Sulfonamides Flashcards
What is the basic mechanism of a sulfonamide?
Inhibit dihydropteroate synthetase (inhibit PABA incorporation into dihydropteroic acid)
Sulfonamides alone are bacteri_____
Bacteriostatic
Trimethoprim basic mechanism
Inhibits dihydropteroate reductase (inhibit purine formation)
Trimethorpim alone is bacteri_____
Bacteriostatic
Trimethoprim-Sulfamethoxazole is bacteri_____. How does the combination affect resistance and spectrum of activity?
Bactericidal
Decreases resistance
Broadens spectrum of activity
Sulfonamides
Mechanisms of Resistance
Make lots of PABA
Structural change to dihydropteroate synthetase
Make drug resistant enzyme
Decreased permeability to sulfonamides
Trimethoprim
Mechanisms of Resistance
Production of resistant dihydropteroate reductase enzyme
Change cell permeability
TMP-SMX Spectrum of Activity
Gram positives Staph aureus (including some MRSA and CA-MRSA) Strep pyogenes Nocardia Listeria monocytogenes
Pneumocystis carinii
Gram Negatives Stenotrophomonas maltophilia Acinetobacter Enterobacter E coli Klebsiella Proteus Salmonella, Shigella
TMP-SMX Absorption
IV or PO. Rapidly and completely absorbed
TMP-SMX Distribution
Good distirbution to urine, lungs, prostate, CSF
TMP-SMX Elimination
Eliminated by kidney and liver. Adjust dose in renal insufficiency
TMP-SMX Clinical Uses
Acute, chronic, recurrent UTIs Bacterial prostatitis Skin infections from CA-MRSA Norcardia Pneumocystis carinii Stenotrophomonas maltophilia
TMP-SMX Adverse Effects
Nausea, vomiting
Leukopenia, thrombocytopenia
Rash
Crystalluria
TMP-SMX Drug Interactions
Phenytoin (increase phenytoin levels)
Warfarin (increased anticoagulability)
Methotrexate (decrease renal clearance)
