Antimicrobial Modes of Action

Question 1

what are antimicrobials

Answer 1

chemicals that kill or inhibit microbial growth in or on a body surface
includes antifungals, antivirals and antibiotics

Question 2

what is the function of antimicrobials

Answer 2

bacteriostatic or bactericidal

most only kill actively growing bacteria

Question 3

what is semi-synthesis

Answer 3

organic product that is chemically modified to improve efficacy/selectivity

Question 4

what are some antimicrobial properties

Answer 4

specific to target site, selective to infecting organism, cidal, slow emergenge of resistance

Question 5

what are some pharmacological activities of antimicrobials

Answer 5

non-toxic to host, long plasma half life, good tissue distribution, low plasma protein binding, oral and parenteral, no interference with other drugs

Question 6

what are some inhibiotrs of cell wall synthesis

Answer 6

beta-lactams, glycopeptides

Question 7

what are some examples of beta lactams

Answer 7

penicillins, cephalosporins, carbapenems, monobactams

Question 8

what are some examples of glycopeptides

Answer 8

vancomycin, teicoplanin

Question 9

what is the cell wall made from

Answer 9

peptidoglycan

rigidity due to cross linkage (like a fine mesh)

Question 10

what is the structure of cell wall synthesis inhibitors

Answer 10

all contain beta lactam ring with different side chains and R-groups

Question 11

how do cell wall synthesis inhibitors (beta lactams) work

Answer 11

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

Question 12

what inhibitors act on cell membranes

Answer 12

polymyxins (colistin), lipopeptides

Question 13

how do cell membrane inhibitors (polymyxins) work

Answer 13

they disrupt the membrane and cause leakage of cytoplasmic contents
they target the lipopolysaccharides that stick out of the cell membrane

Question 14

what bacteria do polymyxins work on

Answer 14

gram negative bacteria only

Question 15

what antibacterials act on nucleic acid

Answer 15

metabolic inhibitors of NA synthesis (sulphonamides, trimethoprim), affect DNA replication (flouroquinolones), affect RNA polymerase (rifamycins), affect DNA (nitromidazoles)

Question 16

what antimicrobials inhibit DNA replication

Answer 16

flouroquinolones

e.g. ciprofloxacin, levofloxacin

Question 17

how do inhibitors of DNA replication (flouroquinolones) work

Answer 17

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

Question 18

what is the function of DNA gyrase in replication

Answer 18

removes DNA supercoils ahead of replication fork

Question 19

what is the function of topoisomerases during replication

Answer 19

separates DNA after replication

Question 20

what protein synthesis imnhibitors target the 50s ribosomal subunit

Answer 20

macrolides/streptogramins/lincosamides, oxazolinidones, chloramphenicol

Question 21

what protein synthesis inhibitors target 30s ribosomal subunit

Answer 21

fusidic acid

tetracyclines, aminoglycosides

Question 22

what are the steps in the initiation part of protein synthesis

Answer 22

1. tRNA brought to start codon on mRNA
2. 30s subunit attaches to mRNA
3. 50s subunit comes into place and completes the initiation complex

Question 23

what are the steps in the elongation part of protein synthesis

Answer 23

1. 2nd tRNA enters acceptor site
2. aa detaches from 1st RNA - peptide bond formed between 1st and 2nd aa
3. translocation: ribosome moves along ribosome by 3 codons

Question 24

what are the steps in the termination part of protein synthesis

Answer 24

1. ribosome reaches stop codon

2. specific proteins cause ribosomal subunits to separate and peptide chain is released

Question 25

what antimicrobials are inhibitors of protein synthesis

Answer 25

tetracyclines, aminoglycosides

Question 26

how do tetracyclines work

Answer 26

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

Question 27

how does the aminoglycoside gentamicin work

Answer 27

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