Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
ANTIMICROBIALS MAJID MOHIUDDIN
<ul><li>Drugs designed to inhibit/kill the infecting organism and to have no/minimal effect on the recipient. T – Chemothe...
CLASSIFICATION OF ANTIMICROBIALS <ul><li>Chemical structure  </li></ul><ul><li>Mechanism of action </li></ul><ul><li>Type ...
Chemical structure <ul><li>Sulfonamides and related drugs:  Sulfadiazine and other, Sulfones – Dapsone(DDS), Paraaminaosal...
MECHANISM OF ACTION <ul><li>Inhibit cell wall synthesis:  Penicillins, Cephalosporins, Cycloserine, Vancomycin, Bacitracin...
TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE <ul><li>Antibacterial:  Penicillins, Aminoglycosides, Eruthromycin etc. <...
SPECTRUM OF ACTIVITY <ul><li>NARROW SPECTRUM: Penicillin G, Streptomycin Erthromycin </li></ul><ul><li>BROAD SPECTRUM: Tet...
TYPE OF ACTION <ul><li>PRIMARILY BACTERIOSTATIC: </li></ul><ul><li>Sulfonamides, Tetracyclines, Chloramphenicol, Erythromy...
ANTIBIOTICS ARE OBTAINED FROM <ul><li>FUNGI:  Penicillin, Cepholosporin,Griseofulvin. </li></ul><ul><li>BACTERIA:   Polymy...
PROBLEMS THAT ARISE WITH THE USE OF AMAs. <ul><li>TOXICITY: </li></ul><ul><li>HYPERSENSITIVITY REACTIONS: </li></ul><ul><l...
<ul><li>TOXICITY: </li></ul><ul><li>A)  LOCAL IRRITANCY:  Erythromycin, Tetracyclines, certain cephalosporins and chloramp...
<ul><li>2.  HYPERSENSITIVITY REACTIONS: </li></ul><ul><li>  Practically All AMAs. </li></ul><ul><li>  Unpredictable and un...
<ul><li>3. DRUG RESISTANCE: </li></ul><ul><li>  Natural resistance:   always resistance.  </li></ul><ul><li>Pencillin G – ...
<ul><li>MUTATION: </li></ul><ul><li>1. Single Step:  high degree of resistance, emerges rapidly – e.g.  Enterococci  to st...
<ul><li>Gene transfer  (infectious resistance) from one organism to another can occur by: </li></ul><ul><ul><li>Conjugatio...
<ul><li>Resistant Organisms can be: </li></ul><ul><li>Drug tolerant:  loss of affinity of the target biomolecule of the mi...
<ul><li>Cross resistance: Acquisition of resistance to one AMA conferring resistance to another AMA, to which the organism...
<ul><li>4.  Superinfection ( Suprainfection) </li></ul><ul><li>Appearance of a new infection as a result of antimicrobial ...
MAJID MOHIUDDIN Thank you
Upcoming SlideShare
Loading in …5
×

Antimicrobials

16,736 views

Published on

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

  • Login to see the comments

Antimicrobials

  1. 1. ANTIMICROBIALS MAJID MOHIUDDIN
  2. 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. 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. 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. 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. 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. 7. SPECTRUM OF ACTIVITY <ul><li>NARROW SPECTRUM: Penicillin G, Streptomycin Erthromycin </li></ul><ul><li>BROAD SPECTRUM: Tetracyclines, Chloramphenicol. </li></ul>
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 19. MAJID MOHIUDDIN Thank you

×