Brainscape's Knowledge GenomeTM

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


See full index

GOBBLERS 2023 > Angela's Chemotherapy > Flashcards

Angela's Chemotherapy Flashcards

1
Q

Calvert Dosing

A

mg = AUC x (GFR +25)

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

Cockgroft-Gault Equation for CrCl

A

[(140-age)(Wt)]/[(SCr x72)] x0.85

x 0.85 for women
Wt in kg
SCr in mg/dL

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

What affects the rate of absorption of chemo from IP to IV?

A

size of molecule

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

What drugs are alkylating agents? (3 drugs)

A
  • Cyclophosphamide
  • Ifosfamide
  • Melphalan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Are alkylating agents cell cycle specific?

A

NO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Antimetabolites (4 drugs)

A
  1. Methotrexate
  2. 5-FU
  3. Capectabine
  4. Gemcitabine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Alkylating agent (3 drugs + bonus!)

A
  1. Cyclophosphamide
  2. Ifosfamide
  3. Alkeran (Melphalan)
  4. Pemetrexed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is amifostine?

A

Chemoprotective agent - prodrug that is dephosphorylated by alkaline phosphatase into a free thiol. The free thiol binds and detoxifies reactive metabolites of cisplatin and can act as a scavenger of free radicals

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

Anti-tumor antibiotics (5 drugs)

A
  1. Adriamycin (Doxorubicin)
  2. Bleomycin
  3. Mitomycin C
  4. Actinomycin D
  5. pEgylated Doxorubicin

Think ABCDE

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

Toposomerase 1 inhibitors (2 drugs)

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

Topo 2 inhibitor (1 drug)

A

Etoposide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Vinca Alkyloids (3 drugs)

A
  1. Vincristine
  2. Vinblastine
  3. Vinorelbine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Methotrexate
1. Most common adverse effect?
2. Clearance?
3. What affects MTX levels? (How does ascites affect MTX)
4. What manipulation of urine can decrease its nephrotoxicity?

A

Methotrexate
1. Most common adverse effect? Stomatitis / mucositis & myelosuppression (vs high dose = NV)
2. Clearance? Renal
3. What affects MTX levels? Highly protein bound, requires evacuation of ascites & effusions
4. What manipulation of urine can decrease its nephrotoxicity? Alkalinization

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

5-FU

  1. Metabolism?
  2. Is it a prodrug?
  3. Where is it activated and cleared?
  4. Is it dose reduced in renal failure?
  5. Does it cause PPE?
A

5-FU

  1. Metabolism? Hepatic
  2. Is it a prodrug? YES – F-UMP is active metabolite
  3. Where is it activated and cleared? LIVER
  4. Dose reduced in renal failure? No
  5. Causes PPE? Yes, rare.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Capecitabine
1. Capecitabine is a prodrug of what other antimetabolite?
2. Causes PPE?

A

Capecitabine
1. Capecitabine is a prodrug of what other antimetabolite? 5-FU
2. Causes PPE? Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Gemcitabine

  1. Prodrug?
  2. If gem is given for >60 mins what happens?
  3. If gem is given for <60 mins what happens?
  4. Clearance?
A

Gemcitabine

  1. Prodrug? YES
  2. If gem is given for >60 mins what happens? increased myelosuppression and liver toxicity
  3. If gem is given for <60 mins what happens? Flu-like symptoms (think: flu is FASTER to get over than myelosuppression)
  4. Clearance? RENAL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which chemotherapy causes radiation recall? (3)

A
  1. GEMZAR (not dermatological radiation recall in chi, but as a risk factor for pulmonary edema in setting of mediastinal RT)
  2. dactinomycin (listed in Chi)
  3. doxorubicin (chi lists Adria, but not doxil)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the toxicity of amifostene?

A

Hypotension

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

Methotrexate MOA

A

Folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication.

Methotrexate binds to and inhibits dihydrofolate reductase, resulting in inhibition of purine and thymidylic acid synthesis –> interfering with DNA synthesis, repair, and cellular replication.

Cell cycle specific for the S phase

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

5-FU MOA

A

Pyrimidine analog antimetabolite that interferes with DNA and RNA synthesis

  1. FU activates to F-UMP (active metabolite) which inhibits thymidylate synthase to deplete DNA nucleoside base thymidine
  2. incorporation of FUTP into RNA to replace uracil and inhibit cell growth.
  3. incorporation of FUTP into DNA

Cell cycle specific to S phase

For 5-FU. I think as if it has 5-floors. Many floors like a pyramid. So it’s a pyrimidine antagonist. The liver is shaped like a pyramid. So it’s metabolized by the liver

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

Gemcitabine MOA

A

Antimetabolite
Gem is phosphorylated into gem-diphosphate and gem-triphosphate
1. Gem-diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase (think di-phosphate is two Ps which inhibits RR [ribonucleotide reductase = two Rs])
2. Gem-triphosphate incorporates into DNA (pyrimidine analog) and inhibits DNA polymerase

It’s active triphosphate inserts itself as a “fraudulent base pair” and causes “masked-chain termination”

Cell cycle-specific for S phase, also blocks G1-S progression

Gemzar. Gems for short 💎. Gem can be found on a chain around the neck. So it does masked chain termination.
Gems are found in pyramids, so gem-triphosphate is a pyrimidine analog

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

3 chemotherapy drugs that cause radiation recall

A

Gemcitabine
Dactinomycin
Doxorubicin

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

Which order should cis and gem be given in?

A

CIS THEN GEM
Gem 1st: doubles Cis-AUC
Cis 1st: increases Gem activity

**this is opposite of taxol before carbo

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

What is the lease effective IP chemo?
- adriamycin
- cis
- carbo
- taxotere
- gem

A

GEMZAR because it is a pro drug

Chemos that require liver activation CANNOT:
Ifosfamide and cyclophosphamide (require activation by P450 system)

Excess toxicity given IP (per Chi):
- mitoxantrone
- doxorubicin

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

Which drug cannot be given as IP chemotherapy?
- cyclophosphamide
- 5-FU
- doxorubicin
- paclitaxel

A

cyclophosphamide because it requires activation by liver P450 microsomal oxidase system

Not 5FU - it can be used in IP and discussed as such in Chi

Others that require liver activation CANNOT:
Ifosfamide (also requires activation by P450 system)

Excess toxicity given IP (per Chi):
- mitoxantrone
- doxorubicin

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

What is the cardiac toxicity of cyclophosphamide?

A

cardiomyocyte necrosis

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

What chemotherapy causes SIADH?

A

Cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What premedication should be avoided with cyclophosphamide and ifosfamide, and why?
Duplicate

A

Cimetidine (weak inhibitor of CP450, may worsen myelotoxicity by increasing concentrations of cyclophos/ifos)

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

When barbiturates and cyclophosphamide OR ifosfamide are given together, what is the primary adverse effect?

Duplicate

A

Sedation and possible accumulation of toxic metabolites

Barbiturates are CY450 INDUCERS —> increased metabolism of cyclophos/ifos, which increases the rate of these drugs to their toxic metabolites
Cyclophosphamide may block metabolism of barbiturates, increasing their sedative effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Cyclophosphamide
1. Metabolism?
2. Main toxicity?
3. Excretion?
4. When do you dose-reduce?
5. Prodrug?

A
  1. Metabolism? Hepatic
  2. Main toxicity? Myelosuppression
  3. Excretion? Urinary
  4. When do you dose-reduce? Hemorrhagic cystitis
  5. Prodrug? YES - acrolein, possible chloracetaldehyde

FYI: During hepatic metabolism of both cyclophosphamide and ifosfamide, acrolein is generated, filtered by the kidneys, and concentrated in the bladder. Acrolein is a reactive, unsaturated aldehyde that causes cell death through upregulation of reactive oxygen species, and that activates inducible nitric oxide synthase, leading to the production of nitric oxide.

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

Cyclophosphamide MOA

A

Alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis (DNA adducts).
Cell cycle phase nonspecific but causes arrest and death in G2.
Also possesses potent immunosuppressive activity.

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

Which chemotherapeutic drugs should not be given with Cimetidine?

A

Cyclophosphamide
Ifosfamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Why can’t cyclophosphamide be administered IP?

A

Prodrug - requires hepatic metabolism for an active metabolite

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

Cyclophosphamide
1. Metabolism?
2. Excretion?
3. Prodrug?
4. Main toxicity?

A
  1. Metabolism? Hepatic
  2. Excretion? Urine
  3. Prodrug? YES - acrolein, chloracetaldehyde
  4. Major toxicity? Myelosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Ifosfamide
1. Metabolism?
2. Excretion?
3. Prodrug?
4. Main toxicity?

A
  1. Hepatic
  2. Urinary
  3. Yes - acrolein, chloracetaldehyde
  4. Myelosuppresion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Ifosfamide MOA

A

Alkylating agent. Causes cross-linking of strands of DNA by binding with nucleic acids and other intracellular structures, resulting in cell death. Inhibits protein synthesis and DNA synthesis.

Cell cycle non-specific

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

In what situation is ifosfamide neurotoxicity more common?
What is the mechanism of ifosfamide neurotoxicity? What is the antidote?

A
  • Hypoalbuminemia or elderly
  • Chloracetaldehyde, methylene blue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the mechanism of ifosfamide cystitis? What is the antidote?

A

Acrolein, Mesna
Mesna is oxidized to dimesna in blood, which in turn is reduced in the kidney back to mesna, supplying a free thiol group which binds to and inactivates acrolein

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

Uremia occurs in what percentage of people on ifosfamide?

A

66% if >150 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Does cimetidine increase or decrease cyclophos/ifos levels?

A

INCREASE - CY450 inhibition

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

Does phenobarbital increase or decrease cyclophos/ifos levels?

A

DECREASE - CY450 inducer

It causes faster accumulation of toxic byproducts leading to greater neurotoxicity when combined with sedating effects of phenobarbital

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

What is the treatment for extravasation of Ifosfamide at the primary IV site?

A

Nothing, it is activated in the liver

Remember vesicants DAMN TV
Doxorubicin (also Epirubicin/ idarubicin/ daunorubicin)
ActinomycinD
Mitomycin C
Nitrogen mustard
Trabectedin
vincas (Vinblastine, vincristine, vinorelbine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Is alopecia a common side effect with ifosfamide?

A

Yes

Most common here are: microtubule agents (taxanes), anthracyclanes, topoisomerase inhibitors, and alkylating agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Is ifosfamide processed more rapidly or more slowly than cyclophosphamide? What does this result in?

A

More slowly. Resulting in more chloracetaldehyde and neurotoxicity

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

What is the DLT of Melphalan?

A

Prolonged myleosuppression with nadir at 30 days and 40 day recovery

*alkylating agent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What class of chemotherapy drug is Melphalan? is it cell cycle specific?

A

Alkylating ageint
Not cell cycle specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Bleomycin
1. Metabolism?
2. Excretion?
3. Prodrug?
4. Main acute toxicity? Chronic toxicity?

A
  1. Metabolism? Enzymatic inactivation by bleomycin-hydrolase, found in most normal tissues except lungs and skin
  2. Excretion? Urinary
  3. Prodrug? No
  4. Main acute toxicity? Mucocutaneous - rash, striae, pruritis, hyperpigmentation. Pulmonary fibrosis.

—> bc bleomycin-hydrolase not in lungs and skin, this is where toxicity is!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Bleomycin DLT
Max lifetime dose?

A

Cumulative pulmonary fibrosis
400 units (=mg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the most sensitive way to diagnose bleomycin-induced pulmonary toxicity? What is the cheapest way?

A

Gold standard: Carbon monoxide diffusing capacity (DLCO) - needs to be done with each cycle of bleo
Cheapest is physical exam (crackles)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What phase of the cell cycle is bleomycin most active in?

A

G2 phase

Chi: G1, G2, S

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is an iron chelator?
Which chemo drugs are iron chelators?
duplicate

A
  • Iron chelators enter cells, bind free iron, and remove it from the body
  • Doxorubicin and bleomycin (chelation causes free-radical formation that results in cardiac or pulmonary toxicity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Bleomycin MOA

A

Binds to DNA leading to single and double strand breaks –> inhibits synthesis of DNA, RNA, and protein synthesis.

Binds to guanosine-cytosine-rich portions of DNA via association of the “S” tripeptide and by partial intercalation of the bithiazole rings

Also is an iron chelator which results in ROS

Angela’s says single-strand breaks, UpToDate says single and double

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Which chemo is least myelosuppressive?

A

Bleomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Which two tissues lack bleomycin-hydrolase?
Duplicate

A

Skin, lungs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Doxorubicin DLT

A

Cumulative cardiac toxicity

PharmD: Risk for cardiomyopathy increases at cumulative dose 550 over 18.
Test answer on pharmacy exams is usually 550 but no one ever pushes that high since the recommendation to start dexrazoxane is at 300mg/m2 which is probably why you’re seeing that range!

the US prescribing information for doxorubicin recommends limiting the lifetime cumulative dose to no more than 400 mg/m2.

There is conflicting information between 400-550

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Doxorubicin
1. Metabolism?
2. Major toxicity?
3. Max dose?

A
  1. Hepatic (think: Hepatic metabolism for Heart toxicity)
  2. Cardiac - CHF
  3. 450mg/m2 (there is conflicting info between 400-550)

From PharmD: Risk for cardiomyopathy increases at cumulative dose 550 over age 18.

Incidence is 1 to 20% from 300mg/m2 to 500mg/‘m2 if given every 3 weeks.

Test answer on pharmacy exams is usually 550 but no one ever pushes that high since the recommendation to start dexrazoxane is at 300mg/m2 which is probably why you’re seeing that range!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

How do you treat doxorubicin extravasation?

A

DMSO and cold packs

Dimethylsulfoxide (DMSO)

Dmso for Doxorubicin (D for D)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Which chemotherapies cause radiation recall?

A

dactinomycin (Actinomycin D), doxorubicin, gemcitabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

How does phenobarbital interact with doxorubicin?

A

increases hepatic clearance of doxorubicin and decreases serum concentration by inducing P450 system

60
Q

Is Doxorubicin cell-cycle specific?

A

No, but it is most active in S-phase

61
Q

Doxorubicin MOA

A

1) Inhibits DNA and RNA synthesis by intercalation between DNA base pairs
2) Inhibition of topoisomerase II
3) Steric obstruction - intercalates at points of local uncoiling of the double helix
4) Iron chelator - produces free radicals that cleave the DNA and cell membranes.

62
Q

Pegylated liposomal doxorubicin DLT

A

PPE

63
Q

Paclitaxel DLT

A

Neutropenia (nadir day 10-12)

64
Q

In what order do you administer cisplatin and paclitaxel? Why?

A

Taxol first then cis - avoids increased myelosuppression

65
Q

What is the difference in toxicity between 24h vs 3h paclitaxel infusions?

A

24h - increased myelosuppression
3h - increased neurotoxicity

66
Q

Paclitaxel MOA

A

1) Promotes microtubule assembly by enhancing action of tubulin dimers, then stabilizes and inhibits disassembly at G2-M transition –> inhibits cell replication
2) Can distort mitotic spindles, resulting in the breakage of chromosomes
3) May also suppress cell proliferation and modulate immune response

M-phase specific

67
Q

Paclitaxel
1) Metabolism?
2) Adverse effects?

A

1) Hepatic - highly protein-bound
2) Hypersensitivity (urticaria, angioedema) - usually due to solvent castor oil [Cremaphor]), alopecia, peripheral neuropathy (cumulative dose-dependent), bradycardia

68
Q

Cisplatin MOA

A

1) Inhibits DNA synthesis by forming DNA cross-links (inter-strand and intra-strand by binding two adjacent guanines) –> strand breakage
2) Denatures the double helix
3) Covalently binds to DNA bases and disrupts DNA function; may also bind to proteins

69
Q

Cisplatin
1) Metabolism?
2) Excretion?
3) Adverse effects?

A

1) Nonenzymatic - inactivated by glutathione and thiosulfate
2) Urine
3) Neurotoxicity, nausea/vomiting, nephrotoxicity, ototoxicity, dose-dependent ovarian failure

70
Q

What is the mechanism of resistance to cisplatin?

A

Increased damage tolerance, decreased drug accumulation, increased glutathione levels, enhanced DNA repair, May be related to ERCC1 (excision repair cross complementation group 1)

71
Q

Which platinum agent is most associated with sodium wasting nephropathy?

A

Cisplatin

72
Q

Electrolyte disturbances with cisplatin?

A

Hypomagnesemia
Hyponatremia

73
Q

Which platinum agent is most associated with high-frequency hearing loss?

A

Cisplatin (30%)

74
Q

What are symptoms associated with Cisplatin neurotoxicity?

A

Stocking-glove neuropathy, focal encephalopathy, cortical blindness

75
Q

What is cisplatin aquation?

A

The process by which chloride is displaced by H2O, activating cis and carboplatinum

76
Q

What is Lhermittes’s sign?

A

Electrical-like pain or shock with neck flexion. Is seen with RT to the spine and some chemo (platinum).

(Lhermitte’s syndrome is eye issues).

77
Q

Cisplatin DLT

A

Nephrotoxicity

78
Q

What is the mechanism of platinum electrolyte disturbance?

A

Interfere with loop of henle and distal convoluted tubule

79
Q

Carboplatin DLT

A

Thrombocytopenia

80
Q

Why do we use AUC instead of BSA to calculate carboplatin?

A

Better in predicting myelosuppression than BSA

81
Q

When does carboplatin hypersensitivity manifest?

A

Usually after 6+ cycles

82
Q

Carboplatin MOA

A

1) Alkylating agent which covalently binds to DNA
2) Interferes with the function of DNA by producing interstrand DNA cross-links

not cell-cycle specific

83
Q

Carboplatin
1) Metabolism?
2) Excretion?
3) Adverse effects?

A

1) Minimally hepatic - aquation
2) Urine
3) Myelosuppression esp thrombocytopenia, nephrotoxicity, electrolyte disturbance (decreased Ca, Mg, K, Na), nausea/vomiting

84
Q

What is the function of topoisomerase 1?

A

Causes single strand DNA breaks followed by religation

Topoisomerase I: cleaves ONE DNA strand and pass either one or two strands through the break before resealing it

Topoisomerase II: cleaves TWO DNA strands in concert and pass another double strand through the break followed by religation of the double strand break

85
Q

What is the function of topoisomerase 2?

A

Causes double strand DNA breaks followed by religation

Topoisomerase I: cleaves ONE DNA strand and pass either one or two strands through the break before resealing it,

Topoisomerase II: cleaves TWO DNA strands in concert and pass another double strand through the break followed by religation of the double strand break

86
Q

Topotecan MOA

A

Inhibition of topoisomerase-1, stabilizing the cleavage complex so that re-ligation of DNA breaks cannot occur –> accumulation of ssDNA breaks

(topoteCan Cleavage Complex)

S phase specific

I thought it specific to G2 and S - Jenny
Megan: Chi says S

87
Q

Topotecan DLT

A

Myelosuppression

88
Q

Topotecan
1) Metabolism?
2) Excretion?
3) Best pH to function?
4) Water soluble?

A

1) Metabolism? Hepatic
—> highly protein bound
DECIM TDP

2) Excretion? Renal and hepatic - dose reduce only for renal impairment
3) Best pH to function? Acidic (low pH)
4) Water soluble? Yes

89
Q

Irinotecan DLT

A

Diarrhea

90
Q

Etoposide MOA

A

Topo-2 inhibitor causing dsDNA strand breaks

Forms a complex with topoisomerase II and DNA. Etoposide Poisons topoisomerase II by stabilizing an otherwise transient form of topoisomerase II by covalent linking to DNA. normal topoisomerase II activity is blocked. This causes protein linked DNA strand breaks

May also generate O2 free radicals

G2-phase specific

91
Q

Etoposide
1) Metabolism
2) Excretion
3) Vesicant?

A

1) Hepatic - highly protein bound
—> DECIM TDP

2) Urine (requires renal dosing)
—> A BICC THE MMP

3) NO - it’s an IRRITANT
- If extravasation - but treat with HEAT and hyaluronidase

Irritants: TICE

Taxol, ifosfamide, cisplatin, etoposide

92
Q

Actinomycin-D MOA

A

Binds to the guanine portion of DNA intercalating between guanine and cytosine base pairs –> inhibiting DNA and RNA synthesis and protein synthesis

G1

93
Q

Vesicant vs irritant and treatment?

A

Vesicant - potential to cause tissue necrosis with a more severe and/or lasting injury
Irritants - inflammation but rarely result in direct toxicity to the tissue

Apply COLD to promote vasoconstriction
EXCEPT vinca alkaloids and etoposide - apply HEAT

Vesicants: DAMN TV

Doxorubicin (Anthracyclines - dexrazoxane or DMSO),
ActinomycinD, no treatment
Mitomycin C, Sodium thiosulfate
Nitrogen mustard,
Trabectedin,
vincas (Hyaluronidase)

Irritants: TICE
Taxol, Hyaluronidase
ifosfamide, Hyaluronidase
cisplatin, Sodium thiosulfate
etoposide Hyaluronidase

94
Q

What is the chromosomal abnormality associated with leukemia in patients on etoposide?

A

11q23

Etoposide caused therapy-related leukemia is a chromosomal rearrangement involving the MLL gene on chromosome 11q23

95
Q

Anastrazole adverse effects

A

Hotflashes and osteoporosis

96
Q

What is the cardiac toxicity of trastuzumab?

A

CHF - need echo before treatment

97
Q

Vinca alkaloids MOA
(vincristine, vinblastine, vinorelbine)

A

Bind tubulin, preventing microtubule polymerization during assembly of the mitotic spindle apparatus –> resulting in mitotic arrest
“spindle poison”

UTD: M and S phase specific
Chi: M and G2

98
Q

What is the most common side effect of vinca alkyloids?

A

Notes say: Constipation

Chi: Nausea 38%, constipation 31%
DLT: BM suppression

99
Q

Vinca alkaloids
1) Metabolism?
2) Treatment of extravasation?

A

1) Hepatic
2) Vesicant - HEAT and hyaluronidase

100
Q

Ondansetron MOA

A

Selective 5HT3 antagonist (blocks serotonin)

101
Q

Aprepitant
1) MOA
2) Metabolism

A

1) Neurokinin-1 antagonist
2) Hepatic cp450

102
Q

What drugs should not be given with aprepitant?

A

These drugs are also metabolized by cp450:
Warfarin - increased INR
Cyclophosphamide - increased toxicity
Steroids - increased corticosteroid levels (need to reduce dose if premedicating)

103
Q

Promethazine (phenergan) MOA

A
  • blocks dopaminergic receptors in the brain
  • alpha-adrenergic blocking effect
  • competes with histamine for the H1-receptor
  • muscarinic-blocking effect may be responsible for antiemetic activity
104
Q

Metoclopramide
1) MOA
2) Side effect and how to treat?

A

1) Dopamine antagonist
2) Extrapyramidal symptoms (EPS) [akathisia, dystonia, tardive dyskinesia, Parkinsonism] - treat with benadryl

Also enhances response to acetylcholine of upper GI tract causing enhanced motility and accelerated gastric emptying

105
Q

What is the MOA of tamoxifen in the breast?

A

SERM - binds estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects

106
Q

What is the least likely side-effect of tamoxifen?
A) osteoporosis
B) vaginal bleeding
C) cervical and endometrial polyps

A

Osteoporosis - tamoxifen is protective for BMD for post-menopausal patients

107
Q

Which is NOT a side effect or effect of tamoxifen?
A) ovarian cysts
B) increased LDL
C) decreased DCIS
D) increased uterine sarcoma

A

Increased LDL

Ovarian cysts - 3%
Decreased LDL [increases HDL and triglycerides. Lowers LDL vs AI, which raises LDL!]
Uterine neoplasm < 1%
VTE < 1%

108
Q

Is endometrial cancer more common in tamoxifen or raloxifene?

A

Tamoxifen

109
Q

What does MTORC1 inhibition cause?

A

Decreases phosphorylation of MTOR, so it is not activated. Prevents subsequent overexpression of oncogenes.

110
Q

What are some MTOR inhibitors?

A

Rapamycin, Temserolomus, Everolimus

G1 phase specific

111
Q

Which of the following is least emetogenic?
A) cytoxan
B) cisplatin
C) Act D
D) adriamycin
E) vincristine

A

Vincristine

Highly emetic (>90%)
- Cisplatin
- Anthracycline and cyclophosphamide
- Cyclophosphamide >=1500 mg/m²

Minimally emetic (<10%)
- Bev
- Bleo
- Nivo, pembro
- Trastuzumab
- Vinblastine, vincristine, vinorelbine

112
Q

Emetogenicity classifcations

A

High >90%
Moderate 30-90%
Low 10-30%
Minimal < 10%

113
Q

Which are high-risk emetogenics?

*Angela’s says “NCCN Risk 5” emetogenics but I think that is old lingo

A

Cisplatin, high-dose cyclophosphamide (>1500mg/m2), dacarbazine, anthracycline/cyclophos combo

Angela’s listed doxorubicin and ifos but these are moderate risk

114
Q

Which are moderate risk emetogenics?

*Angela’s says “NCCN Risk 4” emetogenics but I think that is old lingo

A

Carbo, anthracyclines (doxo, dauno, epi-rubicin), ifosfamide, oxaliplatin, temozolamide, trabectidin

Angela also says: ACT-D, megadoses of MTX, melphalaln

115
Q

Which are low risk emetogenics?

A

Docetaxel, etoposide, 5FU, gemcitabine, methotrexate, nab-paclitaxel, paclitaxel, PLD, pemetrexed, temsiroliums, topotecan

Skinny: Taxanes, folate antagonists / anti metabolites, Topoisomerase inhibitors, temsirolimus, doxil

116
Q

Which are minimal risk emetogenics?

A

Bleomycin, bevacizumab, vincas, trastuzumab, monoclonal antibodies (other -mabs)

117
Q

Which renally cleared chemotherapies causes alopecia?

A

Ifosfamide, cyclophosphamide, topotecan

118
Q

Which agents cause peripheral neuropathy?

A

Vinca (dose-limiting), taxol, cisplatin (dose-limiting)

119
Q

Which agents cause peripheral neuropathy and motor disturbances?

A

Vincas

120
Q

Why can you not give 3 hour paclitaxel with cisplatin?

A

Dose-limiting neurotoxicity

121
Q

Which agent can cause a significant number of patients to have permanent neuropathy?

A

Cisplatin

122
Q

Which agents are classic vesicants?

A

mitomycin C, doxorubicin, dactinomycin, vinca alkaloids, Taxol, etoposide at high doses

123
Q

Which vesicants are treated with hyaluronidase?

A

Vincas and taxol

124
Q

What agents are prodrugs that need to be activated for cytotoxicity?

A

cyclophosphamide, 5-FU, gemcitabine, mitomycin C, ifosfamide, capcitabine, irinotecan

125
Q

Which agents cause leukemia?

A

Melphalan, cyclophosphamide, etoposide, nitrosureas, chlorambucil, alkylators

melphalan is most leukemogenic

Etoposide - 11q23 mutation (NOT 13q12 - incorrect in one spot on angela)

126
Q

Which agents cause leukemia?

A

Melphalan, cyclophosphamide, etoposide (associated with mutation at 11q23), nitrosureas, chlorambucil, alkylators

melphalan is most leukemogenic

127
Q

Which chemotherapy agents cross the blood-brain-barrier?

A

Nitrosureas: CCNU, BCNU, DTIC
(carmustine and lomustine)

Also topotecan, niraparib, ipilimumab, nivolumab (ipi and nivo bind peripheral T cells and cross)

128
Q

Which agents are topoisomerase I inhibitors?

A

topotecan
irinotecan

129
Q

Which agents are topoisomerase II inhibitors?

A

doxorubicin, doxil, mitoxantrone, etoposide, teniposide

130
Q

Which drugs cause PPE?

A

Chi: Capecitabine > 5-FU, Doxil, pemetrexed

Also Multitargeted tyrosine kinase inhibitors sorafenib, sunitinib

131
Q

Which drugs are very heavily protein bound?

A

Adriamycin, cisplatin, MTX, etoposide

“MACE”

132
Q

Which drug does not need reduction in renal failure?
A) capecitabine
B) Doxorubicin
C) Topotecan
D) MTX

A

Doxorubicin

133
Q

Most common side effect with G-CSF?

A

Bone pain, followed by fever

134
Q

Which drug is not affected by p-170 glycoprotein MDR1?
A) paclitaxel
B) vinca alkaloids
C) anthracyclines
D) cisplatin

A

cisplatin

“MDR1 has at least three major areas where its activity impacts clinical outcomes and toxicity. First, MDR1 confers resistance to cancer chemotherapeutic agents and is a major cause of treatment failures. Because MDR1 transports a wide range of chemotherapy drugs, such as the anthracyclines, vinca alkaloids, taxanes, etoposide, mitoxantrone, bisantrene, and the histone deacetylase inhibitor depsipeptide”

135
Q

What is p-170 glycoprotein MDR1?

A

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs.

Significance
MDR1 has at least three major areas where its activity impacts clinical outcomes and toxicity. First, MDR1 confers resistance to cancer chemotherapeutic agents and is a major cause of treatment failures. Because MDR1 transports a wide range of chemotherapy drugs, such as the anthracyclines, vinca alkaloids, taxanes, etoposide, mitoxantrone, bisantrene, and the histone deacetylase inhibitor depsipeptide

136
Q

What drug can overcome MDR I (p-170 glycoprotein system)?

A

Verapamil

137
Q

What is not protein bound?
Adriamycin, MTX, Cisplatin, Etoposide, Doxorubicin, Gemcitabine, Bleomycin
(multiple)

A

Gemcitabine, Bleomycin

138
Q

G1 phase specific

A

MTOR, ACTD, tamoxifen

139
Q

G2 phase specific

A

Etoposide, Bleomycin

140
Q

S phase specific

A

5FU, capecitabine, MTX

141
Q

M phase specific

A

Vincas, Taxol, (and Radiation)

Vincas: both M and S

142
Q

Drugs causing radiation recall

this appears multiple times

A

Actinomycin D, doxorubicin (Adria), gemcitabine

Think: It was AAGonizing going through radiation once, I don’t want to recall it again!

143
Q

Where is the gene locus encoding progesterone receptors?

A

PRA and PRB: Chromosome 11q22-23

144
Q

Chemotherapy and Cell Cycle picture (from the internet)

A
145
Q

Chemotherapy and immunotherapy that crosses blood-brain-barrier

A

Topotecan
Cyclophosphamide
Ifosfamide
Temozolamide
Lomustine
Carmustine
Nivolumab (bound to T cells)
Ipilimumab (bound to T cells)

146
Q

Difference between docetaxel and paclitaxel?

A

Docetaxel has:
- LESS neuropathy
- MORE fluid retention / peripheral edema (must give extra steroids)
- Caution in diabetics due to need for extra steroids

147
Q

Difference between nab-paclitaxel and paclitaxel?

A

Nab-paclitaxel is albumin bound. It does not contain crempahor (also known as kolliphor - polyoxyethylated castor oil), which is the agent responsible for hypersensitivity reactions.

GOBBLERS 2023 (28 decks)

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