Pharmacology
Summary
Chloramphenicol is a potent broad-spectrum antibiotic renowned for its effectiveness against a wide range of bacterial infections; however, there are potential adverse effects and hematologic risks that should be taken into account before use.
Chloramphenicol works by reversibly binding to the 50S ribosomal subunit and interrupting the actions of peptidyl transferase. This binding obstructs peptide bond formation, effectively halting protein synthesis and thus, bacterial growth. This antibiotic exhibits an expansive spectrum of activity against both gram-positive and gram-negative bacteria, making it valuable for treating various infections, including respiratory tract infections and certain rickettsial diseases (e.g. Rocky Mountain Spotted Fever caused by Rickettsia rickettsii). Though chloramphenicol is not widely available in the United States, it is still used in developing countries where it is often the cheapest treatment available for meningitis (caused by pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis).
One of the most important adverse effects of chloramphenicol includes dose-dependent, reversible suppression of red blood cell production, irreversible bone marrow suppression that may lead to aplastic anemia, and grey baby syndrome in newborns due to their inability to detoxify and degrade the drug (due to their lack of an effective glucuronic acid conjugation system). Despite its potential toxicities, chloramphenicol could prove to be occasionally efficacious, especially in under-resourced situations in developing countries.
Lesson Outline
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FAQs
Chloramphenicol binds to the 50S subunit of the bacterial ribosome, inhibiting the enzyme peptidyl transferase. This prevents the formation of peptide bonds between amino acids during protein synthesis, effectively halting the process of translation and disrupting bacterial growth and replication.
Chloramphenicol has broad-spectrum antibacterial activity which includes many of the pathogens that commonly cause meningitis, such as Strep pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Additionally, it is relatively inexpensive and readily available, which makes it particularly useful in resource-limited settings.
Chloramphenicol can be used as an alternative treatment for serious rickettsial infections, such as Rocky Mountain Spotted Fever. This tick-borne disease is caused by the bacterium Rickettsia rickettsiae, against which chloramphenicol is effective.
Chloramphenicol can cause anemia due to dose-related reversible suppression of red blood cell production. In rare cases, it can cause aplastic anemia, a serious and potentially fatal condition in which the body's bone marrow doesn't produce enough new red blood cells.
Newborns, especially premature ones, have immature liver enzymes (i.e. ineffective glucuronic acid conjugation system) which results in poor metabolism and elimination of chloramphenicol, leading to its accumulation. This can result in a condition known as "grey baby syndrome", characterized by symptoms like flaccidity, hypothermia, and shock due to cardiovascular collapse.
