Intraintestinal inactivation of residual antibiotics Flashcards
How are antibiotics used in agriculture?
antibiotics are used at sub therapeutic dose as a growth promotion factor in farm animals
How does antimicrobial resistance occur in gut microbiota?
residual antibiotics disturb microbiota balance
sections of resistant bacterial strains fill the microbiological vacuum
the weak antibiotic doses and long/close contact with bacteria encourage resistance emergence (‘mutation’)
resistance transfer to pathogenic bacterial in the gut and in nature
How can resistance to antibiotics be overcome?
avoiding extensive use of antibiotics
protecting colonic microflora
- avoid close contact of residual antibiotics and colonic microflora
- intraintestinal inactivation of residual antibiotics
What factors need to be considered when attempting intraintestinal inactivation of residual antibiotics?
inactivating agents co-administered with antibiotics
antibiotic absorption/pharmacokinetic should not be affected
- should not affect beyond the absorption window
inactivation agent being released as soon as possible after the absorption window
- controlled release dosage form
What are the different inactivation mechanisms?
enzymatic inactivation
inactivation by adsorption
inactivation by complexation
What are the properties of enzymatic inactivation?
it is specific and irreversible
it is limited to specific classes of antibiotics
delivery is problematic - enzyme stability in the GIT is an issue
What are the properties of inactivation by adsorption?
it is non specific and has a high inactivation capacity.
it covers all antibiotic classes
it is possibly reversible
What are the properties of inactivation by complexation?
it is specific and permanent
it is limited to specific classes of antibiotics
How does the GIT change as you move through it?
enzymatic activity decreases
pH and motility increases
What the different strategies to release inactivating agents in specific areas of the GIT?
pH dependent delivery
time dependent delivery
bacteria dependent delivery
pressure dependent delivery
What is pH dependent delivery?
replies on the pH gradient existing in the GIT
- polymeric coatings on solid substrates are used
coating polymer is sensitive to a specific pH value where the drug release happens
- most commonly used is Eudragit
What is time dependent delivery?
relies on delaying the drug release after a predetermined time
for instance, to obtain colonic release, the lag time should equate to the time taken by the system to reach the colon (~5h).
What is bacteria dependent delivery?
relies on the difference in bacteria concentrations and enzymatic activities between the upper and lower gut
- polysaccharide based materials are used for colon delivery
= chitosan or dextran
What is an example of enzymatic inactivation?
β-lactamase is loaded onto calcium pectinate beads for the colonic inactivation of β-lactams
- colonic delivery is needed to avoid gastric low pH and protease
the high concentration of β-lactamase found in the faeces is expected to inactivate the residual amoxicillin and protect the gastrointestinal microbiota
What is an example of inactivation by adsorption?
activated charcoal is loaded onto zinc pectinate beads for the intestinal inactivation of ciprofloxacin
ciprofloxacin absorption window is the duodenum
