04 Study Guide: Antimetabolite & Other Antibiotics

Question 1

What is the major class of folate antagonist antibiotics, and how do you recognize their names?

Answer 1

Sulfonamides, (sulfa)

Question 2

What additional drug is also considered a folate antagonist?

Answer 2

Trimethoprim

Question 3

What is the major class of DNA synthesis inhibiting antibiotics, and how do you recognize their names?

Answer 3

Fluoroquinolones (flox)

Question 4

What is one agent that is considered a urinary antiseptic?

Answer 4

Nitrofurantoin

Question 5

What are the functions of dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes (which one metabolizes PABA and which one metabolizes dihydrofolic acid)?

Answer 5

DHPS is the enzyme that converts a precursor, PABA, to dihydrofolic acid. DHFR metabolizes dihydrofolic acid to tetrahydrofolic acid (folates!).

Question 6

Is folate synthesis from PABA a bacteria specific process? Which portion of the pathway is shared by both bacteria and humans?

Answer 6

Yes, the portion where dihydrofolic acid is converted into folates is shared by both bacteria and humans.

Question 7

Which enzyme is inhibited by sulfonamides, and which by trimethoprim?

Answer 7

Sulfonamides-DHPS
Trimethoprim-bacterial DHFR blocking folate synthesis

Question 8

What is the function of the topoisomerase enzymes (DNA gyrase and Top IV)?

Answer 8

The unwinding process is done by topoisomerase, DNA gyrase (alters DNA supercoiling), topoisomerase IV (separates interlocked strands)

Question 9

Do humans have topoisomerases? If so, how do antibiotics target topoisomerases without affecting human cells?

Answer 9

Yes, humans do have topoisomerase. Fluoroquinolones are specific inhibitors of bacterial topoisomerases.

Question 10

How does nitrofurantoin selectively target bacterial vs. human cells?

Answer 10

Bacterial selectivity is due to more rapid bacterial conversion to reactive intermediates in bacteria vs humans

Question 11

What 3 mechanisms provide bacteria with resistance to sulfonamides?

Answer 11

• Overproduction of PABA
• Structural changes to DHPS enzyme to reduce its affinity to sulfonamides
• Changes in permeability that reduce the ability of sulfonamides to enter the bacterial cell

Question 12

What 3 mechanisms provide bacteria with resistance to trimethoprim?

Answer 12

1. Reduced cell permeability
2. Overproduction of DHFR
3. Production of an altered reductase that doesn’t bind trimethoprim well

Question 13

Is resistance to nitrofurantoin common or rare?

Answer 13

Rare

Question 14

Among the drugs/classes covered in this lecture, which has the broadest spectrum of activity?

Answer 14

Fluoroquinolones

Question 15

Name one class and one combination (class + drug) that have activity against multi-drug resistant bacteria

Answer 15

Fluoroquinolones (one class) Trimethoprim-Sulfamethoxazole (class+drug)

Question 16

For which class is use limited to serious or treatment-resistant infections, and why?

Answer 16

Fluoroquinolones

Question 17

What is the one use of nitrofurantoin?

Answer 17

UTI

Question 18

What class is used topically for burns and as eyedrops for eye infections?

Answer 18

Sulfonamides

Question 19

Which class tends to have cross-allergenicity with many other drug classes?

Answer 19

Sulfonamides

Question 20

Which class tends to produce urine crystals, hematologic toxicity and hemolytic reactions in G6PD deficient individuals?

Answer 20

Sulfonamides

Question 21

Which other drug can also produce hemolytic reactions in G6PD deficient individuals?

Answer 21

Nitrofurantoin

Question 22

Which class is generally well tolerated, but has many FDA warnings for rare serious side effects? (Name 4 examples of rare serious side effects with this class of drug).

Answer 22

1. Fluoroquinolones
   
   1. Tendinitis and tendon rupture
   2. Peripheral neuropathy
   3. CNS effects
   4. Aortic aneurysm/dissection

Question 23

Which class is generally well tolerated, but can produce neuropathy / pulmonary toxicity if the drug can’t be cleared by kidneys?

Answer 23

Nitrofurantoin

Question 24

What drug is often given with sulfonamides, and what are the 2 advantages of this combination

Answer 24

1. Trimethoprim-sulfamethoxazole (TMP-SMX)
   
   1. Effective for a wide variety of infections, including pneumonia and most respiration tract infections, otitis media, UTI’s, prostatitis, uncomplicated skin and soft tissue infections (oral)
   2. Used for severe pneumocystis pneumonia, alternate therapy for some multidrug-resistant infections (IV)