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Oncology > Drugs > Flashcards

Drugs Flashcards

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1
Q

Nitrogen mustards

A
  • Mechlorethamine
  • CTX
  • IFX
  • Melphalan
  • Chlorambucil
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2
Q

Alkylator MOA

A

Electrophilic drug attacks N/O on DNA → crosslink, DNA damage → p53 apoptosis (often via DNA scission)

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3
Q

Which base do alkylators usually attack

A

Guanine

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4
Q

(T/F) alkylators require functional DNA repair enzymes in order to do their thang

A

Yes except oxaliplatin (colorectal cancer)

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5
Q

(T/F) do not combine alkylators

A

False; linear cell kill curve. More alkylator action = more effect

Dose is limited by toxicity

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6
Q

Alkylator resistance (5)

A 
1- MDR1 efflux
2- Reduction in drug uptake
3- Amplify drug target
4- Mutate drug target
5- Inactivate p53 apoptosis
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7
Q

Alkylator pulmonary tox

A

Busulfan

Carmustine: steroid antidote

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8
Q

Alkylator neurotox

A

IFX encephalopathy

Busulfan seizure

Oxaliplatin

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9
Q

Alkylator N/V

A

CISPLATIN

Mechlorethamine

Streptozocin

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10
Q

Alkylator extravasation

A
  • Mechlorethamine
  • Carmustine
  • Cisplatin

Try sodium thiosulfate

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11
Q

Alkylator sterility

A

Pretty much any alkylator at high dose??

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12
Q

Alkylator hepatotox

A
  • Busulfan HD: venoocclusive obstruction
  • Nitrosureas
  • Temozolomide
  • Streptozosin
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13
Q

This agent protects against cisplatin tox

A

Amifostine

caution, causes N/V

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14
Q

Hemorrhagic cystitis drugs and mechanism and solution

A

CTX, IFX

Acrolein active metab. Try MESNA

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15
Q

Careful with IFX in which 3 populations and why?

A

High-dose, oldies, shit kidneys

Chloroacetaldehyde metabolite buildup → neurotox and nephrotox

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16
Q

______ is the best PK parameter for toxicity

A

AUC, esp affected by clearance

ex. Busulfan TDM

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17
Q

Prodrug for brain cancer. Also MOA pls?

A

temozolomide PO → dacarbazine IV

triazine alkylating agents that also inhibit base incorporation into DNA

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18
Q

Alkylating agent phase-specificity

A

Non-phase specific

*will not work on G0

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19
Q

Alkylating agent class toxicities

A

Myelosuppression
sterility
Secondary malignancy

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20
Q

Antimetabolite phase-specificity

A

S-phase specific

-short vs continuous infusion

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21
Q

Target enzyme

  • MTX
  • 5-FU
A
  • MTX DHFR
  • 5-FU thymidylate synthase

Both deplete thymidine pools (dTMP) and reduced folates which are required for DNA synthesis

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22
Q

CNS toxicity and leaky capillary (noncardio pulm edema)

A

Short infusion of antimetabolite (high dose)

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23
Q

Antimetabolite class toxicities

A

Myelosuppression

GI

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24
Q

Antimetabolite resistance

A

Change in target enzyme

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25
Change in target enzyme
5-FU, MTX
26
Antitumor ABX subclasses
Anthracyclines (-rubicin) Anthracenedione - mitoxantrone also, bleomycin and dactinomycin
27
Anthracycline MOA
Intercalate into DNA and inhibit topoisomerase *II* (mitoxantrone too)
28
Anthracycline antitumor ABX class toxicities
Myelosuppression Cardiotoxicity cumulative dose
29
Adjust dose in hyperbilirubinemia
Anthracyclines (antitumor) Vincas (microtubule) Taxols (microtubule)
30
Dexrazoxane
against *anthracycline* cardiotoxicity, but not really used bc inhibits anti-tumor effects Totek for extravasation tho :)
31
Colorful fluoresce
- Doxorubicin red - Mitoxantrone blue (antitumor ABX)
32
Bleomycin MOA
Topoisomerase inhibitor (antitumor antibiotic)
33
Causes little myelosuppression :) but really bad pulmonary fibrosis :(
Bleomycin
34
MOA: inhibits microtubule assembly vs disassembly
ASSembly: vincas, eribulin DISassembly: taxanes, ixabepilone
35
Disrupt microtubules → which major toxicity?
Neurotoxicity
36
Vinca differences in toxicity
vin*c*ristine = *C*NS neurotox vinblastine = myelosuppression
37
Infusion reaction differences with taxanes
Docetaxel cytokine third spacing: try dexamethasone Paclitaxel allergic hypersensitivity: try dexamethasone + H-blockers (ranitidine + Benadryl)
38
Foot drop syndrome
Vincristine (neurotoxicity)
39
Topoisomerase inhibitor that does not intercalate | Hint: from pacific yew
Etoposide and teniposide
40
Caution solubility, ppt. Developed a water-soluble prodrug
Etoposide (IV and PO!)
41
Diarrhea is the major ADE. Which drugs and their MOA? Treatment?
Campothecins: topotecan and irinotecan (Topo I inhib) - Atropine for early diarrhea - Loperamide for chronic diarrhea
42
(T/F) anti-cancer agents covalently bind DNA
Just alkylating agents. Anthracyclines and other topoisomerase inhibitors intercalate but do not bind. *exception alert*: etoposide is the topo inhib that does not intercalate
43
Mycosis fungoides treatment
*topical* mechlorethamine gel (Valchlor)
44
Drug that causes hemorrhagic cystitis and is available IV and PO
CTX | IFX is only IV
45
Methylene blue
Rescue for IFX encephalopathy (via chloroacetaldehyde)
46
MESNA
To prevent hemorrhagic cystitis -required for IFX, recommended for CTX as well
47
Where is MESNA active
Activated when hydrolyzed in urine, inactive dimer in serum
48
Venoocclusive disease of the liver
Busulfan high-dose
49
Give (before/after) paclitaxel
Give platins after paclitaxel
50
Dosing is based on AUC, not BSA
Carboplatin Calvert dosing formula | busulfan too?
51
Alkylating agent whose dose-limiting toxicity is cumulative peripheral neuropathy
Oxaliplatin
52
Vitamin B6
↓ neurotoxicity of altretamine/hexamethylmalamine (Hexalen), an alkylating agent but eh bc reduces anti-tumor activity
53
These bad boys can alkylate AND carbamoylate DNA ligase which is involved in DNA repair. They also rapidly decompose under physiologic conditions
Nitrosureas
54
Delayed myelosuppression
Nitrosureas
55
Nitrosurea dosage forms
Lomustine PO Carmustine and streptozocin IV
56
(T/F) streptozocin dose-limiting tox is myelosuppression
False; nephrotoxicity is dose-lim Just mild-mod myelosup :)
57
∼MAOI
Procarbazine | alkylating agent
58
Premedicate this drug with folic acid and vit B12. Why?
Pemetrexed (Alimta) to ↓ myelosuppression
59
NSAIDs, ASA, and penicillins compete for renal excretion and may lead to toxicity of this drug
MTX
60
Topical drug form available
Mechlorethamine 5-FU
61
Requires reduced folate for activity
5-FU . . . leucovorin can help
62
5-FU toxicities of short vs continuous infusion
Bolus: myelosup Continuous: diarrhea, mucositis, hand-foot
63
5-FU prodrug
Capcetibine (Xeloda) - PO | 3-step conversion process
64
ara-C resistance
1- Lack of phosphorylation enzymes | 2- ↓ Cytarabine transport into cell
65
Enhances cytotoxicity of alkylating agents by inhibiting repair of alkylating damage
ara-C
66
Pretreat this drug with _______________ to sync cells in S-phase
Pretreat ara-C with hydroxyurea
67
Dexamethasone to prevent conjunctivitis
ara-C high dose (bolus infusion)
68
DDI allopurinol
6-MP (Purinethol) *reduce the dose of 6-MP
69
Triphosphorylation
-Gemcitabine -Fludarabine -Cladribine- 2CdA (antimetabolites)
70
Inhibits DNA methyltransferase → hypomethylation apoptosis
Decitabine (Dacogen) and low-dose 5-Azacitidine (Vidaza) | antimetabolites
71
Electrolyte abnormalities ADE
HYPOMg, HYPOK Decitabine (Dacogen) and 5-Azacitidine (Vidaza) (antimetabolites)
72
50:50 elimination in liver and kidney
Hydroxyurea
73
Forms radicals that lead to DNA scission
Antitumor antibiotics
74
Most active in S-phase and G2-phase
Bleomycin
75
Lung and skin toxicity. Why?
Bleomycin. These organs lack bleomycin hydrolase which inactivates the drug in many tissues
76
Lifetime dose > 300U → pulmonary fibrosis
Bleomycin
77
Bleomycin has many ADE, but what is dose-limiting
Mucositis
78
Antitumor antibiotic for pediatric solid tumor
Dactinomycin (Cosmegen)
79
Max dose 2 mg
Vincristine
80
SIADH
Vincristine | IFX/CTX high-dose
81
PO topoisomerase inhibitors
Topotecan | Etoposide PO is available but never used
82
Topoisomerase *I* inhibitor
Campothecins: topotecan and irinotecan
83
UGT1A1
Irinotecan
84
Extrahepatic elimination
ara-C Bleomycin: bleomycin hydrolase -NOT decitabine cytidine deaminase??
85
Renal elimination (6 for sure)
``` Platins MTX Hydroxyurea 50:50 Nelarabine Bleomycin Dactinomycin ``` Streptozocin? Bendamustine?? Eribulin?
86
Aziridine/epoxide
Thiotepa and mitomycin C | alkyating agents
87
Premed with steroids + Benadryl + ranitidine
Taxols -docetaxel just dexamethasone
88
Microtubule toxin classes
Vincas Taxanes E-drugs
89
M-phase specific
Vincas Ixabepilone (microtubule toxins)

Oncology (4 decks)

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