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Amitha's Pharm test 3


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What reaction do beta-lactam agents inhibit? This prevents synthesis of?
Inhibit the transpeptidation reation or cross-linking that is important for formation of cell walls.
Which mechanism of resistance to beta-lactam agents is the most problematic clinically?
Bacterial production of a different penicillin binding protein with less affinity for antimicrobial agents but still effective for its bacterial function
How are most beta-lactam agents eliminated?
Most are eliminated renally except for a few penicillins excreted by the liver and biliary system.
What is the MIC or minimum inhibitory concentration
MIC is the minimum amount of drug at which the organism stops reproducing.
What is the most common adverse effect of beta lactam agents?
Skin rash. Begins on the trunk and can spread if the drug is continued.
Allergies are mediated by Ig? and drug rashes are mediated by Ig?
Allergies- IgE
Drug Rash- IgM
Are allergies dose or duration related adverse effects to drugs?
How is Penicillin G administered?
Administered IV as a sodium or potassium salt.
How is phenoxymethylpenicillin or penicillin V administered?
What microbes are naturaly penicillins (i.e. penicillin G) effective against? (3)
group A beta-hemolytic stroptococci, meningococci, normal oral flora (both aerobic and anaerobic)
What types of organsims are extended spectrum penicillins effective against?
gram negative bacilli
Two families of drugs in the extended spectrum penicillins are
Aminopenicillins (i.e. amoxicillin and ampicillin) and ureidopenicillins (i.e. piperacillin)
Are natural penicillins safe in pregnancy?
Cephapirin cefazolin and cephalexin are what generation cephalasporins?
Earlier generations of cephalosporins are effective against gram __________ bacteria while with each increasing generation there is more coverage of gram ________ bacteria
1. positive
2. negative
What is the usual mechanism behind multi drug resistance to chemotherapeutic agents?
efflux of drugs by membrane pumps
What are 3 classes of cell specific chemo drugs
DNA synthesis inhibitors, topoisomerase II inhibitors, mitotic spindle poisons
And are 3 classes of cell cycle nonspecific inhibitors
DNA crosslinkers DNA intercalators, and topoisomerase I inhibitors
What is the main difference between the cell cycle specific inhibitors and cell cycle nonspecific inhibitors
cell cycle specific inhibitors tend to be used for rapidly proliferating tumors such as leukemia.
What is the dose limiting toxicity of alkylating agents?
Bone marrow suppression
What is the mechansim of action of alkylating agents?
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.
What are 6 general classes of alkylating agents?
Nitrogen mustards, nitrosureas, ethylenimines, alkyl sulfonates, traizines, others (including platinums)
Cisplatin, carboplatin, and oxaliplatin are all in what class of alkylating agents?
What is the dose limiting toxicity of cisplatin? Which drug has a simlar spectrum of activity without the nephrotoxicity?
Nephrotoxicity. Carboplatin has a similar spectrum of activity.
Oxaliplatin is approved as 2nd line treatment for which type of cancer?
metastatic colon cancer
Which types of cancer are platinums commonly used for?
squamous cell carcinomas, esophageal, lung, head, and neck cancers
What are the mechanisms of resistance to platinums?
decreased intracellular accumulation, glutathione deactivation, and nucleotide excision repair pathway.
What are the 3 major groups of antimetabolite chemotherapeutic agents?
folic acid antagonists, pyrimidine antagonists, purine antagonists
What are 3 folic acid antagonists?
methotrexate, ralitrexed, and premetrexed
What types of cancer is methotrexate useful for?
Burkitt's lymphoma, lymphoblastic leukemia, breast cancer, head and nec cancer, ovarian cancer, cervical carcinomas, trophoblastic choreocarcinoma
Which folic acid antagonist is approved for use against colon cancer?
What is premetrexed approved for use against?
mesothelioma and lung cancer
What is the mechanism of action of folic acid antagonists? Which one has an additional mechanism?
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
What is the major toxicity of folic acid antagonists?
myelosuppression and oral and GI ulceration
what are the mechanisms of resistane of folic acid antogonists
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.
What type of chemotherapeutic agents are 5-fluorouracil, capecitabine, cytarabine, gemcitabine, and clorfarabine?
Pyrimidine antogonist.
Which cancers is 5-fluorouracil effective against?
colon cancer and other solid cancers
What is the dose limiting toxicity of pyrimidine antagonists
myelosuppression and oral and GI toxicity.
What is the mechanism of inhibition of DNA synthesis of 5-fluorouracil? Where does it cause cell cycle arrest?
It is a thymidine synthetase inhibitor. Causes arrest in the G1 phase.
What is the mechanism of resistance of cancers to 5-fluorouracil?
increased thymidine synthetase.
What type of chemotherapeutic agents are mercaptopurine, thioguanin, cladribine, and fludarabine?
purine antagonists
Which 2 purine antagonists are the major ones used in leukemias ans lymphomas?
mercaptopurine and thioguanine
What is the dose limiting toxicity of purine antagonists?
What is the mechanism of resistance to purine antagonists?
decreased metabolic activation as well as alkaline phosphatase activation
What type of chemotherapeutic agents are vincristine vinorelbine, and vinblastine?
vinca alkaloids (a type of plant alkaloid)
Which vinca alkaloid does not have myelosuppression? What is its dose limiting toxicity?
vincristine. Neurotoxicity
What types of cancers are vinca alkaloids used for?
used for hematological malignancies, solid tumors, and pediatric cancers.
What is the mechanism of action of vinca alkaloids? Cell cycle arrest occurs in which phase?
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
which type of cancer is irenotecan used for?
Colorectal cancer
Which types of cancer is topotecan used for?
ovarian and small cell lung caner
What is the dose limiting toxicity with topetecan?
hemotological toxicity
What is the dose limiting toxicity with irenotecan?
diarrhea and myelosuppression
What are 2 camptothecins?
irenotecan and topetecan
What is the mechanism of action of camptothecins? Which phase of the cell cycle is the cell arrested in?
topoisomerase inhibition and DNA damage by single strand breaks. S phase cell cycle arrest
What is the mechanism of resistance to camptothecins?
efflux mechanisms involving the MRP transporter protein
What are 2 drugs that are epipodophyllotoxins?
etoposide and teniposide
Which cancers is etoposide effective against?
testicular, lung, gastric, and hematological
Which cancer is teniposide effective against?
lymphoplastic leukemia in children
What is the dose limiting toxicity of epipodophyllotoxins?
nausea, vomiting, myelosuppression, and alopecia
What is the mechanism of action of epipodophyllotoxins? Cell cycle arrest occurs in which phase
topoisomerase inhibition, DNA damage by causing single strand breaks. cycle arrest in either S or G2 phase.
What are 2 drugs that are taxanes
paclitaxel and docetaxel
Which types of cancers are taxanes effective against?
solid tumors, particularly breast and ovarian
What is the mechanism of action of taxanes?
stabilizes microtubule assembly and inhibits mitosis, blocks cell division in S phase
What is the mechanism of resistance to taxanes?
p-glycoprotein mediated efflux and tubulin mutations
Which drug pump is prevalent in the colon and is responsible for the resistance of colon cancer to taxanes?
which anthracyclines are used against acute leukemias?
daunamycin and idarubicin
Which anthracyclines are used against solid tumors?
doxorubicin and epirubicin
What are the general dose limiting toxicities of anthracyclines?
meylosuppression and mucositis.
Which anthracycline has cardiotoxicity
What is the mechanism of action of anthracyclines?
Very pleotropic- includes topoisomeraes II inhibition, DNA intercalation, alterations in membrane fluiditiy and ion transport, and generation of free radicals.
What type of cancers is mitoxantrone used against?
prostate cancer when the cells have become refractory to antiandrogens and require cytotoxic treatments, also non-hodgkin's lymphoma, breast cancer, and myeloid leukemia
What is the dose limiting toxicity of mitoxantrone?
What is the mechanism of action of mitoxantrone?
DNA strand breakage and inhibition of DNA and RNA synthesis.
What type of cancer is dactinomycin used for?
pediatric solid tumors or choriocarcinoma
What are the dose limiting toxicities of dactinomycin?
myelosuppression, anorexia, nausea, and vomiting
What is the mechanism of action of dactinomycin?
binds doubl stranded DNA and intercalates between guanine and cytosine to inhibit transcription (blocks RNA polymerase), causes single strand DNA breaks
What type of cancer can mitomycin be used against?
hypoxia tumors
What is the mechanism of action of mitomycin?
it is a prodrug that undergoes reductive metabolism under hyposic conditions and can target necrotic tumors. It inhibits the DNA by crosslinking.
What are the dose limiting toxicities of mitomycin
thrombocytopenia, anemia, and renal failure
What are the mechanisms of resistance to mitomycin?
deficient metabolic activation, p-glycoprotein efflux, and intracellular deactivation of the metabolite
Which type of cancers can bleomycin be used against?
squamous cell carcinoma of the cervix, lymphoma, and testicular tumors
What is the mechanism of action of bleomycin?
DNA copper and iron binding peptide that causes DNA strand breaks
What is the toxicity of bleomycin?
pulmonary toxicity
Which enzyme can be used in combination with vincristine and prednisone against pediatric leukemia?
What is the mechanism of action of aspariginase?
catalysis of deamination of asparagine to form aspartic acid thus depriving neoplastic cells of asparagine
What is a dose limiting toxicity of asparaginase?
allergic reaction
Which types of cancers can interferon alpha be used against?
leukemia, sarcoma, and squamous cell carcinoma
What is the mechanism of action of interferon alpha in its use against cancer?
stimulate tumor cytomacrophages which have direct toxicity to tumor cells.
Which types of cancers can interleukin-2 be uased against?
malignant melanomas, squamous cell carcinomas
What is the mechanism of action of interleukin 2 against cancer cells?
increase activity of natural killer cells
What is the mechanism of action of hydroxyureas in the treatment of cancer?
Inhibit ribonucleotide diphosphate reductase and block DNA synthesis
What type of cancer is tretinoin used for?
promyeloid leukemia
What is the mechanism of action of tretinoin?
Binds a specific nuclear receptor protein to induce differentiation of tumor cells
What are the side effects of tretinoin?
skin dryness and elevation of liver enzymes
What heavy metal can be used to treat certain types of leukemia?
Arsenic trioxide
What type of cancer is thalidomide used against?
certain types of leukemia
What type of cancer can estramustine be used for?
prostate cancer
What is a toxicity of thalidomide?
It is teratogenic
What is the mechanism of action of thalidomide?
Inhibits angiogenesis-target is unclear
What steroid hormone can be used to treat leukemia and lymphoma?
What are the uses of progestins in anti cancer treatment?
Endometrial cancer and stimulates appetite in cachectic patients
What are the indications for use of anti-estrogens?
estrogen receptor positive breast cancer
What drug is a selective estrogen receptor modulator?
What drug is a selective estrogen receptor down regulator?
What types of drugs are anastrozole and letrozole?
aromatase inhibitors
What are the side effects of selective estrogen receptor modulators and estrogen receptor down regulators (SERD)
cardiovascular toxicity, increased risk of endometrial cancer, nausea and vomiting, hot flashes. SERDs have less toxicity
What is a side effect of aromatase inhibitors?
bone loss
What 2 classes of drugs suppress serum testosterone and can be used in treatment of androgen dependent prostate cancer?
Androgen receptor antagonists and GnRH agonits
What are side effects of anti-androgen therapy?
hot flashes, impotence, and gynecomastia
What is neoadjuvant therapy with regards to cancer therapy?
treatment administered prior to primary therapy (i.e. radiation done before surgery)
What do the terms complete response, partial response, measurable response, stable disease, and progressive disease mean with regards to cancer therapy?
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
What do the stages mean with regards to cancer diagnosis?
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
Chemotherapy kills cancer cells following ______ order kinetics
What is Imatinib (gleevec) used to treat?
Chronic myelogenous leukemia
What is the mechanism of action of imatinib (gleevec)?
Binds to the bcr-abl protein
How is celecoxib used in cancer therapy?
Helps induce apoptosis by inhibiting COX 2 which is effective when given with other chemotherapy agents
Which tissues with high growth fractions are adversely effected with chemotherapeutic agents?
bone marrow, GI tract mucosal membranes, hair follicles, and skin
What is the newer oral drug prodrug that is metabolized into active flurouracil?
5% of people have a deficiency of what enzyme that produces life threatening toxicity to normal doses of 5-Fluorouracil
Dihydropyrimidine dehydrgenase (DPD).
High levels of DPD in a tumor means that which chemotherapeutic agent will be less effective?
Echinacea combined with what class of drugs can become toxic?
Immunosuppressants (corticosteroids)
What two herbal supplements should a patient taking NSAIDS avoid?
garlic and ginseng
St. John's wort should be avoided by a patient taking what class of drug?
MAO inhibitors
Evening primrose should be avoided by a patient taking what class of drugs?
What is St. John's wort used to treat?
What 4 botanicals should be avoided?
Yohibe, comfrey, chaparral, and ephedra
What substance found in broccoli has been shown to have anti-cancer properties?
What substance found in garlic has anti-oxidant, anti-inflammatory properties?
What substance found in St. John's Wort activates a CYP450 enzyme to increase metabolism of cyclosporin and theophylline?
What are 2 drugs that are polyene antifungals?
nystatin and amphotericin B
What is the mechanism of action of Amphotericin B?
acts against ergosterol to create a pore. The organism is leaky, osmotically fragile, and dies
Is Amphotericin fungicidal or fungistatic?
How is amphotericin administered?
What toxicity limits the use of Amphotericin?
What is amphotericin used to treat?
common agents such as candida, aspergillus, coccidiodides, histoplasma, blastomyces, cryptococcus, and zygomycetes
What are risk factors for nephrotoxicity with aphotericin use? How would one prevent this?
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.
What toxicities are related to Amphotericin infusion?
Most common- fever
Rare-myalgias, bronchospasms, anaphylaxis
What are the advantages of lipid formulations of amphotericin B?
Less nephrotoxicity- L-AmB has only 15% of the nephrotoxicity but maintains infusion toxicity
Which lipid formulations of AmB can target the prain and can thus be used for cryptococcal meningitis?
AmB-D and L-AmB
How is ketoconazole administered/
topically or orally
What is the mechanism of action of azoles?
Inhibits synthesis of ergosterols from lanosterol by inhibiting 14-alpha demethylase
Are azoles fungistatic or fungicidal
What is the most important treatment for systemic and mucosal candida infections and cryptococcal meningitis worldwide?
Which is the only azole available for once daily dosing?
What is the first line therapy for aspergillosis?
Which is the broadest spectrum oral antifungal agent?
What is the treatment for zygomycosis?
An induction dose of AmB to get the infection under control and then switch poconazole
Which 2 azoles have CNS availability
voriconazole and fluconazole
Which azole must be taken with a high fat meal?
What toxicities are common to all azoles?
hepatic toxicity rash, and vomiting
Which azole has unique visual abnormalities such as photopsia an dhallucinations?
Which is the only azole that is renally excreted?
What class of drugs are anidulafungin caspofungin, an dmicafungin?
echinocandin antifungals
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
Which organisms are echinocandins active against?
Aspergillus and candida
Are echinocandins orally available?
How are echinocandins metabolized?
hepatically metabolized
What is the mechanism of action of flucytosine
Goes through the cell wall and is metabolized into 5-FU and inhibits DNA synthesis
Why is flucytosine not used very often as monotherapy (except for UTIs)
Induced resistance rapidly.
What is the spectrum of activity of flucytosine?
cryptococcus and candida
What are the toxicities of flucytosine?
bone marrow suppression, anemia, GI ulcers
What is the dosing of echinocandins?
once a day or once every other day
What is the dosing of flucytosine
4 times a day-short half life
How is flucytosine metabolized?
renally excreted
Which antifungal drugs exhibit time dependent killing?
flucytosine and triazoles
Which antifungals exhibit concentration dependent killing?
AmB and Echinocandins
What is the traditional gold standard anti-fungal therapy
What species are not susceptible to AmB?
Aspergillus terreums, Fusarium, candida glabrata
What is the first line treatment for blastomycosis?
What is the first line treatment for pulmonary infection with Histoplasmosis?
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?
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?
Trimethoprine is commonly used in combination with which drugs
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
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?
What is the drug of choice for chlamydia infections?
Can tetracyclines be used in pregnancy?
What is the druge of choice for brucellosis and tularemia?
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?
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?
What drug is useful for treatment of diarrhea or enteritis caused by campylobacter jejuni?
What drug is used to eliminate the carrier state of corynebacerium diphtheriae?
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?
Absorption of erythromycin and azithromycin is increased or decreased with food?
absorption of clarithromycin is increased or decreased with food?
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?
What 2 drugs can be used to treat C. difficile coliis?
metronidazole or vancomycin

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