Topoisomerase inhibitors and Microtubule Inhibitors + more Flashcards
Topoisomerase I cuts one or two strands?
One
Topoisomerase II cuts one or two strands?
Two
Topoisomerase inhibitors are not cell-cycle specific. True or False?
False. They are cell-cycle specific (S-phase)
Which of the following are Topoisomerase I inhibitors? Select all that apply
A) Camptothecins
B) Anthracyclines
C) Podophyllotoxins
A) Camptothecins
Which of the following are Topoisomerase II inhibitors? Select all that apply
A) Camptothecins
B) Anthracyclines
C) Podophyllotoxins
B) Anthracyclines
C) Podophyllotoxins
Topoisomerase inhibitors cause cell death by:
A) Block DHFR and preventing the formation of purines
B) Block DNA polymerase and incorporating itself into DNA
C) Block the enzyme necessary for relaxing DNA supercoils during replication and transcription
D) Crosslinking and methylating DNA
C) Block the enzyme necessary for relaxing DNA supercoils during replication and transcription
The following all describe the physiology of topoisomerase (TOP) EXCEPT:
A) Resolve topological problems during DNA replication and transcription
B) Form covalent and reversible breaks in the DNA backbone
C) Allow rearrangements and maneuvering of DNA strands and re-ligation of DNA
D) Type I enzymes remove supercoiling in unwound DNA via single-stranded cuts while Type II enzymes separate & unknot DNA via double-stranded breaks
E) All of the above are true
E) All of the above are true
Choose the Camptothecins in the Topoisomeraise I inhibitors: A) Etoposide B) Irinotecan C) Idarubicin D) Topotecan
B) Irinotecan
D) Topotecan
The mechanism of action of Irinotecan and Topotecan is best described as:
A) Intercalate into the DNA at the topoisomerase-DNA interface to prevent the reversal of the topoisomerase cleavage complex
B) Inhibits topoisomerase II and intercalates into DNA to prevent replication
C) Inhibits topoisomerase II to prevent the re-ligation of DNA strand breaks, leading to cell death
D) Inhibits topoisomerase I causing overwinding of DNA helix during replication
A) Intercalate into the DNA at the topoisomerase-DNA interface to prevent the reversal of the topoisomerase cleavage complex
What are the class toxicities for Camptothecins? (Match drug and toxicity) Select all that apply:
A) Irinotecan; myelosuppression
B) Doxorubicin; myelosuppression
C) Teniposide; Cardiotoxicity
D) Topotecan; GI toxicities (diarrhea, abdominal cramping)
A) Irinotecan; myelosuppression
D) Topotecan; GI toxicities (diarrhea, abdominal cramping)
Irinotecan has a specific pathophysiology to explain its notable toxicity of early/late forms of diarrhea. Select the most accurate explanation:
A) Its non-liposomal form is more difficult to metabolize
B) The short half-life of the drug makes it more potent depending on the patient
C) This drug is a prodrug metabolized into an active metabolite, SN-38
D) The drug name sounds like “I RUN TO THE CAN” so seems legit
C) This drug is a prodrug metabolized into an active metabolite, SN-38
Does Irinotecan require supportive care? Select all the apply
A) Yes; to acute anticholinergic symptoms with IV/SQ atropine or pre-medicate
B) No; it is a generally well tolerated drug with no notable toxicites
C) Yes; to manage delayed diarrhea with antidiarrheals
D) No; the symptoms are generally self-limiting or can be reversed by holding the agent
A) Yes; to acute anticholinergic symptoms with IV/SQ atropine or pre-medicate
C) Yes; to manage delayed diarrhea with antidiarrheals
Which of the following are true about Irinotecan? Select all the apply
A) It is interchangeable with its liposomal formulation
B) The name of the liposomal formulation is Onivyde
C) It requires hepatic adjustment
D) BBW: Bone marrow suppression, early/late forms of diarrhea
B) The name of the liposomal formulation (Onivyde)
C) It requires hepatic adjustment
D) BBW: Bone marrow suppression, early/late forms of diarrhea
What are the proposed mechanisms for free intestinal luminal SN38 responsible for irinotecan-induced diarrhea?
A) Direct mucosal damage via water/electrolyte malabsorption and mucous hypersecretion
B) Altered luminal environment leading to proliferation of bacterial beta-glucuronidase to convert SN38-G to SN-38
C) Severe colonic damage via increased cell apoptosis, crypt hypoplasia and dilation, and villous atrophy
D) All of the above
D) All of the above
Why would classical chemotherapeutic agents be re-formulated with advanced delivery systems (i.e. liposomes, protein-bound)?
i) Lower cost
ii) Provide targeted drug delivery
iii) Reduce toxic effects of drugs
iv) Usually interchangeable
v) Improve therapeutic index and efficacy of drug
A) i, ii, v
B) ii, iii, iv
C) ii, iii, v
D) ii, iii, iv, v
ii) Provide targeted drug delivery
iii) Reduce toxic effects of drugs
v) Improve therapeutic index and efficacy of drug
C) ii, iii, v
Topotecan is only PO formulation and is a prodrug like Irinotecan. True or false?
False. Topotecan is IV and PO, and it is NOT a prodrug = no active metabolite
Topotecan requires renal or hepatic adjustment?
Renal
How does Topotecan’s notable toxicites compare to Irinotecan’s notable toxicities?
A) They are exactly the same and require the same supportive care measures
B) Irinotecan has a BBW for only early/late forms of diarrhea while Topotecan has a BBW for bone marrow suppression
C) Irinotecan has a BBW for only early/late forms of diarrhea and bone marrow suppression while Topotecan has a BBW for bone marrow suppression
D) Topotecan is generally well tolerated overall since it is not a prodrug and does not have an active metabolite
C) Irinotecan has a BBW for only early/late forms of diarrhea and bone marrow suppression while Topotecan has a BBW for bone marrow suppression (diarrhea - mild)
Doxorubicin, Daunorubicin, Epirubicin, and Mitoxantrone are all from which class?
A) Anthracyclines; Topoisomerase I inhibitors
B) Anthracyclines; Topoisomeraise II inhibitors
C) Campothecins; Topoisomerase I inhibitors
D) Podophyllotoxins; Topoisomerase II inhibitors
B) Anthracyclines; Topoisomeraise II inhibitors
Choose the best description for anthracyclines:
A) Antitumor antibiotic that intercalates into DNA, inhibits topoisomerase II, and generate free oxygen radicals
B) Semisynthetic analog that inhibits microtubule assembly during M phase of the cell cycle
C) Natural derivative that inhibits microtubule disassembly during G2/M phase of the cell cycle
D) Antitumor antibiotic generates free oxygen radicals to induce single and double strand breaks
A) Antitumor antibiotic that intercalates into DNA, inhibits topoisomerase II, and generate free oxygen radicals
Describe the main class toxicities for Doxorubicin and Mitoxantrone: Select all that apply A) Cardiotoxicity B) Hematopoietic cell suppression C) Extravasation risk D) Diarrhea
A) Cardiotoxicity
C) Extravasation risk
“Early” cardiotoxicity means
A) Occurs as soon as after 1st one with elevated troponins and pre-clinical myocardial cell damage
B) May occur years later and become symptomatic because LVEF is very low
C) Potentially asymptomatic with LVEF reduction that may occur months later
C) Potentially asymptomatic with LVEF reduction that may occur months later
“Late cardiotoxicity means:
A) Occurs as soon as after 1st one with elevated troponins and pre-clinical myocardial cell damage
B) May occur years later and become symptomatic because LVEF is very low
C) Potentially asymptomatic with LVEF reduction that may occur months later
B) May occur years later and become symptomatic because LVEF is very low
“Acute” cardiotoxicity means
A) Occurs as soon as after 1st one with elevated troponins and pre-clinical myocardial cell damage
B) May occur years later and become symptomatic because LVEF is very low
C) Potentially asymptomatic with LVEF reduction that may occur months later
A) Occurs as soon as after 1st one with elevated troponins and pre-clinical myocardial cell damage
Match the correct chemotherapy-related cardiotoxicity with its characteristic:
A) Cardiomyocyte death via necrosis/apoptosis; irreversible; anthracyclines
B) Cardiomyocyte dysfunction; reversible; Anti-HER2 agents
C) Cardiomyocyte death via necrosis/apoptosis; reversible; anthracyclines
D) Cardiomyocyte dysfunction; irreversible; Anti-HER2 agents
A) Cardiomyocyte death via necrosis/apoptosis; irreversible; anthracyclines
Since anthracyclines have dose-related cardiotoxicity, it is best to limit total lifetime dose and use the liposomal agent when possible. Additionally, symptoms are managed similarly to HF. True or False?
True
The pathophysiology behind the cardiotoxicity of anthracyclines involves:
A) Generation of ROS from Doxorubicin interaction with iron
B) High density of mitochondria in cardiomyocytes increases sensitivity to oxidative stress
C) ROS induces cardiomyocyte apoptosis via release of pro-inflammatory cytokines
D) All of the above
A) Generation of ROS from Doxorubicin interaction with iron
B) High density of mitochondria in cardiomyocytes increases sensitivity to oxidative stress
C) ROS induces cardiomyocyte apoptosis via release of pro-inflammatory cytokines
D) All of the above
Which cardioprotective agent can be used for anthracyclines? A) Dextrazoxane (Zinecard/Totect) B) Glucarpidase C) Loperamide D) None of the above
A) Dextrazoxane (Zinecard/Totect)
How does Dexrazoxane help with cardioprotection?
A) Reduces incidence of CHF and decrease in LVEF
B) Can be used to anthracycline extravasation
C) Prevents myelosuppression
D) A & B
A) Reduces incidence of CHF and decrease in LVEF
B) Can be used to anthracycline extravasation
D) A & B
Which anthracycline drug is considered the "Red Devil" because of its color and strcuture? A) Doxorubicin B) Daunorubicin C) Epirubicin D) Idarubicin
A) Doxorubicin
