Antimicrobial Modes of Action Flashcards
what are antimicrobials
chemicals that kill or inhibit microbial growth in or on a body surface
includes antifungals, antivirals and antibiotics
what is the function of antimicrobials
bacteriostatic or bactericidal
most only kill actively growing bacteria
what is semi-synthesis
organic product that is chemically modified to improve efficacy/selectivity
what are some antimicrobial properties
specific to target site, selective to infecting organism, cidal, slow emergenge of resistance
what are some pharmacological activities of antimicrobials
non-toxic to host, long plasma half life, good tissue distribution, low plasma protein binding, oral and parenteral, no interference with other drugs
what are some inhibiotrs of cell wall synthesis
beta-lactams, glycopeptides
what are some examples of beta lactams
penicillins, cephalosporins, carbapenems, monobactams
what are some examples of glycopeptides
vancomycin, teicoplanin
what is the cell wall made from
peptidoglycan
rigidity due to cross linkage (like a fine mesh)
what is the structure of cell wall synthesis inhibitors
all contain beta lactam ring with different side chains and R-groups
how do cell wall synthesis inhibitors (beta lactams) work
they bind and inhibit penicillin binding proteins (transpeptidases) which prevents cross linking and causes cell lysis
they get incorporated into peptide side chains which prevents cross linking
they can stimulate autolysins which break down the cell wall and cause lysis
what inhibitors act on cell membranes
polymyxins (colistin), lipopeptides
how do cell membrane inhibitors (polymyxins) work
they disrupt the membrane and cause leakage of cytoplasmic contents
they target the lipopolysaccharides that stick out of the cell membrane
what bacteria do polymyxins work on
gram negative bacteria only
what antibacterials act on nucleic acid
metabolic inhibitors of NA synthesis (sulphonamides, trimethoprim), affect DNA replication (flouroquinolones), affect RNA polymerase (rifamycins), affect DNA (nitromidazoles)
what antimicrobials inhibit DNA replication
flouroquinolones
e.g. ciprofloxacin, levofloxacin
how do inhibitors of DNA replication (flouroquinolones) work
bind to and inhibit DNA gyrase and/or topoisomerases when complexed with bacterial DNA
this inhibits DNA replication and packaging of DNA within the bacterial cell - causing lysis
what is the function of DNA gyrase in replication
removes DNA supercoils ahead of replication fork
what is the function of topoisomerases during replication
separates DNA after replication
what protein synthesis imnhibitors target the 50s ribosomal subunit
macrolides/streptogramins/lincosamides, oxazolinidones, chloramphenicol
what protein synthesis inhibitors target 30s ribosomal subunit
fusidic acid
tetracyclines, aminoglycosides
what are the steps in the initiation part of protein synthesis
- tRNA brought to start codon on mRNA
- 30s subunit attaches to mRNA
- 50s subunit comes into place and completes the initiation complex
what are the steps in the elongation part of protein synthesis
- 2nd tRNA enters acceptor site
- aa detaches from 1st RNA - peptide bond formed between 1st and 2nd aa
- translocation: ribosome moves along ribosome by 3 codons
what are the steps in the termination part of protein synthesis
- ribosome reaches stop codon
2. specific proteins cause ribosomal subunits to separate and peptide chain is released
what antimicrobials are inhibitors of protein synthesis
tetracyclines, aminoglycosides
how do tetracyclines work
e.g. doxycycline
bind reversibly to A-site on 16S rRNA in 30s subunit
inhibits binding of tRNA to A-site
selectively through better binding to bacterial ribosome and better accumulation of antibiotic inside bacterial cell
how does the aminoglycoside gentamicin work
binds irreversily to the A-site on 16S rRNA on 30S subunit
inhibits binding of tRNA to A-site, prevents formation of initiation complex, causes misreading of codons along mRNA which increases membrane impermeability
