Med Chem - Intro + Sulfa Flashcards
true or false
the development of drugs to treat infectious disease is one of the most important advances in the history of medicine
TRUE
what was the life expectancy in 1900 and what was the leading cause of death
47
infections
what year and event marked the birth of anti-infective chemotherapy
1911
Paul Erlich showed that arsphenamine (salvarsan) was active for syphilis in an experimental rabbit model
as mentioned, in 1911 marked the birth of anti-infective chemotherapy when paul erlich should salvarsan/arsphenamine was active for syphilis in an experimental rabbit
what did Ehrlich do next?
he introduced the concept of systemic screening
this lead to the discovery of sulfa drugs by bayer chemists
later, systemic screening became the cornerstone of strategies of searching for drugs
who and what year was penicillin discovered
1929
alexander fleming
true or false
penicillin is not a natural product
FALSE
it is a natural product derived from penicillium mold
name 4 subclasses of beta lactams
penicillins
cephalosporins
carbepenems
monobactams
why were antimicrobial advances in discovering sulfa drugs and penicillin perfectly timed?
bc they helped in ww2
death from sepsis had previously been an almost certain consequence following injury
with the discovery of antibiotics (specifically sulfa and penicillin), it became avoidable
macrolides and ______ are structural cousins
ketolides
true or false
quinolones are synthetic
true
lincosamides are _____ containing
sulfur
structural derivatives of tetracyclines
what makes them better
glycylcyclines
they have better resistance profile
2 glycopeptides
vancomycin and daptomycin
what class is gramicidin
peptide class
true or false
streptogramins are 2 components combined
true
sulfa drugs are derivatives of…..
p-aminobenzene sulfonamides
are sulfa drugs bacteriostatic or cidal?
static
is spectrum of sulfa drugs broad or narrow spectrum
broad
true or false
sulfa drugs were once used wisely but not as much anymore
true
what year were sulfa drugs discovered
1935
what is the simplest sulfa drug
sulfanilamide
the R substituion is just an H
explain what sulfanilamide is
its prodrug is PROTONSIL
protonsil gets bioreduced to form its ACTIVE METABOLITE - sulfanilamide
why is protonsil not used anymore
when it gets bioreduced to produce sulfanilamide, the N=N is clipped
the biproduct is polyamino benzene, which is a potent carcinogen
name for N=N
azo
TYPICALLY, aliphatic amines are considered acidic, neutral, or basic?
basic
when N connected to sulfonyl as in the case of sulfonamide, is it acidic, neutral, or basic?
NEUTRAL, but polar
behaves like carboxamide
azo gets bioreduced to….
amine (NH2)
name 4 precursors that depend on bioreduction to get activated to a primary amine for sulfonamide activity
azo (N=N)
nitro (NO2)
-NHOH
-N=O (nitroso)
carboxamide depends on HYDROLYSIS
main MOA of sulfonamides
inhibit dihydropteroate synthase
(the enzyme that catalyzes the conversion of PABA + dihydropteroate diphosphate to dihydropteroic acid which ic converted to THF, thymine, and then DNA)
what does PABA stand for
p-aminobenzoic acid
differentiate between the durations of different sulfonamides
WHICH IS IDEAL
short/medium acting (t1/2 6-12 hours)
long acting (t1/2 20-40 hrs)
ultra long acting (t1/2 100-200 hours)
6-12 hours (short-medium acting) IS IDEAL
Name the sulfonamides in the short/medium acting (6-12 hours) class
sulfisoxazole
sulfacetamide
sulfadiazine
sulfamethoxazole
name the sulfonamides in the long acting class (20-40 hours)
sulfamerazine
name the sulfonamides in the ultra long acting class (100-200 hours)
sulfalene
give a scenario in which the ultra long acting sulfonamides may actually be beneficial
cases of war where you can’t really get meds on a regular basis
2 drugs used for burn therapy
mafenide (NOT A TRUE SULFONAMIDE - DOES NOT FOLLOW SULFONAMIDE SAR)
silver sulfadiazine - is a sulfonamdie
silver sulfadiazine
a sulfonamide silver salt used for external application for burns
true or false
mafenide is not antagonized by PABA
TRUE
it’s not a true sulfur drug
2 trade names of trimethoprim-sulfamethoxazole
bactrim
septra
structurally, what is trimethoprim
a diamonopyrimidine
true or false
trimethoprim is bactericidal
FALSE
both trimethoprim and sulfamethoxazole are bacteriostatic when used alone, BUT CIDAL WHEN COMBINED – SYNERGY
what does trimethoprim inhibit
MICROBIAL dihydrofolate reductase (DHFR)
humans have this enzyme, but trimethoprim has 100,000-fold selectivity for the BACTERIAL enzyme
mafenide is _____-acting and ____ spectrum
short acting and broad spectrum
true or false
mafenide is not an active antibiotic
FALSE - it is - just not a true sulfonamdie
true or false
it is hard for bacteria to develop resistance to bactrim
TRUE
2 different steps are being attacked
what route are sulfonamides usually admjinisterd
orally
true or false
sulfonamides do not cross the placenta or blood brain barrier
FALSE
it crosses both readily
true or false
sulfonamides are highly protein bound
true
name all the ways that sulfonamides are aexcreted
-parent (not metabolized)
-N4-acetate (acetylated)
-glucuronides
sulfonamides can cause renal crystalluria
explain the logic behind this
as mentioned, it’s excreted as parent, N4 acetate, and glucuronides.
therefore, 2/3 is excreted as the parent molecule and N4 acetate – which are not necessarily water soluble
this can cause renal crystalluria – can precipitate out
(advise pt to stay hydrated!!!)
what is the “triple sulfa” method
old method used to try to enhance water solubility of sulfonamides and prevent renal crystalluria
combines 1/3 of 3 different sulfonamides (sulfadiazine, sulfamerazine, and sulfamethazine) with the idea that their water solubilities will combine to enhance water solubiliy
aside from the triple sulfa method, name other methods to overcome the metabolite water insolubility issue with sulfonamides
-take or instill bicarbonate to enhance urine flow
-substitute the sulfonamide for one with a lower pka (6-7) – like sulfamethoxazole! so this isn’t really concern anymore
aside from renal crystalluria, name 3 other concerns with sulfonamides
hypersensitivity - can cause SJS (erythema multiforme)
kernicterus (brain damage caused by hyperbilirubinemia) so CONTRAINDICATED IN PREGNANT WOMEN
bb’s have lack of glucuronidation and competition for plasma proteins – sulfonamides bind to same binding site as bilirubin – can displace
can cause hypoglycemic shock by interfering with the excretion of oral hypoglycemics for diabetes
