Exam 8: Sulfonamides

Question 1

Name 2 Oral Sulfonamides

Answer 1

Sulfadiazine

Sulfamethoxazole

Question 2

Name 1 Topical Sulfonamide

Answer 2

Silver sulfadiazine

Question 3

Name 1 Pyrimidine

Answer 3

Trimethoprim

Question 4

Name one popular sulfonamide combination product

Answer 4

Trimethoprim-Sulfamethoxazole

Bactrim

Question 5

What is the mechanism of Sulfonamides?

Answer 5

Inhibition of bacterial Folate synthesis
Via competitive inhibition of Dihydropteroate Synthase
They do this by mimicking PABA

Question 6

Are Sulfonamides -cidal or -static?

Answer 6

Bacteriostatic

Question 7

What is an advantage of combining a sulfonamide with trimethoprim?

Answer 7

The combo is bactericidal, rather -static

Question 8

What is the mechanism of Trimethoprim?

Answer 8

Inhibition of bacterial folate synthesis

Via inhibition of Dihydrofolate Reductase

Question 9

What is Folate?

Answer 9

Vitamin B9
Required for DNA synthesis
Bacteria produce it, humans have to consume it.

Question 10

What is folate deficiency most associated with?

Answer 10

Birth defects
Neural tube defects
Also megaloblastic anemia

Question 11

What is an important consideration with any drug that his antifolate properties?

Answer 11

They all have teratogenic potential, at least in principle.

Question 12

What types of organisms are susceptible to Sulfonamides? Resistant?

Answer 12

Organisms that produce their own folate

Those that obtain pre-formed folate

Question 13

What are 4 resistance mechanisms to Sulfonamides?

Answer 13

1. Mutated dihydropteroate synthase (lowered affinity)
2. Increased efflux (Pseudomonas)
3. Plasmids with drug-resistant enzymes (enteric gram negatives) Leads to MDR
4. Auxotrophy for folate (E. faecalis)

Question 14

What is the mechanism of resistance to sulfonamides for E. faecalis?

Answer 14

Auxotrophy for Folate

Question 15

What is a common mechanism of sulfonamide resistance for Pseudomonas?

Answer 15

Increased drug efflux

Question 16

What is a mechanism of resistance to Sulfonamides that leads to MDR?

Answer 16

Plasmids with drug-resistant enzymes

Question 17

What happens to Sulfasalazine in the gut? What happens to each metabolite?

Answer 17

Metabolism to sulfapyridine and 5-ASA
5-ASA has topical anti-inflammatory effects
Sulfapyridine has a systemic anti-inflammatory effect

Question 18

What Sulfonamide is used in burn therapy?

Answer 18

Silver Sulfadiazine

Topical (applied as cream)

Question 19

What happens to the silver and the sulfa that is topically applied to burns?

Answer 19

They are both anti microbial
Sulfa gets absorbed
Silver does not get absorbed

Question 20

How long is the half-life of Sulfadoxine? Why?

Answer 20

7-9 days (Really long)

Probably because of protein binding

Question 21

What sulfonamide could be used in malaria? Why is its use limited?

Answer 21

Sulfadoxine combined with pyrimethamine

Limited by severe side effects and resistance

Question 22

How do sulfonamides circulate in the plasma?

Answer 22

Bound to albumin to varying degrees

Question 23

How do Sulfonamides distribute in the body?

Answer 23

Pretty much everywhere
Cross BBB
Cross placenta, enter breast milk
Pregnancy Category C

Question 24

Why doesn’t Trimethoprim affect human cells, since we do have DHFR?

Answer 24

100,000x more affinity for bacterial DHFR

Question 25

What is a mechanism of resistance to Trimethoprim?

Answer 25

Altered DHFR enzyme

Question 26

How does Trimethoprim's volume of distribution compare to Sulfonamides?

Answer 26

9x higher

Question 27

How is Trimethoprim removed from the body?

Answer 27

Excreted unchanged in the urine

Question 28

What ratio is dosing for TMP:SMX?

Answer 28

1:5 (more sulfa) | Results in 1:20 ratio in plasma concentration

Question 29

What is a scary bug that is usually susceptible to TMP-SMX?

Answer 29

Community acquired MRSA

Question 30

What are some bugs that are resistant to TMP-SMX?

Answer 30

``` Ineffective against Bacteroides fragilis, most anaerobes, P. aeruginosa, M. tuberculosis, T. pallidum, Campylobacter, penicillin- resistant pneumococci, and rickettsiae ```

Question 31

What is a super common use for TMP-SMX?

Answer 31

UTIs (E. coli)

Question 32

What is a weird organ that sulfonamides are able to penetrate?

Answer 32

Prostate | Useful in prostatitis

Question 33

What bug causes most uncomplicated UTI? Complicated?

Answer 33

Uncomplicated: E. coli Complicated: Probably still E. coli, but some E. faecalis too

Question 34

Treatments for complicated vs uncomplicated UTIs?

Answer 34

Both use TMP-SMX Days for uncomplicated 2 weeks for complicated

Question 35

Definition of complicated UTI?

Answer 35

Any UTI in a male | Or associated with a predisposing lesion

Question 36

What could you use for a UTI with resistance to TMP-SMX?

Answer 36

Fluoroquinolones

Question 37

What are 3 GI bugs that can be treated with TMP-SMX?

Answer 37

Salmonella E. coli (traveler's diarrhea) Listeria monocytogenes

Question 38

What are 4 atypical/rare infections treatable with TMP-SMX?

Answer 38

Nocardia (esp with immunocompromise) Toxoplasmosis Pneumocystis j. Yersenia (Plague)

Question 39

Cats are a buzzword for...

Answer 39

Toxoplasmosis | Pregnant women should be careful

Question 40

Two big reasons sulfonamides aren't used more often?

Answer 40

Side effects can be bad | Resistance is common

Question 41

Sulfonamide adverse effects?

Answer 41

Skin rashes/hypersensitivites Crystalluria Hyperkalemia (TMP reduce renal K secretion) Acute Hemolytic anemia related to G6PD deficiency Agranulocytosis, aplastic anemia

Question 42

What is a big predisposing factor to Sulfa hypersensitivity reactions?

Answer 42

HIV

Question 43

What condition can predispose patients to non-immune hemolysis?

Answer 43

G6PD deficiency (oxidative stress) Most common enzyme deficiency worldwide X linked Sulfa drugs are more likely to cause anemia in these patients

Question 44

Sulfonamide drug interactions?

Answer 44

Interfere with other drugs that bind albumin | Warfarin, phenytoin, sulfonureas

Question 45

Who should avoid Sulfonamides when possible?

Answer 45

Pregnant women Pregnancy Category C Especially avoid them in the first trimester *** Less of a concern late in pregnancy

Question 46

Other than teratogenesis, what else can sulfonamides cause in the fetus?

Answer 46

Kernicterus (hyperbilirubinemia causing neurologic problems) | Related to albumin binding/bilirubin binding to albumin