Sulfonamide Antimicrobial Agents

Question 1

Activity of prontosil?

Answer 1

Inactive in vitro, prodrug in that its metabolites are active

Question 2

Prontosil used to treat?

Answer 2

Candida albicans

Question 3

What do sulfonamides competitively inhibit?

Answer 3

Incorporation of p-aminobenzoic acid into folic acid nucleus via inhibition of dihydropteroate synthase

Question 4

Why do sulfonamides not hurt mammalian cells, but hurts bacterial cells?

Answer 4

Mammalian cells utilize preformed folate in the diet while bacterial cells make their own folic acid

Question 5

Antibiotic activity of sulfonamides can be reversed by what?

Answer 5

Adding large quantities of PABA (p-aminobenzoic acid) to diet

Question 6

Structure of sulfanilamide resembles what

Answer 6

PABA

Question 7

Acidity of PABA vs sulfanilamide?

Answer 7

PABA pKa 6.5

Sulfanilamid pKa 10.4

Question 8

What type of acid is sulfanilamide?

Answer 8

Weak acid

Question 9

What enhanced the potency and acidified the sulfonamide nitrogen of sulfanilamide drug?

Answer 9

Attachment of electron withdrawing heteroaromatic rings

Question 10

Increase in acidity decrease the incidence of what?

Answer 10

Crystalluria (Crystallization of the sulfonamide in urine resulting in kidney damage)

Question 11

What do they recommend be done when taking sulfonamides to reduce crystalluria?

Answer 11

Drink large amounts of water

Question 12

Sulfonamides in general inhibit what?

Answer 12

Gram + and Gram -
Nocardia
Chlamydia trachomatis
Protozoa/fungi

Question 13

How are sulfonamides usually used in treatment?

Answer 13

In combination

Question 14

Why are sulfonamides usually used in combination?

Answer 14

Resistance factors are too widespread

Question 15

Most popular sulfonamide?

Answer 15

Sulfisoxazole

Question 16

What are sulfisoxazole and sulfamethoxazole used to treat>

Answer 16

Urinary tract infections

Question 17

What is used in a 1:1:1 ratio to treat Gardnerella vaginalis?

Answer 17

Sulfabenzamide, sulfacetamide, and sulfathiazole

Question 18

What is sulfasalazine?

Answer 18

Prodrug not well absorbed from GI tract

Question 19

What do bacteria metabolize sulfasalazine to?

Answer 19

Sulfapyridine and 5-aminosalicyclic acid

Question 20

Function of 5-aminosalicyclic acid?

Answer 20

Antiinflammatory

Question 21

What is sulfasalizine used to treat?

Answer 21

Ulcerative colitis and Chron’s disease

Question 22

Why don’t we just administer 5-aminosalicyclic acid directly?

Answer 22

Irritating to gastric mucosa

Question 23

Sulfadoxine and pyrimethamine are used together to prevent what?

Answer 23

Malaria

Question 24

Pyrimethamine is inhibitor of what?

Answer 24

Plasmodium falciparum dihydrofolate preductase

Question 25

First line chemotherapy to treat acute toxoplasmosis?

Answer 25

Sulfadiazine and pyrimethamine

Question 26

How to sulfonamides and their derivatives interact?

Answer 26

Cross-allergenic

Question 27

Rare skin and mucous membrane rash that is potentially fatal due to sulfonamide interaction?

Answer 27

Stevens-Johnson syndrome

Question 28

Resistance to sulfonamides occurs through what mechanisms?

Answer 28

1) Mutations cause overproduction of PABA 2) Mutations in target enzyme (dihydropteroate synthase) 3) Mutations result in decrease of cell permeability to sulfonamides

Question 29

What has happened with trimethoprim and resistance?

Answer 29

Plasmid borne copy of dihydrofolate reductase gene decreases binding to enzyme

Question 30

How is Trimethoprim cleared?

Answer 30

Inactive metabolites cleared in urine

Question 31

What are sulfonamides metabolized by?

Answer 31

N-4 N-acetylation | N-1 glucuronidation

Question 32

Metabolites of sulfonamides are what when acetylated/glucuronidated?

Answer 32

Inactive

Question 33

Which metabolites of sulfonamides are toxic?

Answer 33

Hydroxylamine and nitroso

Question 34

Human population divided into what types of acetylators?

Answer 34

Rapid or slow

Question 35

First generation Quinolones good against what?

Answer 35

Gram -

Question 36

First generation QL only useful for what?

Answer 36

Lower urinary tract infections

Question 37

How is 2nd generation differ from 1st generation?

Answer 37

Fluorine at C-6 Heterocyclic ring at C-7 Broader spectrum and more potent

Question 38

what do 2nd generation QLs work on?

Answer 38

Gram - Gram + Mycoplasma

Question 39

Most potent fluoroquinolone?

Answer 39

Ciprofloxacin

Question 40

How do 3rd and 4th generation QL differ from 2nd?

Answer 40

Multiple fluorine atoms | Improved activity against Gram + (Strep pneumonia)

Question 41

Are 3rd/4th generation better than Ciprofloxacin for gram -?

Answer 41

No, Cipro still best

Question 42

What QL is known as "drug of last resort"?

Answer 42

Moxifloxacin

Question 43

Why is Moxifloxacin known as drug of last resort?

Answer 43

Sever side effects

Question 44

How many strands of DNA do Topoisomerases cuts?

Answer 44

Topoisomerase 1 cuts 1 and topoisomerase 2 cuts 2

Question 45

How do topoisomerase and gyrases cut DNA>

Answer 45

Nucelophillic attack on phosphodiester link

Question 46

How do QL work?

Answer 46

They inhibit relegation reaction which eventually leads to apoptosis/death

Question 47

Which topoisomerase type has been crystallized and had X-ray structures determined?

Answer 47

Type 2

Question 48

Most common use of QLs?

Answer 48

Urinary tract infections

Question 49

First line treatment of Neisseria Gonorrhoeae due to QL resistance?

Answer 49

Ceftriaxone

Question 50

Increased fluoroquinolone resistance rates correlated with what?

Answer 50

Use

Question 51

Spontaneously occuring point mutations where causes QL resistance?

Answer 51

A-subunit of DNA gyrase

Question 52

What does point mutation of gyrase A-subunit achieve?

Answer 52

Enzyme with altered binding affinity

Question 53

Fluoroquinolone penetration of Gram - bacteria dependent on what?

Answer 53

Diffusion through porin channels

Question 54

Under-dosing runs the risk of whaT?

Answer 54

Selecting for resistant organisms

Question 55

How are fluoroquinolone taken?

Answer 55

Orally, high bioavailability

Question 56

Renal and hepatic clearance are important for all QLs except which?

Answer 56

Oxafloxacin (95% renal)

Question 57

How long until QLs interstitial concentration exceed serum concentrations?

Answer 57

4-24 hours

Question 58

What do you want to avoid mixing with QLs?

Answer 58

Heavy metals/food drugs with heavy metals due to insoluble chelates

Question 59

Major inactive metabolite of QLs?

Answer 59

Glucuronide at 3 carboxyl position

Question 60

Most common adverse side effect of QLs?

Answer 60

Nausea, vomiting, and diarrhea

Question 61

Who do you not want to give QLs to?

Answer 61

Patients under 18 due to interference with growing cartilage

Question 62

What adverse effect can happen with lomefloxacin?

Answer 62

Photosensitivity

Question 63

Gatifloxacin associated with what?

Answer 63

Hyperglycemia and hypoglycemia in diabetic patients