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74 Cards in this Set
- Front
- Back
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___ binds 23S subunit of 50S, prevents formation of initiation complex
time dep bacteristatic some PAE |
oxazoladinones (Linezolid)
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___ bind 30S, prevent binding of aminoacyl tRNA to A-site -->
time dep Bacteristatic some PAE |
tetracycline
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___ bind 30S, interfere with initiation complex and cause misreading of mRNA ->
concentration dependent bactericidal significant PAE |
aminoglycosides
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___ binds 50S, inhibits peptidyl transferase elongation of peptide
time dep bacteristatic some PAE |
chloramphenicol
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___, ___, ___, and ___ bind 50S and inhibit translocation (also worded as: they inhibit the peptidyl transferase reaction)
all time dep bacteristatic w/ PAE except one |
macrolides (erythromycin)
lincosamines (clindamycin)- bind A and P sites of 50S Type B streptogramins Ketolides (telithromycin)-concentration dep bactericidal, sig PAE |
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binding of chloramphenicol may inhibit binding of which other two drugs due to close proximity of binding site
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clindamycin and
macrolides |
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what is the general MOA for oxazoladinones
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bacteriostatic
type III time dependent- moderate to prolonged PAE |
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name an oxazoladinone
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linezolid
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name five bugs sensitive to linezolid
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enterococcus faecalis
enterococcus faecium staph epidermidis staph haemolyticus staph pneumoniae |
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specific MOA of linezolid
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prevents formation of 70S by binding 23S rRNA of 50S subunit -> prevents formation of initiation complex for protein synthesis
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linezolid- oral absorption?
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yup, good
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bug's mechanism of resistance to linezolid
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mutations of 23S RNA prevent binding of linezolid
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three adverse effects of linezolid
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MAOI
GI thrombocytopenia, anemia, myelosuppression |
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what is the general MOA of tetracyclines
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bacteriostatic- type III
time dependent moderate to prolonged PAE |
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tetracycline
doxycycline minocycline |
all tetracyclines
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drugs with more lipophilic substituents (minocycline and doxycycline) are most active by...
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weight
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what is the specific MOA of tetracyclines
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binds 30S -> prevents binding of aminoacyl-tRNA during protein synthesis
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how do tetracyclines get through the outer membrane of gram neg bacteria?
through the plasma membrane? how is this different in mammalian cells |
outer- passive diffusion through porin channel
inner- active transport mammalian- lack the active transport system required |
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tetracyclines- oral absorption?
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adequate but incomplete
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name three ways bugs become resistant to tetracyclines
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1. decreased influx or acquisition of an energy-dependent efflux mechanism
2. ribosome protecting proteins 3. enzymatic inactivation of drug |
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is hypersensitivity to tetracyclines common
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no
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Name some adverse effects of tetracyclines (7)
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1. GI: pseudomembranous enterocolitis
2. perm tooth discoloration in pregnant women and kids <8 3. IV admin -> venous thrombosis 4. IM admin -> painful local irritation 5. renal toxicity 6. hepatic toxicity 7. photosensitivity |
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streptomycin
neomycin gentamycin kanamycin tobramycim sisomicin amikacin netilmicin |
aminoglycosides
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general MOA of aminoglycosides
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bactericidal type I ->
conc dependent significant PAE |
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what group of bugs is susceptible to aminoglycosides
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gram neg
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aminoglycosides specific MOA
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bind 16S part of 30S -> irreversibly inhibiting protein synthesis- interfere w/ formation of initiation complex; misreading mRNA code; premature termination
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with aminoglycosides, a PAE persists even after serum concentration has fallen below...
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the MIC
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how do aminoglycosides get through the outer membrane?
the plasma membrane? Name 4 things that inhibit passage through plasma membrane |
outer- passive diffusion
inner- active transport 1. divalent cations 2. hyperosmolarity 3. lowered pH 4. anaerobic conditions |
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aminoglycosides- oral absorption?
accumulations in CSF? excretion by kidney? IM or IV absorption |
oral absorption- poor
low accumulation in CSF rapid excretion by kidney rapid IM and IV absorption |
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there is ___ activity of aminoglycosides in the presence of beta-lactam antibiotics
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enhanced (synergism)
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Name two ways bugs gain resistance to aminoglycosides
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1. acquisition of inactivating enzymes (acetylases, adenylases, phosphorylases- plasmid encoded)
2. if drug fails to permeate the inner bacterial membrane |
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Name 5 adverse effects of aminoglycosides
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1. ototoxicity
2. nephrotoxicity 3. curare-like NM block (-> resp paralysis, tx w/ Ca and neostigmine) 4. nerve dysfunction 5. allergic skin reax and contact dermatitis |
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is chloramphenicol used in the US
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no- but we have to learn about it anyway :)
it's used in other countries because of very low cost |
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what is the general MOA of chloramphenicol
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bacteriostatic type III
time dependent moderate to prolonged PAE |
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when do you use chloramphenicol
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only when benefits outweigh the risks of potential toxicities
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what is the specific MOA of chloramphenicol
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binds reversibly to 50S -> prevents binding of aminoacyl-tRNA to A site -> inhibits peptidyl transferase step of protein synthesis elongation
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how does chloramphenicol get into cell
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facilitated diffusion
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chloramphenicol- oral absorption?
gets into CSF? cross placenta? half life correlated w/? |
good oral absorption
gets into CSF crosses placenta half life related to plasma bilirubin concentrations (requires hepatic function for later secretion in urine) |
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name two mechanisms of resistance to chloramphenicol
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1. decreased membrane permeability (influx)
2. chloramphenicol acetyl transferase (plasmid encoded) |
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Name five adverse effects of chloramphenicol
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1. direct bone marrow toxicity due to dose-related normocytic anemia, due to erythroid suppression
2. allergic reax resulting in idiosyncratic blood dyscrasia 3. inhibits mammalian 80S 4. Gray Baby syndrome (inadequate glucuronic acid conjugation after inadequate renal secretion) 5. inhibits P450 |
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macrolides
lincosamides streptogramins type B ketolides |
MLS antibiotics
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what was recently added to the MLS antibiotics
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ketolides (MLKS?)
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what is the general MOA of macrolides
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type III bacteriostatic ->
time dependent moderate to prolonged PAE |
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erythromycin
clarithyromycin azithromycin |
macrolides
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which two macrolides have broader spectrum due to modifications
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clarithromycin
azithromycin |
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macrolide specific MOA
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bind 50S and inhibit translocation of protein synthesis
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if erythromycin is inactivated by gastric acid, where is it absorbed?
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still in the upper small intestine
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what does insertion of the azo group into the lactone ring provide azithromycin
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increased bioavailability and stability -> requires only once a day dose instead of 3x per day
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which macrolides are eliminated by liver?
which are eliminated through renal and non-renal mechanisms? |
erythromycin and azithromycin- liver
clarithromycin- renal and non-renal mechanisms (clarithromycin uses the kidney) |
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name four mechanisms of resistance to macrolides
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1. efflux via ATP dependent pump (except clindamycin)
2. make a methylase that modifies ribosomal target (=MLSb determinants- resistance to whole MLS group) 3. hydrolysis by esterases 4. mutation of 23S |
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which two macrolides inhibit hepatic enzymes
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erythromycin (p450) and clarithromycin
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clindamycin
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lincosamide
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general mechanism of action of lincosamides
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bacteriostatic type III
time dependent moderate to prolonged PAE |
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___ is a congener of lincomycin that has improved pharmacokinetics and less toxicity
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clindamycin
(for those of us who didn't major in English... congener = n. A member of the same kind, class, or group. ) |
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bugs susceptible to clindamycin
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gram positive cocci
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specific MOA of clindamycin
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binds the P and A sites in 50S and suppresses protein synthesis
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clindamycin- oral absorption?
bone penetrance? cross placenta? reaches CNS? |
good oral absorption
gets into bone crosses placenta DOES NOT get into CNS |
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how do bugs get resistance to clindamycin
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MLSb induced ribosomal methylation
*not a substrate for efflux pump* |
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name 3 adverse effects of clindamycin
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1. GI
2. inhibited neuromuscular transmission 3. skin rashes (esp in HIV patients) |
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synecid
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type B streptogramin
= streptogramin B (quinupristin) + streptogramin A (dalfopristin) |
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general MOA of type B streptogramins
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bacteriostatic type III
time dependent moderate to prolonged PAE |
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type B streptogramins are semisynthetic derivatives of the naturally occurring ___
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pristinamycins
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type B streptogramins effective against...
inactive against... often reserved for ... and ... |
good for gram pos cocci
bad for gram neg's reserved for vancomycin resistant E. faecium or multi-drug-resistant Gram positives |
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mechanism of action of streptogramin B
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quinupristin binds 50S -> inhibits translocation; occupies same site as macrolides
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mechanism of action of streptogramin A
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dalfopritin binds near quinupristin and induces conformation change in 50S -> enhancing binding of quinupristin
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administration of type B streptogramins?
t 1/2? elimination by? |
IV only!
short half life biliary excretion |
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name two mechanisms of resistance to type B streptogramins
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1. active transport efflux and acetyltransferases against streptogramin A
2. MLSb ribosome methylation and lactonases |
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name three adverse effects of type B streptogramins
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1. infusion related pain and phlebitis at site of infusion
2. arthralgias 3. myalgias |
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telithromycin
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ketolide
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ketolide general mechanism of action
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bacteriocidal type I
concentration dependent significant PAE |
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specific MOA of telithromycin
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binds 50S like the macrolides do
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telithromycin is especially useful for
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drug-resistant respiratory infections
pneumococcus: community acquired pneumonia, acute sinustitis, acute exacerbations of chronic bronchitis, tonsillitis/pharyngitis |
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name four drugs whose concentrations are increased by telithromycin inhibiting p450
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cisapride
pimozide simvastatin midazolam |
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name five commonly reported adverse effects of telithromycin
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diarrhea
nausea dizziness vomiting headache |
