Nucleic Acid Synthesis and Metabolic Inhibitors Flashcards
What are the 3 AB that inhibit folate synthesis?
Sulfonamides, Trimethoprim, and Dapsone
What is Dapsone used for?
PCP prophylaxis in HIV infected person
Alternative to TMP/SMX
What is Sulfisoxazole acetyl marketed for and with?
In combo with erythromycin ethylsuccinate for kids w/ otitis media
What is the MOA of TMP/SMX?
Inhibits tetrahydrofolate synthesis
What is the MOA of trimethoprim?
Inhibits dihydrofolate reductase and in turn reduces it to tetrahydrofolate
In general, sulfonamides exert a (bactericidal/bacteriostatic) effect
bacteriostatic
What is the spectrum of activity of TMP/SMX?
G+ (strep and staph)
G-
No anaerobes
Pneumocystis jirovecii (PCP)
What is the ratio of TMP:SMX in serum/tissue?
1:20
What is the ratio of TMP:SMX in a oral/IV dose?
1:5
Where is TMP/SMX distributed to?
- Urine
- Prostate
- CSF
Why is the use of TMP/SMX generally limited?
Because of resistance
What is the drug of choice for treatment and prophylaxis of Pneumocystis jirovecii pneumonia?
TMP/SMX
What are the AEs of TMP/SMX?
- GI issues
- Hematological (most serious)
- Skin disorders
- Sun sensitivity (due to sulfa)
What is a serious skin disorder from using sulfa drugs?
Steven’s Johnson Syndrome
What are the 1st GEN fluoroquinolones?
Nalidixic Acid
What are the 2nd GEN fluroquinolones?
- Ciprofloxacin
- Ofloxacin
- Norfloxacin
What are the 3rd GEN fluroquinolones?
Levofloxacin
What are the 4th GEN fluroquinolones?
- Gemifloxacin
2. Moxifloxacin
Quinolone antibiotics target what?
Bacterial DNA gyrase and topoisomerase IV
G+; target = Topoisomerase
G-; target = DNA gyrase
Which quinolones cover Pseudomonas?
Cipro + Levofloxacin + Delafloxacin
Which quinolones cover S. pneum?
Gemifloxacin
Which GEN of quinolones has better G+ coverage?
3rd and 4th GEN
Which GEN of quinolones has better G- coverage?
They are all about the same
What are the atypicals that are covered by quinolones?
- Legionella pneumophila
- Chlamydia sp.
- Mycoplasma sp.
Which quinolone has the highest bioavailability?
Levofloxacin (99%)
Which quinolone has the least bioavailability?
Norfloxacin (50%)
Quinolones are (concentration/time)-dependent
Both
What is special about the distribution of quinolones?
Extensive tissue distribution (prostate, liver, lung, skin, bone, urinary tract)
What are the AE of quinolones? Which one is the black box warning*?
- Articular Damage
- Tendonitis/tendon rupture*
- Dysglycemias
- Hypersensitivity
- Prolongation of QTc interval
What medications should you avoid when using quinolones?
Class III (block K+) and Class IA (block K+ and Na+) antiarrhythmics or erythromycin
What are some drug interactions with quinolones?
- Anything w/ divalent or trivalent cations (Calcium, aluminum)
- Antacids, sucralfate, multivitamins
* *administer doses at least 2 hrs apart, take quinolone first
What kind of drug is Metronidazole?
Prodrug; only anaerobes convert Flagyl to its active form
What is the spectrum of Flagyl?
Anaerobes + Protozoa (Trichomonas vaginalis, amebiasis, and giardiasis)
How is Flagyl distributed?
Penetrates CSF
What is the half-life of Flagyl?
6 to 8 hrs
What is the drug of choice for P. colitis due to C. difficile?
Flagyl
What are the AE of Flagyl?
Metallic taste
Are there any RX interactions w/ Flagyl?
Alcohol
What is Nitrofurantoin used for?
Against G+ or G- infections that cause UTIs
