Antibiotics: Therapeutic Uses and Adverse Drug Reactions
Antibiotics: Therapeutic Uses and Adverse Drug Reactions: Antibiotics are substances produced by various species of microorganisms (bacteria, fungi, actinomycetes) that suppress the growth of other microorganisms and eventually may destroy them. The discovery of antibiotics in 1930 has made it possible to cure diseases such as pneumonia, meningitis, microbial disease, and infection.
Antibiotics are classiﬁed based on their mechanism of action and by their chemical nature.
Classification Based on Mechanism of Action
- Agents that inhibit the synthesis of bacterial cell wall: These include penicillin and cephalosporins that are structurally similar and dissimilar agents, such as cyclo-serine, vancomycin, bacitracin, and the imidazole antifungal agents.
- Agents that act directly on the cell membrane of the microorganisms, affecting permeability, and leading to leakage of intracellular compounds: These include polymyxin, polyene antifungal agents, nystatin, and amphotericin B that bind to cell wall sterols.
- Agents that affect the function of 30s and 50s ribosomal subunits to cause reversible inhibition of protein synthesis: These include tetracyclines, erythromycins, chloramphenicol, and clindamycin.
- Agents that bind to the 30s ribosomal subunit and alter protein synthesis: These include aminoglycosides that lead to cell deaths eventually.
- Agents that affect nucleic acid metabolism: Such as rifamycin, which inhibits DNA-dependent RNA polymerase.
Chloramphenicol, also known as chloromycetin, is a dextrorotatory broad spectrum anti-biotics originally produced from several streptomycetes and by actinomycete S.venezualae, S.omiyamesis, and S.chloromyceticus. it has been reported to be the drug of choice for the treatment of typhus and typhoid fever. It was isolated from Salmonella Venezuela by Ehrlich et al in 1947, which contains chlorine and is obtained from an actinomycete, and thus, named chloromycetin. It is speciﬁcally recommended for treating serious infections caused by H. influenzae, S. Typhi (typhoid), S. pneumoniae, and N. meningitides. Its ability to penetrate the CNS presents an alternative therapy for meningitis and exhibits antirickettsial activity.
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However, Chloramphenicol is of permanent interest owing to the following reasons:
- It is a naturally occurring aromatic nitro compound.
- It can exert its effect against viral diseases as well as those due to bacterial invasive and opens up the whole field of the chemotherapy of virus and rickettsial infections in men including typhus, salmonella, septicemia, whooping cough, gastroenteritis, typhoid, and paratyphoid.
- It can be synthesized on an industrial scale.
Mechanism of action
Chloramphenicol is either bacteriocidal or more commonly bacteriostatic depending upon the organism.it is a broad-spectrum antibiotic that acts as a protein synthesis inhibitor by inhibiting the peptidyl transferase at 50S ribosomal subunit of the bacterial ribosome.
Chloramphenicol is a white or greyish-white or yellowish-white crystalline powder or ﬁne crystals, slightly soluble in water, soluble in alcohol, and propylene glycol. It was the ﬁrst, and still is the only therapeutically important antibiotic to be produced in competition with microbiological processes. It contains a nitrobenzene moiety and is a derivative of di-chloroacetic acid.
- It is primarily used against typhoid fever and similar salmonella infections.
- It is also employed in acute infections due to Haemophilus influenzae including meningitis attributed to ampicillin-resistant strains.
- It has also been used to eradicate vibrios from patients with cholera.
- It is employed for rickettsia infections like typhus and rocky infection spotted fever.
- It is used topically extensively for superficial conjunctival infections and blepharitis essentially caused by E. coli, H.influenzae, Moraxella lacuna, Streptococcus hemolytic, and S.aures. However, it is still a drug of choice for typhoid fever.
Note: the prodrug of chloramphenicol, chloramphenicol palmitate (USP) which is a tasteless product is slowly intended for pediatric usage. Preferably because the parent drug has a distinct bitter taste.
Adverse drug reaction
Hemolytic anemia occurs in patients with low levels of glucose-6-phosphate dehydrogenase reversible and aplastic anemia may also occur.
Gray baby syndrome
Neonates have less ability to glucoronidate the chloramphenicol and have underdeveloped renal functions. So, the drug accumulates in the body and interferes with mitochondrial ribosomes. This leads to poor feeding, CVS collapse, depressed breathing, cyanosis, and death.
And others include:
- Bone marrow depression
- GIT, nausea, vomiting, diarrhea
- Hypersensitivity: skin rashes, urticaria
- Synthesis of chloramphenicol