Antibiotics MOA + classification Flashcards
Define eukaryote and give examples
cells with nuclei/membrane-bound organelles
protozoa, fungi, helminths
Define prokaryote and give examples
cells without nuclei/membrane-bound organelles
bacteria
How do viruses replicate?
utilise metabolic machinery of host in order to replicate
What are the 4 main sites of action of antimicrobials?
cell wall
cell membrane
ribosomes
DNA
How is an antibiotic chosen?
penetrates site of infection
fewest number of side effects
no drug interactions
What is a big part of gram +ve bacteria cell wall?
peptidoglycan
Which antibiotics inhibit cell wall synthesis?
Beta lactam agents (penicillins, cephalosporins, carbapenems, monobactams)
glycopeptides (vancomycin, teicoplanin)
Fosfomycin
Bacitracin
What bacteria does flucloxacillin specifically target?
Staphylococcus Aureus
How do beta lactams work?
bind to penicillin-binding proteins (PBPs) that have transpeptidase activity
disruption of peptidoglycan synthesis
How do bacteria become resistant to Beta lactams?
alterations in penicillin-binding proteins (PBPs):
- hyperproduction of existing PBPs - saturates reaction
- production of new PBP
- modification of existing PBP by recombination
enzyme inactivation by some bacteria - beta lactamases
Name 2 beta lactamase inhibitors, what is the benefit of these?
to overcome resistance
Clavulanic acid
Tazobactam
How do glycopeptides work?
interfere with gram +ve cell wall peptidoglycan synthesis
- prevent addition of new units to peptidoglycan
- unable to crosslink
- autolysis and cell death
Toxicities of glycopeptides (eg. vancomycin)
nephrotoxic
audotoxic (hearing loss)
Which antibiotics disrupt ribosomal function and protein synthesis?
macrolides
aminoglycosides
tetracyclines
Macrolides examples
erythromycin
clarithromycin
Aminoglycosides examples
gentamicin
tobramycin
amikacin
Tetracyclines examples
doxycycline
tigecycline (a glycylcycline)
How do macrolides, aminoglycosides and tetracyclines become resistant?
efflux pumps (antibiotic out)
membrane impermeability
modifying enzymes
modification of target site (eg. alteration of rRNA)
Which antibiotics interfere with DNA synthesis?
trimethoprim
sulphonamides (hard to tolerate)
quinolones (inhibit DNA super coiling)
metronidazole (reduction products break DNA)
nitrofurantoin (causes DNA strand breaks)
What drug must not be given with methotrexate and why?
trimethoprim
both dihydrofolate reductase inhibitors
What is the main use of metronidazole?
anaerobic bacteria
What factors affect the choice of antibiotic?
likely organism and site of infection
culture and sensitivity results
patient characteristics (diseases, allergies, medications, renal/hepatic function, pregnancy, breastfeeding)
infection/severity indicators
spectrum of antimicrobial activity
formulations available (route)
cautions/contraindications/side effects
risk of C.difficile
Antibiotics used for gram +ve bacteria
Rifampicin
Fusidic acid
Clindamycin
Macrolides
Oxazolidinones
Glycopeptides
Penicillin G + Oxicillins
Antibiotics used for gram -ve bacteria
Polymyxin
Aminoglycosides
Monobactams
Temocillin
Antibiotics used for both gram -ve and gram +ve bacteria
Carbapenems
Cephalosporins
Penicillins
Chloramphenicol
Tetracycline
Which antibiotics can penetrate the lungs?
Clarithromycin (high rates of S.pneumoniae resistance)
Levofloxacin
Amoxicillin
Vancomycin
Ceftriaxone
Piperacillin/Tazobactam
Co-trimoxazole
Which antibiotics can penetrate the urinary system?
trimethoprim
co-amoxiclav
penicillins
ciprofloxacin
pivmecillinam
nitrofurantoin for uncomplicated (poor tissue penetration)
Which antibiotics can cross the blood-brain barrier (BBB)?
IV Ceftriaxone
IV Vancomycin
IV Meropenem
IV Benzylpenicillin
Which antibiotic can cross the blood-testis barrier?
Ciprofloxacin
Which Abx are nephrotoxic?
aminoglycosides
vancomycin
nitrofurantoin
Which Abx are contraindicated in pregnancy?
sulphonamides
tetracyclines
trimethoprim (safe after 1st trimester)
Isoniazid MOA
blocks fatty acid synthase
disrupts mycolic acid synthesis
Rifampicin MOA
inhibits DNA-dependent RNA polymerase
Pyrazinamide MOA
blocks fatty acid synthase
Ethambutol MOA
inhibits arabinosyl transferase
mycolic acid unable to bind to peptidoglycans
