Macrolides: A Detailed Overview PDF

MACROLIDES Macrolides are a group of antibiotics with a macro cyclic lactone structure to which one or more deoxy sugars are attached. They inhibit protein synthesis in bacteria. It was first introduce in the 1950s.  CLASSIFICATIONS Macrolides are classified into first- generat...

MACROLIDES Macrolides are a group of antibiotics with a macro cyclic lactone structure to which one or more deoxy sugars are attached. They inhibit protein synthesis in bacteria. It was first introduce in the 1950s.  CLASSIFICATIONS Macrolides are classified into first- generation, second -generation and third – generation First- generation macrolide Erythromycin Second generation macrolide Azithromycin Clarithromycin Roxithromycin Third generation macrolide (ketolides) Telithromycin  MECHANISM OF ACTION Macrolides and ketolides bind irreversibly to a site on the 50s subunits of the bacterial ribosome, thus inhibiting translocation steps of protein synthesis. They are bacteriostatic at low dose but bactericidal for certain bacteria at higher doses. They are actively concentrated within leukocyte and thus are transported into the site of  ANTIMICROBIAL SPECTRUM (a) Erythromycin : Has narrow spectrum of activity. The spectrums are mostly gram positive and a few gram negative organisms. It is highly active against streptococcal pyogenes, pneumonia, N. gonorrhea, clostridia, listeria and Diphtheria and against many of the same organism as penicillin G. (b)Clarithromycin: Has similar activity to erythromycin but is more effective against haemophilus influenza and has greater activity against intracellular pathogens such as chlamydia, legionella, morexella, ureaplasma species and H.pylori.  ANTIMICROBIAL SPECTRUM Continues (c) Azithromycin: This has more activity against respiratory pathogens like H. influenza and Moraxella catarrhalis. (d) Roxythromycin: This has spectrum of activity similar to erythromycin. It is more potent against B.catarrhalis, Gardia Vaginalis and Legionalle (e) Telithromycin: This has an antibacterial spectrum similar to that of Erythromycin with improved activity against resistant strain.  SUMMARY OF SPECTRUM OF ACTIVITY  Gram-postitive bacteria: - Staphylococcus aureus - Streptococcus pneumonia - Streptococcus pyogenes  Gram-negative bacteria: - Haemophilus influenza - Moraxella catarrhalis - Neisseria gonorrhoeae  Intracellular pathogens: - Chlamydia trachomatis - Legionella pneumophila - Mycoplasma pneumonia  PHARMACOKINETICS Absorption: The erythromycin base is destroyed by gastric acid thus, either enteric-coated tablets or esterified forms of the antibiotics are administered and all have adequate oral absorption. Clarithromycin, Azithromycin, Roxythromycin, and Telithromycin are stable in stomach acid and are readily absorbed. Distribution: All macrolides are distributed widely throughout the body except the CNS. Azithromycin has the largest volume of distribution among the macrolide and concentrates in neutrophils, macrophages and fibroblasts. Elimination: Macrolides are metabolized by the liver to varying degrees. Excretion: It is excreted in the bile.  THERAPEUTIC USES  Respiratory tract infections (RTIs)  Skin and soft tissue infections (SSTIs)  Genital infections (chlamydia, gonorrhea)  Helicobacter pylori eradication  Lyme disease  ADVERSE EFFECT  Gastrointestinal - Nausea - Vomiting - Diarrhea  Cardiac - QT interval prolongation - Arrhythmias  Hepatic - Elevated liver enzymes - Hepatitis  Allergic reactions  Ototoxicity  RESISTANCE Resistance to macrolides is associated with:  Inability of the organism to take up the antibiotics  The presence of efflux pumps  Methylation of 23S rRNA  Ribosomal modifications  DRUG INTERACTIONS Macrolide inhibit the hepatic metabolism of a number of drugs like carbamazepine, protease inhibitors, sidenafil, simvastatin, valproate, warfarin and Atorvastatin. This can lead to toxic accumulation of these compounds.  CONTRAINDICATION Patients with cardiac or hepatic dysfunctions should be treated cautiously with macrolides.