Folic acid synthesis inhibitors Flashcards
Why are folic acid synthesis inhibitors work?
bacteria cannot use folic acid obtained from environment
What drugs are considered sulfonamides?
- sulfadiazine,
- silver sulfadiazine,
- sulfisoxazole
- sulfamethoxazole
- sulfacetamine
- sulfasalazine
What is the mechanism of action for sulfonamides? In the chain of folic acid synthesis, what do sulfonamides block?
compete with PABA at 1st biosynthetic step of folic acid
block dihydropteroate synthetase
between PABA and dihydropteroic acid
When do drug interactions occur with sulfonamides? what drugs are contraindicated for them?
since it is a highly protein bound drug, interactions may occur if sulfonamides displace other drugs from plasma protein binding sites (PBPs)
- warfarin
- NSAIDs
- sulfonylureas
What type of patient should not take sulfonamides? why?
contraindicated in pregnant women near term and in infants younger than 2 months
they displace bilirubin from PBPs in neonates
hyperbilirubinemia may cause kernicterus (CNS disorder)
What 4 ways do bacteria develop resistance to sulfonamides?
- reduced bacterial uptake of drugs
- development of alternative metabolic pathway to synthesize folic acid
- production of excessive amounts of PABA to compete with sulfonamides for folic acid synthesis
- alterations or mutations in hihydropteroate synthase, the enzyme that catalyzes the rate-limiting step of folate synthesis
How are sulfonamides metabolized?
hepatically by acetylation, oxidation, and/or glucuronidation
Who is at risk for hypersensitivity reactions wrt sulfonamides?
genetically slow acetylators are at an increased risk
What accounts for most of the adverse effects associated with sulfonamides?
oxidation reactions
How are sulfonamides excreted?
after hepatic biotransformation=> excreted renally
What is the mechanism of action for trimethoprim?
inhibits dihydrofolate reductase
this enzyme catalyzes last step of bacterial folic acid synthesis
Bacteria develop resistance to trimethoprim in what 3 ways?
- reduced bacterial uptake
- alterations or mutations in dihydrofolate reductase
- overproduction of dihydrofolate reductase
