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Heme & Lymph-Unit 1 (Pharm) > Antimitotic And G/M Phase Drugs (Fitz) > Flashcards

Antimitotic And G/M Phase Drugs (Fitz) Flashcards

1
Q

List the anti-mitotic drugs

A

Vinca alkaloids: Vinblastine, Vincristine, Vinorelbine

Taxanes: Taxol (Paclitaxel), Taxotere (Docetaxel)

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2
Q

Basic MOA of vinca alkaloids?

A

Inhibit tubulin polymerization –> block assembly of microtubules

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3
Q

Basic MOA of taxanes?

A

Enhance tubulin polymerization –> stabilize microtubules

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4
Q

Therapeutic uses of vinblastine?

A

Testicular cancer (w/bleomycin and cisplatin), lymphomas, neuroblastoma

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5
Q

Therapeutic uses of vincristine?

A

ALL (pediatric), lymphoma, neuroblastoma, wilms tumor, ewings sarcoma

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6
Q

Therapeutic use of Vinorelbine?

A

Advanced NSCL cancer (alone or with cisplatin)

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7
Q

Therapeutic uses of paclitaxel?

A

Advanced breast and ovarian (with cisplatin)

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8
Q

Therapeutic use of docetaxel?

A

Advanced breast, ovarian recurrence

Taxanes are effective against solid tumors

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9
Q

Dose-limiting toxicity of vinblastine?

A

BM suppression, Vesicant blisters

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10
Q

Dose-limiting toxicity of vincristine?

A

NEUROTOXICITY; PERIPHERAL NEUROPATHY, paralytic ileus, vesicant blisters

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11
Q

Dose-limiting toxicity of vinorelbine?

A

BM suppression; vesicant-blisters

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12
Q

Dose-limiting toxicity of paclitaxel?

A

Neutropenia; thrombocytopenia; peripheral neuropathy; severe hypersensitivity during infusion-requires anti histamine and corticosteroid pre-tx

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13
Q

Dose-limiting toxicity of docetaxel?

A

Neutropenia; peripheral neuropathy

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14
Q

Where do vinca alkaloids bind microtubules and net result?

A

At the forming (Positive) end and inhibit tubulin polymerization –> fraying continues and shortens microtubules

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15
Q

Where do taxanes bind microtubules and what eventually happens?

A

Bind at the forming (Positive) end but reach the negative end and inhibit fraying –> enhances tubulin polymerization and stabilizies microtubules

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16
Q

What phase of the cell cycle do vinca alkaloids and taxanes act?

A

M phase

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17
Q

Adverse effects of Vincristine? What can be substituted for VIncristine d/t this severe adverse effect?

A

Vincristine-peripheral neuropathy, neuritis (worse than Vinblastine)

Vinblastine substitutes for vincristine when neuropathy is severe

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18
Q

Mechanism of anti-mitotic drug resistance?

A

Tx w/vinca and taxane drugs commonly leads to MDR d/t increased expression of P-glycoprotein and its enhanced extrustion of drugs from the tumor cell

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19
Q

Administration and ADME of vinca alkaloids and taxanes?

A

Administered IV

Concentrated and metabolized by liver and excreted to varying degrees in bile or feces

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20
Q

Cancer drugs with mechanisms that involve __ are not prone to P-glycoprostein MDR. Important drugs in this category are monoclonal Abs

A

The exterior cell surface

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21
Q

List the epipodophyllotoxin topoisomerase inhibitors and their MOA:

A

Etoposide and Teniposide

Topoisomerase II inhibition –> DNA DOUBLE strand breaks

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22
Q

List the Camptothecin topoisomerase inhibitors and their MOA:

A

Irinotecan (active metabolite SN38) and Topotecan

Topoisomerase I inhibition –> DNA SINGLE strand breaks

23
Q

Therapeutic uses of Etoposide and route of administration?

A

Oat cell carcinoma of lung; testicular cancer (with cisplatin and bleomycin)

IV, PO

24
Q

Therapeutic uses of Teniposide and route of admin

A

Efficacy vs glioma and neuroblastoma

IV

25
Q

Therapeutic use of Irinotecan and route of admin?

A

Metastatic colorectal cancer

IV

26
Q

Therapeutic use of Topotecan and route of admin?

A

2nd lien various-failed prior 1st line

IV

27
Q

Dose-limiting toxicity of Etoposide? Metabolism?

A

Leukopenia; secondary cancer (leukemia)

CYP450-liver

28
Q

Dose-limiting toxicity of Teniposide? Metabolism?

A

Leukopenia

CYP450-liver

29
Q

Dose-limiting toxicity of Irinotecan? Clearance?

A

SEVERE DIARRHEA (may be life-threatending and require tx with Loperamide); myelosuppression

Renal clearance

30
Q

Dose-limtiing toxicity of Topotecan? Clearance?

A

Neutropenia; mucositis

Renal clearance

31
Q

List the Abx that cause DNA strand breaks by intercalation or oxidative scission

A

Bleomycin and dactinomycin

32
Q

MOA/distinction of Bleomycin?

A

Fe2+/3+ mediated free radical generation –> DNA strand breaks

33
Q

MOA/action of Dactinomycin?

A

DNA intercalating agent

34
Q

List the anthracyclines that cause DNA strand breaks by intercalation or oxidative scission

A

Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone

35
Q

MOA/distinction of Doxorubicin, Daunorubicin, Epirubicin, and Idarubicin?

A

Inhibit topoisomerase II
DNA intercalating agents
Free radical generation –> DNA strand breaks

36
Q

Therapeutic uses of Bleomycin? Administration? Clearance?

A

Testicular cancer (with vinblastine, cisplatin or etoposide

SQ, IM, IV

Renal clearance

37
Q

Therapeutic use of Doxorubicin and epirubicin?

A

Wide spectrum-BREAST, OVARIAN, lung, thyroid, lymphoma, sarcoma, etc

38
Q

Therapeutic use of Daunorubicin?

A

Leukemia (AML, ALL)

39
Q

Therapeutic uses of Idarubicin? Administration? Excretion?

A

Leukemia (AML, ALL, CML and blast crisis)

IV-vesicant

Biliary excretion

40
Q

Therapeutic use of Mitoxantrone? Admin?

A

BREAST, prostate, NHL

IV

41
Q

Dose limiting toxicity of Bleomycin?

A

PULMONARY FIBROSIS - “blemomycin lung”

5-10% develop lung toxicity. Cumulative dose-related toxicity. Lung function improves with recovery but fibrosis remains

42
Q

Dose-limtiing toxicity of Doxorubicin, Daunorubicin, Epirubicin and Idarubicin?

A

CARDIOTOXICITY, DILATED CARDIOMYOPATHY, CHF occurs over time- cumulative dose-related toxicity; myelosuppression; mucositi

43
Q

Dose-limiting toxicity of Mitoxantrone?

A

Similar to -rubicins (anthracenedione relative to anthracyclines)

44
Q

What drug, other than the anthracyclines, may cause heart dysfunctions?

A

Trastuzumab

Thanks Taqui khaja

45
Q

What enzyme is absent that cannot metabolize Bleomycin that can be lead to skin and lung damage?

A

Hydrolase

46
Q

Goal of combo chemotherapy tx?

A

Avoid drug combos that have additive or synergistic toxicities on a particular organs

Use drug combos that distribute toxicities among different organs

47
Q

List the ABVD regimen for Hodgkins lymphoma and toxicities of each drug

A

Adriamycin (doxorubicin)-Cardiotoxicty
Bleomycin-Pulm fibrosis
Vinblastine-peripheral neuropathy
Dacarbazine-Nausea/vomiting, myelosuppression

48
Q

List the CHOP regimen for NHL and toxicities of each drug:

A

Cyclophosphamide-Acrolein–> hemorrhagic cystitis
Doxorubicin-Cardiomyopathy
Vincristine-neuropathy, constipation
Prednisone-hyperglycemia, osteopenia

49
Q

Allopurinol and febuxostat inhibit what enzyme?

A

Xanthien oxidase

50
Q

Acute nephrotoxicity produced by excessive uric acid is managed by co-adminstration of ___ with any chemotherapeutic agent that produces tumor lysis syndrome

A

Allopurinol

51
Q

What happens to potassium, phosphate, calcium, and uric acid in tumor lysis syndrome?

A

HyperK
Hyperphosphatemia
Hypocalcemia
Hyperuricemia

52
Q

Simultaneous admin of allopurionol and 6-MP chemotherapy can result in excessive exposure to 6-MP b/c it is metabolized (inactivated) by Xanthine oxidase. What can you do to avoid this problem?

A

Reduce the dose of 6-MP

53
Q

What is Pegloticase (uricase) indicated for?

A

Hyperuricemia associated with malignancy (tumor lysis syndrome)

IV q 2 weeks

54
Q

List a 5-HT3 antagonist for CINV

A

Ondansetron

Heme & Lymph-Unit 1 (Pharm) (5 decks)

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