Sulfonamide Antimicrobial Agents Flashcards
What is inhibited competitively by the sulfonamides?
the incorporation of p-aminobenzoic acid (PABA) into the folic acid nucleus
The sulfonamides inhibit?
dihydropteroate synthase
Why do sulfonamides have selective toxicity for bacterial cells as opposed to mammalian cells
mammalian cells utilize preformed folates in the diet and some bacterial cells are required to make their own folic acid
How can the antibiotic activity of sulfonamides be reversed?
by adding large quantities of PABA to the diet
Sulfonamides in general inhibit?
gram (+) and gram (-) bacteria nocardia Chlamydia trachomatis some protozoa and fungi enteric bacteria such as E. coli, Klebsiella, salmonella, shigella and enterobacter
Why are sulfonamides usually used in combination
the resistance factors are too widespread for these drugs to be used in a single drug therapy
What is the antifungal activity of trimethoprim-sulfamethoxazole important for?
the treatment of AIDS-infected patients that have developed Pneumocystis carinii (jiroveci)
What does trimethoprim inhibit?
dihydrofolate reductase
so combination with sulfamethoxazole inhibits sequential steps in the biosynthesis of tetrahydrofolic acid
Most popular sulfonamide
sulfisoxazole (broad spectrum antibiotic activity)
Sulfisoxazole and sulfamethoxazole are mainly used to treat
simple urinary tract infections
used as a cream to treat vaginal infections by Gardnerella vaginalis
1:1:1 combination of sulfabenzamide, sulfacetamide, and sulfathiazole (triple sulfas)
Triple sulfas-phenylpropanolamine-pheniramine is also used to treat
used orally in tablet/suspension to treat sinus and throat infections
What is sulfasalizine used to treat
ulcerative colitis and Crohn’s disease
Direct administration of salicylates, including 5-aminosalicyclic acid is?
irritating to the gastric mucosa
What is sulfadoxine?
long-acting sulfonamide used with pyrimethamine to prevent and treat malaria
What is pyrimethamine
inhibitor of Plasmodium falciparum dihydrofolate reductase
first-line chemotherapy to treat acute toxoplasmosis
sulfadiazine in combination with pyrimethamine
All sulfonamides and their derivatives are?
cross-allergenic
sulfonamide derivates in use include
carbonic anhydrase inhibitors, thiazides, furosemide, sulfonylurea hypoglycemic agents etc
Most common adverse reactions of sulfonamides
allergic reactions - present as rash, photosensitivity, and drug fever
potentially fatal adverse reaction of sulfonamides
Stevens-Johnson syndrome: rare skin and mucous membrane rash tha tis potentially fata
Other adverse reactions of sulfonamides
crystalluria and hematopoietic disturbances: asplasmic anemia, granulocytopenia, and thrombocytopenia
anorexia, nausea, and vomiting occurs in 1-2%
Resistance to sulfonamides occurs through the following mechanisms
- mutations that cause overproduction of PABA
- mutations in dihydropteroate synthase that decreases its affinity for the sulfonamides
- mutations that result in a decrease in cell permeability to the sulfonamides
Why do you always give sulfonamides in combination
resistance is very common
resistance to combination therapy targeting two enzymes in highly reduced since the microorganism wold have to carry mutations in two enzymes
What happens when the dihydrofolate reductase (DHFR) gene is mutated
enables the expressed enzyme to be active in the presence of drug through a decreased binding affinity of trimethoprim
