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Antibiotic Chloramphenicol history,classification,mechanism of action and adverse effect
Chloramphenicol is a broad-spectrum antibiotic that was first introduced in 1949. It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking peptide bond formation. While effective against many gram-positive and gram-negative bacteria, its use has limitations due to potential bone marrow toxicity. Common adverse effects include reversible anemia, bone marrow suppression, and gastrointestinal disturbances. It remains an important treatment option for certain life-threatening infections.
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Antibiotic Chloramphenicol history,classification,mechanism of action and adverse effect
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- 2. Chloramphenicol • Chloramphenicol isa bacteriostatic antimicrobial that became available in 1949. • Chloramphenicol was originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb, and introduced into clinical practice in 1949, under the trade name Chloromycetin. • It was the first antibiotic to be manufactured synthetically on a large scale.
- 3. Chloramphenicol • Chloramphenicol isactive against a wide range of gram-positive and gram-negative organisms. • However, because of its toxicity, its use is restricted to life-threatening infections for which no alternatives exist.
- 4. Chloramphenicol • Chloramphenicol inhibitsprotein synthesis in susceptible microorganisms and ,to a lesser extent,in mammalian cells. • Host ribosomes do not bind effectively as do bacterial ribosome.
- 5. Chloramphenicol • Chloramphenicol readilypenetrates into bacterial cells,probably both passive and facilitated diffusion.
- 6. A. Mechanism ofaction
- 7. A. Mechanism ofaction • Once inside bacterial cell,the drug binds reversibly to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction.This interferes with transfer of elongating polypeptide chain in the newly attached aminoacyl t-RNA at ribosome-mRNA complex.
- 9. Mechanism of action •Chloramphenicol prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome • It binds to 50S ribosomal subunit, preventing peptide bond formation.
- 10. Mechanism of action •Chloramphenicol ↓ • Binds reversibly to 50 S ribosomal subunit ↓ • Prevents the formation of peptide bond ↓ • Inhibits protein synthesis
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- 13. B. Antimicrobial spectrum •Chloramphenicol has a very broad spectrum of activity: it is active against Gram-positive bacteria , Gram-negative bacteria and anaerobes.
- 14. B. Antimicrobial spectrum •Chloramphenicol, a broad-spectrum antibiotic, is active rickettsiae. • Pseudomonas aeruginosa is not affected, nor are the chlamydiae.
- 15. Antimicrobial spectrum • Chloramphenicolhas excellent activity against anaerobes. The drug is either bactericidal or (more commonly) bacteriostatic, depending on the organism. • Chloramphenicol is bacteriostatic against Gram negative rods and bacteriocidal for pneumococci.
- 16. Therapeutic uses • Becauseof the risk of bone marrow toxicity and availability of safer drugs, chloramaphenicol is not generally preferred. The indication include • Rickettsial infection • Eye infection • Typhoid fever
- 17. Therapeutic uses • Becauseof its excellent BBB penetration (far superior to any of the cephalosporins), chloramphenicol remains the first choice treatment for staphylococcal brain abscesses. It is also useful in the treatment of brain abscesses due to mixed organisms or when the causative organism is not known.
- 18. Therapeutic uses • Chloramphenicolis active against the three main bacterial causes of meningitis: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.
- 19. C. Resistance • Acetyltransferase and other metabolizing enzymes inactivates chloramphenicol. • Another mechanism for resistance is associated with an inability of the antibiotic to penetrate the organism. This change in permeability may be the basis of multidrug resistance. • Lowered affinity of bacterial ribosome for chloramphenicol
- 20. D. Pharmacokinetics • Chloramphenicolmay be administered either intravenously or orally . It is completely absorbed via the oral route because of its lipophilic nature, and is widely distributed throughout the body. It readily enters the normal CSF.
- 21. D. Pharmacokinetics • Itis metabolised in the liver by reduction and glucuronide conjuction. • The metabolites are excreted in the urine.
- 23. E. Adverse effects •Anemias: Hemolytic anemia occurs in patients with low levels of glucose 6- phosphate dehydrogenase. • Other types of anemia occurring as a side effect of chloramphenicol include reversible anemia, which is apparently dose-related and occurs concomitantly with therapy, and chloramphenicol may inhibit the uptake of iron by erythrocytes and slow their rate of maturation in bone marrow.
- 24. E. Adverse effects Aplasticanemia • The most serious side effect of chloramphenicol treatment is aplastic anaemia. This effect is rare, idiosyncratic and generally fatal: there is no treatment and there is no way of predicting who may or may not get this side effect. The effect usually occurs weeks or months after chloramphenicol treatment has been stopped and there may be a genetic predisposition.
- 25. Adverse effects • Bonemarrow suppression It is common for chloramphenicol to cause bone marrow suppression during treatment: this is a direct toxic effect of the drug on human mitochondria. This effect manifests first as a fall in hemoglobin levels and occurs quite predictably once a cumulative dose of 20 g has been given. This effect is fully reversible once the drug is stopped and does not predict future development of aplastic anaemia.
- 26. Adverse effects • GITdisturbance Nausea,vomiting and diarrhoea
- 27. Adverse effects • Graybaby syndrome: This adverse effect occurs in neonates if the dosage regimen of chloramphenicol is not properly adjusted. Neonates have a low capacity to glucuronylate the antibiotic, and they have underdeveloped renal function. Therefore, neonates have a decreased ability to excrete the drug, which accumulates to levels that interfere with the function of mitochondrial ribosomes. This leads to poor feeding, depressed breathing, hypotension, cyanosis (hence the term gray baby ), and death. • Adults who have received very high doses of the drug can also exhibit this toxicity.
- 28. Adverse effects • Hypersensitivityreactions like rashes • Superinfection
Editor's Notes
- #15 The rickettsiae are a diverse collection of obligately intracellular Gram-negative bacteria found in ticks, lice, fleas, mites, chiggers, and mammals Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1–4 μm long) or thread-like (10 μm long). Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells (typically endothelial cells).[8] Because of this, Rickettsia cannot live in artificial nutrient environments and are grown either in tissue or embryo cultures (typically, chicken embryos are used). In the past they were positioned somewhere between viruses and true bacteria. However unlike Chlamydia, Mycoplasma, and Ureaplasma, Rickettsial organisms possess true cell walls similar to other gram-negative bacteria.[9] The majority of Rickettsia bacteria are susceptible to antibiotics of the tetracycline group.
- #24 Hemolytic anemia (or haemolytic anaemia) is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular).
- #25 Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells.[ Predisposition:susceptibility
- #26 cu·mu·la·tive (kymy-ltv, -y-l-tv) adj. 1. Increasing or enlarging by successive addition
- #28 cy·a·no·sis (s-nss) n. A bluish discoloration of the skin and mucous membranes resulting from inadequate oxygenation of the blood.
- #29 Chloramphenicol superinfection