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1、Variola virus (Smallpox),Random microbe of the week!,2,Principles of Antimicrobial Therapy,Administer a drug to an infected person that destroys the infective agent without harming the hosts cells Antimicrobial drugs are produced naturally or synthetically,3,4,5,Origins of Antimicrobial Drugs,Antibi
2、otics are common metabolic products of aerobic bacteria and fungi Bacteria in genera Streptomyces and Bacillus Molds in genera Penicillium and Cephalosporium By inhibiting the other microbes in the same habitat, antibiotic producers have less competition for nutrients and space,6,7,Interactions Betw
3、een Drug and Microbe,Antimicrobial drugs should be selectively toxic drugs should kill or inhibit microbial cells without simultaneously damaging host tissues As the characteristics of the infectious agent become more similar to the vertebrate host cell, complete selective toxicity becomes more diff
4、icult to achieve and more side effects are seen,8,Mechanisms of Drug Action,Inhibition of cell wall synthesis Breakdown of cell membrane structure or function Inhibition of nucleic acid synthesis, structure or function Inhibition of protein synthesis Blocks on key metabolic pathways,9,10,11,The Spec
5、trum of an Antimicrobic Drug,Spectrum range of activity of a drug Narrow-spectrum effective on a small range of microbes Target a specific cell component that is found only in certain microbes Broad-spectrum greatest range of activity Target cell components common to most pathogens (ribosomes),12,An
6、timicrobial Drugs That Affect the Bacterial Cell Wall,Most bacterial cell walls contain peptidoglycan Penicillins and cephalosporins block synthesis of peptidoglycan, causing the cell wall to lyse Active on young, growing cells Penicillins that do not penetrate the outer membrane are less effective
7、against gram-negative bacteria Broad spectrum penicillins and cephalosporins can cross the cell walls of gram-negative bacteria,13,14,Antimicrobial Drugs That Disrupt Cell Membrane Function,A cell with a damaged membrane dies from disruption in metabolism or lysis These drugs have specificity for a
8、particular microbial group, based on differences in types of lipids in their cell membranes Polymyxins interact with phospholipids and cause leakage, particularly in gram-negative bacteria Amphotericin B and nystatin form complexes with sterols on fungal membranes which causes leakage,15,16,Drugs Th
9、at Affect Nucleic Acid Synthesis,May block synthesis of nucleotides, inhibit replication, or stop transcription Chloroquine binds and cross-links the double helix; quinolones inhibit DNA helicases Antiviral drugs that are analogs of purines and pyrimidines insert in viral nucleic acid, preventing re
10、plication,17,Drugs That Block Protein Synthesis,Ribosomes of eukaryotes differ in size and structure from prokaryotes; antimicrobics usually have a selective action against prokaryotes; can also damage the eukaryotic mitochondria Aminoglycosides (streptomycin, gentamycin) insert on sites on the 30S
11、subunit and cause misreading of mRNA Tetracyclines block attachment of tRNA on the A acceptor site and stop further synthesis,18,19,Drugs that Affect Metabolic Pathways,Sulfonamides and trimethoprim block enzymes required for tetrahydrofolate synthesis needed for DNA and RNA synthesisCompetitive inh
12、ibition drug competes with normal substrate for enzymes active site Synergistic effect the effects of a combination of antibiotics are greater than the sum of the effects of the individual antibiotics,20,21,22,Survey of Major Antimicrobial Drug Groups,Antibacterial drugs Antibiotics Synthetic drugs
13、Antifungal drugs Antiprotozoan drugs Antiviral drugs About 260 different antimicrobial drugs are classified in 20 drug families,Antibacterial Drugs that Act on the Cell Wall,Beta-lactam antimicrobials - all contain a highly reactive 3 carbon, 1 nitrogen ring Primary mode of action is to interfere wi
14、th cell wall synthesis Greater than of all antimicrobic drugs are beta-lactams Penicillins and cephalosporins most prominent beta-lactams,23,24,Penicillin and Its Relatives,Large diverse group of compounds Could be synthesized in the laboratory More economical to obtain natural penicillin through mi
15、crobial fermentation and modify it to semi-synthetic forms Penicillium chrysogenum major source All consist of 3 parts: Thiazolidine ring Beta-lactam ring Variable side chain dictating microbial activity,25,26,27,Subgroup and Uses of Penicillins,Penicillins G and V most important natural forms Penic
16、illin is the drug of choice for gram-positive cocci (streptococci) and some gram-negative bacteria (meningococci and syphilis spirochete) Semisynthetic penicillins ampicillin, carbenicillin, and amoxicillin have broader spectra Gram-negative infections Penicillinase-resistant methicillin, nafcillin,
17、 cloxacillin Primary problems allergies and resistant strains of bacteria,28,Cephalosporins,Account for one-third of all antibiotics administered Synthetically altered beta-lactam structure Relatively broad-spectrum, resistant to most penicillinases, and cause fewer allergic reactions Some are given orally; many must be administered parenterally Generic names have root cef, ceph, or kef,
