Antibiotics Flashcards
Sulfonamides: spectrum and static/cidal?
broad, static
what general mechanism do sulfonamide inhibit?
synthesis of nucleotides - prevention of transcription and DNA replication
what is the exact mechanism of sulfonamides?
sulfonamides inhibit dihydropteroate synthetase by acting as a competitive inhibitor against PABA - they therefore inhibit folic acid synthesis
what drug is often used in conjunction with sulfonamides?
trimethoprim
what is the mechanism for trimethoprim?
it is used in conjunction with sulfonamides to block the folic acid synthesis pathway - it inhibits dihydrofolate reductase by competitively inhibiting DHFA
what is the selective toxicity of sulfonamides?
humans get folic acid from diet - we dont make it
what is the combined use of sulfonamide and trimethoprim an example of?
synergism
what is p-aminosalicylic acid (PAS)
it works similar to sulfonamides but is effective against mycobacterium tuberculosis while sulfonamides are not
what is the spectrum and cidal/static action of rifampin and rifabutin?
narrow: G+ (staph and strep), Neisseria, and Mycobacteria
cidal
spec/stat/cidal for quinolones?
cidal for narrow spectrum of G- (E. coli, Proteus, Klebsiella, Enterobactor)
often used for UTIs
what is the mechanism of quinolones?
block bacterial gyrase and topoisomerase
what are “floxin’s” used for? (spectrum and a specific organism)
broad spectrum
active against pseudomonas
what does metronidazole affect?
nucleic acid synthesis - DNA breaks and secondary mutations
what is the spect for metronidazole?
narrow for anaerobic infections
also for protozoal infections due to Entamoeba histolytica and Giardia lamblia
what is the selevtive toxicity for metridonazole
it is a prodrug that is only metabolized by bacterial nitroreductases
what is the spect for polymyxins?
narrow - pseudomonas
what is an example of a polymyxin?
colistin
mechanism of polymyxin?
has hydrophilic head and tail - tail gets inserted into membrane and head binds to phosphatidylethanolamine )PE) and LPS
what is the enzyme that makes special amino acids for peptidoglycans?
racemase
what is the antibiotic that targets racemase?
cycloserine
what antibiotic prevents transglycosylation?
vancomycin - it binds the D-ala-D-ala and sterically hindering the assembly of disaccharide units
what species can you use vancomycin for?
MRSA and enterococcus (G+)
what is the conferred resistance that bacteria have developed to vancomycin?
use D-ser or D-lac instead of D-ala
what type of cross-linking is present in Gram - bacteria?
adjacent D-ala’s
what type of cross-linking is present in Gram + bacteria?
adjacent D-ala’s
also pentaglycine bridges
*this makes the cell wall thicker
what enzymes perform transpeptidation?
transpeptidases and carboxypeptidases - they recognize D-ala-D-ala and catalyze the cross links
what enzymes work against transpeptidation?
beta-lactmas like penicillin which look a lot like D-ala so they sequester transpeptidases and carboxypeptidases
what are some examples of beta-lactams?
monobactam, penicillin, cephalosporin, cephamycin, carbapenem
what is the name for the class of molecules that includes transpeptidases and carboxypeptidases?
penicillin-binding proteins
what are the two ways bacteria inhibit penicillins/beta-lactams?
make substance that inactivates it; alter the target of the beta-lactam
what is an example of a bacterial resistance enzyme against beta-lactams?
beta-lactamase (aka penicillinase) - it breaks down the beta-lactam ring of penicillin
also have cephalosporinases
what are the first generation penicillins?
penicillin G, V
best for GM+
what are the 2nd and 3rd generation penicillins
ampicillin (GM- too)
amoxacillin (GM+ and -)
methicillin, oxacillin, nafcillin (beta-lactamase resistance)
carbenicillin, ticarcillin, piperacillin ( also works for pseudomonas)
how does methicillin resistance work?
change the target of the antiobiotic method - so you change the transpeptidase so that methicillin cannot bind to it - it is called penicillin binding protein 2
how can you use beta-lactamase inhibitors?
use them in conjuction with a penicillin so that the inhibitor can work and then the the anitbiotic can work
what is an example of the conjuction of a beta-lactamase inhibitor and a penicillin?
augmentin
combo of amoxicillin and clavulanic acid
what is the spect/cidial/static foe daptomycin?
narrow for GM+ and cidal
what is chemical composition of daptomycin?
it is a cyclic amino acid structureq
what is the mechanism of daptomycin action?
it aggregates on the cell membrane of the bacteria and the lipid tail inserts into the cell membrane, making a pore that causes loss of membrane potential - cell death
what is daptomycin a good alternative for?
vancomycin use against MRSA
list the drugs that inhibit cell wall synthesis
penicillin, cephalosporing, carbepenums, monobactams (transpeptidation)
bacitracin (inhibits export of PG components)
vancomycin (inhibits transglycosylation)
list the drugs that disrupt the cell membrane
polymyxins, daptomycin
what are the antibiotics that target amino acid activation in bacterial protein synth?
none!
what are the antibiotics that target formation of the initiation complexes of ribosomes
linezolid
what does linezolid do?
it inihibits the formation of the 70S initiation complex (tRNA, mRNA, 70S complex) by binding peptidyltransferase center
what is the spectrum/static/cidal for linezolid?
static for staph and enterococci
cidal for strep
ONLY approved for G+
can be lethal when given for G-
what do aminoglycosides inhibit?
targets specific proteins in 30S subunit, blocking codon/anticodon interaction
what are some aminoglycosides?
streptomycin, kanamycin, paramomycin, amikacin, tobramycin, neomycin, gentamycin
what is the spectrum/static/cidal for aminoglycosides?
broad (G+,-)
cidal
what is one important thing about aminoglycosides?
it functions against tuberculosis
what are the three mechanisms of action of streptomycin?
misreading: incorrect aa inserted
cyclic polysomal blockade: 70S complex forms but falls apart due to instability
faulty outer membrane proteins: due to misreading, faulty membrane proteins disrupt the membrane
what are some bad side effects of streptomycin?
ototoxicity and nephrotoxicity
what can make aminoglycosides less effective?
anaerobisis, low pH, ions
what is spectinomycin?
an aminocyclitol antibiotic that affects codon/anticodon reaction
is spectinomycin static or cidal?
static
what is the mechanism of action of spectomycin?
it causes unstable formation of 70S initiation complexes
what do we use spectomycin for?
gonorrhea caused by beta-lactamase producing gonococci
spectrum/static/cidal for tetracycline?
broad, static
what is the mechanism of action for tetracycline?
interrupts codon/anticodin interactions -it binds to 30S ribosomal subunit preventing binding of first tRNA
what do we use tetracycline for?
chlamydia, mycoplasma, rickettisa and intercellular pathogens
spect/cidal/static for chloramphenicol?
broad spectrum, static
what is the mechanism for chloramphenicol?
it blocks peptiyl transfer by binding to the 50S subunit and altering the tRNA structure
spect/cidal for lincomycin and clindamycin?
static
narrow - good for G+ bacterial infections, staph, and anaerobic G-
what is the mechanism for lincomycin and clindamycin?
similar to cloramphenicol - binds to 50S subunit and alters tRNA, preventing peptidyl transfer
spect/cidal/static for macrolides?
medium spectrum, static
good against intracellular pathogens - mycoplasma, legionella, chlamydia, campylobacter and G+ in pts allergic to penicillin
what are some examples of macrolides?
azithromycin and clarithromycin
mechanism for macrolides?
block translocation
spect/cidal/static for ketolides?
cidal or static depending on bacterium and strength of interaction
what is the mechanism of ketolides?
works by binding within the exit tunnel of 50S unit, blocking exit of nascent polypeptides; it strongly binds to two domains of RNA of ribosome
what is an example of a ketolide?
telothromycin
what is streptogramin?
a cyclic peptide antibody that is produced by subspecies of streptomyces
what is the mechanism of streptogramin?
blocks translocation
what are some examples of streptgramins?
dalfopristin, quinupristin, and synercid (quinupristin &dalfopristin together - they are cidal together, static alone)
what organisms can you use streptogramins against?
staph, strep, enterococcus, but primarily for treating vancomycin resistant enterococcus
what is the mechanism for rifampin/rifabutin
binds to beta-subunit of RNA polymerase, inhibiting transcriptional initiation
