Para-aminobenzoic acid (PABA) is an intermediate in the synthesis of ___, which undergoes a 2 step enzymatic conversion to ___, a co-enzyme substrate essential for DNA and RNA synthesis in bacteria, plants, and fungi.
- dihydrofolic acid
* tetrahydrofolic acid
___ are structurally similar enough to PABA to compete for its binding sites on the first enzyme, ___
* dihydropteroate synthetase
Bacterial growth is selectively inhibited through ___.
what drug is described by the following:became the the first sulfa antimicrobial drugchanged the world by saving millions of lives between 1934-1942.A bold orange-red drug, it started as an industrial dye, not an antibiotic
who invented prontosil?
Dr. Gerhard Domagk at Bayer
In 1937, ___, a liquid formulation made in ___, was marketed by the S.E. Massengill Company (Bristol, Tenn.)
- elixir sulfanilamide
* diethylene glycol
___ had a sweet taste, so mass production began without testing for toxicity or safety.
what drug is responsible for the most consequential mass poisoning the United States in the 20th century?
In reaction to the elixir sulfanilamidedisaster, U.S. Congress passed the 1938 Federal ___, which required proof of safety before the release of a new drug to humans.
food, drug, and cosmetic act
___ is an oral synthetic sulfonamide antimicrobial agent
isSulfamethoxazole bacteriostatic or bactericidal?
what is the mechanism of sulfamethoxazole?
competitive inhibitor of dihydropteroate synthetase
sulfamethoxazole is no longer used as ___
sulfadiazine inhibits ___
is sulfadiazine broad or narrow spectrum? bactericidal or bacteriostatic?
broad spectrum, bacterostatic
what is the clinical use for sulfadiazine?
oral monotherapy for UTIs and burns
what drug is described as a topical sulfonamide/silver antibacterial cream used for prevention and treatment of infections related to skin burns or superficial wounds
what are the adverse effects of sulfadiazine and silver sulfadiazine?
- allergic patients usually have cross sensitivity to all sulfa-containing drugs
___ inhibits dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid
what are the two key para-aminobenzoic acid drugs?
sulfamethoxazole and trimethoprim
why are folate synthesis inhibitors selective?
- humans lack the enzymes needed to convert PABA to tetrahydrofolic acid
- humans get folate through dietary resources, such as green leafy vegetables
what happens when you have PABA with increasing levels of sulfa drug?
the higher levels of sulfa drug, the more likely to outcompete and bind to enzyme
accumulation of sulfadiazine and silver sulfadiazine in at risk patients can result in what 3 things?
- hemolytic anemia
- kernicterus in infants (brain damage due to excessive bilirubin in the blood and brain)
is trimethoprim bactericidal or bacteriostatic?
bacteriostaticit is 20-50x more potent than sulfonamides alone
trimethoprim is usually used with ___, but can be used on its own for the treatment of recurrent ___
what is the mechanism of trimethroprim?
it inhibits dihydrofolate reductase
trimethoprim’s selectivity comes from what?
its greater affinity for bacterial dihydrofolate reductase than the host’s
what are the adverse effects of trimethoprim?
- pseudomembranous colitis
* hematological disorders including bone marrow suppression (TMP treats marrow poorly)
___ is a combination of TMP and SMX
describe the spectrum of cotrimoxazole
- broad spectrum
- combination is more effective than either of its individual components
- no anaerobic coverage
is cotrimoxazole bactericidal or bacteriostatic?
time-dependent bactericidalcombination provides 2-step blockade of folate synthesis, inhibiting bacterial DNA synthesis
what drug is described as having the following medical uses:drug of choice for treatment of pneumocystis jiroveci (carini) pneumoniagram + aerobes (recurrent UTIs)h. influenzae (respiratory tract infections and otitis)
what is TMP?
what is SMX?
when was salvarsan developed?
when was prontosil developed?
when was sulfanilimide developed?
in 1936, scientists at the pasteur institute discovered that prontosil is a ___ that required ___ by the body to be converted to its active metabolite, sulfanilimide, which is why it didn’t work in vitro