anti-microbials Flashcards
what are the two main targets of antibiotics
bacterial cell wall synthesis
bacterial protein synthesis
what are the main stages of bacterial protein synthesis
-Nucleic Acid Synthesis:
PABA–>DHOp–> DHF–>THF (important in nuc. acid syn)
-DNA Replication:
Topoisomerase releases tension (DNA gyrase)
RNA polymerase produces RNA from DNA template
-Protein Synthesis: Ribosomes produce protein from RNA templates (30s/50s instead of 40s/40s)
what classes of antibiotics target bacterial protein synthesis (state their targets)
-Sulphonamide – inhibits DHOp synthase
-Trimethoprim – inhibits DHF reductase
-Fluoroquinolones (e.g. ciprofloxacin) inhibit DNA gyrase
and topoisomerase IV
-Rifamycins (e.g. rifampicin) inhibits bacterial RNA polymerase
-Ribosomes are inhibited by:
o Aminoglycosides (e.g. Gentamicin)
o Chloramphenicol
o Macrolides (e.g, erythromycin)– MAIN ONE
o tetracyclines
how is the bacterial cell wall synthesised
- a pentapeptide is created on N-acetyl muramic acid (NAM)
- the NAM/ pentapeptide binds to N-acetyl glucosamine (NAG) to form Peptidoglycan (PtG)
- the PtG is transported across cell membrane by BACTOPRENOL
- PtG incorporated into cell wall by cross links formed between pentapeptides by transpeptidase enzyme
which antibiotics target bacterial cell wall synthesis (and state their targets)
-GLYCOPEPTIDES e.g. vancomycin bind to the pentapeptide preventing PtG synthesis
-BACITRACIN inhibits bactoprenol regeneration preventing PtG transportation
-B-LACTAMS bind covalently to transpeptidase inhibiting PtG transportation E.g. CARBAPENEMS, CEPHALOSPORINS, PENICILLINS
Cell wall stability:
o LIPOPEPTIDE e.g. daptomycin disrupts Gram +ve cell walls
o POLYMIXINS bind to LPS and disrupts Gram –ve cell membranes
what are the different types of beta-lactams
carbapenems
cephalosporins
penicillins
what are the 5 mechanisms of antibiotic resistance
1) Production of destruction enzymes
2) Additional target
3) Alterations in target enzyme
4) Hyperproduction
5) Alterations in drug permeation
What are the causes of antibiotic resistance?
unnecessary prescription, livestock farming, lack of regulation, lack of development
give an example of 1)Production of destruction enzymes
Some bacteria produce B-lactamases
Hydrolyses the C-N bond of the B-lactam ring
Confers antibiotic resistance
eg penicillin G & V
give an example of 2) Additional target
Bacteria produce another target that is unaffected by the drug
eg: E.coli produces a different DHF reductase making it resistant to trimethoprim
give an example of 3) Alterations in target enzyme
The original target of the antibiotic is altered
Antibiotic is no longer effective
eg: S. aureus has mutations in the ParC region of topoisomerase IV which confers resistance to quinolones.
give an example of 4) Hyperproduction
Bacteria significantly increase levels of DHF reductase
Essentially bacteria overproduce enzmyes in the hope that the antibiotic will become less effective
This is not sustainable for the bacteria
Eg: E. coli produce additional DHF reductase–>trimethoprim less effective
give an example of 5) Alterations in drug permeation
Some antibiotics will use aquaporins to enter the bacterium
The bacterium reduces aquaporins and increases efflux systems —> Net effect is to stop antibiotic from entering and effluxing any amount that has made it inside the bacterium
what b-lactams are b-lactamase resistant
Flucloxacillin & Temocillin Beta-lactamase resistant (Flucloxacillin is for Gram +ve and temocillin for gram –ve)
Amoxicillin (Broad spectrum Gram -ve) ONLY IF Co-administered with Clavulanic acid.
what are the two classes of anti-fungal drugs
Azoles – prevent ergosterol synthesis via Inhibiting CYP450 enzymes
Polyenes – interact with cell membrane ergosterol forming membrane pores- punch holes in membrane
