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168 Cards in this Set
- Front
- Back
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mechloretheamine properties
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Vesicant
bifunctional non-specific NO LONGER USED |
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cyclophosphamide properties
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not as reactive, easier to use than mechlorethamine
ACTIVATED by cytc P450 |
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ifosfamide properties
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similar to cyclophosphamide but
more bladder toxicity less myelosuppresssive |
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ethylenimines MOA, properties
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cross-linking guanine residues
selectively myosuppressive/used in chronic granulocytic leukemia |
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nitrosurea alkylating agent - nitrosurea CCNU, BCNU properties/MOA
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lipid soluble
activated by alkylating DNA cross links carbamoylated proteins (adds urea moiety) |
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BCNU, CCNU, methyl CCNU are used for
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CNS tumors like astrocytomas
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alkylation of DNA by nitrogen mustards MOA
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cross links guanine to guanine
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BCNU, CCNU, methyl CCNU are used for
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CNS tumors like astrocytomas
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mech of resistance for alkylating agents
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decreased ability to take up drug
increased ability to delete crosslinked DNA S |
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alkylation of DNA by nitrogen mustards MOA
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cross links guanine to guanine
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SE of cyclophosphamide
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nause vomiting metabolized by liver before active
hemorrhagic cystitis |
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mech of resistance for alkylating agents
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decreased ability to take up drug
increased ability to delete crosslinked DNA S |
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BCNU
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CNS, bone marrow suppression
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SE of cyclophosphamide
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nause vomiting metabolized by liver before active
hemorrhagic cystitis |
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BCNU
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CNS, bone marrow suppression
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BCNU, CCNU, methyl CCNU are used for
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CNS tumors like astrocytomas
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alkylation of DNA by nitrogen mustards MOA
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cross links guanine to guanine
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mech of resistance for alkylating agents
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decreased ability to take up drug
increased ability to delete crosslinked DNA S |
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SE of cyclophosphamide
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nause vomiting metabolized by liver before active
hemorrhagic cystitis |
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BCNU
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CNS, bone marrow suppression
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BCNU, CCNU, methyl CCNU are used for
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CNS tumors like astrocytomas
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alkylation of DNA by nitrogen mustards MOA
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cross links guanine to guanine
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mech of resistance for alkylating agents
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decreased ability to take up drug
increased ability to delete crosslinked DNA S |
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SE of cyclophosphamide
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nause vomiting metabolized by liver before active
hemorrhagic cystitis |
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BCNU
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CNS, bone marrow suppression
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BCNU, CCNU, methyl CCNU are used for
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CNS tumors like astrocytomas
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alkylation of DNA by nitrogen mustards MOA
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cross links guanine to guanine
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mech of resistance for alkylating agents
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decreased ability to take up drug
increased ability to delete crosslinked DNA S |
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SE of cyclophosphamide
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nause vomiting metabolized by liver before active
hemorrhagic cystitis |
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BCNU
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CNS, bone marrow suppression
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therapeutic uses: alkylating agents
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various leukemias
hodgkin's disease very general-not all inclusive |
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procarbazine treats
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hodgkin's
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dacarbazine treat
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hodgkins
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atretamine
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resistant ovarian carcinoma
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Cis-diammine dichloro platinum II MOA Cisplatin
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cross link with DNA all stages: guanine-N7
used in combo regimen 2nd generation |
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Cisplatin (1st) generation
Carboplatin 2nd generation Oxaliplatin 3rd generation are used for |
*testicular, ovarian, bladder, endometrium, advanced colorectal (oxaliplatin)
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cisplatin toxicities
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nephrotoxicity:
flush kidney w/ fluid Cl- ion lessen toxicity ototoxicity peripheral neuropathy (at high doses) |
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carboplatin toxicties
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less kidney damage
less ototoxicity thrombocytopenia |
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oxaliplatin
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less resistance
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6-MP how is it activated?
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activated by nucleotide pyrophorylase
to become 6-meraptopurine ribose-P |
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MOA of 6-MP
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blocks IMP--> AMP or GMP
pseudofeedback inhibition of PPRP + glutamine inhibit interconversion reactions among intermediate compounds |
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SE of 6-MP and used for
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hematological
leukopenia thrombocytopenia anemia, GI, anorexia, hepatic (jaundice) anti-leukemic chemotherapy (children) |
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pyrimidine analogues
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5-GU
cytosine arabinoside |
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purine antagonists
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fludarabine phosphate
cladribine |
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fludarabine phosphate is used for
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non-hodgkin's lymphoma
chronic lymphocytic leukemia (CLL) |
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cladarabine uses
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hair cell leukrmie
non-hodgkin's lymphoma CLL |
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purine antagonists like fludarabine phosphate and cladribine MOA
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decrease DNA synthesis and repair
incorporated into DNA DNA strand breaks adenosine derivatives tri-phosphates |
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activation of 5-FU
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5-FU activated by nucleoside phosphorylase to for 5-FU riboside
5-FU riboside convered by nucleoside kinase to active drug |
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activation pathways for 5-FU
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1. inhibit RNA synthese
2. inhibit DNA synthesis 3. inhibit dTMP formation by blocking thymidylate synthase |
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activation of cytosine arabinoside
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by kinase 3x to for ARA-CTP
inhibits DNA polymerase incorporated into DNA/RNA |
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MOA of cytosine arabinoside
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1-incorporated into DNA
2-slow chain elongation (low doses) 3-inhibits DNA polymerase (high doses) 4-incorporated into DNA (affects RNA/DNA metabolism) |
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MOA of vincristine and vinblastine (mitosis)
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block polymerization
continuous disassembly |
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toxicities of vinka alkaloids
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vinblastine-bone marrow depression
vincristine-neurological |
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therapeutic place for vinblastine
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solid tumors
testicular lymphosarcoma hodgkin's disease choriocarcinoma breast |
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therapeutic place for vincristine
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induce remission in acute leukemia, pediatric solid tumors
combination therapy! |
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vinorelbine MOA
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decreases mitosis
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vinorelbine use
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non-small cell lung cancer and breast cancer
myelosuppression w/ neutropenia |
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epi podo phyllo toxins
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block S-G2 phase (cell cycle)
affect topoisomerase II |
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uses of epi podo phyllo toxins
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etoposide: breast cancer, kaposi's sarcoma, testicular tumors
teniposide: all children |
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toxicities of epipodophyllotoxins
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*Leukopenia, *nausea
also cause alopecia, thrombocytopenia, hepatic damage, emetic, cathartic |
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camptothecins
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inhibit topoisomerase I:
topotecan: ovarian cancer, small cell lung cancer irinotecan: metastatic colorectal cancer |
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taxol and its derivatives
paclitaxel and doxetaxel are derived from |
yew trees
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taxol and derivatives MOA
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polymerization stabilized stable microtubules
disrupts mitosis |
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taxol Use
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ovarian, breast, lung cancers
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toxicities of taxol
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myelosuppression
peripheral neuropathies |
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anthracyclines (antibiotics produced by fungus/bacteria)
daunorubicin doxorubicin MOA |
1-intercalate DNA
2-inhibit topoisomerase II 3-affect ion transport membranes 4-*Form free radical-reactive |
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toxicities of daunorubicin and doxorubicin
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**Bone marrow depression
***cardiac toxicity (free radicals): dose dependent causing acute tachycardia, arrythmias, and chronically congestive heart failure alopecia "radiation recall reaction" erythema and desquamation of skin after radiation |
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therapeutic uses of anthracyclines
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daunorubicin: acute leukemia
doxorubicin: adriamycin for lung, breast bladder carcinmas, lymphomas, TESTICULAR, ovary stomach liver lung |
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dactinomycin MOA
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inhibits DNA synthesis
intercalaes w/ DNA |
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toxicities
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general toxicities
bone marrow depression |
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anthracyclines (antibiotics produced by fungus/bacteria)
daunorubicin doxorubicin MOA |
1-intercalate DNA
2-inhibit topoisomerase II 3-affect ion transport membranes 4-*Form free radical-reactive |
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toxicities of daunorubicin and doxorubicin
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**Bone marrow depression
***cardiac toxicity (free radicals): dose dependent causing acute tachycardia, arrythmias, and chronically congestive heart failure alopecia "radiation recall reaction" erythema and desquamation of skin after radiation |
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therapeutic uses of anthracyclines
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daunorubicin: acute leukemia
doxorubicin: adriamycin for lung, breast bladder carcinmas, lymphomas, TESTICULAR, ovary stomach liver lung |
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dactinomycin MOA
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inhibits DNA synthesis
intercalaes w/ DNA |
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toxicities
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general toxicities
bone marrow depression |
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therapeutic uses of dactinomycin
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*wilm's tumor (kidney)
*rabdomyosarcoma *Ewing's sarcoma (bone) PEDIATRIC TUMORS |
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bleomycin MOA
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binds DNA to form free radicals (inhibit DNA synthesis)
inhibits mitosis |
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Toxicities of bleomycin
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pulmonary fibrosis (elderly pts)
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bleomycin uses
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skin cancer
testicular tumors lymphomas |
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toxicities of bleomycin
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pulmonary fibrosis (elderly pts)
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mitomycin MOA
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activated by cytc P450
alkylating agent *temporary beneficial effects** |
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toxicities of mitomycin
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myelosuppression
renala |
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angiogenesis inhibitors -name
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nexavar
sutent |
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MOA of angiogenesis inhibitor
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tyrosine kinase inhibitors
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mitomycin MOA
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activated by cytc P450
alkylating agent *temporary beneficial effects** |
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toxicities of angiogenesis inhibitors
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palmar and plantar syndrome
rash |
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toxicities of mitomycin
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myelosuppression
renala |
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angiogenesis inhibitors -name
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nexavar
sutent |
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MOA of angiogenesis inhibitor
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tyrosine kinase inhibitors
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toxicities of angiogenesis inhibitors
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palmar and plantar syndrome
rash |
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Cetuximab MOA
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monoclonal antibody against EGR
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Gefitinib/erlotinib MOA
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inhibitors of tyrosine kinase
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bevacizumab = avastin
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monoclonal antibody targets vascular endothelial GF-A
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predisone MOA
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inhibits RNA and protein synthesis
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toxicities of predisone
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fluid disturbances, hyperglycemia, peptic ulcers, infection, psychiatric problems, skeletal atrophy
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uses of prednisone
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all children
COP/MOPP |
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use of progesterone use
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palliative tx of metastatic endometrial carcinoma
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toxicities of progesterone
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abnormal menstrual bleeding
amenorrhea fetal masculinization and feminization |
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sex hormones
estrogens and androgens USES |
tx tumors of prostate and mammary gland
normal function of gland depends on testosterone and estrogen |
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hormones USES
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prostatic carcinoma: surgery, orchiectomy (vs estrogen therapy which is no longer used)
leuprolide, goserlin (pharm castration) anti-androgen flutamide inhibit androgen binding |
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flutamide is used for
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prostatic carcinoma
nonsteroidal anti-androgen |
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flutamide toxicities
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Hot flashes**
loss of libido ** impotence ** mild nausea and diarrhea |
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estramustine MOA
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metaphase arrest
binds to microtubule proteins inhibit microtubule assembly and disassembly |
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uses of estramustine
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prostatic carcinoma
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toxicities of estramustine
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breast tenderness
gynecomastia fluid retention mild nausea thrombophlebitis |
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leuprolide MOA
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pharmacological castration
pituitary stops releasing gonadotropin *estrogen/testosterone production decreases |
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use of leuprolide
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estrogen, testosterone production decreases
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toxicities of leuprolide
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hot flashes
some cardiac effects |
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tamoxifen MOA
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selective estrogen receptor modulators (SERMs)
anti-estrogen binds to estrogen receptors concentrated in estrogen target tissues |
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toxicities of tamoxifen
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hot flashes
vaginal dryness discharge nausea exacerbation of bone pain *WELL-TOLERATED |
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Tamoxifen
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increased risk of endometrial cancer
increased venous thrombosis |
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breast cancer-aminoglutethimide MOA
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1-blocks conversion of cholesterol to pregenenlone
2-inhibits extra-adrenal synthesis of estrone and estradiol 3-inhibits aromatse*** prevents conversion of adrogens to estrogens |
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aminoglutethimide uses
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metastastic breast cancer
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leuprolide MOA
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pharmacological castration
pituitary stops releasing gonadotropin *estrogen/testosterone production decreases |
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aromatase inhibitors MOA
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block adrenal androgens to estrone and estradiol
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use of leuprolide
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estrogen, testosterone production decreases
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use of aromatase inhibitors
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advanced breast cancer
if do not respond to tamoxifen on post-menopausal women |
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toxicities of leuprolide
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hot flashes
some cardiac effects |
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tamoxifen MOA
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selective estrogen receptor modulators (SERMs)
anti-estrogen binds to estrogen receptors concentrated in estrogen target tissues |
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toxicities of tamoxifen
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hot flashes
vaginal dryness discharge nausea exacerbation of bone pain *WELL-TOLERATED |
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Tamoxifen
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increased risk of endometrial cancer
increased venous thrombosis |
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breast cancer-aminoglutethimide MOA
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1-blocks conversion of cholesterol to pregenenlone
2-inhibits extra-adrenal synthesis of estrone and estradiol 3-inhibits aromatse*** prevents conversion of adrogens to estrogens |
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aminoglutethimide uses
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metastastic breast cancer
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aromatase inhibitors MOA
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block adrenal androgens to estrone and estradiol
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use of aromatase inhibitors
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advanced breast cancer
if do not respond to tamoxifen on post-menopausal women |
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MOA of herceptin
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monoclonal antibody
binds receptor Her2/neu inhibits tumor cell growth |
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toxicities of herceptin
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congestive heart failure
leukopenia infections increase |
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hydroxyurea
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inhibits ribonucleoside diphosphate reductase --> ribose --> Deoxyribose
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uses of hydroxyurea
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chronic granylocytic leukemia
polycythemia vera melanoma solid tumors synchronizes tumor cells in G1 phase bone marrow depression |
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procarbazine -what? use?
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prodrug methylating agent
hodgkin's disease myelosuppression |
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MOA of herceptin
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monoclonal antibody
binds receptor Her2/neu inhibits tumor cell growth |
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L-asparaginase MOA and Use
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degrade L-asparagine
some tumors like acute lymphocytic leukemia require asparagine from plasma tox: nausea, liver dysfunction, hypersensitivity |
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toxicities of herceptin
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congestive heart failure
leukopenia infections increase |
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Gold AU 198 uses
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pleural effusions
ascites secondary to cancer |
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hydroxyurea
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inhibits ribonucleoside diphosphate reductase --> ribose --> Deoxyribose
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secondary malignancies to cancer tx
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acute myelogenous leukemia
due to: alkylating agents procarbazine etoposide radiation early as 2-4 yrs peaks 5-9 yrs |
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uses of hydroxyurea
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chronic granylocytic leukemia
polycythemia vera melanoma solid tumors synchronizes tumor cells in G1 phase bone marrow depression |
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procarbazine -what? use?
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prodrug methylating agent
hodgkin's disease myelosuppression |
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L-asparaginase MOA and Use
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degrade L-asparagine
some tumors like acute lymphocytic leukemia require asparagine from plasma tox: nausea, liver dysfunction, hypersensitivity |
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Gold AU 198 uses
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pleural effusions
ascites secondary to cancer |
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secondary malignancies to cancer tx
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acute myelogenous leukemia
due to: alkylating agents procarbazine etoposide radiation early as 2-4 yrs peaks 5-9 yrs |
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pt on glucocorticoids must change their diet how?
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high in protein and potassium
low sodium and overall calories monitor serum calcium, glucose and blood pressure antacids: increase in acid, may need proton pump inhibitor |
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what are some non-endocrine uses of GCs?
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allergic reactions: static asthmaticus,exfoliative dermatitis
-cortisol infusion, used in conjunction with other appropriate agents short-acting agents may be used in self-limiting sever allergies that fail to respond to conventional therapy intranasal therapy: first choice approach for rhinitis skin diseases: topical application for acute dermatoses eye diseases: topical GCs frequently used for eye inflammation may increase intraocular pressure --> glaucoma |
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steroid ring modifications impair GC specificity and change pharmacokinetics
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1,2 double bone prolongs half-life
substitute C16 removes mineralocorticoid activity halide at C9 prolongs half-life |
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what does the structure-activity relationship tell us?
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changes in molecular structure alter relative potency, duration of actions, selectivity but CANNOT ELIMINATE specific GC effects
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short--> medium acting
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24-36 hours
cortisol, cortisone, corticosterone, methylprednisolone, prednisolone |
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intermediate acting
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48 hrs
triamcinolone |
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long-acting
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> 48 hrs
dexamethasone betamethason |
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GC for inhalation
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beclomethason
fluticasone flunisolide |
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topical
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amcinonide
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ophthalmic
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medrysone
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intranasal
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nometasone
beclomethasone budnesonide |
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injectable
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methyprednisolone
hydrocortisone |
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about 95% of oral and injected GCs plasma bound
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albumin and corticosteroid binding globulin
plasma half-life of cortisol about 80 min pharmacodynamic half-life much longer |
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biotransformation mainly in liver:
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C3 conjugates, reduced 4,5 double bond:
renal excretion, negligible unaltered cortisol |
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cortisone is a prodrug -->
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cortisol
*cortisone is nt used as an anti-inflammatory due to higher mineralocorticoid action |
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prednisone --> prednisolone by what enzyme?
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11beta-hydroxysteroid DH
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what is the drug of choice for systemic inflammatory effects?
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prednisolone
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fludrocortisone acetate
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250x more potent as mineralocorticoid than cortisol
only orally active mineralocorticoid not used as GC due to salt retention |
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physiological effects
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increased peripheral tissue catabolism
chronic pharm doses can cause: muscle wasting, weakness, osteoporosis, thinning of skin, INHIBITION OF GROWTH IN CHILDREN |
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reversible effects on CNS
|
Addison's disease: do not make their own GC: apathy, depression, irritability, frank psychosis
GC induced--> euphoria, insomnia restlessness, increase motor activity changes in EEG can become anxious depressed manic sometimes psychotics |
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GC withdrawal syndome
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fever, myalgia, arthraglias, malaise, pseudotumor cerebri
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MAJOR adverse effect
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Cushings-too much GC
which is dose-dependent |
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metabolic disorders due to GC
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inhibition of protein synthesis
enhanced catabolism negaitve nitrogen balance decrease wound healing ulcerations altered fat distribution |
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effects on electrolytes and viramins
|
hypokalemic alkalosis
adema, muscular weakness, abnormal EKG, decrease calcium gtu absorption, calciuria (decreased renal tubular reabsorption, inhibit carotene conversion to vit A osteoporosis |
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CV effects
|
increased CO
decreased TPR opposite may occur in addrenal insufficiency hypertension may occur in secondary to mineralocorticoid actions congestic heart disease |
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susceptible to infections
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due to immune suppression
infections often masked by theray esp true for pts w/ immunocompromised host defense mech not usually a prob for asthmatics (inhaled) |
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absolute contraindication for prednisolone
|
measles and varicells
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