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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11-protein synthesis inhibitors- lincomycin & others

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