Chloramphenicol Pharmacology- Topics covered:- 1. Introduction 2. Structure 3. Mechanism Of Action 4. Bacterial Resistance to Chloramphenicol 5. Antimicrobial Spectrum 6. Pharmacokinetics 7. Adverse Effects 8. Drug Interactions 9. Therapeutic Uses Chloramphenicol, a potent and versatile antibiotic, has played a significant role in the field of medicine since its discovery in the late 1940s. This broad-spectrum antibiotic is highly effective against a wide range of bacteria, making it a valuable tool in the fight against infectious diseases. However, its history is marked by controversies and challenges, which have influenced its usage and regulation. Chloramphenicol was first isolated from the bacterium Streptomyces venezuelae in 1947, marking a significant milestone in the development of antibiotics. Its ability to inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit distinguishes it as a bacteriostatic agent. This mode of action makes chloramphenicol effective against various Gram-positive and Gram-negative bacteria, including some drug-resistant strains. Despite its efficacy, chloramphenicol's history is marred by concerns about its safety. In the 1950s and 1960s, it was widely used as a broad-spectrum antibiotic for various infections. However, it was later associated with a potentially life-threatening condition known as "gray baby syndrome" in neonates, leading to restrictions on its use in children and pregnant women. Additionally, it has been linked to aplastic anemia, a rare but serious side effect, which led to further restrictions on its use in many countries. The complex history of chloramphenicol extends to its current status in the medical field. While it is still used in some cases, it is typically reserved for situations where other antibiotics have failed, and safer alternatives are unavailable. The availability and regulation of chloramphenicol vary from country to country due to these concerns. In recent years, research has focused on understanding the molecular mechanisms of chloramphenicol's action and the development of more targeted antibiotics with improved safety profiles. Its unique characteristics and historical significance continue to make it a subject of interest in the ongoing battle against bacterial infections. In conclusion, chloramphenicol is a potent broad-spectrum antibiotic with a rich and complex history. Its discovery revolutionized the treatment of infectious diseases, but safety concerns have led to restricted use. Ongoing research seeks to balance its efficacy with safety, highlighting the ongoing importance of this antibiotic in the field of medicine.

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Chloramphenicol
-Prajwal Waman Ghatol

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Introduction
Structure
Mechanism Of Action
Bacterial Resistance to Chloramphenicol
Antimicrobial Spectrum
Pharmacokinetics
Adverse Effects
Drug Interactions
Therapeutic Uses
What will we
learn?

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01.
02.
03.
Chloramphenicol, a broad-
spectrum antibiotic;
Introduction
It was isolated from
Streptomyces venezuelae.
Even though chloramphenicol has a
broad spectrum of antibacterial
activity, its use is limited to only a few
conditions because of its dangerous
side effect – bone marrow suppression.

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Structure

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Mechanism of Action
Chloramphenicol is a bacteriostatic agent, but in high
concentration, it can be bactericidal against H. influenzae,
N. meningitidis and S. pneumoniae. It can also inhibit
mitochondrial protein synthesis in mammalian cells by
acting on 70S ribosomes.

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Bacterial Resistance to
Chloramphenicol
Resistance to chloramphenicol is caused by:
1. Production of inactivating enzyme – acetyltransferase, e.g. H. influenzae, S.
typhi,
S. aureus
2. Decreased permeability of the microbial cell wall
3. Ribosomal mutation

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Antimicrobial
spectrum
Chloramphenicol is primarily bacteriostatic, though high concentrations have
been shown to exert cidal effect on some bacteria, e.g. H. influenzae and N.
meningitidis. It is a broad-spectrum antibiotic, active against nearly the same
range of organisms (gram-positive and negative cocci and bacilli, rickettsiae,
mycoplasma) as tetracyclines.

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Antimicrobial
spectrum
Notable differences between these two are:
• Chloramphenicol was highly active against Salmonella including S. typhi, but resistant
strains are now rampant.
• It is more active than tetracyclines against H. influenzae, B. pertussis, Klebsiella, N.
meningitidis and anaerobes including B. fragilis.
• It is less active against gram-positive cocci and spirochetes, while Chlamydia,
Entamoeba and Plasmodia are not inhibited.
Like tetracyclines, it is ineffective against mycobacteria, Pseudomonas, many Proteus,
viruses and fungi.

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Pharmacokinetics
Chloramphenicol is commonly given by oral route and is rapidly
absorbed from the gut. It is also available for parenteral and topical
administration. It has a bitter taste; to improve the taste, chloramphenicol
palmitate suspension has been developed for paediatric use. It gets
activated in the intestine by pancreatic lipase. Chloramphenicol is widely
distributed to all tissues including CSF and brain. It also crosses placental
barrier and is secreted in milk. It gets metabolized in liver by glucuronide
conjugation and the metabolite is excreted mainly in urine.

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Adverse Effects
1. HYPERSENSITIVITY REACTIONS: Skin rashes, drug fever and
angioedema may occur rarely.
2. BONE MARROW SUPPRESSION: The most serious adverse
effect of chloramphenicol is on bone marrow. It can occur in two
ways:
(a) Dose-dependent reversible suppression of bone marrow, which
manifests as anaemia, leucopenia and thrombocytopenia
(b) Idiosyncratic non-dose-related irreversible aplastic anaemia,
which is often fatal

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Adverse Effects
3. GI EFFECTS: These include nausea, vomiting and
diarrhoea. Prolonged use may cause superinfection due to
suppression of gut flora.
4. GRAY BABY SYNDROME: In neonates, especially in
premature babies, chloramphenicol can cause a dose-
related gray baby syndrome due to reduced degradation
and detoxification of the drug in liver because of the
deficiency of glucuronyl transferase enzyme.

12. Kernicterus Stevens–Johnson syndrome

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Drug Interactions
Like erythromycin, chloramphenicol increases plasma
concentration of certain drugs, such as warfarin, phenytoin,
rifabutin and antiretroviral protease inhibitors (PIs), by
inhibiting hepatic cytochrome P450 isoenzymes.

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Therapeutic Uses
1. TYPHOID FEVER: Chloramphenicol was the first-choice drug for
typhoid. Antibiotics useful in typhoid are third-generation
cephalosporins, FQs, azithromycin, ampicillin, cotrimoxazole, etc. Now,
FQs (ciprofloxacin, ofloxacin, levofloxacin, etc.) or third-generation
cephalosporins (ceftriaxone, cefoperazone) are the drugs of choice for
typhoid fever. The dose of ciprofloxacin is 750 mg 12 hourly for 10
days. It also eliminates carrier state. MDR cases are treated with
ceftriaxone (2–4 g i.v. daily for 10 days) or azithromycin.

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Therapeutic Uses
2. BACTERIAL MENINGITIS: Third-generation cephalosporins are the
preferred drugs for the treatment of bacterial meningitis caused by H.
influenzae, N. meningitidis and S. pneumoniae. However,
chloramphenicol can be used alone or in combination with ampicillin.
3. ANAEROBIC INFECTIONS: Chloramphenicol is effective against
most anaerobic bacteria including B. fragilis. It is often used in
combination with metronidazole for the treatment of brain, lung, intra-
abdominal or pelvic abscesses.

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Therapeutic Uses
4. RICKETTSIAL INFECTIONS: Tetracyclines are the drugs of choice
for the treatment of rickettsial diseases. Chloramphenicol can be used
to treat rickettsial infections in children and pregnant women.
5. EYE AND EAR INFECTIONS: Chloramphenicol is used topically for
eye and ear infections due to susceptible organisms.
6. BRUCELLOSIS: Chloramphenicol can be used when tetracyclines are
contraindicated.

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Thank you!