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216 Cards in this Set
- Front
- Back
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Trade name of 5-FU?
Chem name? |
EfFudex
5-fluorouracil |
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5-FU classification
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Antimetabolite/chemo
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5FU mechanisms (4)
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1. Active metabolite, FdUMP inhibits thymidylate synthase.
2.Metabolite FUTP incorporates into RNA and messes it up. 3. FdUTP into DNA to mess up its synthesis and function. 4.Inhibiting TS leads to buildup of dUMP, which gets misincorporates into DNA to mess with synthesis and function. |
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Drug that stabilizes the TS-FdUMP-reduced folate complex to enhance 5FU activity.
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Leukovorin
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Antifolate drugs that increase production of 5FU nucleotide metabolites if given 24 hours prior to 5FU.
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Methotrexate and trimetrexate
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Can be used to rescue from TS-and-DNA mediated toxic effects.
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Thymidine
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Drug that rescues from 5FU
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Vistonuridine (uridine triacetate)
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Vitamin that can reduce/prevent 5FU hand foot syndrome.
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B6 (pyridoxine)
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A way to reduce mucositis from 5FU.
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Ice chips for 10-15 min before and after 5FU injection.
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Mucositis and diarrhea are more common with IV or bolus 5FU?
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Severe and dose limiting for infusion.
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Myelosuppression more common with 5FU infusion or bolus?
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Bolus
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5FU N/V?
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Rare and mild
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5FU hand-foot syndrome more common with infusion or bolus?
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Infusion-can be dose limiting
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5FU neurotoxicities
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somnolence, confusion, seizures ataxia
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Trastuzumab brand name
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Herceptin
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Trastuzumab class
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monoclonal antibody
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Herceptin mechanism (2)
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1.Antibody directed at Her2Neu growth factor receptor, present in several cancers including breast and gastric.
2. May have some immunological antitumor activity. |
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Cancer must have what receptor in order for Herceptin to work?
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Her-2/neu
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Increased cardiotox if Herceptin is used with what other 2 classes?
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taxanes and anthracyclines
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Watch Herceptin for what type of heart problem?
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heart failure
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Pulmonary tox with Herceptin?
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Cough, rhinitis, sinusitis, dyspnea, pleural effusion
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Herceptin infusion related rxn can be treated with what 2 drugs, and occur when?
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W/in 24 hours of infusion and can be treated with diphenhydramine and APAP. If severe fluids and pressors.
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Herceptin infusion rxn?
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fever, chills, itching, rash, flusing, fatigue, H/A, bronchospasm, dyspnea, angioedema, hypotension
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Trastuzumab myelosuppressive?
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Yes
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Why might someone on Herceptin need Mg?
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Generalized pain????
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Brand name of docetaxel?
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Taxotere
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Docetaxel class/cat?
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antimicrotubule/chemo drug
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Docetaxel mechanism?
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Enhances microtubule polymerization and messes with microtubule network, mitosis and cell division.
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Docetaxel PO?
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no
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Drugs that inhibit what enzyme system may interfere with docetaxel effects/toxicities?
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P450 3A4
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Premed with what to reduce docetaxel hypersensitivity and fluid retention?
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steroids
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Docetaxel require special storage?
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Yes- glass, polypropylene or polyoefin plastic for infusion bags. Give thru polyethylene-lined admin sets.
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Monitor pt daily for what docetaxel side effect?
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Edema-measure weight and ins/outs
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Doxetaxel mech...myelosuppression?
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Yes
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Tx for doxetaxel hypersensitivity during infusion? How can u premed for them?
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IV hydrocortisone, dyphenhydramine and/or cimetidine. Steroids.
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50% docetaxel pts develop what problems with skin/nails within 1st week after therapy?
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maculopapular skin rash, dry, itchy commonly on forehead/hands. brown fingernails.
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Docetaxel alopecia? mucositis/diarrhea?
Nausea/vomitin? |
Alopecia very common
pretty common mild-mod/brief |
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Peripheral neuropathy more common with docetaxel or paclitaxel?
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Paclitaxel
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Docetaxel vesicant?
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Yes
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Cisplatin brand name?
Class? Cat? |
Platinol
Platinum analog Chemo |
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Cisplatin mechs-3
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1. covalent binding to DNA N7 on guanine and adenine.
2. reacts with 2 different sites to produce either intra or interstrand crosslinking and messes up DNA synthesis, function and transcription. 3. maybe cytotoxic from binding cytoplasmic/nuclear proteins |
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Cisplatin PO
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No, peritoneal
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Cisplatin/ phenytoin rxn?
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Cisplatin reduces phenytoin effect, may need to increase dose.
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Inactivate nephrotoxicity of cisplatin with what 2 rx?
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MESNA, amifostine
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Cisplatin/aminoglycosides, amphotericin B DDI?
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nephrotoxicity
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Cisplatin/etoposide, MTX ifosfamide, bleomycin DDI
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Cisplatin can reduce the renal Cl of these drugs.
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Cisplatin/etoposide DDI
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enhanced etoposide activity
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Paclitaxel/Cisplatin DDI
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Cisplatin should be givenafter Paclitaxel to prevent delayed paclitaxel Cl and increased tox.
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Cisplatin/furosemide, aminoglycosides
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ototoxicity risk increase when used with loops
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Carefully monitor what organ function with cisplatin?
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Renal
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Cisplatin emetogenesis?
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Potent-premed for acute/delayed with dexamethasone and 5HTs antagonist (granisetron, odansetron/
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Precips with ciplatin and what kind of needle?
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Al
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cisplatin inactivated by what type of soln's?
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sodium bicarb
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Cisplatin classic peripheral neuropathy pattern
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stocking-glove
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Cisplatin effects on eyes?
Ears? taste? Hair? |
Optic neuritis, blindness
tinnitus, highfreq loss metallic taste of food, app loss alopecia |
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Trade name of hydroxyurea?
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Hydrea
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Hydrea class/category?
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Antimetabolite/chemo
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Hydrea mechanism?
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Inhibits ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides, critical precursors to DNA synthesis and repair.
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Oral hydrea?
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Yes
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Hydrea/5FU DDI?
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Hydrea enhances the risk of 5FU host toxicity..
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Hydrea/antiretroviral DDI?
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Hydroxyurea can enhance the activity of azidothymidine, dideoxycytidine, and dideoxyinosine.
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Hydrea dose limiting toxicity?
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Myelosuppression with neutropenia starting around 7-10 days
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What cells are affected by myelosuppression?
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blood cells-made in bone:
Platelets-thrombocytes RBC's Leukocytes |
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Chem name of Avastin?
Class? |
Bevacizumab
Anti-VEGF monoclonal antibody |
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Bevacizumab mech?
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Binds VEGF and prevents it from binding VEGF receptors. Tumor cells can't form bloodvessels.
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Avastin carries a black box warning. AGE>65, hx angina, stroke, thromboembolic events are risk factors, what is the warning for?
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Arterial thromboembolic events such as MI and stroke.
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Avastin carries several other black box warnings. What is one specific to NSC-lung cancer pts?
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Pts with recent hemoptysis (>1/2tsp) should not receive the rx.
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Avastin has a black box warning about wounds and GI stuff?
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Avastin can cause GI perforations. Also would dehiscence, so anyone with recent invasive surgery should wait several weeks before taking it.
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From its name, what pretreatment would you expect to need with bevacizumab?
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Benadryl and APAP
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20-30% of pts on Avastin experience...?
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HTN
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Camptosar chem name?
Class/Cat? |
Ironotecan
Topoisomerase I inhibitor/Chemo |
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Camptosar mech?
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Active form is SN-38, which stabilizes the topoisomerase I-DNA complex and prevents religation of the DNA after TI cleaves it. Ends up breaking DNA-->cell death.
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Why is Camptosar a good drug in colorectal cancer?
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Colorectal tumors express higher levels of topoisomerase I than the normal colonic mucosa.
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Camptosar oral?
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No
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What types of drugs increase the metabolism of ironotecan, decreasing levels and efficacy?
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3A4 inducers like carbamazepine, rifampin, phenobarbital, St. John's Wort
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What type of drugs inhibit the metabolism of ironotecan and may increase tox?
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3A4 inhibitors like ketoconazole, itraconazole, erythromycin and clarithromycin.
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Is ironotecan emetogenic?
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Yes, pretreat with 5HT3 antagonist with or without dexamethasone.
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Describe the early diarrhea seen with Camptosar?
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Early-during or within 24 hours of infusion. Thought to be a cholinergic effect and treated with atropine. Routine prophylaxis is not recommended, unless they have experienced a choliergic event prior.
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Describe Camptosar late diarrhea.
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Late-Staring after 24 hours post infusion. Tx with loperamide 4 mg loading dose, 2mg every 2 hours around the clock until diarrhea free for 12 hours. Can be serious.
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What OTC should patients on ironotecan be warned about taking?
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Laxatives, No St. John's Wort for 2 weeks prior or during tx.
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Ironotecan vesicant?
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Yes-flush with sterile h2O, elevate, ice
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Irinotecan conversion to active SN-38 is inhibited by what OTC herbal?
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SJW
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Pemetrexed brand name?
Class/Cat? |
Alimta
Antimetabolite/chemo |
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Main mech of Alimta?
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Inhibits thymidylate synthase leading to reduced DNA synthesis.
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4 enzymes inhibited by Alimta?
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Thymidylate synthase
DHFR GART=glycinamide ribonucleotide formyltransferase AICART=aminoimidazole carboxamide ribonucleotide flormyltransferase --the last 2 are involved in purine synthesis |
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Drug converted to polyglutamate form intracellularly. This poly form is way more potent than parent compound.
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pemetrexed
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Pemetrexed is used in what type of cancer?
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non-squamous, non-small
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Use this to rescue from pemetrexed?
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Thymidine
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What 2 drugs can reduce renal clearance of Alimta?
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asa and other NSAIDs
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what 2 vitamins should be given a week prior to starting alimta?
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Folate and B12
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Alimta rash?
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Pretreat with steroids
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Alimta mech/class?
So myelosuppression? Mucositis, Diarrhea? Hand foot? |
Yes to all of them
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Gemcitabine trade name
Class? Cat? |
Gemzar
anitmetabolite chem |
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gemcitabine mech?
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Must be activated intracellularly to triphosphate form (dFdCTP). Incorporates into DNA, RNA. inhibits ribonucleotide reductase, so fewer precursors for DNA synthesis/function. inhibs dna polymerase-->inhibs dna synthesis, repair, chain elongation
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PO Gemzar?
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no
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Gemcitabine enhances the cytotoxicity of what rx?
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Cisplatin, it helps increase the formation of cytotoxic platinum-DNA adducts
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Gemcitabine dose limiting tox?
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Myelosuppression
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more gemcitabine tox
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what
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MTX chem name?
Class/cat |
methotrexate
antimetabolite chemo |
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MTX requires what to be active
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polyglutamation
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MTX inhibits what enzyme?
Inhibits synthesis of...(2) How does it affect DNA |
-DHFR
-purine and thymidylate -dUTP into DNA inhibits synthesis and function |
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MTX +asa, penicillins, probenicid, NSAIDs, phenytoin or cephalosporins
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INhibition of MTX renal excretion
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5FU + MTX
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MTX enhances 5FU if given 24 hours prior.
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MTX +thymidine or leukovorin
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rescue from MTX, reduce activity
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MTX +Folic acid
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Stop the folic acid, MTX is an antifolate drug, duh
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MTX + omeprazole
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Increases mTX concentrations, toxicity, activity
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MTX + L asparaginase
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Antagonizes MTX activity
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MTX 2 dose limiting side effects?
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myelosuppression and mucositis
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MTX may cause failure of what organ
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renal failure
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Everolimus trade name?
class/cat? |
Affinitor
signal transduction inhibitor chemo |
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Affinitor mech (3)
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-mTOR inhibitor, a serine-threonine kinase involved in signalling growth/proliferation of tumor cells.
-Inhibits HIF1 (hypoxia-inducible factor) which in turn reduces VEGF expression -inhibit mTOR-->cell cycle arrest, apoptosis, inhibition of angiogenesis |
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Everolimus absorption?
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Oral drug, abs reduced with high fat food
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Everolimus DDI's?
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-everolimus met inhibited by 3A4 inhibitors: keto, itra, fluconazole, verapamil, diltiazem, clarithromycin, erythromycin
-Everolimus met increases with 3A4 inducers: rifampin, carbamazepine,phenobarb, dexamethasone, SJW |
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Class effect of rapamycin inhibitors?
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non-infectious pneumonitis
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Pts on Affinitor are at increased risk of what...
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Opportunistic nfections-avoid live vac
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Monitor what with everolimus (3)?
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glucose, Tg's and cholesterol
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Everolimus myelosuppression?
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yes
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What is myelodysplastic syndrome (MDS)?
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Dysplasia of 10% of at least one myeloid type cell. Results in ineffective hematopoeisis-->thrombocytopenia, anemia, leukocytopenia.
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Lenalidomide trade name?
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Revlimid
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Lenalidomide class?
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immunomodulatory analog of thalidomide, anti-angiogenic agent
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Lenalidomide is indicated for what 2 disorders?
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MDS and multiple myelome
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Lenalidomide mech?
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Who knows...may stimulate TCells, INF, IL2; antiangiogenic
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Can you use the thalidomide analog, lenalidomide, if cancer is resistant to thalidomide?
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Yes, it can overcome thalidomide resistance
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Lenalidomide PG category?
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X--must have two negative pg tests, one 2 weeks prior and one 24 hrs prior to tx. double up on bc a month prior and at least 1 month after tx. even affected men.
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Lenalidomide main concern?
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it increasees thromoembolic events like PE and DVT, especially when combined with dexamethasone in multiple myeloma pts
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Lenalidomide pregnancy concern?
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teratogenic
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Doxorubicin brand name
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Adriamycin, Hydroxydaunorubicin
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doxorubicin class/cat?
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antitumor antibiotic/chemo
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Doxorubicin mech? 4
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1. intercalcates into DNA and messes with synthesis and function
2. inhibits transcription through dna-dependent rna polymerase 3. forms a cleavable complex with DNA and topoisomerase II, leading to DNA breakage. 4. free radicals damage DNA to inhibit synthesis and function |
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What to use in doxorubicin cardiotoxicity?
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dexrazoxane
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Doxorubicin +cyclophosphamide increases risk of (2)? What SE of dox complicates matters?
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Cardiotoxicity and hemorrhagic cystitis.
Dox turns pee red-orange, making it difficult to tell if they have h. cystitis |
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Doxorubicin+ phenytoin or barbiturates
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increased dox cl
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doxorubicin +mitomycin c or herceptin?
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cardiotox
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digoxin +doxorubicin
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decreases digoxin oral bioavailability
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6MP + doxorubicin
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hepatoxicity
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tx doxorubicin extravasation?
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stop infusion, withdraw fluid, elevate, ice, local steroids
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docorubicin cardiotox?
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acute- 2-3 days, ekg changes, arrythmias myocarditis; transient, asx, not dose related
Chronic-dose related, cum dose>450/m2; dilated cardiomyopathy-->Heart failure |
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2 pt counseling pts for doxorubicin
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sun sensitivity and red-orange pee
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doxorubin myelosuppression?
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Yep, dose limiting
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doxorubicin n/v/d/mucositis
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yes
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doxorubicin alopecia?
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universal
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cyclophosphamide brand names
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CTX, Cytoxan
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CTX PO?
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yes, good absorption
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CTX class/cat
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alkylating agent/chemo
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CTX Mech (3)
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1. prodrug
2. P450 activation to acrolein and phosphoramide mustard 3. cross links dna to inhibit synthesis and function |
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CTX+Pheny/Pheno 450 inducers
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p450 inducers increase the rate of CTX activation
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CTX + anticoags
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CTX can increase their effects and may need to reduce anticoag dose
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CTX + digoxin
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CTX increases digoxin metabolism, reducing dig levels
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dox + CTX
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CTX may increase risk of doxorubicin cardiotox
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CTX and fluids/urination
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keep pts well hydrated and encourage frequent urination to reduce damage to bladder (pee q2h).
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CTX myelosuppression?
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Yes, dose limiting
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CTX bladder tox?
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hemorragic cystitis, dysuria, frequency increases can begin in a day or weeks; protect with mesna and hydration when high-doses used
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CTX N/V/alopecia, Diarrhea
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yes, except no mention of diarrhea
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CTX cardio tox?
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at high doses
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CTX problem done the road?
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alkylating agent that increases risk of 2ndary cancer, esp if they had hemorrhagic cystitis-->bladder cancer; AML as well.
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CTX allergy?
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hypersensitivity rhinitis, throat irritation-->benadryl/steroids
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What is ITP
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idiopathic thrombocytopenia purpura; bleeding disorder from immune destruction of platelets
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ITP+ASA/NSAIDS/Warfarin?
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don't do it, they already have trouble clotting
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Votrient chem name
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pazopanib
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Votirent class/cat
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signal transduction inhibitor/chemo
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Votrient mech?
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Inhibits several growth factor receptors--VEGFR1-3, platelet derived growth factor receptors, and fibroblast growth factor receptors, and some tyrosine kinases
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Pazopanib PO?
|
yes
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Pazopanib DDIs from metabolism?
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CYP 3A4
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Pazopanib administration instructions?
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Take orally without food, at least one hour before or 2 hours after a meal.
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Pazopanib S/E in 50% of pts that we can control with meds?
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HTN
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Pazopanib GI S/E's?
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D/N/V and abdominal pain
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Pazopanib cardiotox?
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prolong QT, Torsade de Pointes
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Pazopanib and thyroid?
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hypothyroidism
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Pazopanib and blood/vascular probs?
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risk of bleeding, thromboembolic events: MI, TIA, stroke, angina
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Sunitinib brand name?
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Sutent
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Sutent class/cat
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signal transduction inhibitor/chemo
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Sunitinib mechanism?
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multiple receptor tyrosine kinase inhibitor: VEGFR's, PDGRR's, KIT (stem cell factor receptor)
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Sunitinib PO?
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yes, and can be taken with/without food as bioavailability is not affected.
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Sunitinib DDI's?
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CYP 3A4 inhibitors/inducers
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Sutent SE occurring in 30% that can be controlled with meds
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HTN
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Sunitinib and skin?
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yellowing of skin, rash, dry, cracking
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Sutent and bleeding?
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Epitaxis-nosebleeds, myelosuppression
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Sutent and the heart
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LV dysfunction, HF
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Bleomycin trade name
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Blenoxane
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Bleomycin class/cat
|
antitumor antibiotic/chemo
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Bleomycin mech?
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1. small peptide with an iron binding region and a dna binding region
2. iron is a necessary cofactor for its free radical generation and cytotoxicity 3.generates active free radical oxygen species that causes single and double stranded dna breaks and leads to cell death |
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What element can enhance bleomycin pulmonary toxicity?
|
O2
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Bleomycin +phenothiazines
|
enhance bleomycin activity due to competition for P450's
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Bleomycin + cisplatin
|
Cisplatin decreases renal cl of bleomycin and may enhance toxicity
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Most common bleomycin S/E?
|
Skin rxn's: erythema, hyperpigmentation, striae; peeling/thickening of skin and nails, hyperkeratosis, ulceration; usually starts around 2-3 weeks and cummulative dose 150-200 units. Alopecia too.
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Bleomycin dose limiting toxicity?
|
Pulmonary toxicity that is dose and age related, worse >70. pneumonitis, cough, dyspnea, infiltrates. can lead to pulmonary fibrosis/death
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Bleomycin myelosuppression?
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pretty mild
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Vinblastine trade name
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Velban
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Vinblastine class/cat
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Vinca alkaloid, anti-microtubule agent/chemo
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Vinblastine mech?
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Inhibits tubilin polymerization and messes up tubule formation during mitosis, leading to cell death.
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Vinblastine DDI metabolism?
|
3A4 inhibitors
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vinblastine + phenytoin?
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vinblastine reduces blood levels of phenytoin somehow someway
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vinblastine + bleomycin
|
increases risk of reynaud's syndrome, a vasospastic condition that cuts of circulation causing discoloration of fingers/toes
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vinblastine dose limiting tox?
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myelosuppression
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vinblastine mucositis/D compared to vincristine?
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vinblatine is worse
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most common cardiac se of vinblastine?
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HTN
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Vinblastine neurotox vs vincristine?
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less than vincristine, but same sx: periperhal neuropathy, loss of tendon reflexes, constipation, paralytic illeus
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Vinbastine vesicant?
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Yes
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dacarbazine class/cat
|
nonclassic alylating chemo agent
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dacarbazine mech?
|
Not completely explained, but it methylates nucleic acids and inhibits DNA, RNA and, protein synthesis.
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dacarbazine PO?
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oral is slow and variable, so IV is preferred
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Dacarbazine + heparin/lidocaine/hydrocortisone
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incompatible with these
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Dacarbazine + drugs like phenytoin/phenobarb
|
decreased efficacy with 3A4 inducers
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dacarbazine vesicant?
|
yes, potent
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dacarbazine emetogenic?
|
highly, aggressive antiemetics prior to dosine
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Pt counseling with dacarbazine?
|
stay out of the sun for a few days, sun sensitivity
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dacarbazine dose limiting tox
|
myelosuppression
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dacarbazine diarrhea?
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rarely
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other than pukey, how might a dacarbazine pt feel?
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like they have the flu-fever, chills, muscle/joint pains for days post therapy
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dacarbazine neuro?
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parasthesia, neuropathies, ataxia, lethargy, ha, confusion, seizures possible
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azacitidine brand name
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Vidaza
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azacitidine class/cat
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antimetabolite/hypomethylating, chemo agent
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azacitidine mech?
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1. cytidine analog prodrug requires activation to triphosphate form
2. incorporates into rna and messes it up 3. incorporates into dna, inhibiting dna methyltransferases-->hypomethylation and loss of gene reactivation, while aberrantly silenced tumor suppressor genes are turned back on |
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azacitidine GI tox
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n,v,c, ab pain
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azacitidine use
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MDS myelodysplastic syndromes
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azacitidine organ tox?
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renal
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