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Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
Antimicrobials
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Antimicrobials

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antimicrobials, classification of antimicrobials, drug resistance, mode of action.

antimicrobials, classification of antimicrobials, drug resistance, mode of action.

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  • nothing special in it, its only micro stuff u have incorporated in it and nohing else
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  1. ANTIMICROBIALS MAJID MOHIUDDIN
  2. <ul><li>Drugs designed to inhibit/kill the infecting organism and to have no/minimal effect on the recipient. T – Chemotherapy </li></ul><ul><li>Treatment of systemic infections with specific drugs . </li></ul><ul><li>Both synthetic and microbiologically . </li></ul><ul><li>Antimicrobial agent (AMA) to designate synthetic as well as natural. </li></ul>
  3. CLASSIFICATION OF ANTIMICROBIALS <ul><li>Chemical structure </li></ul><ul><li>Mechanism of action </li></ul><ul><li>Type of organisms against which primarily active. </li></ul><ul><li>Spectrum of activity </li></ul><ul><li>Type of action </li></ul><ul><li>Antibiotics are obtained from. </li></ul>
  4. Chemical structure <ul><li>Sulfonamides and related drugs: Sulfadiazine and other, Sulfones – Dapsone(DDS), Paraaminaosalicyclic (PAS) </li></ul><ul><li>Diaminopyrimidines: Trimethoprim, Pyrimethamine. </li></ul><ul><li>Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin etc. </li></ul><ul><li>β -lactam antibiotics: Penicillins, Cephalosporins, Monobactams, Carbapenems. </li></ul><ul><li>Tetracyclines: Oxytetracycline, Doxycycline etc. </li></ul><ul><li>Nitrobenzene derivative: Chloramphenicol </li></ul><ul><li>Aminoglycosides: Streptomycin, Gentamicin, Neomycin etc. </li></ul><ul><li>Macrolide antibiotics: Erythromycin, Roxithromycin, Azithromycin etc. </li></ul><ul><li>Polypepetide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin. </li></ul><ul><li>Nitrofuran derivatives: Nitrofurantoin, Furazolidone. </li></ul><ul><li>Nitroimidazoles: Metronidazole, Tinidazole. </li></ul><ul><li>Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide. </li></ul><ul><li>Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin. </li></ul><ul><li>Imidazole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole. </li></ul><ul><li>Others: Rifampin, Lincomycin, Clindamycin, Spectinomycin, Vancomycin, Sod. Fusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone, Clofazimine, Griseofulvin. </li></ul>
  5. MECHANISM OF ACTION <ul><li>Inhibit cell wall synthesis: Penicillins, Cephalosporins, Cycloserine, Vancomycin, Bacitracin. </li></ul><ul><li>Cause leakage from cell membranes: </li></ul><ul><ul><li>Polypeptides : Polymyxins, Colistin, Bacitracin </li></ul></ul><ul><ul><li>Polyenes – Amphotericin B, Nystatin, Hamycin. </li></ul></ul><ul><li>Inhibit protein synthesis: Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin. </li></ul><ul><li>Cause misreading of m-RNA code and affect permeability: Aminoglycosides – Streptomycin, Gentamicin etc. </li></ul><ul><li>Inhibit DNA gyrase: Fluoroquinolones – Ciprofloxacin. </li></ul><ul><li>Interfere with DNA function: Rifampin, Metronidazole. </li></ul><ul><li>Interfere with DNA synthesis: Idoxuridine, Acyclovir, Zidovudine. </li></ul><ul><li>Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS, Trimethoprim, Pyrimethamine, Ethambutol. </li></ul>
  6. TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE <ul><li>Antibacterial: Penicillins, Aminoglycosides, Eruthromycin etc. </li></ul><ul><li>Antifungal: Griseofulvin, AmphotericinB, Ketoconazole etc. </li></ul><ul><li>Antiviral: Idoxuridine, Acyclovir, Amantadine, Zidovudine etc. </li></ul><ul><li>Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide etc. </li></ul><ul><li>Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine etc. </li></ul>
  7. SPECTRUM OF ACTIVITY <ul><li>NARROW SPECTRUM: Penicillin G, Streptomycin Erthromycin </li></ul><ul><li>BROAD SPECTRUM: Tetracyclines, Chloramphenicol. </li></ul>
  8. TYPE OF ACTION <ul><li>PRIMARILY BACTERIOSTATIC: </li></ul><ul><li>Sulfonamides, Tetracyclines, Chloramphenicol, Erythromycin, Ethambutol </li></ul><ul><li>PRIMARILY BACTERICIDAL: Penicillins, Aminoglycosides, Polypeptides, Rifampin, Cotrimoxazole, Cephalosporins, Vancomycin, Nalidixic acid, Ciprofloxacin, Isoniazid. </li></ul>
  9. ANTIBIOTICS ARE OBTAINED FROM <ul><li>FUNGI: Penicillin, Cepholosporin,Griseofulvin. </li></ul><ul><li>BACTERIA: Polymyxin B, Colistin, Bacitracin, Tyrothricin, Aztreonam. </li></ul><ul><li>ACTINOMYCETES: Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides, Polyenes. </li></ul>
  10. PROBLEMS THAT ARISE WITH THE USE OF AMAs. <ul><li>TOXICITY: </li></ul><ul><li>HYPERSENSITIVITY REACTIONS: </li></ul><ul><li>DRUG RESISTANCE </li></ul><ul><ul><ul><li>Mutation </li></ul></ul></ul><ul><ul><ul><li>Gene Transfer </li></ul></ul></ul><ul><ul><ul><li>Cross resistance </li></ul></ul></ul><ul><ul><ul><li>Prevention of drug resistance. </li></ul></ul></ul><ul><li>SUPERINFECTION (SUPRAINFECTION) </li></ul>
  11. <ul><li>TOXICITY: </li></ul><ul><li>A) LOCAL IRRITANCY: Erythromycin, Tetracyclines, certain cephalosporins and chloramphenicol. </li></ul><ul><li>B) SYSTEMIC TOXICITY: Dose related and predictable organ toxicities </li></ul><ul><li>- High therapeutic index – Penicillins, some cephalosporins and erythromycin. </li></ul><ul><li>- Lower Therapeutic index – individualized and toxicity watched </li></ul><ul><li>Aminoglycosides: 8 th cranial nerve and kidney toxicity. </li></ul><ul><li> Tetracyclines : Liver and kidney damage, antianabolic effect. </li></ul><ul><li>Chloramphenicol: Bone marrow depression. </li></ul><ul><li>- Very low Therapeutic index - Use is highly restricted </li></ul><ul><li>Polymyxin B : neurological and renal toxicty. </li></ul><ul><li> Vancomycin : hearing loss, kidney damage. </li></ul><ul><li>Amphotericin B : kidney, bone marrow and neurological toxicity. </li></ul>
  12. <ul><li>2. HYPERSENSITIVITY REACTIONS: </li></ul><ul><li> Practically All AMAs. </li></ul><ul><li> Unpredictable and unrelated to dose. </li></ul><ul><li> Reactions from rashes to anaphylactic shock. </li></ul><ul><li> Penicillins, cephalosporins, sulfonamides. </li></ul>
  13. <ul><li>3. DRUG RESISTANCE: </li></ul><ul><li> Natural resistance: always resistance. </li></ul><ul><li>Pencillin G – Gram –ve bacilli. </li></ul><ul><li>Tetracyclines – M.tuberculosis </li></ul><ul><li>Acquired resistance: develop resistance </li></ul><ul><li>rapid acquisition – staphylococci, coliforms, tubercle bacilli. </li></ul><ul><li>Strep.pyogenes & spirochetes – penicillin when >40 years. </li></ul><ul><li>Gonococci – quick to sulfonamides but low to penicillin. </li></ul><ul><li>Resistance may be developed by mutation or gene transfer </li></ul>
  14. <ul><li>MUTATION: </li></ul><ul><li>1. Single Step: high degree of resistance, emerges rapidly – e.g. Enterococci to streptomycin </li></ul><ul><li>E.Coli and Staphylococci to Rigampin </li></ul><ul><li>2. Multistep: Resistance to erythromycin, tetracyclines and chloramphenicol </li></ul><ul><li>Low grade penicillin resistant gonococci have decreased virulence. Staphylococci to rifampin. </li></ul>
  15. <ul><li>Gene transfer (infectious resistance) from one organism to another can occur by: </li></ul><ul><ul><li>Conjugation: R – factor (Resistance transfer factor (RTF)). Chloramphenicol resistance of typhoid bacilli, streptomycin resistance of E.coli, Penicillin resistance of Haemophilus and gonococci. </li></ul></ul><ul><ul><li>Transduction: Penicillin, erythromycin and Chloramphenicol – phage mediated. </li></ul></ul><ul><ul><li>Tranformation: Pneumococcal resistance to penicillin G due to altered penicillin binding protein. </li></ul></ul>
  16. <ul><li>Resistant Organisms can be: </li></ul><ul><li>Drug tolerant: loss of affinity of the target biomolecule of the microorganism for a particular AMA. E.g., resistant Staph.aureus and E.coli developa RNA polymerase that does not bind rifampin. </li></ul><ul><li>Drug destroying: β - lactamase by Staphylococci, Haemophilus, Gonococci etc., which inactivate penicillin G. Chloramphenicol acetyl transferase is acquired by resistant E.coli, H.influenzae and S.typhi. </li></ul><ul><li>Aminoglycoside resistant coliforms – produce enzymes which adenulate/acetylate/phosphorylate specific aminoglycoside antibitotics. </li></ul><ul><li>c) Drug impermeable: Many hydrophilic antibiotics access though porins, or need specific transport mechanisms. Glycosides and tetracyclines in the resistant gram negative bacterial strains. </li></ul>
  17. <ul><li>Cross resistance: Acquisition of resistance to one AMA conferring resistance to another AMA, to which the organism has not been exposed, is called cross resistance. </li></ul><ul><li>Sulfonamide – to all others. </li></ul><ul><li>Tetracycline – insensitivity to all others. </li></ul><ul><li>Aminoglycoside – not extend to another </li></ul><ul><ul><li>Gentamicin - amikacin also </li></ul></ul><ul><ul><li>Cross resistance e.g., between tetracyclines and chloramphenicol, between erythromycin and lincomycin. </li></ul></ul><ul><ul><li>Newmycin resistance by enterobacteriaceae – insensitive to streptomycin. </li></ul></ul>
  18. <ul><li>4. Superinfection ( Suprainfection) </li></ul><ul><li>Appearance of a new infection as a result of antimicrobial therapy. </li></ul><ul><li>The normal flora contributes to host defence by elaborating substances called bacteriocins which inhibit pathogenic organisms. </li></ul><ul><li>Superinfections are more common when host defence is compromised, as in: </li></ul><ul><li>Corticosteriod therapy </li></ul><ul><li>Leukemias and other malignancies (WBC count) </li></ul><ul><li>Acquired immunodeficiency syndrome (AIDS) </li></ul><ul><li>Agranulocysis </li></ul><ul><li>Diabetes, disseminated Lupus Erythematosus. </li></ul>
  19. MAJID MOHIUDDIN Thank you

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