Term
Methotrexate
1. analog of
2. action |
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Definition
1. folic acid analog
2. competitive inhibitor of dihydrofolate reductase |
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Term
Methotrexate
1. blocks formation of?
2. intracellular form, may make it stay longer intracellularly?
3. administration? |
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Definition
1. dTMP (thymidylate)- inhibits dihydrofolate reductase, stops de novo synthesis of purines also, as well as 2 amino acids, basically inhibits DNA, RNA and protei nformation
2. gets polyglutamated, active in this form, longer effects
3. IV, IM, oral, or intrathecally (into CSF) |
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Term
| Methotrexate side effects |
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Definition
| alopecia, N&V, fever, hepatic necrosis, Hypersensitivity rxn, oral and GI ulcer, BM depression, pulmonary infiltrates and fibrosis |
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Term
| Fluorouracil 3 step mech of actin |
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Definition
1. converted to fraudulent F-dUMP
2. fraudulent F-dUMP forms covalent complex with thymidylate synthase and methyelene THF
3. result is inhibition of DNA synthesis |
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Term
Flurouracil (5 FU)
inhibits set of rxns at diff step then what other drug |
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Definition
| methotrexate (methotrexate inhibits dihydrofolate reductase (DHF->THF), FU inhibits thymidylate synthase (THF->DHF and dUMP --> dTMP) |
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Term
5FU
1. Given how- why?
2. distribution (To CNS?)
3. metabolized where? |
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Definition
1. IV - v. toxic to GI
2. distributes throughout body and CNS
3. liver |
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Term
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Definition
| SEVERE ulceration of oral and GI mucuosa, N&V, diarrhea, alopecia, BM depression |
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Term
| What drug potentiates FU action (starts with L) |
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Definition
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Term
|
Definition
| prodrug of 5 FU- orally well taken up |
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Term
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Definition
| diarrhea, BM suppresion and progressive hand foot syndrome (erythema -> desquamation, pain and sensitivity to touch of palsm and soles |
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Term
| Capecitabine - drug interaction |
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Definition
| Significant w/ coumarin derived anticoagulants |
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Term
6 mercaptopurine
1. general action - more specifically?
2. needs activation? |
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Definition
1. purine antagonist (guanine) - can also be incorporated into DNA resulting in DNA strand breaks
2. yes via HPGRT (hypoxanthine guanine phosphoribosyl transferase) becomes 6 mercapto purine ribose phosphate |
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Term
6 mercaptopurine
1. best use |
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Definition
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Term
6 mercaptopurine
1. administration (oral, IV?), IV 1/2 life?
2. metabolism?
3. toxicity |
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Definition
1. oral bioavailaibilty 5-37%, IV half life 50 minutes
2. liver
3. BM depression, N&V, diarrhea |
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Term
| What happens w/ 6 mercaptopurine in people w/ mutations in TPMT - how common |
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Definition
| People w/ homozygous mutations for thiopurine methyltransferease have rapid accumulation in BM --> infections; 1 in 300 caucasions. Should not be taken, will kill them. |
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Term
| What is azathioprine, what is use? |
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Definition
| Converted to 6 mercaptopurine - used for ulcerative colitis, crohn's disease and RA |
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Term
| Cytarabine - shares what unique characteristic w/ methotrexate |
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Definition
| can be given intrathecally |
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Term
Cytarabine (cytosine arabinoside)
1. activation?
2. mechanism? what does it look like? |
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Definition
1. Phosphorylated to aracytidine triphosphate
2. looks like cytosine w/ one hydroxyl stereochemically different - inhibits DNA chain elongation and repair, also incorporated in DNA and RNA |
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Term
Cytarabine 1. administration 2. deactivation? quick slow where? |
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Definition
1. IV 2. rapid via cytadine deamine in GI and liver |
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Term
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Definition
| bone marrow depression, N&V diarrhea, anaphylaxis, oral ulcers, heaptic damage, fever, pulmonary edema and sudden respiratory distress w/ high doses |
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Term
Pyrimidine antimetabolites analogs 1. Thymine (3) 2. cytosine (1) |
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Definition
1. 5 FU, capecitadine, methotrexate 2. cytarabine |
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Term
1.Purine antimetabolite - 1 2. Guanine 2 |
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Definition
1. methotrexate 2. 6 mercaptopurine, azathioprine |
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Term
GENERAL (one sentence mechanism) antimetabolites |
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Definition
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Term
GENERAL (one sentence mechanism)
Methotrexate |
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Definition
| inhibits dihydrofolate reductase and ultimately dTMP synthesis |
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Term
GENERAL (one sentence mechanism)
5Fu |
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Definition
| inhibits thymidylate synthase and dTMP synthesis |
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Term
| GENERAL (one sentence mechanism) 6 mercaptopurine |
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Definition
| inhibits purine (guanine) synthesis & causes DNA strand breaks |
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Term
GENERAL (one sentence mechanism)
Cytarabine |
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Definition
| inhibits DNA chin elongation |
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Term
Doxorubicin
1. What category of drug?
2. mechanism? |
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Definition
1. chemo antibiotic
2. inhibits resealing of nicked DNA by DNA topisomerase II |
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Term
Doxorubicin
1. administration- distribution
2. metabolism |
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Definition
1. IV - distributes widely but not to CNS
2. liver, excreted in bile |
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Term
Doxorubicin
1. toxicitiy
2. mech of toxicity |
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Definition
1. main - BM suppression, of note also acute cardiac (transient ECG changes, and ventricular arrythmia need baseline ECG), chronic cardaic toxicity (congestive heart failure, unresponsive to digitalis, related too total cumulative dose - there is a LIFETIME maximum dose), as well as N&V, red urine (not hematuria), anaphylactoid RXN, diarrhea, fever, severe local tissue damage w/ extravasation
2. mech of toxicity - free radical damage, doxorubicine + Fe2+ generate hydroxyl radical from peroxie |
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Term
Epirubicin -IV in 21 day cycles
1. Analog?
2. toxic- what is 1 risk?
4. more or less toxic then analog
3. other risk factor is a drug |
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Definition
1. doxirubicin analog-action same
2. delayed metabolism w/ liver failure can lead to severe Bone marrow depression
3. cimetidine - (h2 antagonist for ulcers) can increase serum concentration by 50%
4. requires higher lifetime dose for chronic cardiac toxicity then doxirubicin |
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Term
Dactinomycin
1. mechanism 3 places it works |
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Definition
1. intercalates into DNA btw adjacente G-C base pairs
2. innhibits transcription by RNA polymerase
3. interfreres w/ topisomerase II leaving nicked DNA |
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Term
Dactinomycin
1. pharm - Iv oral? metabolism? tissue distribution?
2. toxicity |
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Definition
1. IV - minimal metabolism, excreted in bile and urine, 1/2 life 36 hours, does not cross BBB
2. N&V, hepatic tox, diarrhea, severe local tissue damage and necrosis w/ extravasation, anaphylaxis, oral ulceration, BM depression alopecia |
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Term
Bleomycin
1.mixture of?
2. 5 step mech |
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Definition
1. 2 copper chealing glycopeptide antiobiotics
2. dna bleomcin Fe2+ complex forms, this complex intereacts w/ oxygen, forms superoxide and hydroxyl free radicals, radicals produce DNA fragmentation, DNA repair mechanisms determine cytotoxicity |
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Term
Bleomycin pharm
1. how given
2. where localized
3. metabolize/excretion
4. side effects (what about breakdown enzyme and SE sites?) |
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Definition
1. IV, subQ, IM
2. localizes to skin, lung lymphatic and peritoneum tissue
3. excreted unchanged in urine, degraded by hydrolase
4. MILD BM tox, N&V, fever, anaphylaxis phlebitis- degraded by hydrolase which is low in lungs (pulmonary fibrosis 5-10%) and skin (ulcers, hyperpigmentation) |
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Term
1 sentence review of antibiotics
Doxorubicin |
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Definition
| topisomerase II nicked DNA, cardiac toxicity free radical damage as side effect |
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Term
GENERAL (one sentence mechanism) antibiotics
Epirubicin |
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Definition
| topisomerase II nicked DNA, cardiac tox, cimetidine free radical damage as side effect |
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Term
GENERAL (one sentence mechanism) antibiotics
Dactinomycin |
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Definition
| topoisomerase II nicked DNA, inhibit RNA polymerase, intercalation btw DNA G-C pairs |
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Term
GENERAL (one sentence mechanism) antibiotics
Bleomycin |
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Definition
| Free radical induced DNA fragmentation, pulmonary toxicity, localizes to skin lung lymphatic and peritoneum tissue |
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Term
Chemo drugs from plants
Vincristine and vinblastine - periwinkle
Paclitaxel - pacific yew tree
Etoposide - semisynthetic derivative from mayapple |
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Definition
| well, it might be on the test? |
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Term
Vincristine and Vinblastine
1. mechanism (where stop?) |
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Definition
| 1. bind to tubulin and inhibit polymerization of MTs, major component of mitotic spindle --> metaphase arrest --> apoptosis |
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Term
Vincristine Vinblastine pharmacology
1. admin
2. metabolism
3. half life of 2 comparatively? |
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Definition
1. IV
2. liver --> bile
3. 1/2 life vincristine > vinblastine |
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Term
Toxicity:
1.Vincristine
2. Vinblastine |
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Definition
1. MILD BM tox, inhibits axonal transprot causing sensory and motor neuropathy (cumulative dose
2. less neurotoxic, more BM toxic |
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Term
| What 2 drugs cause mild bone marrow suppression |
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Definition
| Vincristine and bleomycin |
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Term
Paclitaxel, Docetacel
1. mechanism
2. admin? metabolism?
3. tox? |
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Definition
stabilizes, or freezes polymerized MTs, blocks mitosis metaphase arrest
2. IV, liver
3. BM, peripheral sensory neurophaty, hypersensitivty RXN |
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Term
| Drugs that cause peripheral neurotoxicity (4) (CVPE) |
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Definition
| cisplatin, vincristine, paclitxel, etoposide |
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Term
| Drug that causes central neurotoxicity |
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Definition
|
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Term
|
Definition
| 1. DNA breaks by blocking resealing action of topisomerase II ( remains bound to free end of DNA) |
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Term
etoposide
1. administration oral v. IV
2. 1/2 life
3. breakdown |
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Definition
1. oral - 50% bioavailability, IV over 30-60 min to avoid hypotension
2. 8 hours
3. 40% excreted unchanged in urine |
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Term
etoposide
1. toxicity (special one) |
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Definition
| 1. sensory neuropathy- all the other bad stuff too |
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Term
Tretinoin (all trans retinoic acid (ATRA))
1. what category of drug?
2. mechanism |
|
Definition
1. differentiating agent
2. binds retinoid X receptor-RARalpha dimer and displaces a repressor of differentiation |
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Term
Tretinoin (ATRA)
1. tx for? special
2. tox? |
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Definition
1. acute promyelocytic leukemia- high rate complete remission as a single agent- APL is T(15:17) combo of retinoic acid receptor and PML
2. retinoic acid syndrome like vitamin A toxicity - fever, dyspnea, weigh gain, pulmonary infiltrates, pleural or pericardial effusions |
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Term
Arsenic trioxide - put in differentiation group
1. mechanism (4) |
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Definition
| 1. uncouples mito ox-phos, genereates free radicals, causes differentiation of APL celsl by breaking down PML/RAR alpha dimer, inhibits angiogenesis |
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Term
Arsenic trioxide
1. use
2. tox |
|
Definition
1. relapsed acute promyelocytic leukemia
2. atrial or ventricular arrythmais - lengthening of QT interval on 40% pts |
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Term
|
Definition
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Term
|
Definition
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|
Term
|
Definition
|
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Term
1. Exemestane, letrozole, anastrozole are aromatase inhibitors meaning?
2. use?
toxicity : musculoskeletal pain, headache, joint pain, fatigue, difficulty breathing |
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Definition
1. block conversation of androgen to estrogen
2. breast cancer |
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Term
Tamoxifen
1. action
2. important metabolism? (oral)
3. use |
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Definition
1. competitive partial agonist inhibitor of estrogen and binds estrogen receptors - not as strongly as estrogen so much ablate estradiol synthesis
2. yes it's a prodrug, liver, to more and less active metabolites
3. estrogen sensitive BC |
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Term
Tamoxifen
1. tox - what weird thing
2. side effect- what weird thing |
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Definition
1. N&V, hot flashes (menopause!), transient increase in bone or tumor pain when cancer has metastasized
2. acts as an agnost of the receptor in some tissue resulting in reduced serum cholesterol and maintenance of bone density |
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Term
Imatinib- ORAL
1. mechanism,
2. use |
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Definition
AKA Gleevac
1. inhibit of constitutively active BCr-ABl tyrosine kinase blocks ATP binding site, also inhibits PDGF receptor
2. CML, and chronic myelomonocytic leukemia |
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Term
Trastubzumab (AKA)
1. mechanism (made of?)
2. target |
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Definition
AKA - Herceptin
1. monoconal antibody against HER2 receptor tyrosine kinase that can be overcexpressed on breast cancer cells
2. it says metastatic breast cancer |
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Term
Trastubuzumab- IV
1. what 2 tests before use
2. tox |
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Definition
1. FISH to determine number of HER2 copies in genome of cancer, and immunohistochemistry of tumor to detect HER2 on surface
2. weakening of heart muscle, congestive heart failure; neutropenia, anemia |
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Term
Cetuximab
1. mechanism
2. target |
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Definition
1. monoclonal antibody to EGFR (AKA HER1) (receptor tyrosine kinase), blocks binding of EGF and transforming growth factor alpha- inhibits cell growth and induces apoptosis
2. metastatic colorectal cancer (60-75 express EGFR), non small cell lung, pancreatic, breast |
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Term
Cetuximab - IV
1. toxicity? |
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Definition
| 1. servere infusion reaction as rapid onset of airway obstruction and hypotension |
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Term
Bevacizumab _IV
1. action
2. target cancer
3. SE (IV dose) |
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Definition
AKA avastin
1. monoclonal antibody against vascular engothelial growth factor, inhibits angiogenesis (NOT AGAINST RECEPTOR)
2. metastatic colorectal cancer
3. hypertension, pulmonary hemorrahge, GI performation, proteinuria, CHF |
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Term
agent/antibody - target - tumor type
1. tamoxifen
2. imatinib
3. trastubzumab |
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Definition
1. (not a antibody), estradiol, breast
2. not an antibody - BCr-ABL tyrosine kinase and PDGF - CML and chronic myelomonocytic leukemia (CMML)
3. Ab against Her 2- metastic breast |
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Term
| antibody target tumor type 1. cetuximab 2. bevacizumab |
|
Definition
| 1. HER1 - metastatic colorectal, non-small cell lung, pancreatic, breast 2. VEGF metastatic colorectal |
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Term
antibody target tumor type
1. gemtuzumab |
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Definition
|
|
Term
antibody target tumor type
1. rituximab |
|
Definition
| 1. CD20 - b cell lymphoma, CLL |
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Term
antibody target tumor type
alemtuzumab |
|
Definition
| CD52, B cell chyronic lymphocytic leukemia, T cell lymphoma |
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Term
antibody target tumor type
Daclizumab |
|
Definition
| CD25 T cell mycosis fungoides |
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Term
Monoclonal ab toxicities
1. trastubzumab
2. cetuximab
3. bevacisumab |
|
Definition
1. cardiomopathy; infusion
2. SEVERE infusion related
3. HTN, proteinuria, CHF |
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|
Term
| Mechlorethamine - how used -toxicity |
|
Definition
| made->immediately given IV, most reactive nitrogen mustard |
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Term
Cyclophosphamide
1. class
2. side effect
3. anything special? |
|
Definition
1. nitrogen mustard
2. cardiotoxic, hemorrhagic cystitits - give MESNA b/c of acrolein
3. prodrg, broken down by p450 to active phosphoramide, and bladder burn causing acrolide |
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Term
ifosfamide
1. group?
2. administration?
3. side effect
4. anything special? |
|
Definition
1. nitrogen mustard, greater activity then cyclophosphamide
2. IV
3. neurotoxicity, nephrotoxicity, hemorrhagic cystitis, cardio tox w/ high dose
4. prodrug, p450 converts, must Give w/ MESNA |
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Term
|
Definition
Nitrosurea - inhibits DNA, RNA and protein synthesis (alkylating agnet, unique class b/c carbamoylates lysine residues, IV infusion, CROSSES BBB
-profound delayed and cumulative BM depression, pulmonary fibrosis, renal damage, reversible liver damage and leukemia |
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|
Term
|
Definition
Nitrosurea - inhibits DNA, RNA and protein synthesis (alkylating agnet, unique class b/c carbamoylates lysine residues, taken Orally (difference w/ carmustine), CROSSES BBB
-profound delayed and cumulative BM depression, pulmonary fibrosis, renal damage, reversible |
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Term
|
Definition
| Alkyl sulfonate, plasma 1/2 life 2-3 hrs,taken orally; bone marrow depression, pulmonary infiltrates and fibrosis |
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Term
|
Definition
| Platinum complex, crosslinks w/ GG base pair (bends DNA), given IV, most bound to plasma protein, concentrates in liver, kidney, intestine and ovary, excreted in urine - SE - PERIPHERAL NEUROPATHY (paresthesia loss of proprioception), RENAL (reduced w/ hydration),, HSN rxn (rash), bone marrow depression |
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Term
Alkylating agents 1-2 word tox (all GI and bone marrow suppression
Cyclophosphamide 2 |
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Definition
|
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Term
Alkylating agents 1-2 word tox (all GI and bone marrow suppression
Ifosfamide 2 |
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Definition
|
|
Term
Alkylating agents 1-2 word tox (all GI and bone marrow suppression
Carmustine 2 |
|
Definition
|
|
Term
Alkylating agents 1-2 word tox (all GI and bone marrow suppression
Busulfan 1 |
|
Definition
|
|
Term
Alkylating agents 1-2 word tox (all GI and bone marrow suppression
Cisplatin 2 |
|
Definition
| Peripheral neuropathy, renal |
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