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246 Cards in this Set
- Front
- Back
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How do fluoroquinilones get their name? |
fluorine on position 6 |
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how do fluoroquinilones work on bacteria? |
2 MOA's In Gram (-) bacteria: inhibit the DNA gyrase that handles DNA supercoiling when the DNA is split for replication. Result: DNA can not properly replicate, cell lyses. In Gram (+) bacteria: inhibit the topoisomerase IV enzyme that is responsible for separating the two new genomes. Result: Replication inhibited, cell lyses |
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Are fluoroquinilones considered bacteriostatic or bactericidal? |
bactericidal |
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Can ciprovloxacin work on both Gram (-) and Gram (+) bacteria? |
No, only on Gram (-) |
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What two fluoroquinilones are used for pseudomonas aeruginosa? |
ciprofloxacin and levofloxacin |
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what are the characteristics of pseudomonas aeruginosa? |
Gram (-) aerobic skin infections, urinary tract infections |
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what is the commonality in naming of the fluoroquinilones |
afloxacin |
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which fluoroquinolones are useful in Gram (+) bacteria? |
Levofloxacin Moxifloxacin (no renal excretion) gemfloxacin |
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which fluoroquinolone is useful in anaerobic bacteria |
Moxifloxacin |
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What is the black box warning for fluoroquinolones? |
fluoroquinolone are associated with an increased risk of tendonitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 yo, in pts taking corticosteroids, and in pts with kidney, heart, or lung transplants. |
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what age does the black box warning of fluoroquinolone say increases risk of tendon rupture? |
age 60 |
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what increases the risk of tendon rupture with fluoroquinolone? |
age 60+ corticosteroid use pts with kidney, heart, or lung transplants |
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side effects of fluoroquinolones |
- nausea/diarrhea/dizziness/confusion - tendonitis/tendon rupture - QT prolongation - peripheral neuropathy |
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what are the major drug interactions of levoquin (levofluoroquinolone) |
warfarin multivalent cation products: antacids diabetic meds didanosine metal cations |
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what decreases absorption of FQs? |
antacids sucralfate magnesium calcium iron |
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why must you adjust the dose of FQs for pts in renal failure with the exception of moxifloxacin? |
Fas are metabolized in the kidney with the exception of moxifloxacin |
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what cardio precautions with FQs and why |
with pts with ventricular arrhythmias secondary to QT prolongation because they increase QT prolongation (and therefore more arrhythmias will result) |
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what antibiotic contains the only oral agent against pseudomonas? |
fluoroquinolones |
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Qwhy caution with FQs in pts with hepatic dysfunction |
FQs act on CYP450IA2 |
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routes of administration for FQs |
oral iv |
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can FQs be used in pregnancy? children? location? |
NO no exposure to children either via pregnancy, lactation, or direct |
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What sulfa med are we studying? |
Sulfamethoxazole/Trimethoprim (SMX-TMP) (Bactrim DS, Septra) |
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Is sulfamethoxazole trimethoprim oral or iv? |
oral |
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distribution of SMX-TMP |
good distribution to body tissues + CSF, plearual fluid, synovial fluid |
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elimination of SMX-TMP |
liver and kidneys |
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MOA of SMX-TMP |
folic acid synthesis inhibitors |
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what does sulfamethoxazole inhibit? |
dihydropteroic acid synthase |
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what does trimethoprim inhibit |
dihydrofolate reductase |
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most common side effects of sulfamethoxazole-trimethoprim |
Rash, fever, GI others: nausea, vomiting SJS Vasculitis Hemolytic anemia (G6PD) Thrombocytopenia |
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Clinical uses of SMX-TMP |
UTI PCP or P. jiroveci pneumonia Toxoplasmosis Gram +/- infections MRSA Sinusitis and otitis media in the past but now has drug resistance so not recommended |
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what is one of the few oral drugs that covers MRSA |
SMX-TMP |
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Describe SJS |
- Cell death causes the dermis and epidermis to separate Is a hypersensitivity reaction of skin and mucous membranes |
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How protein bound is SMX-TMP |
Up to 70% Displaces other drugs |
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SMX- TMP potentiates the effects of (4): |
- Warfarin - Phenytoin - Hypoglycemic agents - Methotrexate - Beta Blockers (resulting in bradycardia) |
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How are sulfonamides metabolized? |
liver |
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how are sulfonamides excreted? |
kidneys |
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what is the minimum age for use of sulfonamides in children? |
2 months |
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how/when to reduce sulfonamide dose |
by 50% if CrCl 15-30 do not use if CrCl <15 |
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can you use sulfonamides iv? |
no, oral only |
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What is the pregnancy category of sulfonamides? |
C |
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what is kernicterus |
bilirubin-induced brain dysfunction |
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why are sulfonamides contraindicated at term with infants? |
development of kernicterus in infants (bilirubin induced brain dysfunction) |
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which ABX induces kernicterus |
sulfonamides at term |
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What ABX is good for MRSA and skin infections? |
sulfonamides |
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What is the other name for nitrofurantion |
Macrobid |
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route of administration for nitrofurantion |
PO |
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route of administration for macrobid |
PO |
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Use of nitrofurantion |
uncomplicated UTIs |
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How fast is nitrofurantion absorbed |
rapidly |
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how long is macrobid in the serum |
30 minutes |
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how is macrobid cleared |
kidneys |
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where is nitrofurantion concentrated |
urine |
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What happens in the bladder with macrobid if Creatinine clearance is abnormal? |
GFR<60, inadequate drug levels in the bladder |
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explain why macrobid is contraindicated in patients with CrCl<60 |
if CrCl is low, the drug isn't clearing |
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what is the cut off for CrCl for use of macrobid |
<60 |
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MOA of macrobid |
poorly understood: thought to disrupt cell wall synthesis through inhibition of bacterial enzymes |
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Some emerging resistance to macrobid by these two bacteria |
enterobacter klebsiella |
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5 common bacteria that cause UTIs |
1 - E. Coli 2 - Citrobacter 3 - Staph saprophyticus 4 - Enterococcus faecalis 5 - Enterococcus faecium |
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most common side effect of macrobid (nitrofurantoin) |
nausea and vominting others: pulmonary reactions pulmonary infiltrates, pneumonitis, pulmonary fibrosis (long term), can get acute pulmonary reaction from this hepatic effects (rare) hepatitis, hepatic necrosis Peripheral neuropathy in long term use in pts with renal failure |
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acute pulmonary reactions to macrobid usually manifested by sudden: |
severe dyspnea chills chest pain fever cough |
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are pulmonary reactions to macrobid reversible |
yes, usually when drug is discontinued resolution often is dramatic |
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which antibiotic may have eosinophilia, pleural effusion, or pulmonary infiltration with consolidation? |
nitrofurantoin |
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what are the drug interactions of macrobid? |
No significant drug interactions |
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why is nitrofurantoin contraindicated at term? |
possibility of causing hemolytic anemia in the newborn due to immature erythrocytes |
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can nitrofurantoin be used in lactation? |
no |
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safety and efficacy of nitrofurantoin not established in children < ____years old |
12 |
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nitrofurantoin is contraindicated under this age |
<1 month |
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why avoid use of macrobid in older adults |
due to concerns for pulmonary toxicity |
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why avoid using nitrofurantoin for long term suppression of infection |
due to concerns for pulmonary toxicity |
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what is the other name for metronidazole |
flagyl |
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what is the other name for flagyl |
metronidazole |
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how is flagyl metabolized |
liver |
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what do you do with the dose of flagyl for pt w/ho liver failure |
adjust |
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is flagyl absorbed well PO? |
yes |
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half-life of flagyl |
6-9 hours |
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moa of flagyl |
causes dna strand breakage; inhibits protein synthesis |
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flagyl is good against what? |
Gm +/- anaerobes H. pylori Trichomonas vaginalis |
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what ABX is good for Trichomonas vaginalis |
Flagyl |
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Flagyl is the treatment of choice for (4): |
1 - anaerobic infections 2 - Bacterial vaginosis 3 - Trichomoniasis 4 - C. diff diarrhea |
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Formulations of flagyl |
oral iv topical (roseacea) intravaginal |
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Based on the black box warning for Flagyl (metronidazole) |
carcinogenic in rats and mice, do not use unless necessary |
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most common side effects of metronidazole |
nausea vomiting abdominal pain metallic tasete other: seizures (high doses) peripheral neuropathy (prolonged course) pancreatitis |
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Drug interactions of metrodinazole (flagyl) |
- enhances anticoagulation effect of warfarin - alcohol (flushing, palpitations, nausea, vomiting) - inhibitor of cyp34 so potential for many drug interactions - phenobarbital, phenytoin, rifampin these drugs increase the metabolism of metronidazole which decreases serum concentration and may lead to tx failure |
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which drugs increase metabolism of metronidazole |
phenobarbital( seizure), phenytoin (, rifampin (TB) |
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what does it mean if something is resistant to methicillin? |
it's resistant to something that most things are not resistant to |
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why is mycoplasma pneumonias resistant to penicillins and cephalosporins |
it does not have a cell wall |
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Describe the ribosomal subunits in bacteria vs humans |
80 S for humans/70s for bacteria humans 60s/40s bacteria 50s/30s |
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what are the two drug classes of protein synthesis inhibitors and the two other individual drugs |
1 - tetracyclines 2 - macrolides 3 - chloramphenicol 4 - clindamycin |
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how does streptomycin interfere with protein synthesis
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binds to 30s subunit and causes the mRNA codons to be read incorrectly |
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how does tetracycline interfere with protein synthesis |
binds to 30s ribosome and blocks attachment of tRNA to the mRNA complex |
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List 4 50s ribosomal inhibitors |
chloramphenicol erythromycin lincomycin clindamysin |
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chloramphicol moa |
protein synthesis inhibitor on 50s subunit binds at P site of 50s subunit and prevents the amino acids from being added to the polypeptide chain |
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erythromycin MOA |
protein synthesis inhibitor on 50s subunit stops the 50s subunit from moving down the mRNA, halting prolongation of polypeptide |
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lincomycin moa |
protein synthesis inhibitor on 50s subunit |
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chlindamycin moa |
protein synthesis inhibitor on 50s subunit |
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what is the most important tetracycline we will learn |
doxycycline |
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what are the four tetracyclines? |
tetracycline doxycycline minocycline demeclocycline |
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explain the moa of both ahminoglycosides and tetracyclines |
both act on 30s subunit to prevent protein synthesis ahminoglycosides make the subunit misread the mRNA tetracyclines prevent the tRNA from attaching to the mRNA |
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are tetracyclines narrow spectrum or broad |
broad active against many Gm +/- including anaerobes |
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do tetracylines work on anaerobes |
yes |
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if an organism is resistant to tetracycline, will they be resistant to doxycycline? |
yes |
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explain the resistance of tetracyclines |
efflux pumps formation of ribosomal protection proteins |
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explain dairy with tetracyclines |
tetracyclines are adequately but incompletely absorbed after oral ingestion, but if taken with dairy, absorption is reduced doxycycline is not affected by dairy as much |
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explain distribution of tetracyclines |
concentrate in liver, spleen, kidney, and skin bind to tissues undergong calcification (teeth/bones) levels are insufficient for therapeutic efficacy in CNS all tetracyclines cross the placental barrier and concentrate in fetal bones and dentition |
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is there gastric discomfort with tetracyclines?
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yes but it is controlled if taken with dairy |
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Common adverse effects of tetracyclines (4) |
1 - effects on calcified tissues 2 - gastric discomformt 3 - phototoxicity 4 - vestibular problems |
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severe sunburn can occur with use of which antibiotic |
tetracycline |
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which tetracycline causes dizziness, nausea, and vomiting |
minocycline |
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side effects of minocycline |
dizziness, nausea and vomiting (vestibular problems) |
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contraindications of tetracyclines (6) |
1 - pregnant women (crosses placenta and deposits in bones and teeth of fetus) 2 - breast feeding women 3 - children under age 8 4 - caution if impaired renal function (except doxycycline) 5 - caution if impaired liver function 6 - caution in SLE |
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routes of administration of tetracyclines |
oral iv im (not recommended because of pain and inflammation at injection site) |
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dose of doxycycline |
100mg BID |
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describe the relationship between doxycycline and s aureus |
s aureus has plasmids for resistance to doxycycline that are inducible |
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tetracyclines are useful in: |
sti atypical pneumonia exacerbations of chronic bronchitis acne vulgaris great alternative for sinusitis and acute prostatits |
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which antibiotic is good for acne |
doxycycline |
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what antibiotic causes teeth staining? and what is the age cut off for this |
tetracyclines under age 8 |
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can doxycycline be used against mycoplasma pneumoniae? |
yes, it does not have a cell wall so don't use beta lactams, but still has ribosomes so can use. this is an atypical pneumonia, and tetracyclines are good for those |
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which bacteria is responsible for a variety of STIs and for which doxycycline is a drug of choice? |
chlamydiae |
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which bacteria is associated with ticks? |
rickettsiae |
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which antibiotic is used with tick bites |
doxycycline |
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what is rickettsiae? |
rocky mountain spotted fever (ticks) |
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what antibiotic works well with lyme disease? |
doxycycline |
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_____ is often used for acne vulgaris but nothing else |
minocycline |
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what is siadh |
syndrome of inappropriate antidiuretic hormone secretion |
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what antibiotic is used in siadh? why? |
democlocycline because of its inhibiting action of ash in the renal tubule |
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what are three macrolide? |
erythrymycin azithrymycin (zithromycin) clarithrymycin (biaxin) |
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moa of macrolides |
bind to 50s subunit of ribosome irreversibly, inhibiting translocation steps of protein synthesis |
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are macrolide bacertostatic or cidal |
static |
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____ effective against same bacteria as penicillin G |
erythromycin |
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____ effective against chlamydial species and mycoplasma pneumoniae a d legionella pneumophilia |
erythromycin |
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_____ is similar to pin but also effective against H. influenzae |
clarithromycin (Biaxin) |
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what is another name for biaxin |
clarythromycin |
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what is another name for clarythromycin |
biaxin |
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_____ excellent for urethritis caused by chlamydia trachomatis |
azithromycin |
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what is another name for zithromax |
azithromycin |
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what is another name for azithryomycin |
zithromax |
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_____ is less active against strep and staph than erythromycin |
azithrymycin |
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most strains of staph in hospital isolates are resistant to _____ |
erythromycin |
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are macrolide used with s. aureus? Are tetracyclines |
no; no |
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resistance mechanisms with macrolides
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1 - alteration of ribosome 2 - manifestation of an efflux pump 3 - enzyme inactivation |
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what is an issue with erythromycin absorption? |
base is destroyed by gastric acid and an enteric coating ins required. It is adequately absorbed orally |
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is erythromycin adequately absorbed orally? |
yes, with an enteric coating |
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absorption issues with clarithromycin |
stable in stomach acid and readily absorbed |
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absorption issues with azithrymycin |
stable in stomach acid and readily absorbed |
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distribution of macrolides |
widely distributed in tissues except for CSF |
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which macrolide are P450 drugs? |
erythromycin |
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which macrolide are metabolized in the liver? |
erythromycin clarithromycin NOT azithromycin |
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why does erythromycin have a lot of drug interactions |
it's a P450 drug |
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does clarithromycin interfere with other drugs |
yes because it's metabolized by the liver |
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does azithromycin interfere with other drugs |
no, it's not a P450 drug and tends to have very few drug interactions |
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are macrolide concentrated in bile? |
erythromycin and azithromycin are primarily concentrated in bile clarithromycin and its metabolites are excreted in the kidney as well as the liver and it is recommended that the dosage be adjusted in patients with compromised renal function |
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which macrolide requires dosage adjustment in patients with renal failure and why? |
clarithromycin and its metabolites are excreted in the kidney as well as the liver and it is recommended that the dosage be adjusted in patients with compromised renal function |
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which macrolide has a problem with GI distress including diarrhea? |
erythromycin |
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which macrolide has been used as tx for constipation? |
erythromycin |
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why would erythromycin have poor patient compliance |
GI upset, diarrhea requires more doses per day |
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are macrolide ototoxic? |
erythromycin can be associated with transient deafness in high doses |
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are macrolide associated with long QT issues? |
erythromycin clarithrymycin (rare) |
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______ is the easiest macrolide to use. 4 reasons: |
azithromycin 1 - fewer adverse effects 2 - fewer drug interactions 3 - don't need to worry about liver/kidney dosage adjustment unless severe 4 - long 1/2 life, fewer daily doses: better patient compliance |
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is doxycycline good for staph? |
no |
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which abx is "absolutely cake" to use in chlamydial cervicitis and urethritis STIs? |
macrolides |
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these abx are excellent for broad spectrum coverage of both typical and atypical pneumonias |
macrolides |
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these abx are used all the time for exacerbations of chronic bronchitis in patients with COPD |
macrolides |
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_____ are the first line ALTERNATIVE tx for group A strep pharyngitis (strep throat) |
macrolides |
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most important thing to know about chloramphenicol |
active against a wide range of Gm +/- organisms, BUT, because of its high toxicity, its use is restricted to life-threatening infections in which there are no alternatives!! |
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when to use chloramphenicol |
life-threatening infections in which there are no alternatives |
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MOA of chloramphenicol |
binds to 50s subunit and inhibits protein synthesis at the peptide transferase reaction |
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which two organisms is chlorampenicol not effective against? |
pseudomonas or chlamydiae |
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pharmacokinetics of chloramphenicol |
completely absorbed orally readily enters csf |
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is chloramphenicol good for csf? |
yes |
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adverse effects of chloramphenicol (4) |
1 - hemolytic anemia 2 - aplastic anemia 3 - gray baby syndrome 4 - can interfere with a number of other drugs |
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which abx is associated with gray baby syndrome |
chloramphenicol |
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which abx is associated with aplastic anemia |
chloramphenicol |
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what is the moa of clindamycin? |
same as macrolides bind irreversibly to 50s subunit, inhibiting translocation steps of protein synthesis bacterostatic |
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is clindamycin absorbed well orally |
yes |
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does clindamycin distribute into csf? |
no |
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coverage of clindamycin |
great against anaerobes also Gm+ cocci (strep/staph) |
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_____ is ALWAYS resistant to clindamycin |
C. diff |
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which abx is C. diff ALWAYS resistant to? |
clindamycin |
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what is the fatal disease resulting from C. diff |
pseudomembranous colitis |
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what is pseudomembranous colitis |
fatal disease resulting from C. diff |
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common side effects of clindamycin |
diarrhea, nausea, skin rash |
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when you think about common medications used against anaerobes, you typically think _____ or _____ |
clindamycin metronidazole (Flagyl) |
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gut infections, including penetrating wounds of abdomen and gut, use: |
clindamycin |
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when you think anaerobic, think |
gut flora or female genital tract flora |
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_____ is excellent in peds |
azythromycin |
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list the 5 aminoglycosides |
1 - gentamicin 2 - tobramycin 3 - amikacin 4 - streptomycin 5 - neomycin |
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what are the three most commonly used aminoglycosides |
1 - gentamicin 2 - tobramycin 3 - amikacin |
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MOA of aminoglycosides |
works on 30s subunit of ribosome causes misreading of mRNA, resulting in nonsense mutations and cell lysis |
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which class of abx cause nonsense mutations |
aminoglycocides via misreading of mRNA |
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what enzyme inactivates aminoglycosides |
transferase |
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mechanisms of resistance of aminoglycosides |
1 - transferase enzyme inactivates abx 2 - impaired entry of abx into cell 3 - ribosomal subunit 30s is altered resistance depends on which aminoglycoside |
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which aminoglycoside shows least resistance |
amikacin |
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what class is amikacin |
aminoglycoside |
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why does amikacin show less resistance |
only 1 locus that is inactivated by enzymes |
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which aminoglycosides have most resistance |
gentamycin and tobramycin 6 loci that may be inactivated by enzymes |
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discuss the distribution of aminoglycosides |
poorly distributed and poorly protein bound, distribution increases with ascites, burns, pregnancy, and cystic fibrosis |
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discuss metabolism of aminoglycosides |
not metabolized...99% is excreted unchanged in urine |
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discuss dose adjustments of aminoglycosides |
dose adjustment required in renal insufficiency dose adjustment not required for hepatic disease |
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do aminoglycosides enter the CNS? |
no |
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are aminoglycosides available orally |
no |
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routes of administration of aminoglycosides |
IV IM only. no oral |
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what is the most common clinical application of aminoglycosides (either alone or in combination therapy) is the treatment of: |
serious infections caused by aerobic gram - bacilli eg pseudomonas, eterobacter, serratia, acinetobacter, klebsiella |
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which abx work well with mycobacterial infections |
tobramycin, streptomycin, and amikacin |
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aminoglycosides work synergistically with ____ against Gm + cocci |
beta lactams eg E. faecalis endocarditis (ampicillin or penicillin + gentamicin or streptomycin) S. aureus endocarditis (naficillin + gentamicin) |
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do aminoglycosides work on anaerobic organisms |
negligible |
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what is post antibiotic effect and which abx exhibit |
antibacterial activity persists despite unmeasurable drug concentrations may last for several hours, varies with type of bacteria |
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which abx class exhibits dose dependent killing? |
aminoglycosides |
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aminoglycosides are most frequently used in combination with another abx for empiric therapy of: |
septicemia nosocomial RTI endocarditis complicated UTI complicated intraabdominal infections osteomyelitis caused by aerobic Gm- bacilli often discontinued after organism is identified and replaced with less toxic abx |
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____ is used for uncomplicated UTIs _____ is used for complicated UTIs |
nitrofuntoin (Macrobid); aminoglycocides |
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which abx treat tularemia |
aminoglycosides |
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which abx treat plague |
aminoglycosides |
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which abx treat UTIs caused by drug-resistant Gm- organism |
aminoglycosides |
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which aminoglycosides is most widely used |
gentamicin (garamycin) |
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gentamicin is almost always used with |
beta-lactams |
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route of administration of gentamicin |
IV, IM, topical, ophthalmic |
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why adjust dose of gentamicin |
obesity |
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what does tobramycin (nebcin) cover better than gentamicin |
pseudomonas |
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which is more expensive? gent or tobra |
tobra |
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which abx comes as a solution for inhalation of cf? |
tobramycin |
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route of administration of tobramycin |
IV IM ophthalmic |
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why adjust dose of tobra |
obesity |
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this aminoglycoside is used for resistant bacteria |
amikacin (amikin) |
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route of administration of amikacin |
IV IM |
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why adjust amikacin |
obesity |
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which aminoglycoside is the 2nd line for TB in combo with other agents |
streptomycin (in combo with penicillin or ampicillin for E. faecalis endocarditis or viridian's streptococcus endocarditis) |
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route of administration of streptomycin |
IM only |
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which aminoglycoside route of admin is IM only |
streptomycin |
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which aminoglycoside is limited to topical and oral use |
neomycin (mycifradin) |
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use this aminoglycoside with erythromycin for bowel prep |
neomycin |
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can aminoglycosides be used during lactation? why or why not? |
yes..pass through to breast milk but not absorbed well orally |
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pregnancy category of aminoglycosides |
D sometimes need outweighs risk |
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with which autoimmune disorder is an aminoglycoside abx contraindicated and why |
Myasthenia graves because the neuromuscular blockade risk is too high (diaphragm paralysis = respiratory arrest = death) |
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black box warnings of aminoglycosides (4) |
1 - Nephrotoxicity 2 - ototoxicity 3 - neurotoxicity 4 - neuromuscular blockade this is why we monitor serum levels |
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why does viral growth resume after drug removal |
anti-viral agents inhibit active replication only |
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do anti-virals eliminate non-replicating or latent viruses |
no, so effective hose immune response remains essential for the recovery from the viral infection |
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clinical efficacy depends on what with anti-virals |
achieving inhibitory concentration at the site of infection within the infected cells, since anti-viral only work on actively replicating viruses...immune response must take care of the rest and if drugs can bring down the numbers, the host can handle the rest |
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3 Anti-HSV/VZV agents |
1 - acyclovir (zovirax) 2 - Famciclovir (famvir) 3 - valacyclovir (valtrex) |
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moa of acyclovir, famciclovir, valacyclovir |
inhibit viral DNA polymerase |
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formulations of acyclovir (zovirax) |
topical oral IV |
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spectrum of acyclovir (zovirax) |
HSV1, HSV2, varicella-zoster, possibly epstein-barr |
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Treatment of choice for HSV genital infections, cold sores, HSV encephalitis, and HSV infections in immunocompromised and pg pts |
acyclovir (zovirax) |
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Pharmicokinetics of acyclovir (zovirax) |
oral bio: 20-30% distribution: all tissues including CNS renal excretion: 80% 1/2 life: 2-5 hours admin: topical, oral, iv |
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can acyclovir (zovirax) reach CNS |
yes |
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pg cat of acyclovir (zovirax) |
B lactation safe |
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renal dosing of acyclovir (zovirax) |
iv crcl 25-50 q12 crcl <25 q24 |
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is acyclovir activated in cells without herpes virus |
no. it is selectively activated in cells infected with herpes virus uninfected cells do no phosphorylate acyclovir |
