Antibiotics Antibiotics can be classified according to their chemical structure & mechanism of their action Inhibitors of cell wall

l synthesis Unique to bacteria, this structure is not found in mammalian cells It's a polymer og glycan units joined to each other by peptide cross-links, hence, the designation of peptidoglycan cell wall

-lactam antibiotics Important members of this group is beta lactam ring, essential to their activity :

Penicillins Cephalosporins Carbapenems

Penicillins They are the most widely effective antibiotics & among the least toxic drug known, major adverse reaction to penicillin is hypersensitivity Mechanism of action: 1. Penicillin interfere with last step of bacterial cell wall synthesis (transpeptidation), thus exposing the osmotically less stable membrane 2. Cell lysis can occur, these drug are bactericidal 3. Only effective against rapidly growing organism that synthesize peptidoglycan cell wall Antibacterial spectrum They are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi & viruses Antibacterial spectrum of various penicillin is determined In general, gram positive microbe have cell walls that easily traversed by Penicillins

Aiman Tymer 2012

Gram negative microbe have outer lipopolysaccharide membrane surrounding cell wall that presents as barrier to water-soluble penicillin. For this reason, penicllin have little use in treatment of intracellular pathogens

Cephalosporin They have same mode of action as penicillin, but they tend to be more resistant than Penicillin to lactamase (this family of enzyme hydrolyzes cyclic amide bond of -lactam ring, which result in loss of bactericidal activity) Now we have 1st, 2nd, 3rd, 4th generation of cephalosporins Cefepime most clinically useful 4th generation cephalosporin & has a wide antibacterial spectrum

Carbapenems This group include only drug Imipenem. Active against penicillinase producing gran positive & negative organism anaerobes

Other agents affecting cell wall Vancomycin It is tricyclic glycopeptide that become increasingly important because of its effectiveness against multiple drug resistant organisms such as methicillin-resistant staphylococci Moa: its inhibits synthesis of bacterial cell wall phospholipids as well as peptidoglycan polymerization at site earlier than that inhibited by -lactam antibiotics

All antibiotic affecting cell wall have very specific anti-bacterial effect & have not any adverse effect without allergy n superinfection (overgrowth of Candida)- adverse effect of all antibiotics

Protein synthesis inhibitors Tetracycline : Doxycycline Aminoglycoside : Streptomycin, Gentamycin Macrolides : Erythromycin, Roxithromycin, Azithromycin Chloramphenicol (one drug)

Tetracycline have 4 fused rings in structure Moa: Inhibit bacterial protein synthesis (binding of drug to 30S subunit of bacterial ribosome believed to block access of amino acyl-tRNA to mRNA-ribosome complex at acceptor site)

Aiman Tymer 2012

Antibacterial spectrum: very wide & they also effective against organisms other than bacteria (for eg. Entamoeba histolytica) They are generally bacteriostatic Adverse effect: gastric discomfort, effects on calcified tissues (discoloration & hypoplasia of teeth), fatal hepatotoxicity, phototoxicity, vestibular problems (vertigo), superinfection (overgrowth of Candida) Attention: Avoid pregnancy

Aminoglycosides Have 2 amino sugars structure Moa: Inhibit bacterial protein synthesis by binding to 30S subunit, interfering with assembly of functional ribosomal apparatus , / causing 30S subunit of complete ribosome misread the genetic code. Polysomes became depleted because aminoglycosides interrupt process of polysomes disaggregation & assembly Aminoglycosides synergize with -lactam antibiotic because of latters action on cell wall synthesis, which enhance diffusion of aminoglycosides into bacterium Antibacterial spectrum: All aminoglycosides are bactericidal; Effective only against aerobic organisms, since anaerobic organism lack of oxygen-requiring transport system Streptomycin used to treat to tuberculosis, plaque, tularemia Adverse effect: ototoxicity (directly related to high peak plasma levels & duration of treatment), nephrotoxicity, neuromuscular paralysis, allergic reaction, superinfections (overgrowth of Candida), skin rash [Neomycin]

Macrolides Have macrocyclic lactone structure Moa: Bind to irreversibly to site 50S subunit of.bacterial ribosome, thus inhibiting translocation steps of protein synthesis. They are bacteriostatic but may cidal at higher doses Antibacterial spectrum: Effective against same organisms as penicillin plus chlamydia & mycoplasma Adverse effect: epigastric distress, cholestatic jaundice, ototoxicity, allergic reaction & superinfectins are little

Chloramphenicol Active against range gram-positive & - negative organisms, but because of its toxicity, it's use is restricted to life-threatening infection which there are no alternatives Moa: Drug bind 50S subunit & inhibit protein synthesis at peptidyl transferase reaction because of similarity of mammalian mitochondrial ribosome to those of bacteria, protein synthesis in organelles maybe inhibited at big doses, producing bone marrow toxicity

Aiman Tymer 2012

Adverse effect: anaemias, gray baby syndrome (cardivascular collapse, cyanosis hence the term gray baby- death), dermatitis, psychosis (maybe), allergic reaction, superinfections (overgrowth of Candida)

Polymyxin Cause cell membrane destroyment, Bactericidal & very toxic Adverse effect: nephrotoxicity, neuromuscular paralysis

Aiman Tymer 2012