Term
[image]
can ONLY modify the R group at the amino group on the bottom
[image]
no substituents on the phenyl ring other than the amine (which has to be primary)
drugs with the highest activity have a pKa close to that of PABA (pKa = 6.5). to do this you have to add EWGs on the R position, commonly heterocycles. |
|
Definition
|
|
Term
bacteriostatic effect (when used alone)
folic acid inhibitors = antimetabolites
[image]
folic acid
PABA is very similar to sulfonamides. the drug will be inserted instead of the normal building block in the synthesis of folic acid.
[image]
dihydropteroate synthetase will recognize the sulfonamide instead of the normal building block of folic acid synthesis |
|
Definition
|
|
Term
|
Definition
| as the pKa of sulfonamides increases, what happens to the activity of the drugs? |
|
|
Term
increased production of PABA
alterations in the dihydropteroate synthetase
reduced drug uptake (permeability barrier and/or efflux pumps)
regulational changes in the target enzymes |
|
Definition
| mechanisms of bacterial resistance to sulfonamides |
|
|
Term
BROAD SPECTRUM
small molecules so can cross porins and membranes
urinary tract infections
combinations - to reduce resistance |
|
Definition
| spectrum of activity of sulfonamides |
|
|
Term
well absorbed from the GI tract
binding to plasma proteins (differs between different classes)
pass into body fluids (peural, synovial, ocular, and cerebrospinal)
excretion via renal |
|
Definition
| absorption, distribution, and excretion of sulfonamides |
|
|
Term
metabolism by acetylation of the para amino group:
[image]
acetylsulfonamides are toxic: toxicity is related to the precipitation of the metabolite during excretion, can be prevented if patient drinks a lot of water to dissolve it better
both sulfonamide and acetylsulfonamide are excreted renally
sulfonamides are filtered and exhibit reabsorption
metabolism by glucuronidation:
[image]
less common than acetylation |
|
Definition
| metabolism of sulfonamides |
|
|
Term
hypersensitivity
toxicity to the hematopoietic system
toxicity to the urinary tract |
|
Definition
| adverse effects of sulfonamides |
|
|
Term
| long acting sulfonamides: sulfamethoxypiridazine and sulfamethoxydiazine |
|
Definition
| which class of sulfonamides are associated with Steven-Johnson syndrome? |
|
|
Term
very long acting sulfonamides: sulfadoxine
administered once weekly |
|
Definition
| what class of sulfonamides is used in combination with pyrimethamine for prophylaxis of malaria? |
|
|
Term
inhibitor of dihydrofolate reductase
used for urinary tract infections in combination with sulfonamides
[image]
trimethoprim binds to the enzyme in the last step of the synthesis of folic acid |
|
Definition
MOA of trimethoprim
[image] |
|
|
Term
available PO and IV
volume of distribution greater than sulfonamides
excreted in the urine
metabolism by acetylation |
|
Definition
| pharmacology of trimethoprim |
|
|
Term
GI upset
folate deficiency may occur in some patients
CONTRAINDICATED in pregnant women to avoid folate deficiency
trimethoprim and sulfonamides are SELECTIVE b/c humans do not synthesize folate, we get it from our diets. |
|
Definition
| adverse effects of trimethoprim |
|
|
Term
plasmid-encoded TMP resistance
chromosomal TMP resistance |
|
Definition
| bacterial resistance of trimethoprim |
|
|
Term
bactericidal
broad spectrum
urinary tract infections, respiratory tract infections, GI tract infections |
|
Definition
| spectrum of trimethoprim/sulfonamide combinations |
|
|
