Antimicrobial drugs Farah Morad IUG Faculty Of Medicine 220061056.
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Transcript of Antimicrobial drugs Farah Morad IUG Faculty Of Medicine 220061056.
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Antimicrobial drugs
Farah MoradIUG
Faculty Of Medicine220061056
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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 ?
Selective toxicity
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Broad & narrow spectrum :
1- Broad spectrum
both gram-positive and gram-negative
the critically ill patient delay ..example ??
tetracycline ,chloramphenicol
Superinfection
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2- Narrow spectrum:
more specific..
Isoniazid for Mycobacteria ..Name? , Penicillin
3- Extended spectrum:
effective against gram-positive & significant Number ofgram-negative bacteria
Ampicillin
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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
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Inhibition of bacterial Cell Wall Synthesis: III. Mechanisms of Antimicrobial Drugs
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B-Iactam drugs: Penicillins and cephalosporins. Non B-Iactam drugs: Vancomycin ,Cycloserine & Bacitracin
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Inhibition of bacterial Cell Wall Synthesis:
Penicillin
1-Transpeptidases (pbps)
No cross-linking peptidoglycan
2- Autolytic enzymes : murein hydrolases Staphylococcus aureus, : Tolerant
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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
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Penicillin Mechanism of Action - Animation
Shift +F5 to see the animation
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penicillin Kills Bacteria in log phase
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Disadvantages:
1-limited effectiveness against many gram-negative rods.. Why ?
Extended-spectrum penicillins
ampicillin & amoxicillin.. modified R
Ampicillin 4 /dailyAmoxicillin 3/ daily.. Compliance
Pseudomorms aeruginosa,,No effect Because it Lacks porins
2-hydrolysis by gastric acids ..oral effectiveness ??
oxygen : penicillin V amino group: ampicillin
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(3) inactivation by B-lactamases.
A -methicillin, oxacillin, nafcillin,
large aromatic rings contain- bulky methyl or ethyl
B-inhibitors such 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 !
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• 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
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B- lactamases- Animation Shift +F5 to see the animation
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Forms of penicillin G
1-Aqueous
2-Procaine..IM
3-Benzathine..depot
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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
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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.
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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
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Vancomycin:
not B-lactam
Transpeptidase compititive inhibition
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
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Vancomycin Action –Animation
Shift +F5 to see the animation
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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
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Bacitracin
1- prevents dephosphorylation of the phospholipid carrier of the
peptidoglycan
2- Treatment of superficial skin infections (Topical)
too toxic for systemic use.
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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
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Principle:
- differences between bacterial and human ribosomal proteins, RNAs
- Bacteria 70S ..50S and 30S subunits,
- human cells have 80S ..60S and 40S subunits
3- INHIBITION OF PROTEIN SYNTHESIS
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I. Drugs That Act on the 30S Subunit Aminoglycosides
No Initiation complex .. and misreading (mRNA)
Are bactericidal drugs.. Broad spectrum
Streptomycin, neomycin, gentamycin ,tobramycin ,Kanamycin.
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Aminoglycosides Animation-1 Shift +F5 to see the animation
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Aminoglycosides Animation 2 Shift +F5 to see the animation
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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
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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)
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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
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* Advantages of drug combinations • show synergism
- B-Iactams and aminoglycosides,.
- B-lactams + calvulanic acid
• Disadvantages of drug combinations
bacteriostasis & bactericidal.
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Needs To modify drugs :
1- Change route of administration ..Compliance
2- Overcome resistance
3- Minimize side effects
4-Wideninig Spectrum of activity
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Thank you !