Bailey 2 Flashcards
What is an ideal antibiotic
- Broad spectrum
- No resistance
- High TI
- Selective toxicity
Therapeutic index
Toxic dose:effective dose
Higher the better
How do you achieve selective toxicity?
- Cell wall unique in microbes
- Enzymes
- Unique metabolites
- ribosomal structure in microbes
5 ways that antibiotics inhibit bacteria
1) Cell wall synthesis
2) Cell membrane function
3) Protein synth
4) DNA synth
5) Antimetabolites
Penicilin mode of action
Disrupts cell wall formation by adding a D-ala, preventing cross links from forming
Polymyxin B sulfate
Disrupts cell membrane by binding to phospholipids
How is nucleic acid synth disrupted
DNA Binding: -Metronidazole- inert but can be converted into active form by anaerobic microbes DNA gyrase: -Nalidixic acid -Quinolones RNA pol: -Rifamycin
Antimetabolite drug ex.
PABA is the metabolite
PAS (para-aminosalicylic acid) is anti metabolite
Sulfonamide also anti metabolite
Steps in the action of antibiotics related to drug resistance
1) Drug penetrates envelope
2) Transport into cell
3) Drug binds to target
-Resistance occurs at each step
Mechanisms of drug resistance
1)Synth of enzymes that inactivate drug
-B-lactamases break bond in penicillin
2)Prevention of access to the target site
(A) Inhibiting uptake
-Tetracycline and quinolone resistance by blocking porins
(B) Increasing secretion of drug
-Tetracycline resistance by efflux pumps
-All classes have drug efflux transporters
3)Modification of target site
-Modify enzyme affinity
-Alteration of metabolic pathway
How does resistance spread?
1) Chromosome associated resistance
2) Plasmid mediated resistance
3) Rapid spread of resistance
What happens if antibiotics are stopped prematurely?
Only highly resistant organisms fluorish
How do we combat antibiotic resistant pathogen?
Synergism
Antagonism
Indifference
Drawbacks of antibiotic cocktail
- Failure to eliminate pathogen may lead to superinfection
- synergistic toxicity
