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Sulfadiazine
- Orally absorbed
- Protein bound
- CYP2C9
- Concentration in urine higher than plasma
- weak acid, more soluble in alkaline urine
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Mafenide (Sulfamylon)
- insoluble
- topical
- prevents wound infection
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sulfasalazine (Azulfidine)
- insoluble
- prodrug
- poor oral absorption
- hydrolyzed to active form (5ASA and sulfapyridine)
- used for intestinal infections
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Sulfisoxazole (Sulfafurazol)
- more soluble than sulfadiazine in urine
- achieves high concentration in urine
- excreted unchanged
- used for UTI
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Trimethoprim (Proloprim, Trimpex)
- Inhibitor of DHFR
- highly selective for bacterial DHFR (>5000-fold)
- used for UTI
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Trimethoprim/sulfamethoxazole (trimplex/gantanol)
- combo blocks folate metabolism
- synergistic effect: MIC of combo is 1/4 of MIC for either drug alone
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What is the role of folic acid?
supports synthesis of thymidine by dividing cells
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What inhibits folic acid synthesis?
Sulfonamides
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Bacteria synthesize folic acid from what?
P-aminobenzoic acid (PABA)
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How to vertebrates get folic acid?
ingest it
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Sulfonamides block which step of folic acid synthesis?
Pteridine + PABA --> dihydropteroic acid
enzyme: dihydropteroate synthase
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Trimethoprim blocks which step of the folic acid synthesis?
Dihydrofolic acid --> tetrahydrofolic acid
enzyme: dihydrofolate reductase
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Methotrexate (rheumatrex, trexall)
- Tight binding inhibitor of DHFR from all sources
- no selectivity for microorganisms
- selective toxicity for cancer cells; high demand for nucleic acid
- resistance due to elevated levels of DHFR in resistant cells
- Used in rheumatoid arthritis and psoriasis
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What medications target cell wall syntheis?
penicillin, cephelosporins, bacitracin, vancomycin
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What medications target protein syntheis?
chloramephenicol, erythromycin, tetracycline, streptomycin
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what medication target plasma membrane?
Polymyxin B
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What medications inhibit synthesis of essential metabolites?
sulfanilamides, trimethoprim
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Nalidixic acid (nevigramon, Neggram)
- Early quinolone antibiotic
- relatively weak activity and susceptible to bacterial resistance
- Used for lower UTI
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Fluoroquinolones
- Ciprofloxacin (cipro, proquin)
- ofloxacin (floxin)
- Much more effective than nalidixic acid
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Cyclophosphamide (cytoxan, Neosar)
- For lymphoma, breast cancer, ovarian cancer
- IV or oral
- decrease in blood cell counts
- N/V, ab pain
- decreased appetite
- hair loss
- bladder damage
- fertility impairment
- lung or heart damage (with high doses)
- secondary malignancies (rare)
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