Chloramphenicol

Mechanism of action and target

The antibiotic penetrates the microbial cell and disrupts the translation process. Its main target is the 50S subunit of the bacterial ribosome.

• Biochemical effect: inhibition of the peptidyl transferase enzyme.
• Result: the formation of peptide bonds between amino acids is blocked, completely halting the assembly of protein molecules.

An important pharmacodynamic feature is that the drug is capable of inhibiting ribosome function in the host's own cells (human cells), particularly in mitochondria. This exact property underlies its serious adverse effects.

Antimicrobial spectrum and indications

The drug exhibits a broad spectrum of activity: it is effective against gram-positive and gram-negative microorganisms, including aerobic and anaerobic strains.

The most sensitive pathogens include:

• Haemophilus influenzae;
• Neisseria meningitidis;
• Pneumococci;
• Certain strains of bacteroides.

Due to its pronounced toxicity, systemic administration is strictly limited. Chloramphenicol is prescribed as a reserve drug only when resistance has developed to safer alternatives or if other effective agents cause dangerous allergies in the patient. The main indications for systemic administration include typhoid fever, bacterial meningitis, and rickettsiosis.

Externally and topically, the medication is used for skin problems (furunculosis, trophic ulcers, infected burns, nipple fissures) and eye infections (conjunctivitis, keratitis, blepharitis).

Toxicity and adverse effects

The toxic reactions of the body are based on the inhibition of mitochondrial protein synthesis. The most dangerous manifestations include:

1. "Gray syndrome" (Gray syndrome). Occurs in newborns when high doses are used. The pathogenesis is due to the immaturity of liver enzymes (lack of conjugation with glucuronic acid), causing the drug to accumulate in toxic concentrations.
2. Hematotoxicity.
3. Reversible form: dose-dependent suppression of erythropoiesis.
4. Irreversible form: aplastic anemia—a rare, potentially fatal complication of an idiopathic nature.
5. Dyspepsia: frequent complaints of nausea, vomiting, and diarrhea.

Drug interactions and resistance

Bacteria develop resistance to chloramphenicol through two pathways:

• Barrier mechanism: reduction of the outer cell membrane permeability to antibiotic molecules.
• Enzymatic mechanism: plasmid transfer of genetic information regarding the synthesis of specific acetyltransferases that inactivate the drug.

Pharmacokinetic interactions: by inhibiting microsomal liver enzymes, chloramphenicol slows down the breakdown of substances such as phenytoin and warfarin. This increases their half-life ($t_{1/2}$) and raises the risk of toxic effects.

Pharmacodynamic interactions: being a bacteriostatic agent, chloramphenicol may weaken the efficacy of bactericidal antibiotics (e.g., penicillins and aminoglycosides), whose action directly depends on cell division.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Features of chloramphenicol metabolism in the liver of adults and children
• Comparison of reversible and irreversible hematotoxicity
• Mechanisms of plasmid resistance and enzymatic inactivation
• Pharmacokinetic features of interactions with anticoagulants and anticonvulsants
• Specifics of external and topical use in ophthalmology and dermatology

Other topics in the section "Antibacterial Chemotherapeutic Agents"

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