Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PT 2 > Block 10 - L3, L5 > Flashcards

Block 10 - L3, L5 Flashcards

(75 cards)

Start Studying
1
Q

What is the role of topoisomerase I?

A

Introduces transient protein-bridged DNA breaks in one single strand of DNA, relaxes the strand and re-anneals the strand

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

What is the role of topoisomerase II?

A

Introduces transient protein-bridged DNA breaks in BOTH strands of DNA, relaxes the strand and re-anneals the strand

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

List the types of topoisomerase inhibiting drugs.

A
  1. Topoisomerase I inhibitors (topotecan, irinotecan)
  2. Topoisomerase II inhibitors - intercalators (daunomycin, doxorubicin, mitoxantrone, dactinomycin)
  3. Topoisomerase II inhibitors - non-intercalators (etoposide)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which of these drugs are cross resistant and why?

A

Both types of topoisomerase II inhibitors and the tubulin inhibitors (vinc…)

Multidrug resistance due to a membrane bound efflux pump (P glycoprotein)

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

How can resistance of these drugs be reversed?

A
  1. Giving some of these drugs as continuous infusions

2. Giving quinine, verapamil, and cyclosporine to block the efflux pump

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

What is the cell cycle specificity and MOA of doxorubicin?

A

CCNS

MOA - intercalates into DNA and inhibits topoisomerase II, producing double-stranded DNA breaks

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

When is doxorubicin dose-reduced?

A

In the presence of jaundice (Excreted as a thiol adduct into the bile)

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

What are the AE and DL of doxorubicin?

A

N/V, hair loss, stomatitis, myelosuppression

DL - myelosuppression

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

What is the cumulative toxicity of doxorubicin and how is it monitored?

A

Cardiomyopathy; obtain EF prior to therapy

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

What is the maximum lifetime dose of doxorubicin?

A

400 mg/M^2

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

Discuss the schedule dependency of the cardiac toxicity and anti-tumor effect of doxorubicin.

A

Cardiac toxicity - schedule dependent

Anti-tumor effect - schedule independent

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

How can the cardiac toxicity of doxorubicin be addressed?

A

Longer infusion times are less cardiotoxic; pretreatment with dexrazoxane (iron chelator) may also be helpful

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

What is the cell cycle specificity and MOA of irinotecan?

A

CCNS

Prodrug, upon activation to SN-38, it inhibits topoisomerase I, leading to single strand DNA breaks

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

When is irinotecan dose-reduced?

A

Jaundice (hepatic metabolism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the AE and DL of irinotecan?

A

AE - N/V, myelosuppression, stomatitis, hair loss, early cholinergic diarrhea, late secretory diarrhea

DL - myelosuppression

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

What is irinotecan indicated for?

A

Colon cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is topotecan indicated for?

A

Ovarian cancer (resistant to other chemo)

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

What genetic mutation affects treatment with irinotecan?

A

Patients with UGT1A1*28 = Gilbert’s syndrome - (decreases glucuronidation, increases myelosuppression and diarrhea)

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

How is irinotecan-induced early diarrhea treated?

A

Atropine

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

How is irinotecan-induced late diarrhea treated?

A

Imodium, hydration

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

What is the cell cycle specificity and MOA of bleomycin?

A

CCS - G2-M

Free radical damage to DNA

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

When is dose reduction needed for bleomycin?

A

Renal insufficiency

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

What are the AE and DL of bleomycin? What is the cause of the unique AE?

A

AE - skin hyperpigmentation, pulmonary toxicity, stomatitis, hair loss, fever, chills, anaphylaxis

DL - pulmonary toxicity

Lungs and skin cannot inactivate the drug

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

How is bleomycin cumulative toxicity monitored/protected against?

A
  1. Monitor with pulmonary function tests; obtain baseline
  2. Avoid administering high oxygen concentrations
  3. Test dose to prevent anaphylaxis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the indication of bleomycin?
Testicular cancer
26
What are two hormone dependent cancers?
Breast and prostate cancer
27
What are the indications of prednisone in cancer treatment?
Myelo- and lymphoproliferative disorders Multiple myeloma Hodgkin' disease Non-Hodgkin's lymphoma Some leukemia
28
What are the AE of prednisone?
Weight gain, HTN, edema, carbohydrate intolerance, suppression of pituitary-adrenal axis, weakness, euphoria, increased appetite
29
How is dexamethasone used in treating cancer?
1. Treatment of cerebral edema in patients with brain metastases 2. Adjunct with 5-HT3 inhibitors to prevent/ameliorate chemo-related N/V
30
What is the MOA and indication of tamoxifen?
Oral SERM that antagonizes the E2 receptor on cancer cells; breast cancer treatment AND prevention
31
What are the AE of tamoxifen?
Hot flashes, thrombosis, endometrial cancer, decreased rates ob one loss in post-menopausal women
32
What is the MOA of anastrozole/letrozole/exemestane?
Rapid reduction of estrogen levels via inhibition of aromatase
33
What is the indication of aromatase inhibitors?
Breast cancer
34
What are the AE of aromatase inhibitors?
Arthralgias, bone pain, bone loss, osteoporosis, hot flashes
35
What is the goal of treatment of prostate cancer?
Decrease testosterone production via androgen deprivation therapy
36
What is the MOA of fluatmide/bicalutamide and what is it used for?
Inhibit cancer cell uptake of testosterone; prostate cancer
37
What is the MOA of leuprolide acetate/goserelin?
Decreases levels of testosterone by decreasing FSH and LH (GnRH agonist)
38
What are the AE of leuprolide acetate?
Weakness, decreased libido, ED, loss of muscle mass, gynecomastia, change in body fat distribution
39
What is the general MOA of anti-metabolites?
These are structural analogs of naturally occurring metabolites; they can substitute for the naturally occurring metabolites and cause cessation of synthesis (usually of nucleic acids)
40
What is the cycle specificity of methotrexate?
S phase
41
What is the MOA of methotrexate?
Binds to dihydrofolate reductase (DHFR), decreasing tetrahydrofolate and impairing purine synthesis
42
How does polyglutamation affect the MOA of methotrexate?
Polyglutamation retards cellular egress of methotrexate, increasing the inhibition of enzymes involved in purine and thymine synthesis
43
What rescues a cell treated with methotrexate?
Administration of tetrahydrofolate (leucovorin)
44
What are the AE and DL of methotrexate?
N/V, stomatitis, myelosuppression DL - myelosuppression
45
When is methotrexate dose-reduced?
Renal insuficiency
46
What are the indications of methotrexate?
``` Lymphoma Leukemia Brain tumors Breast cancer RA Psoriasis *Meningitis - can be given intrathecally ```
47
Discuss the clinical impact of protein binding on administration of methotrexate.
Highly protein bound; when co-administered with drugs (aspirin, sulfonamides, penicillins) that displace methotrexate from albumin, toxicity may increase
48
Discuss the clinical impact of volume distribution on administration of methotrexate.
Methotrexate can access third space accumulations of fluid and will slowly leak out, causing prolonged excretion (contraindicated in ascites and pleural effusions)
49
When should methotrexate be dose-reduced?
Patients with impaired renal function (filtered, secreted, and reabsorbed by the kidney)
50
What is the clinical important of methotrexate being excreted by the kidney?
Aspirin and penicillins are also excreted this way, and can interfere with urinary excretion of methotrexate; probeneecid blocks the organic acid transport system and will also interfere
51
What happens to methotrexate in alkaline pH?
Increased solubility (can alkalinize the urine to promote excretion)
52
Methotrexate penetrate the ___ at high doses.
CNS
53
Describe the process of giving high dose methotrexate with leucovorin rescue.
1. IV hydration with sodium bicarbonate to alkalinize the urine 2. Check the urine pH each void; do not administered MTX unless pH >/= 7 3. Administer MTX IV 4. Variable time period later, begin IV or oral leucovorin 5. Monitor MTX levels 6. Stop rescue when MTX level is <5E-7 M at 48 hours
54
Which cells are rescued by leucovorin and why?
Bone marrow and GI epithelial cells - they do not form polyglutamates
55
What is the MOA of pemetrexed?
Inhibition of thymidylate synthase
56
What are the AE and DL of pemetrexed?
AE - rash, stomatitis, diarrhea, hand foot syndrome, myelosuppression DL - myelosuppression
57
How can the extent of myelosuppression be reduced in pemetrexed treatment?
Pre-treat with vitamin B12 and oral folic acid
58
What are the indication of pemetrexed?
Lung cancer | Mesothelioma
59
What is the cell cycle specificity and MOA of cytosine arabinoside?
CCS - S-phase Undergoes sequential phosphorylation to the triphosphate and is incorporated into the DNA; inhibits DNA polymerase and chain elongation
60
What are the AE and DL of cytosine arabinoside?
AE - myelosuppression, N/V, hair loss, stomatitis, hepatic toxicity DL - myelosuppression
61
What is the indication of cytosine arabinoside?
Leukemia
62
What is the 3+7 regimen for treatment of AML with cytosine arabinoside?
3 days IV anthracycline | 7 days continuous infusion of cytosine arabinoside
63
What are the AE of high dose cytosine arabinoside therapy?
Myelosuppression, cerebellar toxicity, conjunctivitis
64
What are the indications of gemcitabine?
Pancreatic and lung cancers
65
What is the cell specificity and MOA of 5-flurouracil?
CCS - S phase Production of FdUMP, which inhibits thymidylate synthase and decreases thymidine production
66
What are the AE and DL of 5-flurouracil?
AE - N/V, stomatitis, rash, diarrhea, myelosuppression, hyperpigmentation of the palms, increased sensitivity to sunlight, coronary artery vasospasm (rare), cerebellar toxicity (rare), excess lacrimation, hand foot syndrome
67
What enhances the cytotoxicity of 5-FU and why?
Leucovorin 5-FDUMP + leucovorin form a strong inhibitory complex with thymidylate synthetase, leading to thymineless death (also enhances GI toxicity)
68
Initial metabolism of 5-FU requires what enzyme?
Dihydropyrimidine dehydrogenase (DPD) Patients who lack this enzyme (3-5% of population) can have severe toxicity
69
What are the indications of 5-FU?
Breast cancer Head and neck cancer GI cancer
70
5-FU is frequently given with ___.
Radiation therapy (as a radiation sensitizer)
71
Why can capecitabine replace 5-FU?
Oral administration (5-FU is IV)
72
What is the cell cycle specificity and MOA of 6-mercaptopurine?
CCS - S Inhibits enzymes of de novo purine nucleotide synthesis
73
Why must 6-mercaptopurine be dose-reduced in patients taking allopurinol? What is an alternate option?
It is inactivated by xanthine oxidase; allopurinol inhibits xanthine oxidase = toxicity 6-thioguanine - no adjustment needed
74
What is the indication of 6-mercaptopurine?
Childhood acute leukemia
75
What is the AE and DL of 6-mercaptopurine
AE - myelosuppression DL - myelosuppression

PT 2 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions