antibiotics are naturally occurring substances made
by certain bacteria and fungi (these can be modified
chemically, as well)
antimetabolites are synthetic substances made from
chemicals by humans in factories
mechanisms of CTA action - CTAs work by interfering
with the synthesis or function of:
metabolites - sulfonamides, trimethoprim, and
sulfones all block generation of metabolic intermediates needed
for generation of folic acid, a vital growth factor neeed for
thymidine synthesis
membranes - amphotericin B, nystatin, polymyxin B,
imidazoles and triazoles all cause disruption of membrane
structure
cell walls - penicillin, cephalosporin, bacitracin,
and vancomycin all interfere with peptidoglycan synthesis;
isoniazid (isonicotinic acid hydrazide, INH) inhibits synthesis
of mycolic acids, which are part of the cell walls of
mycobacteria
proteins - erythromycin, streptomycin, tetracycline,
chloramphenicol all bind to ribosomes to inhibit protein
synthesis
nucleic acids - naladixic acid, rifampin, AZT, and
acyclovir all interfere with nucleic acid synthesis
considerations for use of CTAs
spectrum - indicates the variety of microbes killed;
broad-spectrum CTAs kill many different microbes and may be
preferred because of this
selective toxicity - a selectively toxic agent is
harmful to one living thing (e.g., microbe) but not to another
(e.g., host)
effectiveness - CTAs must be administered by an
appropriate route so they can reach infected
sites in an appropriate concentration to act against
the organism(s) within their spectrum
susceptibility of microbe - microbial
resistance to a CTA acquired by via mutation or acquisition
of resistance genes (especially those transmitted on plasmids)
makes antibiotic sensitivity testing of bacterial and fungal
isolates from infected persons very important for proper CTA
therapy - mechanisms
of resistance include:
permeability decreases - frequently due to
changes in membrane structure
export of CTA from microbe via active transport
mechanisms
target modification - changes in the structure of
the microbial protein, ribosome, etc. that is affected by
the CTA
CTA modification - examples of enzymatic
modification of CTAs include beta-lactamases (which
inactivate CTAs, such as penicillin, whose activity depends
on a beta-lactam ring and acetyl transferases (which
inactivate CTAs such as chloramphenicol by adding acetyl
groups to the molecule)
allergenic potential - the CTA must not induce
allergic (hypersensitivity) reactions in the host because this
can be uncomfortable, and might even be life-threatening in
some cases
