Folic Acid Synthesis Inhibitors

Question 1

Are folic acid synthesis inhibitors cidal or static?

Answer 1

Static alone, cidal when combined, usually used in combination

Question 2

What are the mechanisms of action for the 2 classes of folic acid synthesis inhibitors?

Answer 2

• Sulfonamides structurally-similar to PABA and compete for enzyme
• Trimethoprims inhibit the reductase at a subsequent step in folic acid synthesis
• Both inhibit folic acid which is needed for protein and nucleic acid metabolism

Question 3

How do bacteria develop resistance to folic acid synthesis inhibitors?

Answer 3

• Bacteria produce increased concentrations of PABA
• Bacteria produce increased concentrations of dihydrofolate reductase

Question 4

What are the important side effects of folic acid synthesis inhibitors?

Answer 4

Some diarrhea in horses
Hematological in prolonged usage
Dogs: dry eye, hypersensitiviity in dobermans

Question 5

Why don’t folic acid synthesis inhibitors affect mammalian cells?

Answer 5

Our cells bypass the PABA stage (sulfonamides) and trimethoprim has much lower affinity for mammalian reductase

Question 6

What are the spectrums of activity of folic acid synthesis inhibitors?

Answer 6

* Aerobic Gram (+) and (-)
* Little anaerobic activity
HOWEVER, MANY ORGANISMS HAVE DEVELOPED
RESISTANCE

Question 7

What are special considerations for trimethoprim-sulfa in cattle?

Answer 7

• Ruminants must use IV form- Oral preparations destroyed in rumen
• EXTRA-LABEL USE IN DAIRY CATTLE IS PROHIBITED!!!!

Question 8

What are the important pharmacokinetic factors of folic acid synthesis inhibitors?

Answer 8

Concentrates in urine therefore good candidate for
urinary tract infections