Sulfa Flashcards
Sulfa MOA
• All sulfas are PABA – pathogens only susceptible if they require PABA to synthesize folic acid
o Most are competitive inhibitors of DHPS
• Some are indirect and exhaust pteridne cofactor (substitute themselves for PABA)
o People use dietary folate, so don’t rely on metabolic paths to produce
Sulfa Resistance
o Develop due to reduced drug uptake or increased efflux
o Altered binding site on DHPS
o Can cause overproduction of PAPA (competition for binding site)
o Development of alternative pathway for folate synthesis
Sulfa Primary Use
UTI - due to concentration in urine
Sulfa PK
o Oral absorption
o Widely distributed (sulfadiazine best for CSF)
o Acetylation occurs in liver and inactivates and decreases solubility (increases crystallization)
o Renal elimination
• Crystals can cause renal damage (less common with sulfisoxazole)
• Most common with sulfadoxine (give fluids and bicarb)
• Reduce dose if renal impairment
Sulfa SE
o Hypersensitivity • Fever, rash, photosensitivity • SJS o Hematopoietic anemia - agranulocytosis o Vasculitis o Hepatotoxicity o Kernicterus (bilirubin become free and crosses BBB in newborn – kills clusters of brain cells) • Don’t give to near term women • Secreted in milk
Sulfisoxazole
- Use – uncomplicated UTI
- Oral sulfa of choice
- Very soluble in water so unlikely to cause crystalluria
- Shortest t1/2 – problem
- Ineffective for CNS due to low lipophilicity
Sulfamethoxazole (SMX)
• Similar to sulfisoxazole, but with longer t1/2
• More likely to cause crystalluria
o Tell pts to drink lots of water
• Typically marketed with TMP
Sulfadiazine
• Achieves highest concentration in CSF
• Best for CSF
• Causes crystalluria (like sulfadoxine) – problematic
o Urine flow must be brisk
o Bicarb reduces renal tubular reabsorption and accelerates clearance
Sulfasalazine (poor oral)
• Held in GI and excreted in feces
• Used for IBD, UC, regional enteritis because of anti-inflammatory properties
• Prodrug – makes 5AS (mesalamine)
o Mesalamine active anti-inflammatory compound that inhibits cox
Silver Sulfadiazine
- Prophylaxis for burns
- Silver is broad spec
- Reduces colonization and prevents sepsis
- Not useful against deep infections
Sulfacetamide (opth)
- Used for sulfa sensitive ophthalmic infections
- Alternative tx for chlamydia trachomatis
- High concentrations aren’t irritating or allergenic
TMP-SMX
• Use – Gram (-) bacilli, actinomycetes, parasites, pneumocystis jiroveci
• TX
o Oral tx of UTI and Prostatitis (backup to fluroquinolones)
• Esp useful for recurrent UTIs
o Bacterial respiratory tract infections
• Sinusitis, bronchitis, otitis
o GI infections
• Shigella, travellers diarrhea, e coli
o MRSA – backup only
o AIDS TX of cyclosporiasis, isospora belli diarrhea, toxoplasmosis
o TX of choice for pneumocystis jiroveci pneumonia
• SE – drug induced glossitis or stomatitis
o Hypersensitivity – rash, fever, photosensitivity
o Rash very common – SJS
o Contraindicated in renal failure – but crystalluria is rare
o Antifolate effects (anemia, etc)
Trimethoprim
• MOA
o Competitively inhibits DHFR
• Sulfa decreases concentration of dihydrofolate and TMX finishes it off
o Synergistic effect – bactericidal
• Very specific to bacteria
o Pyrimethamine specific for protozoans
o MTX specific to humans
• Can be used mono tx for uncomplicated UTI caused by gram (-) bacilli
o Leads to resistance for SMX-TMX
• Resistance
o Alteration of dihydrofolate reductase
o Reduced permeability
o Conversion to thymidine dependence (in bacteria)
• Resistance to TMP-SMX less common due to two MOA
o Requires two simultaneous genetic alterations in bacteria
