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23 Cards in this Set
- Front
- Back
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What is the MOA of tetrahydrofolate synthesis?
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- Pteridine + PABA -> dihydropteroic acid -> dihydrofolic acid -> tetrahydrofolic acid
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Are sulfonamides and trimethoprim bacteriostatic/bacteriocidal?
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Bacteriostatic
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What do sulfa drugs do?
Tx of sulfa drugs and trimethoprim? |
- Inhibit of Folic Acid Biosynthesis
- Broad spectrum: bacterial and parasitic inf |
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MOA of sulfonamides?
How does MOA differ from trimethoprim? |
- Inhib dihydropteroate synthetase -> inhib Dihydropteroic acid prod -> inhib Dihydrofolic acid prod-> Production Inhibition of Folic acid production (tetrahydrofolic acid) -> inhib de novo synthesis of DNA nucleosides thymidine and uridine -> bacteria can’t undergo DNA replication and transcription).
- doesn’t touch dihydropteroate synthetase (thus makes dihydropteroic acid) -> Inhib dihydrofolate reductase -> inhib dihydrofolic acid prod -> inhib tetrahydrofolic acid prod -> … |
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How is sulfonamides selective for pathogens and not host?
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- The host acquires folic acid from diet, but bacteria must synthesize folic acid
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How do sulfonamides and trimethoprim act synergistically?
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- Sulfonamides only inhibit new synthesis of tetrahydrofolic acid.
Accordingly, pre-exisiting dihyrofolic acid and tetrahydrofolic acid are utilized until they are diluted out to limiting amounts as a result of cell division. However, until such time as they become rate limiting, dihyrofolate can be converted to tetrahydrofolate (the active form of folate) by dihydrofolate reductase. The presence of trimethoprim precludes the utilization of pre-existing pools of dihyrofolate. Thus, the combination of sulfonamides and trimethoprim results in the inhibition of new dihydrofolate and the inability of the cell to utilize pre-existing pools of dihyrofolate. |
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MOA of p-aminosalicylic Acid (PAS)?
Tx? |
- similar to that of the sulfonamides.
- Mycobacterium tuberculosis whereas sulfonamides are not |
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Are rifampin and rifabutin bacteriostatic/bactericidal?
MOA? Tx? Explain their selective toxicity. |
- Bactericidal
- Binds to the b subunit of RNA polymerase -> inhibits transcriptional initiation, but not transcription already in progress - Narrow Spectrum: G+ bacteria (Staphylococci and Streptococci), Neisseria, and Mycobacteria - Host RNA polymerase is not sensitive. In addition, mitochondria, which contain sensitive polymerase subunits are impermeable to rifampin |
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Tx of specific mycobacteria by rifabutin?
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- Mycobacterium avium
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What are the drugs that are quinolones?
Are quinolones bacteriostatic/bactericidal? |
- -floxacin, nalidixic acid
- Bactericidal |
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Tx by –floxacin (quinolones)?
How does spectrum differ from nalidixic acid? |
- broad, Pseudomonas
- Nalidixic acid is narrow spectrum; primarily for the treatment of urinary tract infections caused by G- bacteria (E. coli, Proteus, Klebsiella, Enterobactor, but not Pseudomonas) |
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How does quinolones affect pathogen w/o affecting host?
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- specifically inhibits bacterial DNA gyrases (topoisomerase II) -> inhib DNA replication
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How does pathogen obtain resistance from quinolone?
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- Decreased uptake;
- Mutations in the Bacterial DNA gyrase subunits |
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Is metronidazole bacteriostatic/bactericidal?
MOA? Tx? |
- Bactericidal
- Activated due to metabolization of drug by bacterial oxidoreductase -> activated drug disrupts DNA structure -> inhibits DNA replication -> causes DNA breaks and causes secondary mutations - Narrow Spectrum- anaerobic infections, H. pylori infection and Protozoal infections due to Entamoeba histolytica and Giardia lamblia |
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Explain selective toxicity of metronidazole.
How does pathogen obtain resistance? |
- Enzymes required to convert drug to active form are present in some bacteria and not in host cells
- Mutations in the oxidoreductases that affect conversion to the pro-drug form |
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Are polymyxin bacteriostatic/bactericidal?
Tx? MOA? |
- Bactericidal
- Narrow spectrum (primarily for the treatment of Pseudomonas infections) - hydrophobic tail inserts into cell membrane, hydrophilic head binds to the polar region of phosphatidylethanolamine (PE) and (LPS) that disrupts the cytoplasmic membrane of growing and nongrowing cells). |
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Explain selective toxicity of polymyxin.
How does it form resistance? |
- Host cells have no PE or LPS
- in G- bacteria, structural modification of the lipid A moiety of LPS renders the outer membrane impermeable to the drugs. |
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MOA of Amphotericin B/Nystatin?
Tx? |
- amphotericin B has both a hydrophobic face and a hydrophilic face -> inserts into fungal membranes, and the hydrophobic portion associates with sterols -> forms hydrophilic "channel" or "pore" -> H2O, electrolytes, and nonelectrolytes leak
- Fungicidal used intravenously for systemic mycoses, and topically in ointments. |
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Explain selective toxicity Amphotericin B/Nystatin.
Side effects? How does resistance form? |
- Major sterol for mammalian cell memb is cholesterol while for fungal cell memb is ergosterol
- nausea, vomiting, diarrhea, nephrotoxicity, and anemia - altering of sterols |
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MOA of azoles?
Which azole is particularly affective against Aspergillus? |
- inhibit synthesis of ergosterol (block the 14-alpha-demethylase)
- voriconazole |
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What are glucan synthesis inhibitors (echinocandins)?
MOA of Glucan Synthesis Inhibitors? Tx? |
- caspofungin, micafungin, anidulafungin
- inhibit 1,3-beta glucan synthase -> block fungal cell wall synthesis - effective against azole resistant strains |
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What drug is an antimetabolite?
MOA? |
- flucytosine
- replace uracil with 5-flurouracil in fungal RNA -> inhib fungal ptn synthesis; ALSO inhib thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate -> interfere with fungal DNA synthesis |
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What drug is an allylamine?
MOA? |
- terbinafine
- inhib squalene epoxidase -> inhib ergosterol synthesis |
