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210 Cards in this Set
- Front
- Back
What reaction do beta-lactam agents inhibit? This prevents synthesis of?
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Inhibit the transpeptidation reation or cross-linking that is important for formation of cell walls.
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Which mechanism of resistance to beta-lactam agents is the most problematic clinically?
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Bacterial production of a different penicillin binding protein with less affinity for antimicrobial agents but still effective for its bacterial function
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How are most beta-lactam agents eliminated?
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Most are eliminated renally except for a few penicillins excreted by the liver and biliary system.
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What is the MIC or minimum inhibitory concentration
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MIC is the minimum amount of drug at which the organism stops reproducing.
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What is the most common adverse effect of beta lactam agents?
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Skin rash. Begins on the trunk and can spread if the drug is continued.
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Allergies are mediated by Ig? and drug rashes are mediated by Ig?
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Allergies- IgE
Drug Rash- IgM |
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Are allergies dose or duration related adverse effects to drugs?
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No
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How is Penicillin G administered?
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Administered IV as a sodium or potassium salt.
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How is phenoxymethylpenicillin or penicillin V administered?
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Orally
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What microbes are naturaly penicillins (i.e. penicillin G) effective against? (3)
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group A beta-hemolytic stroptococci, meningococci, normal oral flora (both aerobic and anaerobic)
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What types of organsims are extended spectrum penicillins effective against?
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gram negative bacilli
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Two families of drugs in the extended spectrum penicillins are
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Aminopenicillins (i.e. amoxicillin and ampicillin) and ureidopenicillins (i.e. piperacillin)
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Are natural penicillins safe in pregnancy?
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yes
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Cephapirin cefazolin and cephalexin are what generation cephalasporins?
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first
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Earlier generations of cephalosporins are effective against gram __________ bacteria while with each increasing generation there is more coverage of gram ________ bacteria
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1. positive
2. negative |
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What is the usual mechanism behind multi drug resistance to chemotherapeutic agents?
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efflux of drugs by membrane pumps
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What are 3 classes of cell specific chemo drugs
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DNA synthesis inhibitors, topoisomerase II inhibitors, mitotic spindle poisons
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And are 3 classes of cell cycle nonspecific inhibitors
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DNA crosslinkers DNA intercalators, and topoisomerase I inhibitors
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What is the main difference between the cell cycle specific inhibitors and cell cycle nonspecific inhibitors
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cell cycle specific inhibitors tend to be used for rapidly proliferating tumors such as leukemia.
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What is the dose limiting toxicity of alkylating agents?
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Bone marrow suppression
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What is the mechansim of action of alkylating agents?
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transfer of alkyl groups to a nucleophile on proteins or DNA hwhich causes a bifunctional crosslink of DNA molecules to prevent separation of the strands and causes cell cycle arrest.
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What are 6 general classes of alkylating agents?
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Nitrogen mustards, nitrosureas, ethylenimines, alkyl sulfonates, traizines, others (including platinums)
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Cisplatin, carboplatin, and oxaliplatin are all in what class of alkylating agents?
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Platinums
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What is the dose limiting toxicity of cisplatin? Which drug has a simlar spectrum of activity without the nephrotoxicity?
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Nephrotoxicity. Carboplatin has a similar spectrum of activity.
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Oxaliplatin is approved as 2nd line treatment for which type of cancer?
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metastatic colon cancer
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Which types of cancer are platinums commonly used for?
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squamous cell carcinomas, esophageal, lung, head, and neck cancers
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What are the mechanisms of resistance to platinums?
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decreased intracellular accumulation, glutathione deactivation, and nucleotide excision repair pathway.
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What are the 3 major groups of antimetabolite chemotherapeutic agents?
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folic acid antagonists, pyrimidine antagonists, purine antagonists
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What are 3 folic acid antagonists?
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methotrexate, ralitrexed, and premetrexed
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What types of cancer is methotrexate useful for?
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Burkitt's lymphoma, lymphoblastic leukemia, breast cancer, head and nec cancer, ovarian cancer, cervical carcinomas, trophoblastic choreocarcinoma
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Which folic acid antagonist is approved for use against colon cancer?
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ralitrexed
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What is premetrexed approved for use against?
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mesothelioma and lung cancer
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What is the mechanism of action of folic acid antagonists? Which one has an additional mechanism?
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Inhibit folic acid that binds the catalytic domain of DHFR which generages essential cofactors for DNA, RNA, and protein synthesis. Premetrexed also inhibits thymidine synthesis
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What is the major toxicity of folic acid antagonists?
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myelosuppression and oral and GI ulceration
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what are the mechanisms of resistane of folic acid antogonists
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decreased uptake and decreased ability to synthesize polyglutamate (which is needed to keep the druge in the cell), reduced affinity of DHFR within the cell, increased efflux by MRP.
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What type of chemotherapeutic agents are 5-fluorouracil, capecitabine, cytarabine, gemcitabine, and clorfarabine?
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Pyrimidine antogonist.
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Which cancers is 5-fluorouracil effective against?
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colon cancer and other solid cancers
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What is the dose limiting toxicity of pyrimidine antagonists
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myelosuppression and oral and GI toxicity.
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What is the mechanism of inhibition of DNA synthesis of 5-fluorouracil? Where does it cause cell cycle arrest?
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It is a thymidine synthetase inhibitor. Causes arrest in the G1 phase.
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What is the mechanism of resistance of cancers to 5-fluorouracil?
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increased thymidine synthetase.
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What type of chemotherapeutic agents are mercaptopurine, thioguanin, cladribine, and fludarabine?
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purine antagonists
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Which 2 purine antagonists are the major ones used in leukemias ans lymphomas?
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mercaptopurine and thioguanine
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What is the dose limiting toxicity of purine antagonists?
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myelosuppression
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What is the mechanism of resistance to purine antagonists?
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decreased metabolic activation as well as alkaline phosphatase activation
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What type of chemotherapeutic agents are vincristine vinorelbine, and vinblastine?
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vinca alkaloids (a type of plant alkaloid)
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Which vinca alkaloid does not have myelosuppression? What is its dose limiting toxicity?
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vincristine. Neurotoxicity
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What types of cancers are vinca alkaloids used for?
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used for hematological malignancies, solid tumors, and pediatric cancers.
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What is the mechanism of action of vinca alkaloids? Cell cycle arrest occurs in which phase?
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inhibit microtubule polymerization and disrupt the mitotic spindle in rapidly dividing cells thus interfereing with the ability of the chromosomes to separate. M phase cycl arrest
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which type of cancer is irenotecan used for?
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Colorectal cancer
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Which types of cancer is topotecan used for?
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ovarian and small cell lung caner
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What is the dose limiting toxicity with topetecan?
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hemotological toxicity
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What is the dose limiting toxicity with irenotecan?
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diarrhea and myelosuppression
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What are 2 camptothecins?
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irenotecan and topetecan
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What is the mechanism of action of camptothecins? Which phase of the cell cycle is the cell arrested in?
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topoisomerase inhibition and DNA damage by single strand breaks. S phase cell cycle arrest
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What is the mechanism of resistance to camptothecins?
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efflux mechanisms involving the MRP transporter protein
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What are 2 drugs that are epipodophyllotoxins?
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etoposide and teniposide
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Which cancers is etoposide effective against?
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testicular, lung, gastric, and hematological
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Which cancer is teniposide effective against?
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lymphoplastic leukemia in children
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What is the dose limiting toxicity of epipodophyllotoxins?
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nausea, vomiting, myelosuppression, and alopecia
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What is the mechanism of action of epipodophyllotoxins? Cell cycle arrest occurs in which phase
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topoisomerase inhibition, DNA damage by causing single strand breaks. cycle arrest in either S or G2 phase.
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What are 2 drugs that are taxanes
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paclitaxel and docetaxel
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Which types of cancers are taxanes effective against?
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solid tumors, particularly breast and ovarian
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What is the mechanism of action of taxanes?
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stabilizes microtubule assembly and inhibits mitosis, blocks cell division in S phase
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What is the mechanism of resistance to taxanes?
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p-glycoprotein mediated efflux and tubulin mutations
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Which drug pump is prevalent in the colon and is responsible for the resistance of colon cancer to taxanes?
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p-glycoproteins
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which anthracyclines are used against acute leukemias?
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daunamycin and idarubicin
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Which anthracyclines are used against solid tumors?
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doxorubicin and epirubicin
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What are the general dose limiting toxicities of anthracyclines?
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meylosuppression and mucositis.
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Which anthracycline has cardiotoxicity
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doxorubicin
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What is the mechanism of action of anthracyclines?
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Very pleotropic- includes topoisomeraes II inhibition, DNA intercalation, alterations in membrane fluiditiy and ion transport, and generation of free radicals.
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What type of cancers is mitoxantrone used against?
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prostate cancer when the cells have become refractory to antiandrogens and require cytotoxic treatments, also non-hodgkin's lymphoma, breast cancer, and myeloid leukemia
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What is the dose limiting toxicity of mitoxantrone?
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myelosuppression
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What is the mechanism of action of mitoxantrone?
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DNA strand breakage and inhibition of DNA and RNA synthesis.
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What type of cancer is dactinomycin used for?
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pediatric solid tumors or choriocarcinoma
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What are the dose limiting toxicities of dactinomycin?
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myelosuppression, anorexia, nausea, and vomiting
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What is the mechanism of action of dactinomycin?
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binds doubl stranded DNA and intercalates between guanine and cytosine to inhibit transcription (blocks RNA polymerase), causes single strand DNA breaks
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What type of cancer can mitomycin be used against?
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hypoxia tumors
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What is the mechanism of action of mitomycin?
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it is a prodrug that undergoes reductive metabolism under hyposic conditions and can target necrotic tumors. It inhibits the DNA by crosslinking.
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What are the dose limiting toxicities of mitomycin
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thrombocytopenia, anemia, and renal failure
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What are the mechanisms of resistance to mitomycin?
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deficient metabolic activation, p-glycoprotein efflux, and intracellular deactivation of the metabolite
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Which type of cancers can bleomycin be used against?
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squamous cell carcinoma of the cervix, lymphoma, and testicular tumors
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What is the mechanism of action of bleomycin?
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DNA copper and iron binding peptide that causes DNA strand breaks
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What is the toxicity of bleomycin?
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pulmonary toxicity
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Which enzyme can be used in combination with vincristine and prednisone against pediatric leukemia?
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aspariginase
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What is the mechanism of action of aspariginase?
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catalysis of deamination of asparagine to form aspartic acid thus depriving neoplastic cells of asparagine
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What is a dose limiting toxicity of asparaginase?
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allergic reaction
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Which types of cancers can interferon alpha be used against?
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leukemia, sarcoma, and squamous cell carcinoma
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What is the mechanism of action of interferon alpha in its use against cancer?
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stimulate tumor cytomacrophages which have direct toxicity to tumor cells.
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Which types of cancers can interleukin-2 be uased against?
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malignant melanomas, squamous cell carcinomas
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What is the mechanism of action of interleukin 2 against cancer cells?
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increase activity of natural killer cells
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What is the mechanism of action of hydroxyureas in the treatment of cancer?
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Inhibit ribonucleotide diphosphate reductase and block DNA synthesis
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What type of cancer is tretinoin used for?
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promyeloid leukemia
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What is the mechanism of action of tretinoin?
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Binds a specific nuclear receptor protein to induce differentiation of tumor cells
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What are the side effects of tretinoin?
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skin dryness and elevation of liver enzymes
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What heavy metal can be used to treat certain types of leukemia?
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Arsenic trioxide
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What type of cancer is thalidomide used against?
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certain types of leukemia
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What type of cancer can estramustine be used for?
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prostate cancer
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What is a toxicity of thalidomide?
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It is teratogenic
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What is the mechanism of action of thalidomide?
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Inhibits angiogenesis-target is unclear
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What steroid hormone can be used to treat leukemia and lymphoma?
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prednisone
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What are the uses of progestins in anti cancer treatment?
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Endometrial cancer and stimulates appetite in cachectic patients
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What are the indications for use of anti-estrogens?
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estrogen receptor positive breast cancer
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What drug is a selective estrogen receptor modulator?
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Tamoxifem
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What drug is a selective estrogen receptor down regulator?
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Fulvestrant
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What types of drugs are anastrozole and letrozole?
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aromatase inhibitors
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What are the side effects of selective estrogen receptor modulators and estrogen receptor down regulators (SERD)
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cardiovascular toxicity, increased risk of endometrial cancer, nausea and vomiting, hot flashes. SERDs have less toxicity
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What is a side effect of aromatase inhibitors?
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bone loss
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What 2 classes of drugs suppress serum testosterone and can be used in treatment of androgen dependent prostate cancer?
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Androgen receptor antagonists and GnRH agonits
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What are side effects of anti-androgen therapy?
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hot flashes, impotence, and gynecomastia
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What is neoadjuvant therapy with regards to cancer therapy?
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treatment administered prior to primary therapy (i.e. radiation done before surgery)
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What do the terms complete response, partial response, measurable response, stable disease, and progressive disease mean with regards to cancer therapy?
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CR-elimination of symptoms for one month (does not mean cured!)
PR-greater than 50% reduction MR- less than 50% reduction Stable disease-no change progressive disease-increase in tumor burden |
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What do the stages mean with regards to cancer diagnosis?
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Stage I-localized, high probabilty of surgical or radiation cure
II/III-more dangerous local spread, requires the tripod approach of surgical, chemotherapy, and radiation therapy IV-distant metastases. chemotheraphy must be used |
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Chemotherapy kills cancer cells following ______ order kinetics
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first
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What is Imatinib (gleevec) used to treat?
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Chronic myelogenous leukemia
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What is the mechanism of action of imatinib (gleevec)?
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Binds to the bcr-abl protein
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How is celecoxib used in cancer therapy?
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Helps induce apoptosis by inhibiting COX 2 which is effective when given with other chemotherapy agents
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Which tissues with high growth fractions are adversely effected with chemotherapeutic agents?
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bone marrow, GI tract mucosal membranes, hair follicles, and skin
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What is the newer oral drug prodrug that is metabolized into active flurouracil?
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Capecitabine
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5% of people have a deficiency of what enzyme that produces life threatening toxicity to normal doses of 5-Fluorouracil
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Dihydropyrimidine dehydrgenase (DPD).
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High levels of DPD in a tumor means that which chemotherapeutic agent will be less effective?
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5-fluorouracil
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Echinacea combined with what class of drugs can become toxic?
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Immunosuppressants (corticosteroids)
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What two herbal supplements should a patient taking NSAIDS avoid?
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garlic and ginseng
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St. John's wort should be avoided by a patient taking what class of drug?
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MAO inhibitors
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Evening primrose should be avoided by a patient taking what class of drugs?
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anticonvulsants
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What is St. John's wort used to treat?
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depression
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What 4 botanicals should be avoided?
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Yohibe, comfrey, chaparral, and ephedra
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What substance found in broccoli has been shown to have anti-cancer properties?
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Indole-3-carbinol
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What substance found in garlic has anti-oxidant, anti-inflammatory properties?
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Allicin
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What substance found in St. John's Wort activates a CYP450 enzyme to increase metabolism of cyclosporin and theophylline?
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hypericin
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What are 2 drugs that are polyene antifungals?
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nystatin and amphotericin B
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What is the mechanism of action of Amphotericin B?
|
acts against ergosterol to create a pore. The organism is leaky, osmotically fragile, and dies
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Is Amphotericin fungicidal or fungistatic?
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Fungicidal
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How is amphotericin administered?
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IV
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What toxicity limits the use of Amphotericin?
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Nephrotixicity
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What is amphotericin used to treat?
|
common agents such as candida, aspergillus, coccidiodides, histoplasma, blastomyces, cryptococcus, and zygomycetes
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What are risk factors for nephrotoxicity with aphotericin use? How would one prevent this?
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use of other nephrotoxins, agents that make pt. volume depleted underlying renal disease. Prevent and manage nephrotoxicity by giving volume expanding drugs and avoiding diuretics.
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What toxicities are related to Amphotericin infusion?
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Most common- fever
Rare-myalgias, bronchospasms, anaphylaxis |
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What are the advantages of lipid formulations of amphotericin B?
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Less nephrotoxicity- L-AmB has only 15% of the nephrotoxicity but maintains infusion toxicity
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Which lipid formulations of AmB can target the prain and can thus be used for cryptococcal meningitis?
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AmB-D and L-AmB
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How is ketoconazole administered/
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topically or orally
|
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What is the mechanism of action of azoles?
|
Inhibits synthesis of ergosterols from lanosterol by inhibiting 14-alpha demethylase
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Are azoles fungistatic or fungicidal
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fungistatic
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What is the most important treatment for systemic and mucosal candida infections and cryptococcal meningitis worldwide?
|
Fluconazole
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Which is the only azole available for once daily dosing?
|
Fluconazole
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What is the first line therapy for aspergillosis?
|
Voriconazole
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Which is the broadest spectrum oral antifungal agent?
|
Posaconazole
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What is the treatment for zygomycosis?
|
An induction dose of AmB to get the infection under control and then switch poconazole
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Which 2 azoles have CNS availability
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voriconazole and fluconazole
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Which azole must be taken with a high fat meal?
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posaconazole
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What toxicities are common to all azoles?
|
hepatic toxicity rash, and vomiting
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Which azole has unique visual abnormalities such as photopsia an dhallucinations?
|
voriconazole
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Which is the only azole that is renally excreted?
|
fluconazole
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What class of drugs are anidulafungin caspofungin, an dmicafungin?
|
echinocandin antifungals
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what is the mechanism of action of echinocandins?
|
inhibit 1,3 beta-D glucan synthesis. Without a cell wall a fungi becomes osmotically fragile and dies
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Which organisms are echinocandins active against?
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Aspergillus and candida
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Are echinocandins orally available?
|
No
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How are echinocandins metabolized?
|
hepatically metabolized
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What is the mechanism of action of flucytosine
|
Goes through the cell wall and is metabolized into 5-FU and inhibits DNA synthesis
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Why is flucytosine not used very often as monotherapy (except for UTIs)
|
Induced resistance rapidly.
|
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What is the spectrum of activity of flucytosine?
|
cryptococcus and candida
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What are the toxicities of flucytosine?
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bone marrow suppression, anemia, GI ulcers
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What is the dosing of echinocandins?
|
once a day or once every other day
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What is the dosing of flucytosine
|
4 times a day-short half life
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How is flucytosine metabolized?
|
renally excreted
|
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Which antifungal drugs exhibit time dependent killing?
|
flucytosine and triazoles
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Which antifungals exhibit concentration dependent killing?
|
AmB and Echinocandins
|
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What is the traditional gold standard anti-fungal therapy
|
AmB
|
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What species are not susceptible to AmB?
|
Aspergillus terreums, Fusarium, candida glabrata
|
|
What is the first line treatment for blastomycosis?
|
Itraconazole
|
|
What is the first line treatment for pulmonary infection with Histoplasmosis?
|
Itraconazole
|
|
What drugs can be used to treat lyphocutaneous sporotrichosis
|
supersaturated potassium iodide, itraconazole, fuconazole/terbinfine
|
|
What is the mechanism of action of sulfonamides?
|
Competitive inhibitor of para-aminobenzoic acid which prevents PABA from being incorporated into folic acid-safe for humans because we unlike bacteria can use preformed folate
|
|
What do sulfonamides still have good activity against?
|
Toxoplasmosis, Nocardia asteroides, topical use for conjunctivitis w/ Chlamydia trachomatis, topical use for burn wounds
|
|
How are sulfa drugs administered?
|
topically, orally, IV
|
|
Which one of the following drugs can penetrate the CNS; sulfonamides, tetracyclines, macrolides, and clindamycin?
|
sulfonamides
|
|
What combination fo drugs can treat plasmodium falciparum?
|
sulfadoxine with pyrimethamine
|
|
What are common toxicities of sulfonamides?
|
Gi distress, hypersensitivity, Stevens Johnson syndrom, vasculitis, crystal induced nephropathy, hemolytic syndromes, bone marrow suppression
|
|
Should sulfa drugs be used in pregnancy?
|
No
|
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Trimethoprine is commonly used in combination with which drugs
|
Sulfonamides
|
|
How are sulfonamides metabolized?
|
excreted renally
|
|
Which enteric pathogens is the combination of Trimethoprin/sulfamethoxalone used for?
|
shigellosis, salmonella, and enteropathogenic E. Coli
|
|
What is the drug of choice to treat CA-MRSA
|
Trimethoprin/sulfamethoxalone (bactrim)
|
|
What drug is used both in prophylaxis and treatment for pneumocyctis carnii pneumonia
|
Trimethoprin/sulfamethoxalone
|
|
What is the mechanism of action of tetracyclines?
|
bind to the 30s ribosome inhibiting access of tRNA to mRNA and inhibiting bacterial protein synthesis-bacteriostatic
|
|
What drug is used to treat tick borne pathogens?
|
doxycycline
|
|
What is the drug of choice for chlamydia infections?
|
doxycycline
|
|
Can tetracyclines be used in pregnancy?
|
No
|
|
What is the druge of choice for brucellosis and tularemia?
|
doxycycline
|
|
What fetal defects can tetracyclines cause?
|
defect in permanent teeth (turns them a greyish color) and possibly fetal bones
|
|
What toxicities can be caused by tetracyclines in general?
|
GI distress, locally corrosive, photosensitive skin reactions, acute fatty liver of pregnancy, candida superinfections, pseudomotor cerebrii
|
|
What is the only organism that is usually resistant to tigecycline?
|
Psudomonas aeruginosa
|
|
How is tigecycline administered?
|
IV
|
|
What are 3 macrolides?
|
erythromycin, clarithromycin, and azithromycin
|
|
What is the mechanism of action of macrolides?
|
bind to 50s ribosome and block the transpeptidation reaction. bacteriostatic
|
|
What is erythromycin active against?
|
gram positive cocci
|
|
Is dose adjustment necessary in renal failure for macrolides?
|
No
|
|
What drug is useful for treatment of diarrhea or enteritis caused by campylobacter jejuni?
|
erythromycin
|
|
What drug is used to eliminate the carrier state of corynebacerium diphtheriae?
|
erythromycin
|
|
Erythromycin causes activation of the receptors for which hormone? What systemic effect does this have?
|
motilin, hormone responsible for inducing peristalsis and thus causes nausea.
|
|
What is a specific side affect caused by demeclocycline that allows it to be used to treat SIADH?
|
nephrogenic diabetes insipidus
|
|
vertigo, ataxia, and vestibular dysfunction occur with which tetracycline?
|
minocycline
|
|
Absorption of erythromycin and azithromycin is increased or decreased with food?
|
decreased
|
|
absorption of clarithromycin is increased or decreased with food?
|
increased
|
|
What adverse affect caused by erythromycin can cause ventricular arrhythmias?
|
prolonged QT intervals
|
|
What adverse effect can occur when erythromycin is used in neonates?
|
syndrome of hypertrophic pyloric stenosis
|
|
Clarithromycin and azithromycin are effective against which 2 important respiratory tract pathogens?
|
H. influenzae and moraxella catarrhalis
|
|
What is the mechanism of action of clindamycin?
|
blocks the 50s ribosome blocking transpeptidation reaction blocking protein synthesis. bacteriostatic
|
|
What is clindamycin used primarily to treat?
|
anaerobic infections
|
|
what antibiotic causes antibiotic associated colitis caused by C. difficile?
|
clindamycin
|
|
What 2 drugs can be used to treat C. difficile coliis?
|
metronidazole or vancomycin
|