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52 Cards in this Set
- Front
- Back
Why is a high therapeutic ratio better than a low reading?
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A high therapeutic index is preferable to a low one: this corresponds to a situation in which one would have to take a much higher dose of a drug to reach the lethal threshold than the dose taken to elicit the therapeutic effect.
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What is Bacteriocidal and what is Bacteriostatic?
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Bacteriocidal kills the bacteria
Bacteriostatic stops bacteria growth |
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Isoniazid is effective against what kind of bacteria?
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Mycobacteria
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What MBC: Minimum Bacteriocidal Concentration and Minimum Inhibition Concentration?
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MIC- The lowest concentration that inhibits visual growth in plates (colony/lawn formation) or liquid culture (turbidity or OD measurement)
MBC- The lowest concentration the kills 99.9% of bacteria in a given time |
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What makes drug usually have a high therapeutic ratio?
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This is usually acquired because the targets mechanisms (enzymes/structures) that the host does not possess.
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What is the target of penicilin?
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Penicillin target transpeptidase enzymes which cross-link peptidoglycan. There are no human enzymes which are inhibited by penicillins. Penicillins are thus usually very well tolerated by humans in high amounts. Toxic effects may not be seen until the concentration is so high that it begins to precipitate.
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Describe how the Kirby-Bauer Assay helps to determine the MIC?
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Bacteria plated at high concentration so they will grow as a “lawn” on plate
Then place a antibiotic paper plate on the bacteria plate and see the variety in growth around that, zone of inhibition |
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If you are using the bacteriostatic drugs, what are you relying on to kill the bacteria?
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The host but remember some sites do not have good immune clearence (endocardium, brain, spine) and will require bacteriocidal antibiotics
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What is an example of a site that is difficult for antibiotics to reach and a site that can concentrate antibiotics?
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Urinary tract-concentrate
Blood brain barrier-DIfficult |
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What are the three main mechanisms to fight antibiotics?
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Permeability of antibiotic attacking the bacteria
Mutate the site the antibiotic attacks Destroy the antibiotic (beta lactamase, CAT, AMEs) |
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What is a mechanism that some bacteria use to keep antibiotics from entering the outer membrane, capsules or the peptidoglycan layer?
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Efflux pumps – transmembrane proteins that specifically remove antibiotics
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Concerning bacteria: natural selection + time + large population size =
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Resistance
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Peptidoglycan is a drug that similar to the structure of _ ____ and acts as a _______ _____ of enzyme(s) which cross link peptidoglycans (composed in part of D – alanine)
i.e. it binds the active site of transpeptidase |
D-Alanine
Competitive inhibitor |
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How do beta lactamase attack beta lactams (penicillin) and where are they usually secreted?
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They will open the 4 membered ring in beta lactams and they are secreted into medium (gram pos) or stored in periplasmic space (gram neg)
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Name a beta lactam and a beta lactamase inhibitor?
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Amoxicillin (transpeptidase inhibitor) + clavulonate (lactamase inhibitor)
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What is a subclass of beta lactams that are among most widely used antibiotics?
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Cephalosporins
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Explain the importance of:
THF-Tetrahydrofolate |
Tetrahydrofolate is necessary for thymidine synthesis. The reaction dUMP → dTTP requires Tetrahydrofolate
Therefore, without THF, dTTP cannot be made, therefore DNA cannot be made. |
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Why is sulfoamides effective?
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Sulfoamide inhibits the enzyme Dihydropteroate synthetase.
Dihydropteroate synthetase catalyzes the conversion of PABA to Dihydrofolate. Dihydrofolate is a precursor of THF. With this gone dUMP → dTTP will not occur and DNA cannot be synthesized. |
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Sulfonamides are structural analogs of ?
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PABA
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Bacteria cannot absorb folate they must make it. What do enzyme is responsible for this?
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Dihydrofolate synthetase
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Sulfa and Trimethoprim both interfer with folate production but what is the difference?
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Sulfa inhibits PABA to DHF
Trimethoprim inhibits DHF to THF |
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The reaction of Dihydrofolate to Tetrahydrofolate is done by the enzyme?
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dihydrofolate reductase or DHFR
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What is usually the resistance against Trimethoprim ?
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Mutated or altered dihydrofolate reductase or DHFR.
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Penicillin + ________ are drugs used together because Drug A interferes with ability of bacteria to overcome effects of drug B.
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aminoglycosides
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Tetracyclines competes with ________ for binding to ____ ribosome
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tRNA
30S For tetracyclines bacterial active transport system will increase cellular concentration |
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How is resistance given for tetracyclines?
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Mutation of active transport system confers resistance
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How do the macrolides function?
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They bind 50S ribosomal subunit and sterically block progression of nascent peptide.
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How can bacteria become more resistant to macrolides (Erythromycin, Lincomycin)
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The bacteria ribosomes can become modified
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Describe how Rifamycin/Rifampin/Rifampicin functions?
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The Rifamycin/Rifampin/Rifampicin will bind to RNA polymerase and inhibit transcription. This is done by Rifamycin/Rifampin/Rifampicin displacing the Mg++ from the RNA polymerase.
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How can there be resistance from Rifamycin/Rifampin/Rifampicin?
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Modification of RNA polymerase
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What is Rifamycin/Rifampin/Rifampicin usually reserved for attacking?
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It is usually reserved for attacking TB in combination with isoniazid
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Rifamycin/Rifampin/Rifampicin is a fairly hydrophobic molecule, why is this a benefit to the human body?
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This is important because it allows the molecule to cross the blood brain barrier and Mycobacterial cell walls.
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Describe the function of Isoniazid
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Isoniazid inhibits a fatty acid synthase in Mycobacteria, meaning inhibits the production of mycolic acid. This antibiotic is bacteriocidal and will only effect mycobacteria (myco produce mycolic acid)
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What is the antibiotic will target fatty acid synthesis?
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Isoniazid
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What is the antibiotic will target cell wall synthesis?
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Penicillin and cephlaosporins
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What is the antibiotic will target RNA synthesis?
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Rifamycin, rifampicin
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What antibiotic targets Nucleic acid synthesis
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Trimethoprim
Sulfa |
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What antibiotic targets DNA replication
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fluoroquinolones (DNA gyrase inhibitors)
AZT – chain terminator |
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What antibiotic targets Protein synthesis
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macrolides - 50S subunit
Tetracycline – 30S codon:anticodon |
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E.coli is ____trichous the spin of flagella determines the direction of movement.
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Multi
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If the flagella spins CCW the E.coli will go ______
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Forward
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If the flagella spins CCW the E. Coli will _______
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Tumble
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Describe the biased random walk
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This is the way in which the flagella will propel the E. Coli.
With an increase in attractants the frequency of run is increased and the frequency of tumbling is decreased. With an increase in repellents the frequency of tumbles is increased and the frequency of runs is decreased |
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What is the ratio of runs:tumbles in flagella?
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95:5
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What is the name for the following:
In a liquid medium, E. coli shows long straight “runs” followed by short tumbles, followed by another run in a different, random direction. |
Random walk
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Describe the structure of MCP's?
Methyl Accepting Chemotaxis Proteins |
MCPs are membrane spanning proteins with a binding domain on the periplasmic side and a cytoplasmic domain.
The cytoplasmic side will interact with CheW and CheA. The periplasmic side will interact with attractors (amino acids and sugars). |
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Describe how CheA starts the process of flagella start tumbling. Using CheB, CheY, CheZ.
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CheA has the chance of undergoing autophosphorylation
-ATP to ADP Once phosphorylated it will then move the phosphate to CheB or CheY. CheY phosphorylated will then diffuse away and cause the flagella motor to cause the tumbling to occur. After a few seconds, cheZ removes the phosphate from cheY, and the flagella resumes CCW rotation (the cell swims straight again) |
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What will attractants do to MCP's?
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This will inhibit the phosphorylation of CheA
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What will repellents do to MCP's?
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This will activate CheA
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What does the CheB function as in MCP'?
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CheB acts to adjust methylation levels on the MCP. This adjusts the sensitivity of the MCP to the current environment.
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Will repellents activate the demethylase activity of CheB?
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Yes
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If there is a high level of attractants, how will this affect the ratio of running:tumbling?
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This won't change the ratio 95:5
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