lecture -6-antibiotics (2).ppt

Dr. Reem Mohamed Elfatih Chemotherapreutic agents : are chemical agents which combat disease in the body. Anti micobial drugs :are chemical agents that destroy microorganisms. Anti microbial may be synthetic (prepared in lab) or natural produced by certain fungi and bacteria....

Dr. Reem Mohamed Elfatih Chemotherapreutic agents : are chemical agents which combat disease in the body. Anti micobial drugs :are chemical agents that destroy microorganisms. Anti microbial may be synthetic (prepared in lab) or natural produced by certain fungi and bacteria. CLASSIFICATION OF ANTIMICROBAL DRUGS 1\ according to spectrum of activity : a)Broad spectrum antibiotics: that act against both gram negative as well as gram positive bacteria e.g amoxicillin, ciprofloxacillin,... Narrow spectrum b) antibiotics: act against certain microorganisms eg. Penicillin. a) drugs acting on cell wall eg. Penicillin. b) protein synthesis ,eg. Aminoglycoside. c) cell membrane eg. Polymxin. d) nucleic acid biosynthesis e.g rifampicin. a. Bactericidal : that eliminate bacteria e.g. aminoglycosides. b. Bacteriostatic : inhibit growth of bacteria e.g 4\ according to chemical structure : a) Beta lactams eg. Penicillin and cephalosporins. b) Aminoglycosides they contain amino sugar component ,eg. gentamycin. c) Quinolones eg. Ciprofloxacin. e) Tetracyclines. f) Macrolides: inhibit protein synthesis eg. erythromycin ACTION OF ANTIMICROBIAL drugs The general action: either 1. directly kill microorganism (bactericidal) 2. or inhibit growth (bacteriostatic)  MECHANISM OF ACTION 1\ inhibition of cell wall synthesis : e.g.( Cephalosporins , Penicillins and Vancomycin). Inhibitors of bacterial cell wall synthesis, act on the formation of the peptidoglycan layer. 2\ inhibition of the cell membrane function : e.g.(clostin , ,polymyxin B,) Alter the osmotic properties of the plasma membrane 3\ inhibition of protein synthesis : e.g. (chloramphenicol, erythromycin, clindamycin, tetracyclines and aminoglycosides ).  antimicrobial drugs inhibit protein synthesis in bacterial ribosomes. 4\ inhibition of nucleic acid synthesis : e.g.(quinolones , rifampin, sulfonamides, trimethoprim) - rifampin inhibit bacterial growth by binding strongly to the DNA – dependent RNA polymerase of bacteria, thus inhibits bacterial RNA synthesis. - All quinolones and flouroquinolones inhibit microbial DNA synthesis by blocking DNA gyrase There are two main issues that we will talk about: * mechanisms of drug resistance * Origins of drug resistance 1- mechanisms: a) micro organisms produce enzymes that destroy the activity of the drug eg:  staphylococcus B-lactamase  Gram –ve rods adenylating ,phosphorylating ,and acetylating enzymes ,against aminoglycosides.,  Gram –ve chloramphinicol acetyl transferase against chloramphinicol. d) Microorganisms develop an altered metabolic pathways that bypass the reaction inhibited by the drug, e.g Sulfonamides. e) Microorganisms develop an altered enzyme e.g: Trimethprim resistant bacteria and dihydrofolic acid reductease enzyme.  ORIGINS Non genetic Genetic Extrachromosomalchromosomal  Non genetic Origin 1. Active replication of bacteria is required for most antibacterial drug action eg : Mycobacterim tuberclosis stay many years in the body with slow multiplying.  2. Microorganism may lose specific target structure and so becomes resistant , eg: penicillin susceptible organisms may change to cell wall deficient L forms and so become resistant to cell wall Inhibitor drugs (penicillin + cephalosporins). 3. Intracellular microorganisms are not affected by drugs as long as they stay inside cells ,eg: Aminoglycosides salmonella enteric fever  Because salmonellae are intracellular microorganisms and aminoglycosides can not enter the cell. Genetic : origin Either : 1) chromosomal “mutation” :this develops as a result of spontaneous mutation in a locus that controls susceptibility to a given drug * eg mutation in the gene controlling the structural protein “of streptomycin receptor result in streptomycin resistance. 2) Extrachromosomal “plasmid mediated resistance”:. *R-factor are a class of plasmids , circular ,double stranded DNA that carry genes for resistance to one –and often several – antimicrobial drug. *R-factor composed of two parts : 1\ Resistant – transfer factor “RTF”: segment of plasmid that responsible for intracellular transfer. 2\ R-determinant : that carries the resistance genes. Dissemintion by bacterial conjugation mainly. Genetic material and plasmid can be transferred by:  transformation ,  transduction ,  conjugation Is the up take of the DNA by bacteria thus , altering its genotype. The genetic transfer occur when a fragment of DNA is carried to the recipient cell by virus “bacteriophage “  It is a unilateral transfer of genetic material between bacteria of the same or different genera occurs during a mating (conjugation ) process.  This is mediated by a fertility factor that result in extension or extrusion of sex pili from the donor (F+) cell to the recipient (F-). Microorganisms resistant to a certain drugs may also be resistant to other drugs that share a mechanism of action eg: Aminoglycosides , macrolides. THANK U