Antibiotic

•

• INTRODUCTION

An antibiotic produced by Streptomyces venezuelae, an organism first isolated in 1947 from a soil sample collected in Venezuela.
Acts primarily by inhibits protein synthesis in bacteria by binding reversibly to the 50 S ribosomal subunit.




• Chloramphenicol is available for oral administration in two forms: the active drug itself and the inactive prodrug, chloramphenicol palmitate (which is used to prepare an oral suspension). Chloramphenicol then is absorbed from the gastrointestinal tract
peak concentrations occur within 2 to 3 hours after the administration of a 1-g dose.
The preparation of chloramphenicol for parenteral (IV) use is the water-soluble, inactive sodium succinate preparation.


• Chloramphenicol is well distributed in all body fluids and readily reaches therapeutic concentrations in CSF, where values are approximately 60% of those in plasma (in the presence or absence of meningitis).
• Chloramphenicol is present in bile, is secreted into milk, and readily traverses the placental barrier. It also penetrates into the aqueous humor after subconjunctival injection.
•




• The major route of elimination of chloramphenicol is hepatic metabolism to the inactive glucuronide. This metabolite, as well as chloramphenicol itself, is excreted in the urine by filtration and secretion.

Fate and Excretion cont.

Patients with hepatic cirrhosis have decreased metabolic clearance, and dosage should be adjusted in these individuals.

• Chloramphenicol has a wide range activity that includes gram+, gram-, aerobic and anaerobic bacteria
• Typhoid Fever
• Bacterial Meningitis
• Anaerobic Infections
• Rickettsial Diseases
• Brucellosis

• Adverse effects cont. Hematologic Toxicity

• The most important adverse effect of chloramphenicol is on the bone marrow.
• Chloramphenicol affects the hematopoietic system in two ways:
• by an non-dose-related idiosyncratic response manifested by aplastic anemia, leading in many cases to fatal pancytopenia.
• by a dose-related toxic effect that presents as anemia, leukopenia, or thrombocytopenia, and

• Gray baby syndrome

• Fatal chloramphenicol toxicity may develop in neonates, especially premature babies, when they are exposed to excessive doses of the drug.
• The illness, the gray baby syndrome, usually begins 2 to 9 days after treatment is started.
• The manifestations in the first 24 hours are vomiting, refusal to suck, irregular and rapid respiration, abdominal distention, periods of cyanosis, and passage of loose, green stools. Soon they become flaccid, turn an ashen-gray color, and become hypothermic

• Gray baby syndrome cont

• Two mechanisms are apparently responsible for chloramphenicol toxicity in neonates
• (1) failure of the drug to be conjugated with glucuronic acid, owing to inadequate activity of glucuronyl transferase in the liver, which is characteristic of the first 3 to 4 weeks of life; and (2) inadequate renal excretion of unconjugated drug in the newborn.

• Although relatively uncommon, macular or vesicular skin rashes occur as a result of hypersensitivity to chloramphenicol. Fever may appear simultaneously or be the sole manifestation.
• Angioedema is a rare complication.