cell cycle SPECIFIC agents Flashcards
VINCA ALKALOIDS
- 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
vincristine
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
vinblastine
vinelborine
Velban
Navelbine
- vina alkaloids = inhibit function of microtubules during M phase
- myelosuppressive
B think bone marrow = myelosuppressive
vincristine liposomal
Marqibo
-not interchangeable with vincristine-
VINCA ALKALOIDS
Boxed Warnings
Side Effects
::: Boxed Warnings :::
- vesicants
- for IV administration only
- intrathecal administration = death
::: Side Effects :::
- peripheral sensory neuropathy (paresthesias)
- autonomic neuropathy (gastroparesis, constipation)
- SIADH
TAXANES
- 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
paclitaxel
Taxol
- taxane = inhibit function of microtubules during M phase
HSR = hypersensitivity reaction
- pre meds include diphenhydramine, corticosteroid H2RA
docetaxel
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
cabazitaxel
Jevtana
- taxane = inhibit function of microtubules during M phase
HSR
- pre meds include diphenhydramine, corticosteroid H2RA
- least alopecia of all taxanes
paclitaxel albumin-bound
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
TAXANES
Boxed Warnings
Side Effects
& Notes
::: 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
Topoisomerase I Inhibitors (S phase)
- 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
IRINOTECAN
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
TOPOTECAN
hycamtin
- topoisomerase I inhibitor (S phase)
- ANC must be above >1500
- platelets must be above >100
Topoisomerase II Inhibitors (G2)
- 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
ETOPOSIDE
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????
ETOPOSIDE CAPSULES
VePesid
- requires REFRIGERATION
- oral capsules
IV:PO ratios 1:2
50% bioavailability
doses > 200mg given in divided doses due to reduced bioavailability
PYRIMIDINE ANALOG ANTIMETABOLITES
- 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
fluorouracil (5-FU)
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
cytarbarine conventional
OR
cytarabine liposomal
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)
capecitabine
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
Vistogard
- uridine triacetate
- antidote for 5-FU, capecitabine overdose or severe/early toxicity due to DPD deficiency
gemcitabine
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
FOLATE ANTIMETABOLITES
- 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
METHOTREXATE
- 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
pemetrexed
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)
