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ANTIMICROBIAL AGENTS PowerPoint Presentation

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Description : Check out this medical presentation titled "ANTIMICROBIAL AGENTS", to know about antibiotics, antimicrobial agents, and chemotherapeutic agents.

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Published on : Jul 20, 2021 | Views : 3651 | Downloads : 3

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Slide 1-

ANTIMICROBIAL AGENTS
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ANTIBIOTICS ANTIMICROBIAL AGENTS CHEMOTHERAPEUTIC AGENTS
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ANTIBIOTICS Natural substances produced by various species of microorganisms bacteria fungi actinomycetes suppress growth / kill other microorganisms
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ANTIMICROBIAL AGENTS Synthetic analogues ANTIMICROBIAL AGENTS : includes synthetic as well as naturally obtained drugs that attenuate microorganisms
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CHEMOTHERAPEUTIC AGENTS Drugs in this class differ from all others in that they are Designed to inhibit/kill the infecting organism and have no/minimal effect on the recipient.
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Classification Of AMA’s
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Microorganisms of medical impotance fall into four categories Bacteria Viruses Fungi Parasites
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Anti-bacterial Anti-viral Anti-fungal Anti-parasitic agents
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Mechanism of Action Agents that inhibit synthesis of bacterial cell walls Penicillins & cephalosporins Cycloserine, Vancomycin Bacitracin Azole antifungal agents (clotrimazole, fluconazole, itraconazole)
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Agents that act directly on the cell membranes of the microorganisms Polymixin Polyene antifungal agents (Nystatin, Amphotericin B) Alter cell memb. Permeability, leakage of intracellular comp.
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Agents that affect the function of 30S or 50S ribosomal subunits to cause a reversible inhibition of protein synthesis Bacteriostatic drugs Chloramphenicol, Tetracyclines, Erythromycin, Clindamycin, Pristinamycins
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Agents that bind to 30S ribosomal subunit & alter protein synthesis, which eventually leads to cell death Aminoglycosides
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Agents that affect bacterial nucleic acid metabolism. Rifamycins which inhibit RNA polymerase Quinolones which inhibit topoisomerases
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Anti-metabolites including trimethoprim & sulphonamides Antiviral agents Nucleic acid analogues, Non-nucleoside reverse transcriptase inhibitors, Inhibitors of viral enzymes
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TYPE OF ACTION Bacteriostatic Agents Bactericidal Agents
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Bacteriostatic Agents Sulphonamides Tetracyclines Chloramphenicol Erythromycin Ethambutol
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Bactericidal Agents Penicillins/Cephalosporins/Carbapenems Aminoglycosides Rifampin Isoniazid Pyrazinamide
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Cephalosporins Vancomycin Nalidixic acid Ciprofloxacin Metronidazole & Cotrimoxazole
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Some primarily static drugs may become cidal at higher concentrations (as attained in the urinary tract) & vice-versa.
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SPECTRUM Of ACTIVITY Narrow spectrum Broad spectrum
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SPECTRUM Of ACTIVITY Narrow spectrum Penicillin G Streptomycin Broad spectrum Tetracyclines Chloramphenicol
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Successful Antimicrobial Therapy Concentration: site of infection Concentration should inhibit microorganisms simultaneously it should be below the level toxic to human beings. Host Defences Immunity intact - Bacteriostatic Agents Impaired immunity - Bactericidal Agents
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Source of antibiotics Fungi Bacteria Actinomycetes.
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Source of antibiotics Fungi Penicillin, Griseofulvin, Cephalosporin Bacteria Polymyxin B, Colistin, Bacitracin, Aztreonam. Actinomycetes. Aminoglycosides, Macrolides, Tetracyclines, Polyenes, Chloramphenicol
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Resistance
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Bacterial resistance to ANTIMICROBIAL AGENTS 3 general categories Drug does not reach its target Drug is not active Target is altered
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Drug does not reach its target Porins Absence/mutation Reduce drug entry Reduced effective drug concentration at the target site. Efflux pumps Transport drugs out of the cell Resistance to tetracyclines & β-lactam antib
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Inactivation of Drug Second general mechanism of drug resistance β-lactam antibiotics - β-lactamase Aminoglycosides - Aminoglycoside modifying enzymes Variant: failure of bacterial cell to convert an inactive drug to its active metabolite. Resistance to INH in mycobacterium TB
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Alteration of the Target Mutation of natural target Target modification The new target does not bind the drug for native target Resulting in resistance to antibiotic.
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Components mediating resistance to β –lactam antibiotics in psuedomonas aeruginosa
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β –lactam antibiotics hydrophilic Must cross outer membrane barrier of the cell via outer membrane protein (Omp) channel or porins Mutation/missing/deleted Drug entry slow or prevented.
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β - lactamase concentrated between the inner & outer membrane in the periplasmic space constitutes an enzymatic barrier Drug destroyed Effective concentration not achieved
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Target: PBP penicillin binding protein Low affinity for drug Altered
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Efflux transporter Mex A, Mex B & Opr F Pumps the antibiotic across the outer membrane Reduced intracellular concentration of active drug RESISTANCE
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Mutations May occur in Target protein Drug transport protein Protein important for drug activation Random events Survival advantage upon re-exposure to the drug
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Resistance is acquired by horizontal transfer of resistance determinants from a donor cell, often of another bacterial species by Transduction Transformation Conjugation
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Insatiable need for new antibiotics
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Emergence of antibiotic resistance in bacterial pathogens both nosocomially & in the community setting is a very serious development that threatens the end of antibiotic era.
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Responsible approach to the use of antibiotics That are now available & new agents that might be developed in future Is essential If the end of antibiotic era is to be averted.
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CROSS RESISTANCE
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CROSS RESISTANCE Acquisition of resistance to one AMA conferring resistance to another antimicrobial agent to which the organism has not been exposed,is called cross resistance Seen b/w chemically or mechanistically related drugs.
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Resistance to one sulphonamide means resistance to all others Resistance to one tetracyclines means insenstivity to all others Complete cross resistance
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Resistance to one aminoglycoside may not extend to others, Gentamycin resistant strains may respond to amikacin. partial cross resistance
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Sometimes unrelated drugs show partial cross resistance, e.g. Tetracyclines & Chloramphenicol
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Prevention DRUG RESISTANCE
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Prevention DRUG RESISTANCE Use of AMAs should not be: indiscriminate inadequate unduly prolonged Use rapidly acting & narrow spectrum (Selective) AMA whenever possible.
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Prevention DRUG RESISTANCE Combination AMA whenever prolonged therapy is undertaken. Tuberculosis, SABE Infection by organism notorious for developing resistance Staph, E. Coli, M. Tuberculosis must be treated intensively.