MedChem Sulfonamides

Antibiotic

A microbial metabolic product that kills or inhibits growth of another microorganism.

penicillins, cephalosporins, vancomycin

Antibiotics that inhibit cell wall synthesis

tetracyclines, oxazolidinones, chloramphenicol

Antibiotics that inhibit protein synthesis

fluoroquinolones, rifamycins

Antibiotics that inhibit nucleic acid synthesis

sulfonamides, isoniazid

Antibiotics classified as antimetabolites

polymyxins, daptomycin

Antibiotics that alter cell membrane function

intrinsic

Term for inherent/natural resistance

acquired

Term for resistance due to alteration of bacterial genome through horizontal and vertical evolution

exclusion

Term to describe resistance due to barrier protection of outer membrane

target modification

Resistance when bacteria changes structure of drug target, reducing sensitivity

efflux

Resistance due to bacteria pumping out drug

enhanced production of the target

Resistance from up-regulated production of key molecules by bacteria

by-pass target

Resistance from bacteria implementing an alternative route to make key molecules

selective

Type of toxicity where an antimicrobial agent is more toxic to a pathogen than to the host

comparative distribution

Differences in distribution of toxicants based on morphology of different organisms

comparative biochemistry

Differences in the presence of metabolic pathways of organisms

comparative cytology

Differences in cell structure and function across organisms

Prontosil

First commercially available antibacterial drug

sulfonamide

Prontosil antibiotic class

dihydrofolate reductase inhibitor

MOA of trimethoprim

UTI, burns, ophthalmic infections, rheumatic fever, Crohn’s, UC, AIDS

Uses of sulfonamides

SO2NH2

Sulfonamide structural formula

sulfisoxazole

sulfacetamide

sulfamethoxazole

sulfamethazine

urine pH < drug pKa

Why does sulfanilamide cause kidney damage due to crystallization? (think ionization of the acidic drug)

pH= pKa + log (i/u)

Weak ACID Henderson Hasselbalch equation

pH= pKa + log (u/i)

Weak BASE Henderson Hasselbalch equation

%I= (i/u) / (i/u +1) x 100

% ionization formula

acidic

Are sulfonamides acidic or basic

force fluids, raise urine pH, mix or switch sulfonamides

Methods to increase sulfonamide solubility

essential

Folate coenzymes are ____ to life.

dihydrofolic acid

Bacteria and protozoa form what folic acid derivative?

F

T/F Humans can synthesize folic acid.

F

T/F Bacteria utilize folic acid from their host.

cellular impermeability

Why can’t bacteria utilize folic acid from their host?

dihydropteroate synthase

What enzyme is inhibited by sulfonamides?

competitive

What type of inhibition is seen with sulfonamide activity at the enzyme?

PABA

What is the substrate used by microorganisms to form dihydropteroic acid in folic acid biosynthesis?

4-aminobenzoic acid

What is the IUPAC name for PABA?

dihydrofolate reductase

What enzyme is selectively inhibited by trimethoprim?

T

T/F Trimethoprim is selective to the bacterial enzyme, but can still inhibit the human enzyme at high concentration?

dihydrofolic acid

In humans, folic acid is converted to what product by folate reductase?

tetrahydrofolic acid

FAH₂ is converted to what product by dihydrofolate reductase?

bacteriostatic

Are sulfonamides bactericidal or bacteriostatic?

bacteriostatic

Term for an antibiotic that prevents the growth and reproduction of bacteria

bactericidal

Term for an antibiotic that kills bacteria

both

Do sulfonamides have gram positive/negative/both activity?

Pseudomonas aeruginosa

What species are intrinsically resistant to sulfonamides?

PABA

What product has enhanced production during bacterial resistance to sulfonamides?

acquired

Resistance due to R-factor plasmid gene transfer in bacteria is an example of what type of resistance to sulfonamides?

target modification

Alteration of binding affinity to pathway enzymes is an example of what kind of bacterial resistance to sulfonamides?

sulfone

N¹ substitution with what molecule will have activity maintained in sulfonamides?

F

T/F Sulfonamide activity will be maintained with N¹ disubstitution.

EWG

Will N¹ substitution with a EWG or a EDG increase activity in sulfonamides?

6.7-7.4

What is the range of pKa values that have maximum antibacterial effect in sulfonamides?

hypersensitivity

What type of reaction includes Stevens-Johnson syndrome, skin eruptions, allergic myocarditis, photosensitization with sulfonamides?

hematologic

What type of reaction to sulfonamides includes agranulocytosis, aplastic anemia, hemolytic anemia.

crystalluria

What side effect with sulfonamides may occur due to inadequate fluid intake?

free form

Are free form or protein bound fractions active?

increased lipid solubility

What causes an increase in protein binding of sulfonamides?

sulfacetamide sodium, sulfisoxazole diolamine

Sulfonamides used for ophthalmic infections

silver sulfadiazine, mafenide acetate

Sulfonamides used for burn therapy

sulfasalazine

Nonabsorbable sulfonamide used for Crohn’s and IBD