Antifolates Flashcards
What are the two antibiotic classes that are antifolates?
Sulfonamides and Trimethoprim
What is paired with trimethoprim to make it bactericidal?
Sulfamethoxazole
What is the activity of the sulfonamides?
static
What are the sulfonamides a structural antagonist of?
PABA
What is PABA responsible for?
It binds to dihydropteroate synthase to be turned into dihydrofolic acid.
What happens to folic acid production when a sulfonamide binds to dihydropteroate synthase?
It is inhibited
What are all the ways bacterial cells can inhibit sulfonamides?
1) Increase production of PABA
2) Alter dihydropteroate synthase
3) Alternate metabolic pathways to produce THF
4) Active efflux and impaired drug entry
What are the toxicities associated with sulfonamides?
1) Hypersensitivity reactions
2) Hemolytic anemia
3) Aplastic anemia
4) Agranulocytosis
5) Crystalluria
6) Neurotoxicity
How can crystalluria be treated?
Decrease the pKa of the antibiotic, increase the pH of the urine with sodium bicarbonate, and drink plenty of fluids
Why are sulfonamides rarely used as single agents?
Because their usefulness has decreased due to resistance and toxicity
True or False: sulfonamides are NOT readily absorbed throughout the body, CSF, and placenta
false
What is the most synergistic combination of for Bactrim or Septra?
20:1 sulfamethoxazole to trimethoprim
How does trimethoprim inhibit folic acid synthesis?
It is an inhibitor of dihydrofolate reductase which turns dihydrofolic acid into tetrahydrofolic acid
Why is the Bactrim combination bactericidal?
Because they block sequential steps in the production of folic acid
How can bacteria form a resistance to Bactrim?
By encoding for an altered DHFR
