Exam 2 lecture 4 pt 1

Question 1

What does the sulfonamide structure look like? Is it a prodrug?

Answer 1

Sulfanilamide looks like six member ring with H2N on left and SO2NH2 on right

It is active form of prodrug prontosil

Question 2

What is the use of biosynthesis of methylenetetrahydrofolate

Answer 2

To make thiamine. Which is used for DNA. If biosynthesis of methylenetetrahydrofolate does not work can not make DNA

Question 3

How do sulfonamides afect formation of methylenetetrahydrofolate

Answer 3

It stops the incorporation of P-aminobenzoic acid (PABA) into methylenetetrahydrofolate precursor, consequently, it will not form methylenetetrahydrofolic acid. So DNA can not be made.

Question 4

Why does sulfonamide not kill our cells, but kills bacteria cells

Answer 4

Pathogenic microorganisms make their own folates but we get ours through diet.

Question 5

Explain the structural- activity relationship between sulfanilamide and PABA

Answer 5

The structure of sulfanilamide resembles PABA, so it is not surprising that sulfanilamide inhibits incorporation of PABA into folic acid nucleus competitively. There is however, a significat difference in acidity of PABA and sulfanilamide

Question 6

What is the Pka difference between PABA and sulfanilamide

Answer 6

PABA is anionic at physiological PH (4.9) and sulfanilamide is (10.4)

PABA is neutral at physiological PH (7.4)

Question 7

What increases the acidity of sulfonamide? What is the use of this?

Answer 7

Adding a heterocyclic ring increases acidity of sulfonamide.

Increase in acidity decreases the incidence of crystalluria (crystallization leads to kidney damage)

It is still recommeneded to drink large quantities of water

Question 8

Sulfonamides used clinically

Answer 8

Sulfacetamide
Sulfasalazine
Sulfamethoxazole
Sulfasalazine

Question 9

Therapeutic uses of sulfonamide

Answer 9

Active against fungi and protozoa and both gram positive and negative

Enteric bacteria such as E coli, klebsiella, salmonella, shigella and enterobacter are inhibited

Question 10

Are sulfonamides used alone or in combination? Why?

Answer 10

Sulfonamides are usually used in combination. Resistance factors are too wide spread for these drugs to be used in single drug therapy.

Question 11

What is sulfamethoxazole trimethoprim used for?

Answer 11

It is used for antifungal treatment of AIDS infected patients

Question 12

How does sulfamethoxazole trimethoprim work?

Answer 12

Trimethoprim inhibits dihydrofolate reductase and sulfamethoxazole inhibits PABA binding. So the combination inhibits sequential steps in biosynthesis of tetrahydrofolic acid

Question 13

How is sulfasalazine absorbed? Therapeutic use?

Answer 13

Sulfasalazine is a prodrug that is not absorbed well in GI tract. bacteria in GI tract metabolize it into sulfapyridine and aminosalicylic acid.

Sulfasalazine is used to treat UC and crohns disease.

Question 14

Use of sulfadiazine pyrimethamine

Answer 14

1st line chemotherapy to treat acute toxoplasmosis.(malaria)

Question 15

adverse rxn of sulfonamides? Cross allergenicity

Answer 15

They are ALL cross allergenic rxn (Includes sulfonamide derivatives like CAI (acetazolamide), thiazides (hydrochlorethiazide, durosemide, sulfonyl urea (glyburide)

Allergic rxn are the most common and present as rash, photosensitivity and drug fever.

SJS is a rare disease that is potentially fatal

Crystal urea could be caused aswell

N/V/anorexia

Question 16

Sulfonamide resistance mechanism

Answer 16

1. mutation that causes overproduction of PABA
2. Mutations intarget enzyme (dihydropteroate synthase) that decrease its affinity for sulfonamides
3. Mutations that result in a decrease in cell permeability to sufonamides

Question 17

how common is sulfonamide resistance? What gene confers resistance against trimethoprim?

Answer 17

Resistance to sulfonamides is very common and this has largely eliminated their effectiveness as single use agents. (thats why they are used in ocombo)

DHFR gene often bears a mutation of decreased binding affinity of trimethoprim

Question 18

When do we get max concentration of sulfamethoxazole trimethoprim?

Answer 18

Both at 3 hrs

Question 19

What are sulfonamides metabolized by?

Answer 19

N-4 acetylation and N1 glucronidation

Question 20

What is Colistin used for?

Answer 20

last resort tx for MR pseudomonas aeruginosa, acinetobacter and klebsiella

Highly nephrotoxic

Question 21

How does Colistin work?

Answer 21

Disrupts membrane structure by using ammonium cations to displace bacterial cell membrane

Question 22

Metronidazole use?

Answer 22

1st line for C diff

Question 23

2nd line tx of C diff

Answer 23

Vanc

Question 24

Name recently approved drugs? What are they used for? MOA

Answer 24

Lefamulin Acetate- community acquired bacterial pneumonia. Binds 50S ribosomal subunit

Pretomanid- Tx resistant TB. inhibits mycolic acid biosynthesis