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