Traditional Cytotoxic Chemotherapy: CELL CYCLE SPECIFIC

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57 Terms

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S phase specfic agents

antimetabolites, topoisomerase I inhibitors

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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

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topoisomerase I inhibitors

ironetcan, topotecan

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ironetecan generic

camptosar

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ironotecan; safety concern

acute diarrhea during/immediately after infusion plus cholinergic symptoms

delayed dirrhea (>24 hrs after infusion)

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ironotecan; monitoring

frequency of bowel movements, electrolytes (K and Mg, dehydration

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ironotecan; magnement of diarrhea

acute diarrhea; atropoine

delayed diarrhea; loperamide to take home

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G2 phase specific drugs

toposiomerase II inhibitors, antitumor antibiotic (bleomycin)

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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

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topoisomerase II inhibitors

etoposide

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etoposide; safety concerns

infusion rate-related hypotension

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etoposide hypotension management

prevention; infuse over at least 30-60 minutes

treatment; iv hydration, decrease infusion rate upon reinitiation

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m phase specifc drugs

taxanes and vinca alkaloids

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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

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vinca alkaloids

vincristine, vinblastine, vinorelbine

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vinca alkaloids; safety concerns

perhipheral neuropathy, autonomic neuropathy (constipation), paralysis and death if given intrathecally

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vinca alkaloids; management of peripheral neuropathy

limit vincristine doses to 2 mg (regardless of BSA dose), symptomatic care

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vinca alkaloids; prevention of paralysis and death with intrathecal admin

prepare in small IV bag; label products correction with IV use only

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which vinca alkaloid has more CNS toxicity (neuropathy)

vincristine

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which vinca alkaloid has more Bone marrow suppresion

vinblastine/vinorelbine

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vincristine and cyp

major CYP3A4 substrate

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taxane moa

inhibit the depolymerazation of tubulin (a microtubule stabilizer) during the M phase of the cell cycle

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taxanes

paclitaxel, carbzitaxel, docetaxel

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carbazitaxel generic

jevtana

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albumin boun dpaclitaxel

abraxane

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taxanes; safety concerns

peripheral neuropathy, hypersisntivity reactions

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docetaxel; additional safety concerns

severe fluid retention

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taxanes; prevention of hypersensitivity reactions

premedication with systemic steroid, diphenhydramine and H2RA (famotidine). Do not rechallenge if severe reaction

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docetaxel; managment of severe fluid retention

premedication with systemic steroid, symptomatic care

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preparation of taxanes

non-PVC bags; 0.22 micron filter for carbzitaxel and paclitaxel

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ablumin bound paclitaxel has more or less hypersnsitivity reactions

less

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pyrimidine analog antimetabolite moa

inhibit pyrimidine DNA synthesis during S phase of the cell cycle

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pyrimidine analog antimetabolites

fluorouracail (5-FU), capectiabine, cytarabine, gemcitabine

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capecitabine generic

xeloda

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capecitabine relation to 5FU

oral produg of 5FU

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5FU and capectiabine; safety concerns

Hand food syndrome, diarrhea, mucositis, DPD deficiency (increased risk of severe toxicity), drug interactions with warfarin, increasing INR

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what is hand foot syndrome

palmar plantar erythrodysethesia

painful erythema, skin peeling

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cause of hand foot syndrome

capillary drug leakage into palms of hands/soles of feet

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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

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5FU and capecitabine; monitoring

bowel movments and electrolytes (K, Mg), mucosistis, thrush

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treatment of DPD deficiency induced toxicity

uridine triacetate/vistogard wtihin 96 hrs of overdose or early onset toxicity

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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

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cytarabine; safety concerns

neurotxitiy (acute cerbellar toxicity with high doses) and cytarbine syndrome in the hours following admin

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cytarabine; neurotoxicity prevention

dose modification if they are older, pre-eixisting renal/hepatic dystfion

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cytarabine syndrome symptosm

fever, weakness, bone pian, chest pain

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cytarabine syndrome prevention/treatment

systemic steroids

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leucovorin is given wtih 5FU why

to increase efficacy

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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

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foalte antimetaboltes

mtx, premtrexed, pralatrexate

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MTX safety concerns

nephrotoxicity (high doses greater than 500mg/m2), GI toxicity (diarrhea, mucositis, hepatoxicity and photosensitivity

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MTX monitoring

renal function (BUN, SCr, urine output), wt gain (edema), urine ph, MTX levels, electrolytes (K, Mg)

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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)

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Treatment of MTX nephrotoxicity

Antidote; glucarpidase/voraxaze

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glucarpidase/ vloraxaze use

rapidly lowers MTX levels in patients with MTX inducte aki and dleayed methotrexate clearance

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Which folate product do you use for MTX in AUTOIMMUNE disease

folic acid 1-5 mg daily (reduces Gi, hematologic, hepatic) side effects

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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

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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