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What different 2 enzymes do Sulfonamides and Trimethoprim inhibit to stop folate synthesis?
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Sulfonamides inhibit Dihydropteroate Synthase. Trimethoprim inhibits Dihydrofolate Reductase.
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What does the Sulfonamide drug class compete with in bacteria to bind the dihydropteroate enzyme?
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PABA. Bacteria needs this, and Sulfonamides are structural analogs of PABA.
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Why don't Antifolate drugs hurt human cells?
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We only use exogenous folate (from diet).
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You would use this sulfonamide to treat bacterial conjunctivitis of the eye.
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Sodium Sulfacetamide Ophthalmic.
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What is the one major bacteria that Sulfonamides are NOT effective against and most Fluoroquinolones are effective against it?
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Pseudomonas.
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What is known ratio for combining the drugs in Bactrim?
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5:1 - Sulfamethoxazole:Trimethoprim
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Describe 1 way that bacteria develop resistance to Sulfonamides and 1 way to Trimethoprim.
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Sulfonamides - PABA wins out by either producing a dihydropteroate enzyme with less affinity for drug, or PABA is just overproduced. Trimethoprim - the DHF Reductase produced has a decreased affinity for drug.
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What are 3 indications for using Bactrim?
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Pneumocystis pneumonia, UTI, Nocardia infection.
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What is a major Adverse Effect in Sulfonamides that affects roughly 3% of patients?
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Allergic reaction to Sulfa-drugs. *Note: it may just be serum sickness and not to the drug, should be re-tested.
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What is a key difference in coverage between the 2nd and 3rd Generation Fluoroquinolones?
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2nd generation (Cipro, Levo) cover Psuedomonas while 3rd generation does not. And 3rd generation (Moxi,Gemi) have much better Gram(+) coverage
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What is one method of resistance to Fluoroquinolones that bacteria have developed?
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An active efflux mechanism and/or changed permeability - once drug gets in, it is pumped out and cannot kill bacteria.
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What exhibits Concentration-dependent killing - Sulfonamides, Fluoroquinolones, or Trimethoprim?
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Fluoroquinolones.
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How are Fluoroquinolones eliminated - any exceptions?
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Renally. Exception = Moxifloxacin - because of this you cannot treat UTIs with Moxi.
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What is are the Pharmacokinetic advantages of Fluoroquinolones?
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They are nearly 95% bioavailable and they distribute into many places - including bone (which is very tough to do). You can treat osteomyelitis because of this.
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What is the main, serious adverse effect of using Ciprofloxacin if you have pre-disposed factors to it?
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Seizures.
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