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- Orally absorbed
- Protein bound
- Concentration in urine higher than plasma
- weak acid, more soluble in alkaline urine
- prevents wound infection
- poor oral absorption
- hydrolyzed to active form (5ASA and sulfapyridine)
- used for intestinal infections
- more soluble than sulfadiazine in urine
- achieves high concentration in urine
- excreted unchanged
- used for UTI
Trimethoprim (Proloprim, Trimpex)
- Inhibitor of DHFR
- highly selective for bacterial DHFR (>5000-fold)
- used for UTI
- combo blocks folate metabolism
- synergistic effect: MIC of combo is 1/4 of MIC for either drug alone
What is the role of folic acid?
supports synthesis of thymidine by dividing cells
What inhibits folic acid synthesis?
Bacteria synthesize folic acid from what?
P-aminobenzoic acid (PABA)
How to vertebrates get folic acid?
Sulfonamides block which step of folic acid synthesis?
Pteridine + PABA --> dihydropteroic acid
enzyme: dihydropteroate synthase
Trimethoprim blocks which step of the folic acid synthesis?
Dihydrofolic acid --> tetrahydrofolic acid
enzyme: dihydrofolate reductase
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
What medications target cell wall syntheis?
penicillin, cephelosporins, bacitracin, vancomycin
What medications target protein syntheis?
chloramephenicol, erythromycin, tetracycline, streptomycin
what medication target plasma membrane?
What medications inhibit synthesis of essential metabolites?
Nalidixic acid (nevigramon, Neggram)
- Early quinolone antibiotic
- relatively weak activity and susceptible to bacterial resistance
- Used for lower UTI
- Ciprofloxacin (cipro, proquin)
- ofloxacin (floxin)
- Much more effective than nalidixic acid
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)