chapter 10 antimicrobial medications. chemotherapy antibiotic synthetic drugs semi-synthetic drugs
TRANSCRIPT
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Chapter 10Antimicrobial Medications
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• Chemotherapy
• Antibiotic
• Synthetic drugs
• Semi-synthetic drugs
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• In 1910, Paul Ehrlich discovered Salvarsan– Arsenic derivative used to treat syphilis
• In 1935, Gerhard Domagk discovered a red dye that inhibited G+ bacteria– Prontosil
• In 1936, Ernest Fourneau discovered it was the sulfur portion of the dye that was active – stimulated the development of sulfa drugs
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• In 1928, Alexander Flemming -1st true antibiotic– Penicillium mold secretes compound that
inhibits bacterial growth
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• Selman Waksman isolated streptomycin from the soil bacteria Streptomyces
• In 1940s, Howard Florey and Ernst Chain performed first clinical trials of penicillin– Developed a method for mass production– Penicillin G
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• More than ½ of antibiotics in use come from bacteria– Primarily species of Streptomyces– Some are isolated from species of Bacillus
• Some are isolated from various molds – Penicillium and Cephalosporium
• Most antibiotic producers are spore formers
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• Selective Toxicity
• Magic bullet – causes damage to the microorganism without
causing significant harm to the host– Easier with prokaryotic pathogens – Why?
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• Chemotherapeutic index – maximum tolerable dose (per kg body weight) /
minimum effective dose (per kg body weight)– Higher the index the safer for host
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• Spectrum of activity– range of different microorganisms against which
the drug is effective
– Narrow-spectrum • Example – anti-mycobacterials
– Broad-spectrum• May disturb normal microbiota • May lead to superinfection
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• Synergism
– increased effect of two drugs when used together – clavulanic acid and amoxicillin
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• Antagonism – reduction of a drug’s desirable effect when
administered with another • penicillin and tetracycline
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• Adverse effects of antimicrobials– Allergic reactions– Toxic effects– Suppression of normal flora
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Primary Modes of Action
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Inhibition of Cell Wall Synthesis
– Bacterial cell walls are composed of the polysaccharide peptidoglycan • Some antibiotics prevent the synthesis of
intact peptidoglycan• Human cells are unaffected
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Disruption of Cell Membrane
• changes permeability of the plasma membrane – Results in the loss of important metabolites – May target specific membrane components– Ex. particular sterols in fungi cell membranes
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Inhibition of Protein Synthesis
• Common feature of all cells– May target the ribosomes
• Change ribosome shape• Block binding sites for tRNA/rRNA• Inhibit peptide bond formation • Prevent shift of reading frame
– Use is limited
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Inhibition of Nucleic Acid Synthesis
• Interfere with DNA or RNA synthesis – May act as nucleoside/nucleotide analogs – Some have an extremely limited usefulness– Others are widely used because they are more
selectively toxic • May act only on bacterial or viral enzymes
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Metabolic Antagonists
• Inhibition of the synthesis of essential metabolites– enzymatic activity of microbes can be inhibited
by a substance that closely resembles the normal substrate for the enzyme
– Competitive inhibition
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Inhibition of Host Recognition or Attachment
• Depends on chemical reaction between pathogen and host– Pathogen proteins and specific host receptors– Modification of either attachment or receptor
proteins can inhibit attachment and entry
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Mechanisms for Administration of Drugs
• Topical
• Orally
• Intramuscularly (IM)
• Intravenously (IV)
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Tests to Guide Chemotherapy
• Disk-diffusion method (Kirby-Bauer test)
• Minimum Inhibitory Concentration tests (MIC)
• E-test
• Minimum Bactericidal Concentration tests (MBC)
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Kirby-Bauer Test
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MIC Test
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E Test
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MBC Test