mo. of prostate cancer Tx along side GnRH agonist (leuprolide/goserelin) to prevent LH/FSH surge)

103
Q

Signal transduction inhibitors mainly includes ______ type of receptors since they are mutated and constituitively active in malignant cells/transformatiom

A

TK (tyrosine kinase)

104
Q

gefitinib function

A

EGFR TK inhibitor (cellular side)

105
Q

erlotinib function

A

EGFR TK inhibitor (cellular side)

106
Q

lapatinib function

A

EGFR and ErbB2 TK inhibitor (cellular side)

107
Q

imatinib function

A

Bcr-Abl TK inhibitor (cellular side - for CML)

108
Q

trastuzumab function, include major adverse effect

A
  • monoclonal Ab against ErbB2 TK receptor (lumen side)

- reversible cardiotoxicity

109
Q

list the miscellaneous chemotherapy agents

A
  • asaparaginase
  • hydroxyurea
  • interferons
110
Q

describe mechanism of action of asparaginase

A
  • normal tissue synthesizes their own L-asparagine for protein synthesis
  • neoplastic tissues need exogenous sources (absent asparagine synthetase)
  • asparaginase hydrolyzes serum asparagine, depriving necrotic tissue => dec protein synthesis and cell death
111
Q

list adverse effects of asparaginase

A
  • hypersensitivity
  • dec clotting factors
  • liver abnormalities
  • pancreatitis + seizures + coma due to ammonia (NH3) toxicity
112
Q

(1) inhibits ribonucleotide reductase leading to (2) and therefore (3) and (4). It is administered (5).

A 
1- hydroxyurea
2- depleted dNTs pools
3- dec DNA synthesis
4- cell death in S phase
5- orally
113
Q

IFN-(α/β/γ) is used for (2) cancers with (3) as its mechanism and it has the following adverse effects: (4).

A

1- IFN-α
2- hairy cell leukemia, CML, malignant melanoma, Kaposi’s sarcoma
3- stimulates NK to kill cancer + inc HLA-II production (=> inc MHC expression)
4- depression, fever/chills, leukopenia, thrombocytopenia, fatigue/malaise, anorexia/weight loss, alopecia, transient elevated liver enzymes

114
Q

cisplatin and vinblastine are used in combination for _______

A

testicular cancer

115
Q

what are the risks of Tamoxifen

A
  • Estrogen agonist in nonbreast tissue –> endometrial hyperplasia and possible cancer
  • not given to patients with risk or signs of osteoporosis in post-menopausal women

-inc risk of thrombosis, venous thromoboembolism due to weak estrogenic properties => significant procoagulant effect (raloxifene has this risk, but lower)

116
Q

______ is a SERM used is postmenopausal women

A

Raloxifene (» tamoxifen)

FTCM (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions