Protein synthesis inhibition clindamycin

Inhibition of protein synthesis in microorganisms (aminoglycosides, erythromycin, clindamycin, chloramphenicol, and tetracyclines). 

Lincosamides (lincomycin and clindamycin) are representatives of a very small group of drugs synthesized up of an amino acid bound to an amino sugar. Lincosamides bind with the 50 S ribosomal subunit of bacteria and inhibit protein synthesis. They also inhibit pep-tidyltransferase action. Lincosamides are bacteriostatic antibiotics however, when they reach a certain level in the plasma, they also exhibit bactericidal action against some bacteria. Lincosamides are highly active against anaerobic infections such as Peptococcus, Peptostreptococcus, Actinomyces, Propionibacterium, and Clostridium fringens, a few types of Peptococcus and Clostridium. 

Clindamycin is a chlorine-substituted derivative of lincomycin. However it is more potent and is better absorbed from the gastrointestinal tract and has therefore replaced lincomycin in most situations. Clindamycin is in principle a bacteriostatic agent. Its indications are mainly limited to mixed anaerobic infections. As mentioned above it has a similar mechanism of action as erythromycin. It selectively inhibits bacterial protein synthesis by binding to the same 50s ribosomal subunits. Erythromycin and clindamycin can interfere with each other by competing for this receptor. Also cross-resistance with erythromycin frequently occurs. Resistance is rather chromosomal rather than plasmid mediated and is especially found in cocci and Clostridium difficile. 

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the SOS ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States. 

Many antibiotics do not fall into a well-defined subclass. Isolated examples include chloramphenicol (A.38), clindamycin (A.39), and linezolid (A.40) (Figure A.ll). All inhibit bacterial protein synthesis. 

The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis. Generally considered to be bacteriostatic, they may be cidal at higher doses. The binding site is either identical to or in close proximity to that for lincomycin, clindamycin, and chloramphenicol. 

Metronidazole and clindamycin are protein synthesis inhibitors that inhibit bacteria by interacting with the DNA to cause a loss of helical DNA structure and strand break-... 

Examples of antibiotics that attack bacteria by inhibiting protein synthesis at the ribosomal level include the following tetracycline antibiotics (e.g. chlortetracycline) aminoglycoside antibiotics (e.g. neomycin, streptomycin) macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin) also chloramphenicol, fusidic acid and lincosamides (e.g. clindamycin). 

Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. Although clindamycin, erythromycin, and chloramphenicol are not structurally related, they act at sites in close proximity, and binding by one of these antibiotics to the ribosome may inhibit the interaction of the others. There are no clinical indications for the concurrent use of these antibiotics. Macrolide resistance due to ribosomal methylation by encoded enzymes also may produce resistance to clindamycin. However, because cUndamycin does not induce the methylase, there is cross-resistance only if the enzyme is produced con-stitutively. Clindamycin is not a substrate for macrolide efflux pumps thus, strains that are resistant to macrolides by this mechanism are susceptible to clindamycin. Altered metabolism occasionally causes clindamycin resistance. 

MECHANISM OF ACTION Chloramphenicol inhibits protein synthesis in bacteria, and to a lesser extent, in eukaryotic cells. It binds reversibly to the SOS ribosomal subunit (near the binding site for the macrolide antibiotics and clindamycin). The drug prevents the binding of the amino acid-containing end of the aminoacyl tRNA to the acceptor site on the SOS ribosomal subunit. The interaction between peptidyltransferase and its amino acid substrate is blocked, inhibiting peptide bond formation (Figure 46-2). 

FIGURE 46-2 Inhibition of bacterial protein synthesis by chloramphenicol. Chloramphenicol binds to the 50S ribo-somal subunit at the peptidyltransferase site and inhibits the transpeptidation reaction. Chloramphenicol binds to the SOS ribosomal subunit near the site of action of clindamycin and the macrolide antibiotics. These agents interfere with the binding of chloramphenicol and thus may interfere with each other s actions if given concurrently. See Figure 46-1 and its legend for additional information. 

A. Classification and Pharmacokinetics The lincosamides lincomycin and clindamycin inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides, though they are not chemically related. Mechanisms of resistance include methylation of the binding site on the 50S ribosomal subunit and enzymatic inactivation. Cross-resistance between lincosamides and macrolides is common. Good tissue penetration occurs after oral absorption. The lincosamides are eliminated partly by metabolism and partly by biliary and renal excretion. 

Chloramphenicol is a bacteriostatic agent that binds to the 508 ribosomal subunit and inhibits the transpeptidation in protein synthesis. While this agent is not widely used to treat staphylococcal infection, resistance to chloramphenicol is due to inactivation of the antibiotic by chloramphenicol acetyltransferase enzyme (CA7). Macrolides, such as erythromycin and oleandomycin lincosamides, such as lincomycin and clindamycin and streptogramin antibiotics also have a bacteriostatic effect on Staphylococcus spp. by binding to their 508 ribosomal subunit, arresting protein synthesis, but resistance to these antibiotics is also prevalent. Rifampin has also been used to treat staphylococcal infections, but when used alone, resistant strains quickly arise. 

Drugs/toxins Ricin (toxin) from castor oil beans (Ricinus communis) is a ribonuclease that inhibits protein synthesis by cleaving and thus inactivating 28S rRNA. A single molecule of ricin within a cell attacks all the ribosomes and kiUs the ceU Diphtheria toxin an exotoxin secreted by Corynebacterium diphtheriae that inactivates eukaryotic elongation factor 2. A single molecule can kill a ceU Aminoglycosides prevent the formation of the initiation complex Tetracyclines bind to the A site and block the attachment of aminoacyl-tRNA Chloramphenicol inhibits peptidyl transferase (ribozyme) Macrolides and clindamycin bind to the SOS subunit and block translocation... 

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