antibiotics Flashcards
what happens if you give chloramphenicol first and penicillin second?
chloramphenicol is bacteriostatic, so penicillin won’t have an effect.
name the general cell wall inhibitors
- beta lactams
- bacitracin
- glycopeptides
- “others” (cycloserine and those against mycobacteria)
which antibiotic type inhibits transpeptidation AND actives autolysins in the cell wall?
beta lactams
how do bacteria outsmart beta-lactams?
- become resistant by making beta lactamases
- lose their PBPs
- mutate their autolysins
how can we outsmart the bacteria that outsmart the beta lactams?
-give beta lactam antibiotics with beta lactamase inhibitors!
name some beta lactamase inhibitors
- clavulinic acid
- sulbactam
- tazobactam
- augmentin
what is augmentin, really?
amoxicillin and clavulinic acid!
what are the 4 major classes of beta lactams?
- penicillins
- cephalosporins
- monobactams
- carbapenems
natural penicillins (pen G and pen V) are best against what kind of bugs?
gram positive bacteria
which penicillins are beta lactamase resistant, but they have a lower activity?
nafcillin, oxacillin, cloxacillin
which penicillins are expanded spectrum antibiotics?
ampicillin, piperacillin, mezlocillin, ticarcillin
which penicillin is best used against pseudomonas?
ticarcillin
which penicillins are acid resistant and thus can be given orally?
amoxycillin, pen V, oxacillin
compare the effectiveness of penicillins and cephalosporins?
cephalosporins are less sensitive to beta-lactamases
1st generation cephalosporins?
not used anymore, so I won’t ask you to name them.
what are 2nd gen cephalosporins used against?
bacteroides
name some of those 2nd gen cephalosporins
-cefaclor, cefuroxime, cefoxitin
what are 3rd gen cephalosporins used against?
pseudomonas
what’s special about the 3rd gen cephalosporins?
they can penetrate BBB, so useful against bacterial meningitis
which ones are the 3rd gen cephalosporins?
ceftazidime, cephataxime, cephtriaxone, cefdinir
4th gen cephalosporins: used against?
not stated in notes, but this class is the broadest of the 5 generations of cephalosporins
4th gen cephalosporins?
cefepime
what do 5th gen cephalosporins fight?
MRSA and drug resistant pseudomonas, but not regular pseudomonas
which is the 5th gen cephalosporin?
ceftaroline
what’s special about the monobactam antibiotics?
they are resistant to beta-lactamases because of their monocyclic beta lactam structure
which bugs do the monobactam antibiotics work against?
gram negative only
what’s an example of a monobactam antibiotic?
aztreonam
what are carbapenem antibiotics used for?
broad spectrum, but it’s toxic to human cells
what are some carbapenems?
imipenem, ertapenem, meropenem
what are the side effects of beta lactam antibiotics?
allergies and toxicity
which beta lactams are likely to cause allergies?
1st: penicillin, then cephalosporins, then monobactams
which beta lactams are likely to cause toxicity?
1st: carbapenems, then cephalosporins, then penicillins, then monobactams
how does a carbapenem toxicity present?
seizures
how does a cephalosporin toxicity present?
thrombophlebitis
if in cavernous sinus, it would be a 3rd gen because it crosses BBB
how do bacitracins work?
block dephosphorylation of bactoprenol
what are the best uses for bacitracin?
topical against gram positive (typically used with other antibiotics)
why would we not use bacitracins in some cases?
it’s poorly absorbed and it causes renal toxicity (!!)
how go glycopeptide antibiotics work?
- binds to end of AA side chain
- blocks transglycosylation
- blocks transpeptidation
can you name some glycopeptide antibiotics?
vancomycin & telavancin
how do some pesky bacteria outsmart the glycopeptides?
- use an -ala-lactate instead of -ala-ala end of pentapeptide side chain
- chromosomal vanB resistant gene
- plasmid vanA resistant gene
what are glycopeptides used for?
NOT gram negatives; staphylococci and enterococci
you have an intestinal gram positive infection. what kind of antibiotic can you use?
oral dose of glycopeptides
how can we outsmart the bacteria that are vancomycin resistant?
doing a little organic chemistry sorcery by making an amidine in the vancomycin
describe the cycloserine antibiotics
D-ala analog
how does cycloserine work?
inhibits alanine racemase
why would we be careful with cycloserine?
it’s neurotoxic
what is cycloserine used for?
UTI (sometimes) and it’s the 2nd best drug for TB
which drugs are best for mycobacteria?
- isoniazid
- ethionamide
- ethambutol
- pyrazinamide
- rifampicin
how do isoniazid and ethionamide work?
inhibit pyridoxine step in mycolic acid synthesis
how does ethambutol work?
inhibits arabinogalactan synthesis
what should we keep in mind about ethambutol?
its highly resistant, so other antibiotics are needed
how does pyrazinamide work?
activated by mycobacteria enzyme; inhibits translation in a pathway that’s needed to restart stalled ribosomes during stress response
now, name some cell membrane disruptors?
- polymyxins
- daptomycin
what’s a good example of a polymyxin?
colistin
how does colistin work?
dissolves phosphatidylethanolamine (special phosolipid in gram negative and human membranes)
what do we use colistin for?
- topical, used with bacitracin
- last resort for resistant bugs
why is colistin used topically?
ITS TOXIC.
what’s a good example of daptomycin?
cubicin
what does cubicin look like?
cyclic lipopeptide
how does cubicin work?
dissolves in membrane and disrupts membrane potential (PMF)
which bugs do we use cubicin for?
gram positive cocci, including MRSA.
how is cubicin given?
IV; use with beta lactams
which drugs are antimetabolites?
sulfonamides, trimethoprim
how do antimetabolites work?
inhibit steps in this pathway:
PABA -> DHF –> THF –> pyrimidines
how can bacteria outsmart the antimetabolites?
overproduce PABA, and alter their enzymes
what do we use antimetabolites for?
- nocardia
- UTI
- salmonella
- shigella
four classes of nucleic acid inhibitors?
- fluoroquinolones
- fidaxomycin
- rifamycin
- metronidazole
name some fluoroquinolones?
ciprofloxacin, moxifloxacin
how do fluoroquinolones work?
inhibits DNA gyrase
how do bacteria outsmart fluoroquinolones?
- alter DNA gyrase (duh)
- drug exclusion (? not so duh…)
what bugs are fluoroquinolones usesful against?
- UTI bugs
- gram negative & positive infections
- 2nd line against mycobacteria
- pseudomonas
why would we reconsider using fluoroquinolones in some patients?
these drugs are associated with prolonged QT interval (EKG)
example of a fidaxomycin?
dificid
how does dificid work?
targets switch region of RNAP and prevents RNAPs interaction with DNA (whatever that means…)
what do we use dificid for?
- C. diff colitis
- vancomycin resistant c. diff
name some rifamycins
-rifampin, rifabutin, rifaximin
how do rifamycins work?
block RNA polymerase elongation subunit
how do bacteria outsmart the rifamycins?
alter RNA polymerase B subunit
what do we use rifamycins for?
- w/ isoniazid for mycobacteria (delays resistance)
- meningitis (crosses BBB)
- poxviruses
are there any side effects of rifamycins?
yep. its orange when excreted in sweat and urine
how do metronidazoles work?
it’s partially reduced complex with ferredoxin interacts with DNA —> breaks DNA strands —> free radicals
what do we use metronidazoles for?
- giardia (antiprotozoal)
- anaerobic bacteria like bacteriodes and clostridium
what are the 5 main classes of protein synthesis inhibitors?
- aminoglycosides
- tetracylclines
- chloramphenicol
- macrolides
- lincosamides
name some aminoglycosides
streptomycin, neomycin, gentamycin, tobramycin, amikacin
how do aminoglycosides work?
bind to 30s ribosome and blocks initiation by preventing attachment of tRNA-fMet
how do bacteria outsmart the aminoglycosides?
- altered P12 ribosomal protein
- aminoglycosidases
- altered permeability
what do we use aminoglycosides on?
gram negative enteric bacteria
which other antibiotics facilitate the entry of aminoglycosides?
cephalosporins and penicillins
name some tetracyclines?
doxycycline, tigecycline
how do tetracyclines work?
inhibits binding of aa-tRNA to A site of 30s subunit
how do bacteria outsmart tetracyclines
by using efflux pumps
what do we use tetracyclines for?
rickettsia, chlamydia, and mycoplasmas
why might we not give tetracyclines to some patients?
- it’s toxic
- causes dizziness, tinnitus
- makes teeth fluorescent
- possible bone damage in newborns
- crosses blood-placenta barrier (pregnancy class D)
how do chloramphenicol drugs work?
inhibit peptidyl transferase rxn on 50s subunit
what do bacteria use to outsmart chloramphenicol?
chloramphenicol acetyl transferase (CAT)
what should be noted about chloramphenicol?
- no longer used….
- resistant and toxic
name some macrolides
erythromycin, clarithryomycin, azithromycin
how do macrolides work?
bind to rRNA and inhibit translocation on 50s subunit
how do bacteria outsmart macrolides?
methylate their rRNA
what bugs do we use macrolides for?
gram positive and SOME gram negative
why would we reconsider using macrolides in some patients?
associated with prolonged QT interval on EKG and it has increased risk of cardiovascular death (!!)
example of a lincosamide?
clindamycin
how does clindamycin work?
same as macrolides
what do we use clidamycin for?
anaerobes (bacteroides) and malaria
what should we note about clidamycin use?
- does not cross BBB
- long term use linked with c. diff colonization
- one time use disrupts native flora
tell me about nitrofurantoin
- inhibits 30s
- used for UTI
what about mupirosin?
- inhibits ile-tRNA synthase
- used topically for gram +
what’s the deal with streptogramins?
- synercid= quinupristin + dalfopristin
- inhibits 50s
- used for VRE and VRSA (….?)
how about oxazolidinones?
- inhibits 50s
- used for VRE, MRSA
lastly… what’s up with methenamine?
releases formaldehyde in acidified urine… used for UTI
just kidding. what do C10 and BF8 do?
wake up persister cells from dormancy and make them sensitive to antibiotics again!
