Bleo and other Abx Flashcards
What is the most frequent type of bleomycin-mediated cell injury?
a. Induces cell death during S phase
b. DNA cleavage at thymine bases
c. DNA incorporation and termination of elongation
d. Site-specific cleavage of RNA
e. Inhibits protein synthesis
b. DNA cleavage at thymine bases
BLM induces oxidative cleavage of both ss and ds DNA. It preferentially cleaves DNA at thymine bases. BLM also inhibits RNA and protein synthesis, but these are lesser mechanisms of action.
Which of the following anatomic sites has the lowest concentration of bleomycin hydrolase?
a. Liver
b. Kidneys
c. Brain
d. Stomach
e. Lungs
e. lungs
Bleomycin hydrolase is responsible for cleavage of BLM. The lungs and skin have the lowest concentrations of this enzyme and are therefore most susceptible to toxicity.
Which of the following are potential protective mechanisms against bleomycin-induced pulmonary fibrosis?
i. Deletion of Fas ligand
ii. Anti-HER2 antibodies
iii. Increased levels of plasminogen activator inhibitor 1
iv. Inhibition of CXCL12
a. i, ii, iv
b. i, iii
c. ii, iv
d. ii, iii, iv
e. i
a. Fas, anti-HER2, and inhibition of CXCL12
What is the most prominent active component or peptide in bleomycin?
a. bleomycin A2
b. bleomycin A5
c. bleomycin A6
d. bleomycin B2
a. Bleo A2
The multiple glycopeptides found in the clinical preparation of bleomycin have been separated and purified by high-performance liquid chromatography. The predominant active component, comprising ~70% of the commercial preparation, is the A2 peptide. The other bleomycins differ only in their terminal amine. Page 323
Identify which of the following changes may occur with cutaneous toxicity from bleomycin administration.
i. Hyperpigmentation
ii. Nail changes
iii. Photosensitivity
iv. Mucositis
v. Raynaud phenomenon
a. iii, iv, v
b. ii, iv
c. i, iii, iv
d. i, ii, v
d: i, ii, v
Explanation: A more common but less serious toxicity of bleomycin is its effect on skin, which may related to low bleomycin hydrolase levels in skin. Approximately 50% of patients treated with conventional once daily or twice daily doses of this agent develop erythema, induration, and hyperkeratosis and peeling of skin that may progress to frank ulceration. These changes affect digits, hands, joints, and areas of previous irradiation. Hyperpigmentation, alopecia, and nail changes also occur. Rarely patients may develop Raynaud’s phenomenon. Other toxic reactions include hypersensitivity reactions such as urticarial, periorbital edema, and bronchospasm. p. 331
Which statement is true regarding actinomycins (dactinomycin)?
a. Dactinomycin can only bind to single stranded DNA and not double stranded
b. Naturally occurring actinomycins differ in the peptide chains but not in the phenoxazone ring
c. Dactinomycin is not a vesicant, therefore extravasation is not a risk
d. many pharmacokinetic interactions between dactinomycin and other drugs have been found
b - differ in the peptide chains but not in the phenoxazone ring
Explanation:
- Besides binding to double-strand DNA, DACT is also known to bind to single-strand DNA (p. 332)
- Drug extravasation results in soft tissue necrosis (p. 333)
- No pharmacokinetic interactions between DACT and other drugs are known (p. 332)
p. 332
Which of the following binds with bleomycin intracellularly prior to performing cytotoxic effects?
a. Cu(I)
b. Cu(II)
c. Fe(II)
d. Fe(III)
c. - Fe(II)
Explanation: Among the endogenous metals, bleomycin has the highest affinity for Cu(II). After systemic admin, bleomycin appears to speciate rapidly with Cu(II) removed from plasma proteins. The Cu(II)-bleomycin complex is internalized via endocytosis. Cu(II) is then reduced to Cu(I), which is released, and apobleomycin quickly complexes with the more abundant Fe(II). Nuclear translocation of the Fe(II)-bleomycin complex occurs leading to chromatin damage. p. 323-324
Which of the following are risk factors for bleomycin induced pulmonary fibrosis?
i. Previous radiotherapy to the thorax
ii. Renal insufficiency
iii. Hypoxia
iv. Single dose > 25 units/m2
v. Hepatic dysfunction
a. i, ii, iii
b. i, ii, iv
c. ii, iii, v
d. i, ii, v
b. - RT, renal insuff, single dose >25
Explanation: Bleomycin and radiation therapy are synergistic and concurrent or previous RT to the thorax increases the risk of pulmonary fibrosis. Since 45-70% of bleomycin is eliminated by the kidneys, renal insufficiency can increase the risk of pulmonary fibrosis (recommend decreasing dose by 50% or drug substitution in patients with clearances below 80 ml/min). Other things that can increase risk: underlying pulmonary disease, age >70y old, and O2 during surgery.
table 16.1 (p. 323)
Which of the following best describes the cytotoxic action of mitomycin C?
a. Generates free-radicals that interact with DNA to induce single and double strand breaks
b. Topoisomerase II inhibition
c. Inhibits dihydrofolate reductase leading to depletion of reduced folate pools, which is needed for purine and pyrimidine synthesis
d. Inhibits DNA replication via monofunctional alkylation and DNA interstrand cross-linking
d. - inhib DNA via monofunct alkyl and DNA interstrand x-links
Explanation:
- a. MOA of ionizing radiation and bleomycin
- b. MOA of Doxorubicin, mitoxantrone, and etoposide
- c. MOA of methotrexate
p. 333
Which of the following dosing schedules would lead to the HIGHEST risk of pulmonary toxicity from bleomycin?
a. 5 U/m2 intravenously bolus for 5 doses b. 10 U/m2 intralesionally once c. 25 U/m2 intrapleurally once for 8 hours, then removed via tube d. 25 U as a continuous rate infusion once a day for 5 days
d - 25U as a CRI once daily for 5 days
Which of the following enzymes if depleted would cause increased risk of toxicity from bleomycin?
a. bleomycin hydrolase b. glutathione reductase c. ATPase d. NADH reductase
a - bleomycin hydrolase
page 327
Which of the follow would cause resistance to dactinomycin?
a. increase in p450 activity b. decrease in p450 actiity c. increase in p170 activity d. decrease in p170 activity
c - increased p170
page 332
Once bleomycin has been reconstituted into aqueous solution, how long is it stable at 4 degrees C?
a. 24 hours
b. 7 days
c. one month
d. 90 days
c - one month
Which of the following describes bleomycin’s preferred DNA binding site?
a. GpC and GpT of the minor groove
b. CpT and CpG of the minor groove
c. GpC and CpC of the major groove
d. TpG and CpA of the major groove
a. GpC and GpT of the minor groove
Page 325
Which of the following is true regarding bleomycin-related pulmonary fibrosis?
a. A high cumulative dose is of more concern than a single high-dose administration.
b. Hepatic dysfunction has been shown to be a risk factor.
c. Low expression of the αvβ6 integrin facilitates development of pulmonary fibrosis.
d. The drug is directly toxic to the alveolar epithelial cells.
d. directly toxic to the epithelial cells
Page 329. (a) both cumulative dosing and single high-dose treatments are risk factors. (b) renal dysfunction is a concern, not hepatic. (c) knockout mice who do not express the αvβ6 integrin do not develop pulmonary fibrosis from bleo (although they do show an inflammatory response).
