Antimicrobial medications

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Antimicrobial medications history mechanisms ri
sks and benefits How do you test
effectiveness? How is resistance spread?
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First steps chemotherapeutics drugs that killed
the microbe but not the patient! Salvarsan
(Ehrlich arsenic syphilis) Pronotsil (Domagk
sulfa drugs streptococcus) Antibiotics
produced by microorganisms Fleming
penicillin Waksman streptomycin More recently,
compounds have been altered
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Features of antimicrobials (why do most come from
soil microbes?) Selective toxicity Type of
action bactericidal bacteriostatic Depends of
stage of growth of microbe sensi- tivity to
immune mechanisms Spectrum- broad or
narrow broad can be prescribed quickly but
kill normal flora, too
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Metabolism distribution stability Must drug be
injected? How long does drug persist in
system? Can drug cross blood-brain barrier? Does
patient have normal liver and kidney function?
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What are adverse effects? Hypersensitivity Toxic
effects aminoglycosides chloramphenicol Suppre
ssion of normal flora Efficacy Cost
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p. 511 How do these drugs work?
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Inhibitors of cell-wall synthesis Penicillins Ce
phalosporins (what types of organisms make
them?) Enzyme inhibitors (?-lactam
rings) Prevent formation of peptidoglycan
(vancomycin) Interfere with precursor transport
(bacitracin) See table 21.2, pp. 513-514
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p. 515
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Inhibition of protein synthesis
p. 516
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These are pretty toxic Aminoglycosides- kidney
damage, deafness Neomycin cant be taken
internally Tetracyclines can discolor teeth in
children Chloramphenicol- aplastic anemia Newer
drugs are less toxic Tend to be broad spectrum
(not always)
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Other targets nucleic acid synthesis
(fluoroquinolones, rifamycins) metabolic
pathways, etc. folic acid (humans lack this
pathway, therefore these enzymes) trimethoprim,
sulfanolamides cell membranes (polymixin
B) specialty drugs- antituberculars slow
growth waxy coat intracellular
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How do you know if a particular drug will be
effective? Minimum inhibitory concentration
(MIC) Minimum bactericidal concentration
(MBC) (giving combinations is risky for
toxicity, hypersensitivity, drug resistance)
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p. 519
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Kirby-Bauer is quicker and easier
p. 519 tests have been modified
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It doesnt take long for microbes to
become drug-resistant! p. 521
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Mechanisms of drug resistance, p. 522
Mutation or gene transfer?
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p. 522 many resistance genes are on plasmids
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Important resistant organisms Vancomycin-resistan
t enterococci MRSA (methicillin-resistant S.
aureus) Penicillin-resistant S.
pneumoniae Multiple-drug-resistant M.
tuberculosis
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How can we prevent the formation of
drug- resistant microbes? Health workers
prescribe appropriately! Patients take drugs as
prescribed! Dont take antibacterials for viral
infections! Should antibacterials be easily
available? Should we use them in animal feed?
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Not all infections are caused by bacteria. What
are appropriate treatments for viruses fungi pr
otozoans helminths
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Viruses are challenging because many have
no unique target structure If immune system
doesnt control infection Prevent viral
replication Prevent viral polymerase
activity Prevent assembly and release of new
virions
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p. 525
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Fungal cells are similar in structure to
animal cells drugs toxic to fungi are generally
toxic Exception ergosterol (found in plasma
membrane). Drugs are usually safe
topically but not systemically
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Treating protozoan and helminthic
diseases Inhibit cell division or
metabolism Neurotoxins for helminths (see p. 529)
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New strategies New targets for
antimicrobials? Interfere with resistance
mechanisms? Enhance host defenses? New vaccine
concepts?