Antibiotics Flashcards
what are antibiotics
against life
anti-bacterials
where do antibiotics come from?
metabolic products of bacteria or fungi .
Modern synthesised by fermentation then modification
phases of bacterial growth
lag phase
log - exponential phase
stationary phase
death phase
why does bacterial growth halt?
no more space or ran out of nutrients
what does bacteria need to grow?
nutrient
appropriate physical and chemical environment
what are the features of a good antibiotic?
effective safe slow emergence of resistance long half-life good tissue distribution oral bioavailability cheap Ideal antimicrobial agents severely damage microorganisms but have much less effect on human metabolism
what are the 2 types of antibiotics
bacteriostatic agent
bactericidal agent
Bacteriostatic agent
halts bacterial growth, levels out population
bactericidal agent
kills bacteria, reduces number of bacteria present
what are the different modes of action?
inhibition of cell wall synthesis metabolic antagonism interference with nucleic acid synthesis inhibition of protein synthesis action on membrane
cell wall synthesis
peptidoglycan present in bacterial cell walls
long polysaccharide chains and short peptide side chains
for bacterial growth - bonds must be cut
if transpeptidation is inhibited - bacterial cells lyse
prevents formation of cross-links between tetrapeptide chains
cell wall synthesis inhibitors
beta lactam antibiotics inhibit transpeptidation
glyopeptide antibiotics inhibit cross linking
examples of beta lactam antibiotics
penicillins
cephalosporins
carbapenams
example of glycopeptide antibiotic
vancomycin
metabolic antagonism
interrupt bacterial metabolic pathways
block enzyme activity by various mechanisms
Interrupts the folic acid pathway by inhibiting intermediates within the pathway .
e.g. trimethoprim
what is folic acid needed for?
DNA synthesis
Interference with nucleic acid synthesis
bacterial DNA stored as supercoiled
uncoiled for replication and transcription
DNA gyrase assists with unwinding .
selective toxicity
ideal antimicrobial agents severely damage microorganisms but have much less effect on human metabolism
examples of antibiotics that interfere with nucleic acid synthesis
Quinolones - ciprofloxacin which inhibits DNA gyrase
Rifamycins - rifampicin which inhibits RNA polymerase
what is metronidazole?
pro drug
converted to toxic metabolite
inhibits DNA synthesis and breaks down existing DNA
inhibition of protein synthesis
bacterial ribosomes differ from human ones
examples of antibiotics that inhibit protein synthesis
macrolides
aminoglycosides
tetracyclines
what do macrolides do?
target 50S subunit
e.g. clarithromycin
what do aminoglycosides do?
target both subunits
e.g. gentamicin
they are unlike other protein synthesis inhibitors bactericidal
what do tetracyclines do?
target 30S subunit
e.g. doxycycline
antibiotics that act on cell membrane
reserved only for gram negative infections that are resistant to other antibacterials
need to monitor neurotoxicity and nephrotoxicity
rarely use in bacteria but are very important as antifungal drugs
examples of antibiotics that target the cell membrane
colistimethate sodium
polymyxin B
effective use of antibiotics
knowledge of likely infecting organism likely bacterial susceptibility site of infection spectrum of action absorption and distribution of antibiotics
pharmacological considerations of antibiotics
target site of infection affects route of administration
knowledge of route of excretion
modify dose according to patient, specifically renal or liver disease
antibiotic resistance
some microorganisms are naturally resistant to some antibiotics whilst others acquire resistance especially when under selective pressure
natural resistance e.g.
penicillin cannot penetrate cell wall of gram -ve bacteria
acquired resistance e.g.
bacteria produce beta lactamase so beta lactams are no longer effective in some bacteria
mechanisms by which bacteria develop resistance
spontaneous mutation
conjugation
transduction
transformation
what is conjugation?
sharing of DNA between bacteria
what is transduction
genetic recombination in bacteria in which genes from a host cell are incorporated into the genome of a bacterial virus - bacteriophage and then carried to another host cell when the bacterophage initiates another cycle of infection
what is transformation?
incorporates dead bacterial DNA into the genome of a living bacteria
mechanisms of resistanc
altered up take increased exit drug inactivation altered target site altered metabolic pathways
what happens in increased exit?
the bacteria removes the antibiotic from the cell
what happens in altered target site?
mutation of target site
what happens in altered metabolic pathways?
bypasses target action of drug
