CHLORAMPHENIC

OL

PHARMACO LOGY

Dr.Zulcaif Ahmad

CONTENTS

• Pharmacokinetics• Absorption • Distribution • Fate and excretion

INTRODUCTION Although an effective broad-spectrum

antibiotics, its uses are limited by its serious toxicity. Now is rarely used except for severe infective diseases.

It is well absorbed and widely distributed, including to the CNS. It is metabolized by glucuroni-dation in the liver.

PHARMACOLOGIC EFFECTSChloramphenical is active against a

broad range of organisms,including G+and G- bacteria (including

anaerobes).But, its effects on G-bacteria is better

than on G+ bacteria, especially Salmonella typhi.

ABSORPTION Absorbed from the GIT tract.Peak con. Of 10 to 13ug/ml occurs with in 2

to 3 hr after the administration of 1g dose .The hydrolysis of cholremphenicol succinate

is due to the esterases enzyme present in kidney, liver and lungs.

Poor renal function in the neonates and other state of renal insufficiency result in increased plasma conc. Of chloremphinicol succinate

CHLORAMPHENICOL Mechanisms of action Mechanisms of resistance Clinical uses Adverse effects

MECHANISMS OF ACTION inhibits bacterial protein synthesis. CAP binds 50S subunit and block elongation by inhibiting the

formation of initiation complexes and peptidyltransferase; CAP is primarily bacteriostatic, but it may be bactericidal to

some strains of microorganisms even at lower concentration:

MECHANISMS OF RESISTANCE

reduced membrane permeability mutation of the 50S ribosomal subunitelaboration of chloramphenicol acetyltransferase

ADVERSE EFFECTS Bone marrow Disturbance-reversible bone marrow depression Chloramphenicol inhibits protein synthesis in the mitochondria

of human cells. This inhibition may be the. cause of the dose- dependent toxicity of drug to bone marrow

. Toxicity for Newborn Infants (Gray-baby syndrome) Be seen in neonates, especially premature infants, who have been given relatively large doses of CAP.

The inadequate renal elimination mechanism of neonate and the inactive metabolites also contributes to the occurrence of the syndrome.

. Gastrointestinal reaction. nausea, vomiting,diarrhea

. Hypersensitivity reactions . A rare anemia, probably immunological in origin but often

fatal

DRUG INTERACTION Irreversibly inhibit the microsomal enzyme p-450.Conversely other drug may alter the elimination of

chloremphenicol

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