Inhibidores de la síntesis proteica-Parte 5 Lincosamidas, anfenicoles y oxazolidinonas

Overview of Antibiotics: Key Groups and Mechanisms

Introduction to Antibiotic Classes

• The discussion focuses on three main groups of antibiotics: the five-membered rings, lincosamides, and oxazolidinones.

• The structure of these antibiotics is simpler compared to others, with specific emphasis on their chemical composition.

Lincosamides: Clindamycin

• Clindamycin is derived from lincomycin, which was the first antibiotic discovered from Streptomyces lincolnensis but had significant toxicity issues.

• Clindamycin acts as a bacteriostatic agent by binding to the 50S ribosomal subunit, inhibiting translocation during protein synthesis.

• It is effective against certain anaerobic gram-negative bacteria and resistant strains like MRSA (Methicillin-resistant Staphylococcus aureus).

• Clindamycin has about 90% bioavailability and good distribution in body fluids but limited penetration into bone and CNS; it requires caution in patients with severe renal or hepatic impairment.

• Common side effects include gastrointestinal disturbances such as nausea and diarrhea, along with potential hypersensitivity reactions.

Chloramphenicol: A Broad-Spectrum Antibiotic

• Chloramphenicol was first isolated in 1947; its simple structure allows for reversible binding to the 50S ribosomal subunit.

• It inhibits protein synthesis by blocking peptide bond formation through inhibition of peptidyl transferase activity.

• Chloramphenicol can affect mitochondrial protein synthesis due to similarities between bacterial ribosomes and mitochondrial structures, leading to serious side effects at high doses.

• While it has broad-spectrum activity against both gram-positive and gram-negative bacteria, its use is limited due to toxicity when administered intravenously.

• Adverse effects include hematological disorders like aplastic anemia and "gray baby syndrome" in newborns due to their inability to metabolize chloramphenicol effectively.

Oxazolidinones: Linezolid

• Linezolid features a unique structure that includes oxazolidinone rings; it binds specifically to the 23S rRNA of the large ribosomal subunit.

• This binding inhibits initiation complex formation for translation, making it primarily bacteriostatic but potentially bactericidal at higher doses.

• Effective against resistant gram-positive bacteria including MRSA and VRE (Vancomycin-resistant enterococci), linezolid also plays a role in treating tuberculosis infections.

• It has good oral bioavailability with no need for dose adjustments in renal or hepatic impairment; however, monitoring for adverse effects like thrombocytopenia is necessary.

• Notable side effects include serotonin syndrome when combined with serotonergic drugs due to its non-selective MAO inhibition properties.