Mammalian cells are unable to synthesize folic acid (purine -> DNA), but bacteria must synthesize it

Bacteriostatic

competitively inhibit conversion of PABA to folic acid by dihydropteroate synthase

Topical

for burns

Topical

Conjunctivitis, corneal ulcer, other superficial ocular infections

Topical

Hemophilus vaginalis

Oral

Plus phenzaopyridine *urinary analgesic*

Used for uncomplicated UTIs

+ erythromycin - otitis media 

Oral

Used for uncomplicated UTIs

Marketed in combination with trimethoprim 

pyramethamine = dihydrofolate reducatse inhibitor

Fansidar

Used for malaria

Sulfidoxine is very long acting

Oral

Used for leprosy

Used with other drugs in initial treatment

Not absorbed

Active ingredient is 5-aminosalicylic acid

Used for inflammatory bowel disorder

Oral

hypersensitivity (skin rashes, urticaria)

N/V/D

Urinary tract disturbances -- crystalluria

Hematopoietic disturbances (rare)

Hemolytic anemia in G6P deficiency

Displacement of serum albumin can lead to kernicterus (increased bilirubin) and temporary increases in free warfarin and hypoglycemics 

diuretics (furosemide, HCTZ)

sulfonylureas

celebrex

sumatriptan 

Inhibits dihydrofolate reductase of bacteria about 10000x more than human one (in contrast to methotrexate)

When given in combination with sulfonamide, synergism

Trimethoprim is bacteriostatic, but together can be bactericidal

well absorbed from GI tract (high bioavailability)

Readily distributed to most tissues including CSF

Most of the drug is excreted unchanged in the urine (some is biotransformed to inactive products)

Elimination half life is about 10 hours

1. Pneumonia due to pneumocstis carinii

2. GI infections, Shigella enteritis

3. Systemic infections caused by Nocardia and Salmonella 

4. UTIs and respiratory infections caused by H. influenzae or S. pneumoniae 

5. Listeria meningitis 

^ oral; iv reserved for pneumonia due to pneumocystis carinii

Similar to sulfa drugs alone, plus rare hematopoietic disturbances like leukopenia and megaloblastic anemia

Use folinic acid to prevent hematologic toxicity 

Additional side effects from trimethorprim + sulfonamide combination 

Use folinic acid to reduce hematologic toxicity 

Block bacterial DNA synthesis by blocking topoisomerase II (gyrase) and IV

Prevents unwinding of supercoiled DNA required for normal duplication and transcription

Inhibition of topoisomerase 4 interferes with separation of replicated DNA

Drugs have minimal effects on mammalian enzyme

Group 1 - activity against gram - with some against gram =, H influenze (ciprofloxacin)

Group 2 - improved activity against gram + particularly S pneumoniae (levofloxacin, gemifloxacin, moxifloxacin)

1. Microbial modification of DNA gyrase or topoisomerase 4 structure

2. Alteration of membrane permeability into bacterial cell

Generally well absorbed orally (norfloxacin is lowest) 

Food and aluminum and calcium salts (antacids) decrease bioavailability 

Widely distributed to most tissues

Plasma protein binding is low

Small amount is biotransformed in liver to inactive products

Most of drug is eliminated in urine through filtration and must be adjusted in renal dysfunction

elimination half life varies from 3 to 8 hours

Resistant UTIs (not moxi because it doesn't get secreted)

Osteomyelitis and skin infections

Infection diarrhea (shigella, salmonella, e coli, campylobacter) and typhoid fever

Pseudomonas

Anthrax

Respiratory tract infections including CAP

Reserved for patients with comorbid/risk factors

N/V/D, photosensitivity, CNS disturbances (dizziness, confusion, hallucination)

May damage growing cartilage, therefore, not recommended for pregnant women or children; can cause tendonitis 

Some of the drugs can cause prolonged QT interval; avoid use in patients taking some antiarrhythmics and other drugs that prolong QT interval (erythromycin, TCAs)