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Hem/Onc > cell cycle SPECIFIC agents > Flashcards

cell cycle SPECIFIC agents Flashcards

1
Q

VINCA ALKALOIDS

A
  • inhibit function of microtubules during M phase (mitosis phase)
  • IV use only*
  • FATAL IF GIVEN BY OTHER ROUTE***
  • peripheral sensory & autonomic neuropathies (constipation) are common
  • common side effect b/c microtubules play role in axonal transport in neurons
  • *potent VESICANTS**
  • use warm compress & hyaluronidase

vinCristine = more CNS toxicity than other vinca alkaloids

vinorelBine & vinBlastine = more Bone marrow suppression over vincristine

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2
Q

vincristine

A

Vincasar PFS
- vinca alkaloid = inhibit function of microtubules during M phase

  • NOT myelosuppressive
  • capped at 2mg/dose
  • higher doses associated with increased risk of neuropathy
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3
Q

vinblastine

vinelborine

A

Velban
Navelbine
- vina alkaloids = inhibit function of microtubules during M phase

  • myelosuppressive
    B think bone marrow = myelosuppressive
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4
Q

vincristine liposomal

A

Marqibo

-not interchangeable with vincristine-

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5
Q

VINCA ALKALOIDS

Boxed Warnings
Side Effects

A

::: Boxed Warnings :::

  • vesicants
  • for IV administration only
  • intrathecal administration = death

::: Side Effects :::

  • peripheral sensory neuropathy (paresthesias)
  • autonomic neuropathy (gastroparesis, constipation)
  • SIADH
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6
Q

TAXANES

A
  • inhibit function of microtubules during M phase (mitotic phase)
  • peripheral sensory neuropathies common side effects = microtubules are important part of axonal transport in neurons
  • SEVERE infusion-related hypersensitivity reactions
  • FATAL ANAPHYLAXIS
  • metabolized by liver
  • dose adjustment for hepatic impairment
  • DDI = gives taxanes before platinum-based compounds
  • elimination of taxanes is reduced when given after cisplatin/carboplatin

Carbo/Taxol = Taxol runs first

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7
Q

paclitaxel

A

Taxol
- taxane = inhibit function of microtubules during M phase

HSR = hypersensitivity reaction
- pre meds include diphenhydramine, corticosteroid H2RA

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8
Q

docetaxel

A

Taxotere
Docefez
- taxane = inhibit function of microtubules during M phase

HSR
- pre medicate with corticosteroids for 3 days, starting 1 day prior to docetaxel

  • causes severe fluid retention (pleural effusion, cardiac tamponade and/or edema)
  • pre medicate with dexamethasone
  • some formulations contain alcohol and may cause symptoms of alcohol intoxication
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9
Q

cabazitaxel

A

Jevtana
- taxane = inhibit function of microtubules during M phase

HSR
- pre meds include diphenhydramine, corticosteroid H2RA

  • least alopecia of all taxanes
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10
Q

paclitaxel albumin-bound

A

Abraxane
- taxane = inhibit function of microtubules during M phase

  • paclitaxel bound to albumin without a solvent system
  • only isolated case reports of allergic reaction
  • no premedication required
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11
Q

TAXANES

Boxed Warnings
Side Effects
& Notes

A

::: BOXED WARNINGS :::

  • severe HSR except Abraxane
  • myelosuppression
  • docetaxel = fluid retention

::: SIDE EFFECTS :::

  • peripheral sensory neuropathy
  • myalgias
  • arthalgias
  • hepatoxicity
  • alopecia (less with cabazitaxel)

::: NOTES :::

  • HSR are due to solvent systems
  • paclitaxel solvent = Cremophor EL
  • docetaxel solvent = polysorbate 80

*PVC-FREE BAG + TUBING
due to leaching of DEHP
-except for Abraxane

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12
Q

Topoisomerase I Inhibitors (S phase)

A
  • block the coiling and uncoiling of double-stranded DNA helix during S-phase
  • causes single and double strand breaks in DNA and prevents religation of single strand breaks (sealing DNA strands back together)

BOXED WARNINGS
*myelosuppression

SIDE EFFECTS

  • NVD
  • alopecia
  • diarrhea
  • abdominal pain
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13
Q

IRINOTECAN

A

Camptosar

topoisomerase I inhibitor (S phase)

  • give ATROPINE to prevent acute cholinergic symptoms
  • acute cholinergic symptoms = flushing, sweating, abdominal cramps, diarrhea
  • LOPERAMIDE for DELAYED DIARRHEA (up to 24mg/day)
  • homozygous UGT1A1*28 allele are at increased risk for neutropenia and delayed diarrhea
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14
Q

TOPOTECAN

A

hycamtin
- topoisomerase I inhibitor (S phase)

  • ANC must be above >1500
  • platelets must be above >100
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15
Q

Topoisomerase II Inhibitors (G2)

A
  • block coiling and uncoiling of double-stranded DNA during G2 phase
  • causes single and double strand breaks in DNA and prevents religation of single strand breaks

BOXED WARNING
*myelosuppression

SIDE EFFECTS

  • hypersensitivity reactions
  • anaphylaxis
  • secondary malignancies
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16
Q

ETOPOSIDE

A

Toposar
- Topo II inhibitor = block coiling and uncoiling of double-stranded DNA during G2 phase

  • infusion RATE-RELATED HYPOTENSION
  • infuse over at least 30-60 minutes
  • IV preparation : concentration <0.4mg/mL to avoid precipitate
  • in 500mL D5W
  • poor solubility
  • use PVC-Free bag + tubing due to leaching of DEHP???
  • we do not use PVC-Free Bag at Baystate????
17
Q

ETOPOSIDE CAPSULES

A

VePesid

  • requires REFRIGERATION
  • oral capsules

IV:PO ratios 1:2
50% bioavailability

doses > 200mg given in divided doses due to reduced bioavailability

18
Q

PYRIMIDINE ANALOG ANTIMETABOLITES

A
  • inhibit pyrimidine synthesis during S phase
  • active metabolite (F-UMP) is incorporated into RNA to replace uracil and inhibits cell growth, while another active metabolite (5-dUMP) inhibits thymidylate synthetase
19
Q

fluorouracil (5-FU)

A

Adrucil

  • pyrimidine analog antimetabolite
  • inhibit pyrimidine synthesis during S phase
  • LEUCOVORIN given with 5-FU to increase efficacy
  • helps 5-FU bind more tightly to its target enzyme (thymidylate synthetase)
  • DPD deficiency increases risk of severe toxicity
  • DPD = dihydropyrimidine dehydrogenase

::: SIDE EFFECTS :::

  • hand-foot syndrome
  • cardiotoxicity
  • diarrhea
  • photosensitivity
  • dermatitis
  • mucositis

::: NOTES :::
- Vistogard is antidote for overdose or severe/early toxicity due to DPD deficiency

20
Q

cytarbarine conventional
OR
cytarabine liposomal

A

ara-C
OR
DepoCyt = intrathecal administration

  • pyrimidine analog antimetabolite
  • inhibit pyrimidine synthesis during S phase

cytarabine syndrome
= fever, flu-like symptoms, myalgia, bone pain, rash

::: BOXED WARNINGS :::

  • myelosuppression
  • conventional = hepatotoxicity & GI toxicity
  • liposomal = chemical arachnoiditis can be fatal
  • chemical arachnoiditis = NV, HA, fever
  • arachnoid layer of meninges can become inflamed due to intrathecal administration
  • give dexamethasone

::: SIDE EFFECTS :::

  • pulmonary toxicity
  • encephalopathy
  • hand-foot syndrome
  • neuropathy
  • conjunctivitis (high doses use steroid eye drops)
21
Q

capecitabine

A

Xeloda

  • oral prodrug of 5-FU
  • pyrimidine analog antimetabolite
  • 2 divided doses 12 hours apart
  • given with water within 30 minutes after a meal
  • if DPD deficiency = increased risk of severe toxicity

::: BOXED WARNING :::

  • significant increase in INR during and up to 1 month after treatment
  • monitor INR frequently

::: CONTRAINDICATIONS :::
- severe renal impairment CrCl < 30 mL/min

::: SIDE EFFECTS :::

  • hand-foot syndrome
  • cardiotoxicity
  • diarrhea
  • photosensitivity
  • dermatitis
  • mucositis

::: NOTES :::
- Vistogard is antidote for overdose or severe/early toxicity due to DPD deficiency

22
Q

Vistogard

A
  • uridine triacetate

- antidote for 5-FU, capecitabine overdose or severe/early toxicity due to DPD deficiency

23
Q

gemcitabine

A

Gemzar

  • pyrimidine analog antimetabolite
  • inhibit pyrimidine synthesis during S phase
  • infusion rate affects efficacy and toxicity
  • infuse per institutional protocol

::: SIDE EFFECTS :::

  • myelosuppression
  • flu-like symptoms
  • hepatoxicity
  • pulmonary toxicity
24
Q

FOLATE ANTIMETABOLITES

A
  • interfere with the enzymes involved in the folic acid cycle, blocking purine and pyrimidine biosynthesis during S phase
  • NEPHROTOXICITY*
  • associated with all folate antimetabolites
  • most frequently with high dose methotrexate
  • FOLIC ACID + B12 to reduce toxicity caused by interfering with folic acid cycle
  • myelosuppression
  • mucositis
  • diarrhea
25
Q

METHOTREXATE

A
  • folate antimetabolite
  • interfere with enzymes involved in folic acid cycle, block purine and pyrimidine biosynthesis during S phase
  • HIGH DOSE >500 mg/m2
  • requires leucovorin rescue
  • MODERATE DOSE 100-499 mg/m2
  • may require leucovorin rescue
  • LEVOleucovorin* 1/2 of leucovorin dose*
  • monitor renal function daily
  • continue until levels <0.05-0.1 micromolar

glucarpidase to rapidly lower methotrexate levels

  • give HYDRATION and IV SODIUM BICARBONATE to alkalinize urine and reduce risk of nephrotoxicity
  • watch for 3RD SPACING = ascites, pleural effusions, severe edema = delayed clearance of drug

-DRUG INTERACTIONS = NSAIDs, salicylates, beta-lactams, PPIs, sulfonamides, probenecid
= all can reduce clearance of methotrexate

BOXED WARNINGS
\: myelosuppression
\: aplastic anemia
\: renal damage/hepatotoxicity
\: interstitial pneumonitis
\: dermatologic reactions (SJS)
\: diarrhea
\: fetal death or teratogenicity (used to end ectopic pregnancies)

SIDE EFFECTS
: dose-related nephrotoxicity
: hepatotoxicity (common in chronic use)
: hand-foot syndrome

26
Q

pemetrexed

A

Alimta

  • folate antimetabolite
  • interfere with the enzymes involved in the folic acid cycle, blocking purine and pyrimidine biosynthesis during S phase
  • reduce risk of side effects:
    give folic acid, B12, and dexamethasone

SIDE EFFECTS
: nephtoxicity
: hepatotoxicity
: dermatologic toxicity (give dexamethasone)

Hem/Onc (10 decks)

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