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123 Cards in this Set
- Front
- Back
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Theobald Smith Equation
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D = (N*V)/R
D: Susceptibility to disease N: Number of infecting microorganisms V: virulence of microbe R: host resistance to microbe |
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Clindamycin effect on S. aureus
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Reduces the amount of glycocalyx in S. aureus
Therefore limits the microbes adherence ability Therefore decreases its virulence |
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Principle of Selective toxicity
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Established by Dr. Paul Ehrlich
Single essential attribute of a clinically efficacious antibiotic It should be selective for a particular target site on the organism and interaction with that site should cause damage without harming the person |
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Selectivity
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One property of the Selective Toxicity principle
The principle target site on the microbe by the drug should have no counterpart in normal host cells |
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Toxicity
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One property of the Selective Toxicity principle
The interaction of the drug with target sites should cause damage and/or interference of function in target cells without harming normal host cells |
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Chemotherapeutic index
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THe amount of drug that can give rise to the action you are looking for versus the amount of concentration produce host damage
(Drug conc producing specific anti-microbe action)/ (Drug conc producing non-specific host damage) |
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What ways can antibiotics affect the growth of a cell
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1. Affect Cell wall synthesis
2. Affect protein synthesis 3. Competitive metabolic inhibition 4. DNA interfering 5. RNA interfering |
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Cidal antibiotics
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Antibiotics that are bactericidal, meaning they kill the bacteria
Usually are antibiotics that interfere with cell wall synthesis |
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Static antibiotics
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Antibiotics that suppress the growth of the organism give your body a chance to fight
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Why can't large antibiotics affect Gram- but can affect Gram+ bacteria?
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Gram- bacteria have porins that allow the passage of hydrophilic molecules less than 1000 daltons in size.
If the antibiotic is too big, it cannot pass through the porins and therefore not take effect Gram+ bacteria do not have porins and can pass right through |
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What occurs during the 1st stage of peptiglycan synthesis?
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Low MW precursors are synthesized
L-alanine is converted to D-alanine by alanine racemase D-alanine is converted to D-alanyl-D-alanine by synthetase |
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Cycloserine
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Antibiotic that effects the 1st stage of peptidoglycan synthesis
It's a structural analogue to D-alanine and covalently binds to alanine racemase and synthetase (enzymes involved) to prevent cell wall synthesis It is a cidal, broadspecture antibiotic Mostly limited to treat TB because of CNS toxicity |
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Cycloserine Class
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Structural analogue of D-alanine
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Cycloserine Site of Action
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1st stage of cell wall synthesis where low MW precursors are synthesized
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Cycloserine: Cidal or Static?
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Cidal
Binds covalently to enzymes |
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Cycloserine: Spectrum
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Broadspecturm
But mostly used for TB |
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Why is Cycloserine restricted to TB treatment
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Because of CNS toxicity
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Gram+ or Gram-: Staph aureus?
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Gram+
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Gram+ or Gram-: E-coli
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Gram-
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What occurs during the 2nd stage of cell wall synthesis?
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Membrane bound enzymes dephosphorylate lipid pyro-phosphate
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Bacitracin
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A polypeptide Antibiotic that targets the 2nd stage of bacterial cell wall synthesis
It inhibits dephosphorylation of lipid pyro-phosphate Cidal antibiotic Targets only Gram+ (because of size) Has systemic toxicity so used topically only |
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Bacitracin Class
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Polypeptide antibiotic with a thiazoline ring
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Bacitracin Site of Action
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2nd stage of Cell Wall synthesis
Inhibits dephosphorylation of lipid pyro-phosphate |
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Cidal or Static: Bacitracin
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Cidal
It affects cell wall synthesis |
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Bacitracin Spectrum
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G+ bacteria only due to its large size
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Why do you use Bacitracin topically?
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It has systemic toxicity so only use topically
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What occurs during the 3rd stage of peptidoglycan synthesis?
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Formation of cross-links
Transpeptidase enzyme helps form cross-bridge between terminal glycine of one branch with penultimate D-ala already attached |
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Beta-lactam
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Beta lactam antiobiotic
Ex: Penicillin and Cephalosporins Affects 3rd stage of cell wall synthesis by covalently binding to transpeptidase preventing cross-bridging from occurring Cidal antibiotic with broad spectrum taken orally or parenteral Have fewer side effects |
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Penicillin
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Type of Beta-lactam
Structural analogue to D-ala Has a thizolidine ring (5 bonds) Attached to transpeptidase enzyme preventing cross-bridging of cell wall bacteria |
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Cephalosporin
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AKA Cephalomycin
Type of Beta-lactam Has a dihydrothiazine ring (6 bonds) Attached to transpeptidase enzyme preventing cross-bridging of cell wall in bacteria |
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Clavulanic acid
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Type of Beta-lactam antibiotic
Acts as a Beta-lactamase inhibitor |
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Beta Lactam Class
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Beta Lactam
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Beta Lactam Site of Action
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Affects 3rd stage of cell wall synthesisi
Covalently binds to transpeptidase preventing cross link between last glycine residue and penultimate D-ala |
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Penicillin Binding Protein
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AKA Transpeptidase
Enzyme that catalyzes cross link between last glycine residue and penultimate D-ala in the 3rd stage of cell wall synthesis |
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Beta Lactam: Cidal or Statis
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Cidal
Covalently binds to transpeptidase and effects cell wall synthesis |
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Beta Lactam Spectrum
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Broad spectrum depending on the drug
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How are Beta Lactams administered?
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Oral and parenterally
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Vancomycin
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A glycopeptide antibiotic that interferes with transglycosylation during the 3rd stage of cell wall development by binding to both transglycolase
Also attacks transpeptidase It is a cidal antibiotic that affects Gram+ bacteria only |
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Vancomycin Class
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Glycopeptide
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Vancomycin Site of Action
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Cell wall
Blocks transglycosylation Binds to D-ala-D-ala precursors preventing incorporation into growing peptidoglycan |
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Vancomycin Cidal or Static
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Cidal
Affects cell wall synthesis |
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Vancomycin Spectrum
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Gram + Only
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How is Vancomycin administered
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Parenteral because not absorbed through intestines
Oral only when treating C.difficile in intestines |
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What is the treatment for C. difficile Pseudomembranous Enterocolitis?
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Vancomycin
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What can you use to treat MRSA?
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Vancomycin
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Aminoglycosides
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Antibiotic used to disrupt bacterial protein synthesis
They irreversibly bind to the 30S ribosome to inhibit initiation of peptide chains Creates nonsense codon creating defective proteins Cidal antibiotic that has broadspectrum but can't effect anaerobes They are synergistic with Beta-lactams Poorly absorbed orally and cannot penetrate CSF, so only parenteral administration Nephrotoxic and ototoxic |
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Streptomycin
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Ex: of Aminoglycoside antibiotic
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Aminoglycosides Site of Action
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1. Irreversible binds to 30S ribosome subunit interrupting ribosome cycle at initiation of protein synthesis inhibiting initiating of the peptide chain
2. causes misreading of genetic code resulting in nonsense proteins |
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Aminoglycosides Cidal or Static
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Cidal
It irreversible binds to 30S ribosome |
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Aminoglycosides Spectrum
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Broadspectrum
BUT but not on anaerobes |
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How is Aminoglycosides administered
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Parenterally only
It is poorly absorbed orally and cannot penetrate CSF |
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What is synergistic with Aminoglycosides
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Beta-lactams
Facilitates aminoglycoside uptake |
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What is the problem with Aminoglycosides
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They are nephrotoxic and ototoxic
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Tetracyclines
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Antibiotic that effects protein synthesis by binding reversibly to a 30S ribosome inhibiting new amino-aryl tRNA on the right side preventing polypeptide synthesis
Works intracellularly It's a static drug that has broad spectrum Absorption can be impaired by iron, dairy, and food Also causes depression of bone |
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Tetracycline Site of Action
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Intracellular activity
Binds reversibly to 30S ribosome Prevents polypeptide synthesis |
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Tetracycline Cidal or Static
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Static
It binds REVERSIBLY to 30S ribosome |
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Tetracycline Spectrum
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Broad Spectrum
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Tetracycline Problems
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Iron, antacids, dairy and food can impair absorption
Causes depression of bone and stain teeth with sustained usage so need to be >8YO |
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Docycyline
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Tetracycline used to treat community acquired MRSA
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What is the age limit for administering Tetracycline
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Needs to be administered to children >8YO
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Which antibiotics are intracellular acting?
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Tetracycline
Macrolides Sulfonamides (Sulfa drugs) Quinolones |
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Chloramphenicol
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Chloromycetin antibiotic that inhibits peptide bond formation by binding reversibly to 50S ribosome preventing transpeptidation
Broadspectrum, static antibiotic Good for some anaerobes - do susceptibility profile/ antibiogram Causes bone marrow suppression so taken as last resort |
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Chloramphenicol Class
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Chloromycetin
Contains nitrobenzene ring |
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Chloramphenicol Site of Action
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Binds reversibly with 50S ribosomal subunit preventing transpeptidation process of peptide chain elongation
Site of action is similar to Erythromycine and Lincomysin therefore cannot give them together otherwise antagonistic |
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Chloramphenicol CIdal or Static?
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Static
Binds reversibly to 50S ribsome |
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Chloramphenicol Spectrum
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Broadspectrum
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Problems with Chloramphenicol
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Causes aplastic anemia (bone marrow suppression) therefore used as a last resort antibiotic
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How is Chloramphenicol administered
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Oral and Parenteral
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Aplastic anemia
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Bone marrow suppression
Sometimes caused by Chloramphenicol |
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Antagonistic effect of Chloramphenicol
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Antagonistic to Erythromycin and Lincomysin because they compete for the same target site
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Erythromycin
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Macrolide Antibiotic that reversibly binds to 50S subunit blocking translocation reaction of peptide chain elongation (therefore antagonistic to Chloramphenicol)
Static but Cidal at high concentrations Broadspectrum but mainly used on Gram + and special Gram- like Chlamydia, Rickettsia, Mycoplasma Good for people who are allergic to Penicillin to treat Group A strep and pneumo |
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Macrolides
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Class of antibiotics that works intracellularly by binding to 50S subunit
Ex: Erythromycin, Azitromycin, Clairithromycin New class has less GI disturbances and 1/2 life is greater, so lower dose can be taken |
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Erythromycin Class
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Macrolides
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Erythromycin Site of Action
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Binds reversible to 50S subunit blocking translocation reaction of peptide chain elongation
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Erythromycin Cidal or Static
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Static
But Cidal at high concentrations |
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Erythromycin Spectrum
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Broad but used mainly for Gram+ and Special Gram- like
Bartonella Chlamydia Rickettsia Hemophilus Legionella Mycoplasma And for people that are allergic to Penicillin for Group A strep and Pneumo |
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Clindamycin
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Lincosamide antibiotic that binds to 50S ribosome and inhibits peptide bond formation
Static antibiotic used mostly for Gram+ and anaerobes Contains Chlorine which is highly effective against anaerobic bacteria (include GI flora) Causes C. difficile PMEC because becomes the only organism in gut flora left |
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Clindamycin Class
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Lincosamides
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Clindamycin Site of Action
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Binds to 50S ribosome and inhibits peptide bond formation
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Clindamycin Cidal or Static
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Static
But Cidal at high concentrations |
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Clindamycin Spectrum
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Most Gram+ and Anaerobes
Very efficient in taking out gut anaerobes leading to overtake by C.difficile PMEC |
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How is Clindamycin administered
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There is good absorption orally and no interference with food
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What problems are caused by Clindamycin
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Chlorine group on antibiotic is very effective in taking out anaerobes, which includes gut flora leading to overtake by resistance C. difficile PMEC
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Sulphonamides
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Intracellular Sulfa antibiotic analogues of PABA that interferes with folic acid synthesis
Static, broadspectrum drug that effects parasites and protozoa also Has synergistic effects with trimethoprim Nausea, vomiting, diarrhea, hypersensitivity reactions Liver enzymes increase Drink fluids to flush out of system |
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Sulphonamides Class
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Sulfa drugs
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Sulphonamides Site of Action
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Analogue to PABA
Competitive metabolic inhibition of conversion of PABA to dihydropteroic acid by dihydropteroate synthetase in folic acid metabolism |
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Sulphonamides Cidal or Static
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Static
Analogue to PABA in folic acid synthesis |
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Sulphonamides Spectrum
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Broadspectrum
Some Parasites (pneumocystis carinii) and Protozoa (plasmodium) |
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What are some problems associated with Sulphonamides
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Nausea, vomiting, diarrhea, hypersensitivity reactions
Liver enzymes increase Drink fluids to flush out of system |
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Synergistic effects of Sulphonamides
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Synergistic with Trimethoprim
Sulphonamides effects synthetase enzyme Trimethoprim effects reductase enzyme further down folate pathway Therefore enhanced effect |
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Trimethoprim
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Selective inhibitor of dihydrofolate reducatse in folate synthesis
Static antibiotic but cidal at high concentrations Broadspectrum Synergistic with Sulfa drugs Associated with nausea, vomiting, high liver enzmes |
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Quinolones
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Fluoroquinolone antibiotic that inhibits activity of DNA gyrase and topoisosmerase IV needed for regulation of coiling of bacterial DNA
Cidal antibiotic Broadspectrum Effective against MSSA but not MRSA Leads to skeletal abnormalities in patients <18YO or pregnant women |
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Topoisomerase II
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AKA DNA gyrase
Maintains DNA supercoiling |
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Topoisomerase IV
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Responsible for separating daughter DNA strands during cell division
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Quinolones class
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Fluroquinolones
Includes ciproflaxin, levoquin, moxifloxacin and nalidixic acid |
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Quinolones Site of Action
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Inhibits activity of DNA gyrase and topoisomerase IV that regulates supercoiling and separation of bacterial DNA
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Quinolones CIdal or Static
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Cidal
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Quinolones Spectrum
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Broadspectrum
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Problems with Quinolones
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Causes skeletal abnormalities
Not indicated for <18YO or pregnant women |
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Rifampin
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Macrocyclic antibiotic with aromatic ring spanned by long aliphatic bridge
Binds to RNA polymerase inhibiting mRNA synthesis Cidal antibiotic Broadspectrum |
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Rifampin Class
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Aromatic ring system spanned by long aliphatic bridge
AKA Macrocyclic |
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Rifampin Site of Action
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Binds to RNA polymerase thus inhibiting mRNA synthesis
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Rifampin Cidal or Static
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Cidal
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Rifampin Spectrum
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Broadspectrum
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Problem with Rifampin
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Rapidly develop resistance to the drug therefore usually given another antibiotic
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Colistin
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A polymyxin B drug that has detergent-like properties that increases the bacterial cell's phospholipid permeability disrupting integrity
Cidal antibiotic Targets Gram- bacteria including Pseudomonas Major side effects because neurotoxic and nephrotoxic |
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Colistin Class
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Polymyxin B
Cationic cyclic peptide |
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Colistin Site of Action
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Detergent like properties increase cell permeability and disrupts osmotic integrity
Results in leakage after integrity with phospholipid layer |
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Colistin Cidal or Static
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Cidal
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Colistin Spectrum
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Gram- including Pseudomonas
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Problems with Colistin
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Neurotoxic and nephrotoxic
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Amphotericin
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Polyene antibiotic with selectivity for fungi that binds to egosterol causing membrane pores killing the organism
Cidal use for fungi like yeast and mold At high concentrations it can bind to cholesterol in our cells Drug is nephrotoxic Ex: Nystatin and Amphotericin B |
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Amphotericin Class
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Polyene
Includes Amphotericin B and Nystatin |
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Amphotericin Site of Action
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Preferentially binds to egosterol causing membrane pores killing the organism
At high concentrations can bind to cholesterol |
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Amphotericin CIdal or Static
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Cidal
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Amphotericin Spetrum
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Fungi like yeast and Mold
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Problems with Amphotericin
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At high concentrations can bind to our cholesterol
Causes nephrotoxicity |
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Azole
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Imidazole antifungal that interferes with cytochrome P-450 dependent reaction in fungal ergosterol synthesis
Leads to accumulation of less stable methylsterols that creates leaks in the cell envelope killing the fungus Static antifungal targeting yeast and mold Causes hepatic elimination so avoid in patients with hepatic insufficiency |
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Azole Class
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Imidazole
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Azole Site of Action
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Interferes with cytochrome P-450 dependent reaction in fungal ergosterol synthesis leading to accumulation of methylsterols which are less stable than ergosterol and create leakage in membrane
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Azole Cidal or Static
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Static
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Azole Spectrum
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Fungal - yeast and mold
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Problems with Azole
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Hepatic elimination
Can't be given to patients who have hepatic liver insufficiency |
