lecture 12 -antimicrobial drugs
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Antimicrobial Drugs
11 May 2013
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Antimicrobial Drugs
• Chemotherapy The use of drugs to treat adisease
• Antimicrobial drugs Interfere with thegrowth of microbes within a host
• Antibiotic ubstance produced by amicrobe that! in small amounts! inhibits
another microbe• electi"e to#icity A drug that $ills harmful
microbes without damaging the host
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• 1%2& ' (lemingdisco"eredpenicillin!produced byPenicillium)
• 1%*0 ' +oward(lorey and ,rnstChain performed-rst clinical trialsof penicillin)
• All three were
awarded the.obel /rie inMedicine in 1%*
(igure 20)1
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Table 20.1
Many Antibiotics come from Bacterial or Fungal Sources
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Table 20)2
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The Action of AntimicrobialDrugs
• Disrupt Cell all synthesis or throughdamage
•Disrupt /roteins synthesis• Disrupt .ucleic Acid synthesis orfunction
• Disrupts essential metabolicenymesusually by competiti"einhibition)
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Drugs
Figure 20.2
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Drugs
Figure 20.4
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/enicillins
Figure 20.6
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/enicillinase ,nyme Allows4acteria to be 5esistant to
/enicillin
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• Cephlosporinsused /enicillin structure tosynthesie antibiotics more e6ecti"e on 7ram.egati"e bacteria
• /olypeptide antibiotics
4acitracin
• Topical application
• Against grampositi"es
8ancomycin
• 7lycopeptide
• Important 9last line9 against antibiotic resistant S. aureus
:ther Inhibitors of Cell allynthesis
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• Antimycobacterium antibiotics ;T4! <eprosy= Isoniaid ;I.+=
• Inhibits mycolic acid synthesis
,thambutol
• Inhibits incorporation of mycolic acid
:ther Inhibitors of Cell allynthesis
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• Tetracyclines
4road spectrum
• Interferes with t5.A attachment
• ,rythromycin
7rampositi"es• 4inds 0! pre"ents translocation
Inhibitors of /rotein ynthesis
• /olymy#in 4
Topical
Combined with bacitracin and neomycin
in o"erthecounter preparation
In>ury to the /lasma
Membrane
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• 5ifamycin Inhibits 5.A synthesis
Antituberculosis
• ?uinolones and @uorouinolones Cipro@o#acin
Inhibits D.A gyrase
Brinary tract infections
Inhibitors of .ucleic Acidynthesis
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ulfonamides ;ulfa drugs=
• Inhibit folic acid synthesis
• 4road spectrum
Competiti"e Inhibitors
Figure !."
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Figure 20.1#
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n unga rugsInhibition of ,rgosterol
ynthesis
• ,chinocandins Inhibit synthesis of βglucan
Inhibition of Cell allynthesis
• ,rgosterol important part of fungalcell wall) Bniue to fungi! therefore agood drug target
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• (lucytocine Cytosine analog interferes with 5.A
synthesis
Antifungal DrugsInhibition of .ucleic Acids
• Tolnaftate Bsed for athletes foot action un$nown
Antifungal DrugsInhibition of Microtubules
;Mitosis=
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.ucleoside and .ucleotide
Analogs
Figure 20.16a
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.ucleoside and .ucleotide
Analogs
Figure 20.16b$
c
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• /rotease inhibitors Indina"ir• +I8
• Inhibit attachment
Eanami"ir• In@uena
Anti"iral DrugsF ,nymeInhibitors
• Chlorouine
Inhibits D.A synthesis
• Malaria
Antiprotooan Drugs
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• A "ariety of mutations can lead to antibioticresistance)
• Mechanisms of antibiotic resistance
1) ,nymatic destruction of drug
2) /re"ention of penetration of drug
3) Alteration of drugs target site
*) 5apid e>ection of the drug
• 5esistance genes are often on plasmids or
transposons that can be transferred betweenbacteria)
Antibiotic 5esistance
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• Misuse of antibiotics selects forresistance mutants) Misuse includesF
Bsing outdated! wea$ened antibiotics
Bsing antibiotics for the common cold andother inappropriate conditions
Bse of antibiotics in animal feed
(ailure to complete the prescribed regimen
Bsing someone elses lefto"er prescription
Antibiotic 5esistance
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Dis$Di6usion Test
(igure 20)1G
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Chemical Methods ofMicrobial Control
Figure 7.6
Evaluating a disinfectant Disk-diffusion method
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• MIC Minimal inhibitory concentration• M4C Minimal bactericidal concentration
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, Test
(igure 20)1&
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• ynergism occurs when the e6ect of two drugstogether is greater than the e6ect of either alone)
• Antagonism occurs when the e6ect of two drugstogether is less than the e6ect of either alone)
Drugs
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Drugs
Figure 20.22
Th ( t f
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• Antimicrobial peptides 4road spectrum antibiotics from plants and
animals
• ualamine ;shar$s=
• /rotegrin ;pigs=
• Magainin ;frogs=
• Antisense agents
Complementary D.A or peptide nucleicacids that binds to a pathogens "irulencegene;s= and pre"ents transcription
The (uture ofChemotherapeutic Agents