Antibiotics Flashcards
What are antibiotics?
- Natural metabolic product of bacteria and fungi
- Modern antibiotics made from fermentation and modification
What are antimicrobials?
Antibacterials, antifungals, antivirals and antiparasitics
Lag phase
Plentiful nutrients and space
Log phase
Grow exponentially, reaches carrying capacity
Stationary phase
Carrying capacity reached, build up of waste product
Death phase
Waste products and lack of nutrients/space kill bacteria
Good antibiotics
Broad spectrum allows you to have confidence that all bacteria targeted, good when unsure of infection
- Safe - not toxic (cancer drugs)
- Slow emergence of resistance
- Long half life - don’t take drug too regularly
- Good tissue distribution - compartmentalised means use is limited
- Oral bioavailability
- Cheap
What is selective toxicity?
Severely damage microorganisms but have little effect on human metabolism
Magic bullets target bacteria cells but not human
What ribosomes do bacteria have?
70S
Gram positive bacteria
Staph
Clostridium
Strep
Listeri
gran neg bacteria
E.coli
Pseudomonas
Klebseilla
Neisseria
Aerobic bacteria
Pseudomonas and neisseria
Anaerobic bacteria
Clostridium
Both anaerobic and aerobic bacteria
Staph, strep, listeria and e.coli
How do antibiotics affect cell wall synthesis
- Peptidoglycan present in bacteria cell wall
- Long polysaccharide chains + short peptide side chains
- For bacterial growth, bonds must be cut
- If transpeptidation inhibited - bacterial cells lyse - punching holes in wall so ions/fluid pass into cell (osmotic gradient set up)
- B-lactam antibiotics inhibit transpeptidases e.g. penicillin, cephalosporins, carbapenams
- Glycopeptide antibiotics inhibit crosslinking by binding residues on side chain to prevent cross-linking e.g. vancomysin
- If bacteria resistance to B-lactam, possible to be resistant to all classes
Metabolic antagonism
- Interrupt bacterial metabolic pathways
- e.g. trimethoprim, sulfadiazine
- Bacteria can’t use pre-existing folic acid so must make own
- Humans use dietary folic acid
- Tetrahydrofolate from PABA Antibiotics target 2 checkpoints - formation of folate and conversion to tetrahydrofolate
- Trimethoprim is competitive inhibitor to prevent DNA being made
Interference with nucleic acid synthesis
- Bacterial DNA stored ‘supercoiled’
- Uncoiled for replication (DNA polymerase) and transcription to mRNA (RNA polymerase)
- DNA gyrase unwinds DNA
- Quinolones inhibit DNA gyrase
- Rifamycins inhibit RNA polymerase
- Metronidazole - pro drug, converted to toxic metabolite to attack DNA of bacterial cells in anaerobic conditions
- Inhibits DNA synthesis and breaks down DNA
Inhibition of protein synthesis
- Bacterial ribosomes differ from human ones
- Macrolides = 50S (clarithromycin)
- Aminoglycosides = 30S (gentamicin)
- Tetracyclines = 30S (doxycyline
- Aminoglycosides bind to 30 and 50 sub-unit
When is colisicethate sodium used?
Gram -ve infections resistant to other antibacterials
Polymyxin B
Neurotoxicity and nephrotoxicity
Which bacteria causes the community acquired pneumonia?
Streptococcus pneumonia (gram +ve)
Site of infection of strep
lower respiratory tract
Spectrum of amoxicillin
Broad
Can penicillin penetrate wall of gram -ve bacteria?
No
What does B-lactamase do?
Breaks down the B-lactam ring and inactivates penicillin
Spontaneous mutation
When bacteria multiply, mutations mean that the susceptibility of bacteria to a drug changes
Conjugation mutation
From one bacterium to another
Bacterial sex, uses mobile elements like plasmids to move DNA between organisms
Transduction
Virus infects bacterium and takes DNA to another bacterium cell
Transformation
Bacteria incorporate making DNA into genome to get resistance from surrounding environment
What is altered uptake?
Reduce entry to bacteria by removing transporters, opposite is active exit of drug
What is drug inactivation?
B-lactamase in penicillin
What is an altered target site?
Altering either sub-units with ribosomes so ahminoglycosides can’t bond
