Antibiotics Flashcards
penicillins
Beta-lactam - inhibits transpeptidation (cell wall)
Natural: Pen G, Pen V (best for G+)
Beta-lactamase resistant: nafcillin, oxacillin, cloxacillin
G+ and G-: ampi-, pipera-, mezlo-, ticarcillin
Acid resistant/oral: amoxicillin, pen V, oxacillin
Pen + beta-lactamase inhib: Augmentin (amox/clav), ampicillin + sulbactam, piperacillin + tazobactam
penicillin resistance?
beta-lactamases
lack of PBPs
autolysin mutations “tolerance”
cephalosporins
Beta-lactams (cell wall), but less sensitive to beta-lactamases
1G: prophylaxis only - cephalexin, cephalothin, cefazolin
2G: G+ and G-: cefaclor, cefuroxime, cefoxitin
3G: G+ and G-, w/ pseudomonas:
monobactams
monocyclic beta-lactam ring (cell wall), resistant to beta-lactamases for G- only
aztreonam
carbapenems
beta lactam (cell wall) - G+ and G-, but may be toxic allergy, toxicity - seizures
imipenem, ertapenem, meropenem (less toxicity)
bacitracin
blocks dephosphorylation of bactroprenol (cell wall)
topical, G+
poorly absorbed, renal toxicity
glycopeptides
bind aa side chain - block transglycosylation and transpeptidation (cell wall) for G+
Vancomycin, telavancin
glycopeptide resistance
use -Ala-Lac instead of -Ala-Ala for pentapeptide - via chromosomal vanB and plasmid vanA genes
how can you overcome vancomycin resistance?
replace disaccharide with -H
replace =O in amide binding site with =N
cycloserine
D-ala analog - inhibits Ala racemase (cell wall), but neurotoxic
sometimes for UTI, 2nd line TB drug
Mycobacterium drugs
- isoniazid (INH), ethionamide - inhibit pyridoxine step in mycolic acid synthesis
- ethambutol (EMT) - inhibit arabinogalactan synthesis
- pyrazinamide (PZA) - inhibits trans-translation
- rifampicin (RMP)
polymyxins/ colistin
dissolve phosphatidlethanolamine, part of G- (cell membrane)
toxic - topical only, often w/ bacitracin and neomycin
daptomycin/ cubicin
cyclic lipopeptide - dissolves in membrane, disrupts membrane potential (cell membrane)
G+, MRSA - must be IV, synergy with beta-lactams
sulfonamides (sulfone) and trimethoprim, aka bactram/SxT
inhibit steps in path: PABA -> DHF -> THF -> pyrimidines (antimetabolite)
uses: Nocardia, Salmonella, shigella, UTIs
SxT resistance
overproduction of PABA, altered enzymes
(fluoro)quinolones
inhibit DNA gyrase (nucleic acid inhibitor) but can get prolonged QT segment (EKG)
Use: not very soluble, use fluoro instead (ciprofloxacin and derivatives) for UTI, G-, G+, Pseudomonas
ciprofloxacin, moxifloxacin
(fluoro)quinolone resistance
altered DNA gyrase, drug exclusion
fidaxomycin/ dificid
targets “switch region”/ loading clamp of RNA pol - prevents interaction of RNA pol and DNA (nucleic acid inhibitor)
rifamycin
blocks RNA pol elongation subunit (nucleic acid inhibitor) - but makes sweat/urine orange!
rifampin, rifabutin, rifaximin
use: Mycobacterium + INH, crosses BBB, blocks assembly of poxviruses
rifamycin resistance
altered RNA pol beta subunit
metronidazole
partially reduced complex with ferredoxin interacts with DNA and breaks DNA strands - free radical (nucleic acid inhibitor)
use: antiprotozoal, anaerobes (first time for C. diff)
aminoglycosides
bind 30S subunit, block initiation by preventing attachment of tRNA-fMet (protein synthesis inhibitor)
streptomycin, neomycin, gentamicin, tobramycin, amikacin
use: G- enterics, synergy with cephs/pens (facilitate entry)
aminoglycoside resistance
altered P12 ribosomal protein
aminoglycosidases
altered permeability
tetracycline
inhibits binding of aa-tRNA to A-site of 30S subunit (protein synthesis inhibitor) but side effects: toxicity, dizzy, tinnitus, fluorescent teeth, NOT FOR PREGGERS
doxycycline, tigecycline
use: rickettsia, chlamydia, mycoplasmas
chloramphenicol
inhibits peptidyl transferase rxn - 50S (protein synthesis inhibitor)
no longer a drug of choice, toxicity and resistance - chloramphenicol acetyl transferase (CAT)
macrolides
bind rRNA, inhibit translocation - 50S (protein synthesis inhibitor) - prolonged QT interval (EKG), increased CV risk
erythromycin, clarithromycin, azithromycin (Z-pack)
use: G+, some G-
macrolide resistance
methylation of rRNA
lincosamides
bind rRNA, inhibit translocation - 50S (protein synthesis inhibitor) - same as macrolides
clindamycin
use: anaerobes, anti-malarial, doesn’t cross BBB
nitrofurantoin
inhibits 30S (protein synthesis inhibitor)
use: UTIs
mupirosin
inhibits Ile-tRNA (protein synthesis inhibitor)
use: topical, G+
streptogramins/ synercid
inhibits 50S (protein synthesis inhibitor) quinupristin + dalfopristin
use: VRE, VRSA
oxazolidinones - linezolid
inhibits 50S (protein synthesis inhibitor)
use: VRE, MRSA
methenamine
releases formaldehyde in acidified urine
use: UTIs
how do you target persistor cells?
C10, BF8 - wake up persistor cells, then use other abx to target the newly growing cells
which drugs should not be used for pregnant women?
- amikacin
- kanamycin
- streptomycin
- tobramycin
- sulfa drugs
- all tetracyclines
- erythromycin
- macrobid and nitrofurantoin
which drugs are cell wall inhibitors?
- beta-lactams (penicillins, cephalosporins, monobactams, carbapenems)
- bacitracin
- glycopeptides (vancomycin, telavancin)
- cycloserine
which drugs are cell membrane disruptors?
- polymyxins (colistin)
- daptomycin (cubicin)
- sulfonamides (sulfones) + trimethoprim (aka bactram, SxT)
which drugs are nucleic acid inhibitors?
- (fluoro)quinolones (ciprofloxacin, moxifloxacin)
- fidaxomycin (dificid)
- rifamycin (rifampin, rifabutin, rifaximin)
- metronidazole
which drugs are protein synthesis inhibitors?
- aminoglycosides (streptomycin, neomycin, gentamycin, tobramycin, amikacin)
- tetracycline (doxycycline, tigecycline)
- chloramphenicol
- macrolides (erythromycin, clarithromycin, azithromycin)
- lincosamides (clindamycin)
- nitrofurantoin
- mupirosin
- streptogramins/ synercid
- oxazolidinones (linezolid)
- methenamine
