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Pharm Protein Inhibitors
KYCOM Block 10
99
Pharmacology
Graduate
09/21/2013

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Cards

Term
what are the two tetracyclins and one honorary (and its category)
Definition
tetracyclin, doxycyclin
tigecyclin - glycyclin antibiotic
Term
what are the 5 aminoglycosides
Definition
streptomycin
amikacin
gentamycin
tobramycin
neomycin
Term
what are the three macrolides and one honorary (and its category)
Definition
azithromycin
erythromycin
clathromycin
trlithromycin - ketolide antibiotic
Term
what are the other 50S antibiotics (4)
Definition
chloramphemicol
clindamycin
streptogramin
linezolid
Term
what protein inhibitors target the 50S subunit
Definition
macrolides and other 50S category
Term
what protein inhibitors target the 30S subunit
Definition
tetracyclins and aminoglycosides
Term
which tetracyclin is the drug of choice, why
Definition
doxycyclin- wider spectrum
Term
which protein inhibitors are bacteriocidial and which are bacteriostatic
Definition
bacteriocidial: aminoglycocides

bacteriostatic; tetracyclins, macrolides, other 50S
Term
what is the main reason to use amikacin
Definition
stable against R plasmid resistance that occurs in gentamycin and tobramycin
Term
what is the most commonly used aminoglycocide, why
Definition
gentamycin- cheap, effective
Term
what is tobramycin used for
Definition
topical for the eye
Term
what is neomycin used for
Definition
topical for the skin
Term
which macrolides kill MAC
Definition
azithromycin, clathromycin
Term
how are macrolides absorbed
Definition
azithromycin and clathromycin are absorbed well reducing GI upset

erythromycin is destoried by the GI tract and needs to be enteric coated
Term
what durgs penetrate prostatic fluid
Definition
erythromycin
Term
other than antibiotic, what is another use for erythromycin
Definition
increase GI motility
Term
which protein inhibitors are ok to use in pregnacy
Definition
azithromycin
Term
which protein inhibitors are P450 inhibitors (3)
Definition
erythromycin, clathromycin, streptogramins
Term
what is streptogramin composed of
Definition
30% quinuprostin
70% dalfopristin
Term
what are the three steps in protein production
Definition
growtin chain goes to acceptor site to get new AA molecule (via peptidly transferase)

uncharged tRNA moves to donor site to make space for charged tRNA

charged tRNA comes to acceptor site
Term
which drugs stop peptidyl transferase, what does this stop from happening
Definition
chloramphenicol

growing chain cannot get to the acceptor site to get a new AA
Term
which drugs stop tRNA from moving from acceptor site to donor site, what does this stop from happening
Definition
macrlides, telithromycin, clindamclin, streptogramin

new charged tRNA cant get onto the acceptor site to provide more AA to the chain
Term
what drugs stop tRNA travel to the acceptor site
Definition
tetracyclin, tigecycliin
Term
what is the MOA of tetracyclins
Definition
bind 30S and block amino acyl (t)RNA binding
Term
what causes resistance in tetracyclins
Definition
natural R factor makes it so Mg dependent TetA pumps turn on effluxing the drug from the cell

resistance to one = resistance to all
Term
tigecycline MOA (2)
Definition
same as tetracycline except 5x more affinity for 30S

affects ribosomal protection proteins
Term
what causes resistance to tigecycline
Definition
minimal - no TegA concerns
Term
how does aminoglycides get into the cell (3)
Definition
passive diffusion through the cell wall, O2 dependent transport through the cell membrane

helped by synergism with penicillin, ampicillin, or vancomycin to break the wall
Term
what are the 4 MOA of aminoglycocides
Definition
interfere with initiation complex of peptide formation on 30S

induce misreading or mRnA making toxic or non functional AA

break polysomes into monomeres

post antibiotic effect
Term
what is the post-antibiotic effect
Definition
continue to supress growth at sub-inhibitory concentrations because it takes time for bacteria to make new ribosomes
Term
what is the MOA of macrolides
Definition
stops amino acyl(tRNA) translocation

uncharged tRNA cannot move from acceptor to donor site to allow new charged rRNA in
Term
what are 4 ways to get resistance to macrolides
Definition
decrease uptake of drug by microbe

binding site on 50S is methlyated

bacteria make esterase and cleave the macrolide

if there is penicillin resistance there is a 50% chance of macrolide resistance
Term
what do you use if a microbe is macrolide resistant because it is penicillin resistant
Definition
use flouroquinolones
Term
what is the MOA of telithromycin
Definition
same as macrolides but bind to 50S 10x stronger
Term
how can a microbe become resistant to relithromycin
Definition
less of an issue - methylation of the 50S binding site isnt a problem
Term
why dont protein synthesis drugs stop out ribosomes
Definition
ours are different from bacterial, out mitochondrial ribosomes are like theirs but they are all safe and hidden
Term
what is the OA of chloramphenicol (2)
Definition
inhibits peptidyl transferase
bacteriostatic
Term
what is the MOA of clindamycin
Definition
inhibits amino acyl transfer (tRNA) transfer
Term
what is the MOA of streptograims
Definition
simillar to macrolides
Term
what are two contraindications to tetracyclines, why
Definition
antacids and dairy: Ca, Mg, and Al chelate with the drug and form a non-absorbable product

less of an issue with doxycycline
Term
where do tetracyclines distribute to in the body (5)
Definition
liver, spleen, skin, CSF (not well), placenta
Term
what do tetracyclines bind in the body (not the GI) (4)
Definition
calcification (bone, teeth, tumors, gastric carcinomas)
Term
why cant you take tetracycline if you're pregnant
Definition
it accumulates in fetal bones and teeth
Term
how are tetracyclines eliminated
Definition
release into bile, reabsorbed into intestines, release into glomerular filtrate

docycycline is not reabsorbed and is released in feces
Term
what are side effects of tetracyclines (4)
Definition
discoloration of bone
discoloration of teeth
phototoxicity
stunts growth via hypoplasia of calcified tissue
Term
what type of antibiotic is tigecycline, how is it administered
Definition
glycycline
IV
Term
what are the side effects of tigecycline (2)
Definition
discolors teeth, teratogenic
Term
how does resistance develop to tigecycline
Definition
minimal, no TegA exporter issues
Term
how does tigecycline work (2)
Definition
same as tetracycline except binds with 5x more affinity to 30S

affects ribosomal protection proteins
Term
how are aminoglycosides given, why
Definition
IV/IM because they are poorly absorbed
Term
how are amino glycosides metabolized and excreted
Definition
not metabolized
excreted in urine
Term
where do aminoglycosides distribute to
Definition
no CNS
dosent enter cells well because its polar
concentrate in renal cortex causing nephrotoxicity
Term
what are aminoglycosides synergistic with (3), why
Definition
penicillin, vancomycin, ampicillin
the helper breaks through the cell wall and then the aminoglycosidestops protein synthesis
Term
what bugs does aminoglycosides use synergy with a cell wall drug to kill (4)
Definition
strep, enterococcus, endocarditis, listeria
Term
what are the three categories of side effects for aminoglycosides
Definition
nephrotoxicity
ototoxicity
neuromuscular paralysis
Term
how can you tell if someone is getting nephrotoxicity from an aminoglycocide (2), why does this happen, what percautions are taken
Definition
accumulates in cortex of nephron
disrupts ca transport
tubular necrosis
monitor plasma level if getting for >5d
Term
what are 5 signs of ototoxicity when on amino glycocides, what percautions are taken
Definition
tinnitis, high frequency hearing loss, vertigo, ataxia, decreased balance

monitor plasma levels if taking for >5d
Term
why do you get neuromuscular paralysis on aminoglycocides, how does it happen, what is a concerning side effect of this
Definition
occurs at high doses
blocks ACh receptors
can cause respiratory paralysis
Term
what is the antidote to neuromuscular paralysis on aminoglycocides (2)
Definition
cholinesterase inhibitor or Ca gluconate
Term
what two drugs interact with aminoglycocides, what is the outcome of each
Definition
loop duruetics increase ototoxicity
cancer drugs increase nephrotoxicity
Term
where do macrolides distribute
Definition
distribute well, no CNS
Term
where are macrolides excreted
Definition
kidney but dont need to adjust in renal failure except for clathromycin which needs to be adjusted in severe renal failure
Term
which macrolides are teratogenic
Definition
all but azithromycin
Term
which macrolide is enteric coated, why. what are the others like
Definition
erythromycin is enteric coated because it is destoried by gastric acid. the others are stable and absorbed well. they decrease GI upset
Term
what drug pepentrates prostatic fluid
Definition
erythromycin
Term
explain the metabolism of the three macrolides
Definition
erythromycin: metabolized a lot
azithromycin: not metabolized
clathromycin: metabolized to become active
Term
which macrolides are P450 inhibitors, what drugs do they mess up (3)
Definition
erythromycin and clathromycin

theophyline and warfarin

they also kill the bacterial that inactivate digxin so sort of inhibiting for them too
Term
from lest to most, what is the p450 inhibition rank of the macrolides
Definition
azithromycin, clathromycin, erythromycin
Term
thlithromycin: type of antibiotic, MOA, resistance, administration
Definition
ketolide antibiotic
MOA the same as macrolides but binds 10X stronger
less resistance - no methlyation issue
oral administration
Term
telithromycin: side effects (5)
Definition
nausea, diarrhea, vomiting
headache, dizzy
Term
chloramphenicol: side effects (3)
Definition
anemia, marrow toxicity, gray baby (cannot glucorinate)
Term
why is chloramphenicol a bad cjoice
Definition
toxic, resistance, rare in pharmacy
Term
clindamycin: administration, metabolism, side effects (3)
Definition
oral
cleared in liver
C. diff, fever, cramps
Term
what is the number one medicine that causes C. diff
Definition
clindamycin
Term
how is C. diff treated
Definition
metronidazole
Term
streptogrraims: adeministration, side effects (2)
Definition
IV
P450 inhibitor
phlebitis at injection site 10%
Term
inlesolid: administration (2), side effects (2)
Definition
oral, IV
GI upset
tongue discoloration
Term
on a broad level, what do tetracyclines work on (3)
Definition
gram negative and positive
atypicals
Term
what 4 conditions are tetracyclines the drug of choice for
Definition
chlamydia
rickettsia- rocky mt. spotted fever
vrucella- lyme
coxiella- intracellular
Term
what 4 microbes are tetracyclines not the drug of choice for but its pretty good at it
Definition
syphilis- alternative
acne
anthryx
vibro-cholerae
Term
on a broad level, what do tigecyclines work on (3)
Definition
gram negative and positive
anaerobes: bacteroides, C non diff
Term
what specific microbes or types of infections is tigecycline good at (6)
Definition
bacteroides, C non diff
MRSA, VREF
complicated skin infection
intra-abdominal infection
Term
on a broad level what do aminoglycosides work on (3)
Definition
aerobic gram negative rods
Term
what 3 specific microbes do aminoglycosides work on
Definition
pseudomonas
mycobacterium (streptomycin)
moraxella
Term
on a general level, what does telithromycin kill (2)
Definition
gram positive cocci
Term
what 4 microbes does telithromycin kill
Definition
moraxella, chalmydia, mycoplasma, legionella
Term
on a general level, what do macrolides kill (4)
Definition
gram positive and negative rods and cocci
Term
what 5 microbes are important that marolides kill
Definition
hemophalus, legionella, chladymia pneumonia and STI, MAC
Term
what is an alternative to B-lactams in a non life threatening and life threatening infection
Definition
non: macrolides
life threat: vancomycin
Term
what are the atypical bacteria that macrolides kills (4)
Definition
mycoplasma pneumonia
legionella pneumonia
Term
what are 2 every day infections that macrolides kill
Definition
influenza
otitis media
Term
what are 5 other microbes macrolides kill
Definition
MRSI
listeria
clostridium
meningitidis
moraxella
Term
what is chloramphenicol an alternative to
Definition
tetracycline
Term
what does chloramphenicol kill (2)
Definition
broad spectrum
rickettsia: typhys, rocky mt fever (when tetracycline resistant)
Term
what does clindamycin kill (5)
Definition
bacteroides, actinomyces
CA-MRSA
strep, staph
Term
when do yo use streptograims (4)
Definition
life threatening vancomycin resistant VREF, VRSA, MSSA

gram positive cocci
Term
what is streptograims not good at (4)
Definition
gonorrhea,legionella, C not diff
Term
what does linesolid kill (4)
Definition
c not diff, MRSA, VREF, VRSA, nosocomal pneumonia
Term
what is linesolid not good at
Definition
gram negative
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