04 Study Guide: Antimetabolite & Other Antibiotics COPY Flashcards
What is the major class of folate antagonist antibiotics, and how do you recognize their names?
Sulfonamides, (sulfa)
What additional drug is also considered a folate antagonist?
Trimethoprim
What is the major class of DNA synthesis inhibiting antibiotics, and how do you recognize their names?
Fluoroquinolones (flox)
What is one agent that is considered a urinary antiseptic?
Nitrofurantoin
What are the functions of dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes (which one metabolizes PABA and which one metabolizes dihydrofolic acid)?
DHPS is the enzyme that converts a precursor, PABA, to dihydrofolic acid. DHFR metabolizes dihydrofolic acid to tetrahydrofolic acid (folates!).
Is folate synthesis from PABA a bacteria specific process? Which portion of the pathway is shared by both bacteria and humans?
Yes, the portion where dihydrofolic acid is converted into folates is shared by both bacteria and humans.
Which enzyme is inhibited by sulfonamides, and which by trimethoprim?
Sulfonamides-DHPS
Trimethoprim-bacterial DHFR blocking folate synthesis
What is the function of the topoisomerase enzymes (DNA gyrase and Top IV)?
The unwinding process is done by topoisomerase, DNA gyrase (alters DNA supercoiling), topoisomerase IV (separates interlocked strands)
Do humans have topoisomerases? If so, how do antibiotics target topoisomerases without affecting human cells?
Yes, humans do have topoisomerase. Fluoroquinolones are specific inhibitors of bacterial topoisomerases.
How does nitrofurantoin selectively target bacterial vs. human cells?
Bacterial selectivity is due to more rapid bacterial conversion to reactive intermediates in bacteria vs humans
What 3 mechanisms provide bacteria with resistance to sulfonamides?
- 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
What 3 mechanisms provide bacteria with resistance to trimethoprim?
- Reduced cell permeability
- Overproduction of DHFR
- Production of an altered reductase that doesn’t bind trimethoprim well
Is resistance to nitrofurantoin common or rare?
Rare
Among the drugs/classes covered in this lecture, which has the broadest spectrum of activity?
Fluoroquinolones
Name one class and one combination (class + drug) that have activity against multi-drug resistant bacteria
Fluoroquinolones (one class) Trimethoprim-Sulfamethoxazole (class+drug)
For which class is use limited to serious or treatment-resistant infections, and why?
Fluoroquinolones
What is the one use of nitrofurantoin?
UTI
What class is used topically for burns and as eyedrops for eye infections?
Sulfonamides
Which class tends to have cross-allergenicity with many other drug classes?
Sulfonamides
Which class tends to produce urine crystals, hematologic toxicity and hemolytic reactions in G6PD deficient individuals?
Sulfonamides
Which other drug can also produce hemolytic reactions in G6PD deficient individuals?
Nitrofurantoin
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).
- Fluoroquinolones
- Tendinitis and tendon rupture
- Peripheral neuropathy
- CNS effects
- Aortic aneurysm/dissection
Which class is generally well tolerated, but can produce neuropathy / pulmonary toxicity if the drug can’t be cleared by kidneys?
Nitrofurantoin
What drug is often given with sulfonamides, and what are the 2 advantages of this combination
- Trimethoprim-sulfamethoxazole (TMP-SMX)
- 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)
- Used for severe pneumocystis pneumonia, alternate therapy for some multidrug-resistant infections (IV)
