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Antimicrobial drugs

Antimicrobial drugs . Farah Morad IUG Faculty Of Medicine 220061056. Selective toxicity. The ability to kill an invading microorganism without harming the cells of the host .. Why ? differences between microorganisms and human beings Relative, rather than absolute

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Antimicrobial drugs

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  1. Antimicrobial drugs Farah Morad IUG Faculty Of Medicine 220061056

  2. Selective toxicity The ability to kill an invading microorganism without harming the cells of the host .. Why ? differences between microorganisms and human beings Relative, rather than absolute Concentration ..carefully controlled More antibacterial than antiviral …Why ?

  3. Broad & narrow spectrum : 1- Broad spectrum both gram-positive and gram-negative the critically ill patient delay ..example ?? tetracycline ,chloramphenicol Superinfection

  4. 2- Narrow spectrum: more specific.. Isoniazid for Mycobacteria ..Name? , Penicillin 3- Extended spectrum: effective against gram-positive & significant Number of gram-negative bacteria Ampicillin

  5. Bacteriostatic & Bactericidal ** Bacteriostatic (1) the bacteria can grow again (2) host defense mechanisms ** Bactericidal 1- Immediately life-threatening infection 2-leukocyte count is below 500/IuL 3-Endocarditis, phagocytosis is limited

  6. III. Mechanisms of Antimicrobial Drugs Inhibition of bacterial Cell Wall Synthesis:

  7. B-Iactam drugs: Penicillins and cephalosporins. Non B-Iactam drugs: Vancomycin ,Cycloserine & Bacitracin

  8. Inhibition of bacterial Cell Wall Synthesis: Penicillin 1-Transpeptidases (pbps) No cross-linking peptidoglycan 2- Autolytic enzymes : murein hydrolases Staphylococcus aureus, : Tolerant

  9. Penicillins kill bacteria when they are growing which phase of bacterial Growth ? Log Phase Gram +ve or –ve ? Why ? Gram +ve because they have a cell wall Gram –ve have a cell membrane

  10. Penicillin Mechanism of Action - Animation Shift +F5 to see the animation

  11. penicillin Kills Bacteria in log phase

  12. Disadvantages: 1-limited effectiveness against many gram-negative rods.. Why ? Extended-spectrum penicillins ampicillin & amoxicillin.. modified R Ampicillin 4 /daily Amoxicillin 3/ daily.. Compliance Pseudomorms aeruginosa,,No effect Because it Lacks porins 2-hydrolysis by gastric acids ..oral effectiveness ?? oxygen : penicillin V amino group: ampicillin

  13. (3) inactivation by B-lactamases. A -methicillin, oxacillin, nafcillin, large aromatic rings contain- bulky methyl or ethyl B-inhibitorssuch clavulanic acid and and supbactam. -(Augmentin) Combinations, amoxicillin and clavulanic acid .. Expensive !! (4) disadvantage hypersensitiv- anaphylaxis, in 0.5% of patients..fatal skin rashes, hemolytic anemia, nephritis, fever. No solution till now !

  14. Bacterial Resistance to penicillin Beta lactamases Alteration of PBP (Pseudomonas) • Penicilinase-resistant penicillins Augmentin ,Naficillin, sublactam ,Methacillin,Floxacillin • Extended-spectrum penicillins ampicillin & amoxicillin Shift +F5 To see the animation

  15. B- lactamases- AnimationShift +F5 to see the animation

  16. Forms of penicillin G 1-Aqueous 2-Procaine..IM 3-Benzathine..depot

  17. Cephalosporins • against gram-positive cocci primarly..1st Generation • From 1- 4 generations : increased sensitivity to gram –ve • 4 th against a broad range of organisms, • -Same Action of penicilllin • - fewer hypersensitivity reactions than do the penicillin

  18. Carbapenems: (Imipenem) - B-lactam drugs - not inactivated by most B-Lactamases. - structurally different from penicillins and cephalosporins - widest spectrum of activity of the B-Lactam - many gram-positive, gram-negative, and anaerobic bacteria - In combination with cilastatin an inhibitor of dehydropeptidase a kidney enzyme that inactivates imipenem.

  19. Monobactams (Aztreonam) - B-lactam - resistant to most B-lactamases…Good !! - they are monocyclic - Aztreonam, has excellent activity against many gram -ve rods - no cross-reactivity.. Patients hypersensitive to penicillin

  20. Vancomycin: not B-lactam Transpeptidase compititiveinhibition binds directly to the D-alanyl-D-alanine of peptidoglycan bactericidal against gram-positive bacteria Uses: 1-S. aureus strains resistant to the penicillinase-resistant penicillins (MRSA) VMRSA?!!! 2- Antimicrobial induced Cholitis …Oral

  21. Vancomycin Action –Animation Shift +F5 to see the animation

  22. Cycloserine • 1- analogue of D-alanine inhibits dipeptide D-alanyl-D- alanine • 2- It is used as a second line drug in the treatment TB • Remember : What first line ?? Great !! Rifampin & isoniazide

  23. Bacitracin 1- prevents dephosphorylation of the phospholipid carrier of the peptidoglycan 2- Treatment of superficial skin infections (Topical) too toxic for systemic use.

  24. 2. Inhibition of Fungal Cell Wall Synthesis • Caspofungin • - lipopeptide • Inhibition of B-glucan synthase • Aspergillus and Candida but not Cryptococcus or Mucor. • -Disseminated candidiasis and Invasive aspergillosis

  25. 3- INHIBITION OF PROTEIN SYNTHESIS Principle: - differences between bacterial and human ribosomal proteins, RNAs - Bacteria 70S ..50S and 30S subunits, - human cells have 80S ..60S and 40S subunits

  26. I. Drugs That Act on the 30S Subunit Aminoglycosides Are bactericidal drugs.. Broad spectrum Streptomycin, neomycin, gentamycin ,tobramycin ,Kanamycin. No Initiation complex .. and misreading (mRNA)

  27. Aminoglycosides Animation-1 Shift +F5 to see the animation

  28. Aminoglycosides Animation 2 Shift +F5 to see the animation

  29. Aminoglycosides cont. 1- Toxicicity the kidneys How to Avoid ?? Urea & Creatinine tests 2- eighth cranial nerveToxicicity 3- Cannot be given orally. 4- Must be given intrathecally meningitis. 5- Ineffective against anaerobes ..Needs O2 to enter cells

  30. Tetracyclines Bacteriostatic Gram +ve & -ve bacteria, mycoplasmas, chlamydiae, and rickettsiae. The 30S ribosomal & (tRNA) Selectivity : greatly increased uptake into susceptible bacteria compared with human cells. Doxacycline…(Cholera)

  31. Side Effects : 1- Diarrhea & superinfection . 2- Brown staining of the teeth of fetuses and young children 3- Tetracydines are avid calcium chelators 4- Contraindicated for use in pregnant women and in children<8

  32. * Advantages of drug combinations • show synergism • - B-Iactams and aminoglycosides,. • - B-lactams + calvulanic acid • Disadvantages of drug combinations • bacteriostasis & bactericidal.

  33. Needs To modify drugs : 1- Change route of administration ..Compliance 2- Overcome resistance 3- Minimize side effects 4-Wideninig Spectrum of activity

  34. Thank you !

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