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S phase specfic agents
antimetabolites, topoisomerase I inhibitors
topoisomerase I inhibitor moa
block coiling and uncoiling of doulbe stranded DNA helix during S phase; causes single and double strand breaks in DNA and prevents religation of single strand breaks
topoisomerase I inhibitors
ironetcan, topotecan
ironetecan generic
camptosar
ironotecan; safety concern
acute diarrhea during/immediately after infusion plus cholinergic symptoms
delayed dirrhea (>24 hrs after infusion)
ironotecan; monitoring
frequency of bowel movements, electrolytes (K and Mg, dehydration
ironotecan; magnement of diarrhea
acute diarrhea; atropoine
delayed diarrhea; loperamide to take home
G2 phase specific drugs
toposiomerase II inhibitors, antitumor antibiotic (bleomycin)
topoisomerase II inhibitor moa
block coiling and uncoling of double stranded dna in G2 phase; causes single and double strand breaks in DNA and prevention religation of single strand breaks
topoisomerase II inhibitors
etoposide
etoposide; safety concerns
infusion rate-related hypotension
etoposide hypotension management
prevention; infuse over at least 30-60 minutes
treatment; iv hydration, decrease infusion rate upon reinitiation
m phase specifc drugs
taxanes and vinca alkaloids
vinca alkaloid moa
inhibit micrtubule fromation during M phase of the cell cycle. Microtubules are important to axonal transport, which is why neuropathies are so common
vinca alkaloids
vincristine, vinblastine, vinorelbine
vinca alkaloids; safety concerns
perhipheral neuropathy, autonomic neuropathy (constipation), paralysis and death if given intrathecally
vinca alkaloids; management of peripheral neuropathy
limit vincristine doses to 2 mg (regardless of BSA dose), symptomatic care
vinca alkaloids; prevention of paralysis and death with intrathecal admin
prepare in small IV bag; label products correction with IV use only
which vinca alkaloid has more CNS toxicity (neuropathy)
vincristine
which vinca alkaloid has more Bone marrow suppresion
vinblastine/vinorelbine
vincristine and cyp
major CYP3A4 substrate
taxane moa
inhibit the depolymerazation of tubulin (a microtubule stabilizer) during the M phase of the cell cycle
taxanes
paclitaxel, carbzitaxel, docetaxel
carbazitaxel generic
jevtana
albumin boun dpaclitaxel
abraxane
taxanes; safety concerns
peripheral neuropathy, hypersisntivity reactions
docetaxel; additional safety concerns
severe fluid retention
taxanes; prevention of hypersensitivity reactions
premedication with systemic steroid, diphenhydramine and H2RA (famotidine). Do not rechallenge if severe reaction
docetaxel; managment of severe fluid retention
premedication with systemic steroid, symptomatic care
preparation of taxanes
non-PVC bags; 0.22 micron filter for carbzitaxel and paclitaxel
ablumin bound paclitaxel has more or less hypersnsitivity reactions
less
pyrimidine analog antimetabolite moa
inhibit pyrimidine DNA synthesis during S phase of the cell cycle
pyrimidine analog antimetabolites
fluorouracail (5-FU), capectiabine, cytarabine, gemcitabine
capecitabine generic
xeloda
capecitabine relation to 5FU
oral produg of 5FU
5FU and capectiabine; safety concerns
Hand food syndrome, diarrhea, mucositis, DPD deficiency (increased risk of severe toxicity), drug interactions with warfarin, increasing INR
what is hand foot syndrome
palmar plantar erythrodysethesia
painful erythema, skin peeling
cause of hand foot syndrome
capillary drug leakage into palms of hands/soles of feet
management of hand foot syndrome
limit/modifying daily activity to reduce pressure/friction on hands/feet.
Avoid heat exposure to hadns and feed
Col compresses for relifef
Use of emollients (ammonium lactate, urea crea, aquaphor) to retain moisture
Topical steroids and pain meds for inflammation adn pain
Dose modification in severe cases
5FU and capecitabine; monitoring
bowel movments and electrolytes (K, Mg), mucosistis, thrush
treatment of DPD deficiency induced toxicity
uridine triacetate/vistogard wtihin 96 hrs of overdose or early onset toxicity
mucositis management
soft toothbrush, hold ice chips in mouth, bland mouth rinses (sodium bicarb or sodium chloride)
Treatment; magic moouthwash, viscou lidocaine 2%, systemic analgesics if needed. Hydration
Thrush treatment if infected
cytarabine; safety concerns
neurotxitiy (acute cerbellar toxicity with high doses) and cytarbine syndrome in the hours following admin
cytarabine; neurotoxicity prevention
dose modification if they are older, pre-eixisting renal/hepatic dystfion
cytarabine syndrome symptosm
fever, weakness, bone pian, chest pain
cytarabine syndrome prevention/treatment
systemic steroids
leucovorin is given wtih 5FU why
to increase efficacy
folate antimetabolite moa
intefere with enzymes involved int eh folic acid cycle; blocks purine and pyrimidine biosynthesis during the S phase of the cell cycle
foalte antimetaboltes
mtx, premtrexed, pralatrexate
MTX safety concerns
nephrotoxicity (high doses greater than 500mg/m2), GI toxicity (diarrhea, mucositis, hepatoxicity and photosensitivity
MTX monitoring
renal function (BUN, SCr, urine output), wt gain (edema), urine ph, MTX levels, electrolytes (K, Mg)
Prevention of MTX nephrotoxicity
lecuovorin rescue, hydration wtih IV sodium bicarbonate (alkalizes urine, improves TMX solubility), avoid interacting meds (NSAIDS, salicylates, beta-lactams, PPI, sulfonamide antibiotics, probenecid), and caution in patients with third spacing (asciteis, pleural effusions)
Treatment of MTX nephrotoxicity
Antidote; glucarpidase/voraxaze
glucarpidase/ vloraxaze use
rapidly lowers MTX levels in patients with MTX inducte aki and dleayed methotrexate clearance
Which folate product do you use for MTX in AUTOIMMUNE disease
folic acid 1-5 mg daily (reduces Gi, hematologic, hepatic) side effects
Which folate product do you use for MTX in ONCOLOGIC disease
MTX doses are usuall ~40mg/m2; doses higher than 500mg/m2 require LEUCOVORIN rescue. Folic acid not effective
why do we use leucovorin with MTX
Mitigiation of side effects; allows dna synthesis to begin agaoin by competing with MTX for tansport into tissues, and replenishes the supply of folate metabolites that were displaced by MTX