JAL L2 Antimicrobials Flashcards
PG - peptidoglycan AA - amino acid
Define antimicrobials
chemicals which kill or inhibit microbial growth
Sources of antimicrobials? 3
microorganism
synthese
semisynthesis* (most common)
Most antimicrobials kill only …….. bacteria
actively growing
Ideal antimicrobial properties: 3
selective activity
cidal activity
slow emergence of resistance
ideal pharmacological properties of antimicrobials: 6
- non toxic
- long t1/2
- good tissue distribution
- low protein binding
- oral & parenteral
- no interactions
4 sites of antimicrobial action
cell wall
cell membrane
nucleic acid synthesis
protein synthesis
inhibitors of cell wall synthesis inhibit synthesis of…
peptidoglycan
What type of bond is found in peptidoglycan
glycosidic
Initial step of peptidoglycan synthesis
D-Ala-Ala bonds to AA side chain to form pepto peptide
What does pentopeptide attach to that carries if to the exterior of the cell
Bactoprenol c55 lipid carrier.
PG cross linking via amino acid side chain requires…. (2)
transpeptidases
Loss of terminal AA from the side chain
β-Lactam have what common structure
β-Lactam ring (square with =O off bottom left and N at bottom right corner)
what do β-Lactam bind to?
Penicillin binding proteins (transpeptidases)
What do penicillin binding proteins normally do?
x-link
so β-Lactam binding prevents x-linking
What does β-Lactam mimic to bind….
D-Ala-D-Ala - so they get incorporated into the cell wall.
What does incorporation of β-Lactam into the cell wall caus?
autolysins to break down the cell wall
Are β-Lactam more effective on gram negative of gram positive?
negative (as they get trapped between the outer and cytoplasmic membrane and therefore higher conc)
2 e.g. of glycopeptides?
teicoplanin
vancomycin
how do glycopeptides work? (2)
- binds to terminal D-Ala-D-Ala. Prevents transglycosylase enzyme from adding PG monomer onto glycan chain.
(cannot lose terminal D-Ala-D-Ala to provide energy for cross linking) - prevents x linking
2 e.g. of polymyxins
polymyxin C, polymyxin E (colistin)
Where do polymyxins act?
at the cell membrane
Polymyxins work on gram positive or negative?
ONLY gram negative as they bind to outer membrane for effect.
How do polymyxins work?
Disrupt the membrane causing leakage of cytoplasmic contents.
What class of antimicrobials acting on Nucleic Acid Synthesis are ‘Metabolic inhibitors of NA synthesis’? (2)
Sulphonamides
Trimethoprim
What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect DNA replication’?
Fluoroquinolones
e.g. ciprofloxacin and levofloxacin
What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect RNA polymerase’?
Rifamycins
What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect DNA’?
Nitroimidazoles
How do Fluoroquinolones work?
Reduce Type II DNA gyrase AND/OR Type IV topoisomerases.
What does Type II DNA gyrase normally do?
removes DNA supercoils ahead of replication fork
What does Type IV topoisomerase do?
separates DNA after replication
Inhibitors of protein synthesis tend to be static or cidal?
Static
Why more s/e with inhibitors of protein synthesis?
Similar process for eu and prokaryotes
What class is gentamycin?
Aminoglycoside
What class is linezolid?
Oxazolidinones
Where do aminoglycoside bind to act?
on the 30S subunit.
Work by reducing initiation and assembly of the ribosome,
Reduce binding and assembly of tRNA in A site and translocation
Where do oxazolidinones and SOME aminoglycoside bind to act?
50S subunit.
Reduce assembly of the initiation complex
Where to tetracyclines bind to act?
30S subunit of ribosome, reduce binding of tRNA in A site
Where does chloramphenicol bind to act?
50S subunit
reduces peptide bond formation
Where do macrolides bind to act?
50S subunit
reduce translocation and release of tRNA
Where does fusidic acid bind to act?
EF-G complex
to reduced translocation of tRNA from A to P site
