11-Protein Synthesis Inhibitors- Lincomycin & Others
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Transcript of 11-Protein Synthesis Inhibitors- Lincomycin & Others
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Antibiotics-
Protein Synthesis Inhibitors:
Others: Lincosamides,Streptogramins and Oxazoladinones
Pharmacology L3
PHCL-L3-Anti-Micro-
Oct 2011
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Classification of Antibiotics that act by inhibiting
the synthesis of proteins
Protein Synthesis Inhibitors
Macrolides
Tetracyclines
Aminoglycosides & Spectinomycin
Chloramphenicol
Others
Lincosamides
Streptogramins and Oxazoladinones
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Ribosomal Targets
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Lincosamides
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Specific Agents
Clindamycine
Lincomycine
http://en.wikipedia.org/wiki/File:Clindamycin_skeletal.svghttp://en.wikipedia.org/wiki/File:Lincomycin.png -
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Clindamycin
Clindamycin is a semisynthetic derivative
of lincomycin which was isolated from
Streptom yces l incolnesisin 1962;
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Clindamycin
Mechanism of Action
Inhibits protein synthesis by binding
exclusively to the 50Sribosomal subunit
Binds in close proximity to macrolides
competitive inhibition
Clindamycin typically displays
bacteriostatic activity, but may bebactericidal when present at high
concentrations against very susceptible
organisms
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Clindamycin
Mechanisms of Resistance
Altered target sites encoded by the erm
gene which alters the clindamycin binding
site on the ribosome; confers high levelresistance to all macrolides, clindamycin
and Synercid
Active efflux mefgene encodes for an
efflux pump which pumps the macrolide out
of the cell but NOT clindamycin; confers low
levelresistance to macrolides, but
clindamycin still active
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ClindamycinSpectrum of Activity
Gram-Positive Aerobes
Methicillin-susceptible Staphylococcusaureus (MSSA only)
Streptococcus pneumoniae(only
PSSP)
Group and viridans streptococci
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ClindamycinSpectrum of Activity
Anaerobes activity against Above theDiaphragm Anaerobes (ADA)
Peptostreptococcus some Bacteroides spAc t inomyces Prevotel la sp.
Propionibacter ium Fusobacter ium
Clostr id ium sp. (not C. dif f ic i le)
Other BacteriaPneumocy st is car in i i ,Toxop lasmosis gond i i, Malaria
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ClindamycinPharmacology
Absorption available IV and PO Rapidly and completely absorbed (F = 90%); food
with minimal effect on absorption
Distribution Good serum concentrations with PO or IV
Good tissue penetration including bone; minimalCSF penetration
Elimination Clindamycin primarily metabolized by the liver;
half-life is 2.5 to 3 hours
Clindamycin is NOTremoved duringhemodialysis
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ClindamycinClinical Uses
Anaerobic Infections OUTSIDE of theCNS
Pulmonary, intraabdominal, pelvic, diabeticfoot and decubitus ulcer infections
Uncomplicated Skin & Soft TissueInfections
Especially in pen-allergic patientsOther
Alternative forC. perfringens, PCP,Toxoplasmosis, malaria, bacterial vaginosis
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ClindamycinAdverse Effects
Gastrointestinal 3 to 4 %
Nausea, vomiting, diarrhea, dyspepsia
C. d iff ic i lecolitis
Mild to severe diarrhea
Requires treatment with metronidazole
Hepatotoxicity - rareElevated transaminases
Allergy - rare
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Streptogramins
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Synercid Structure
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Synercid
Mechanism of Act ion
Each agent acts on 50S ribosomalsubunits to inhibit early and late stages of
protein synthesis Bacteriostatic (cidal against some
bacteria)
Mechanism of Resistance Alterations in ribosomal binding sites
Enzymatic inactivation
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SynercidClinical Uses
VRE (faecium) bacteremia
Complicated skin and soft tissue
infections due to MSSA orStreptococcus pyogenes
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SynercidAdverse Effects
Venous irritation especially when
administered in peripheral vein
Gastrointestinal nausea, vomiting,
diarrhea
Myalgias, arthralgias 2%
Rash total and unconjugated bilirubin
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