DNA Inhibitors Flashcards
To learn
What is the MOA of Fluoroquinolones?
Inhibit DNA gyrase (topoisomerase II), inhibits DNA synthesis, bactericidal dose dependent
How does resistance for quinolones happen?
Alterations in DNA gyrase binding, mutation in the QRDR of DNA gyrase enzyme
Decreased accumulation of porin proteins, energy dependent efflux system
Classify the generation and activity of fluoros?
1st - Nalidixic acid - Uncomplicated UTI
2nd - Cipro, Ofloxacin - Improved systemic activity, Gram - activity (P. aeruginosa with Cipro)
3rd - Levo, Gemifloxacin - Extended activity of Gram +, retains Gram - (P. aeruginosa with Levo)
4th - Moxifloxacin - Additional anaerobic activity
What is the spectrum of Moxifloxacin?
Gram + organisms such as Strep. sps, S. pneumoniae, Enterococcus, S. aureus (MSSA), anaerobes, atypical bacteria
What is the spectrum of Cipro and Levoflox?
Gram - organisms such as H. influenzae, Enterobacteriaceae (EPK), P. aeruginosa
Levo also does Gram + such as Strep sps, S. pnmae, Enterococcus, atypical bacteria
What are some ADEs of quinolones?
Avoid in pregnancy and children, Rash/photosensitivity, Tendon rupture (incr. risk if above 60 y/o, steroids), Dysglycemia, QTc prolongation, C. diff colitis, False + opioids on urine screen, CNS/neurologic effects
Gemifloxacin can cause what?
Rash/photosensitivity especially females below 40 yo
What is the MOA of Folate antagonists?
Inhibit sequential steps in folate metabolism, bacteriostatic
How does resistance happen for folate antagonists?
Sulfonamides: Alteration in enzyme requiring PABA, Increased inactivation of drug, Alternative metabolic pathway, Increased production of PABA
Trimethoprim: Altered DHFR (lower affinity)
What is the drug target for Sulfonamides?
DHPS (dihydropteroate synthase)
Drug target for Trimethoprim?
DHFR (dihydrofolate reductase)
Spectrum for TMP/SMX?
Gram +: Listeria if allergic to penicillin, mild MRSA
Gram -: UTI (70% EPK), Steno malthophilia, Burkholderia sps, Pneumocystis, Toxoplasmosis, Nocardia
What is the elimination route for TMP/SMX? Combination for TMP/SMX?
Renal, 1 part trimethoprim to 5 part sulfa
Specific dosing and indications?
1 DS daily (SBP, PcjP prophylaxis)
1 DS Q12h (UTI, SSTI)
2 DS Q6-12h by weight (PcjP treatment)
What are the ADEs of TMP/SMX?
Rash - can progress to Steven Johnson syndrome
Heme - Neutropenia, Anemia in G6PD deficiency
Renal - K+ (hyperkalemia), AIN
Neural tube defect risk
Sulfa allergy - Sulfamethoxazole, sulfadiazine, sulfisoxazole, sulfacetamide
Drug interactions with TMP/SMX?
Warfarin - SMX inhibits CYP 2C9
Phenytoin, oral hypoglycemics
What is Dapsone used for?
Mycobacterium leprae, causes hemolytic anemia, CI in patients deficient in G6PD
What is Sulfadiazine with Pyrimethamine used for?
Toxoplasmosis treatment
What is fosfomycin tromethamine?
Phosphonic antibiotic, inhibits bacterial cell wall synthesis (bactericidal), inhibits PEP transferase blocking formation of cell wall precursors
Which drug acts before beta lactams or vancomycin?
Fosfomycin tromethamine
Fosfomycin is helpful for?
Active and clinically useful for UTI and prostatitis caused by enterococcus (including vancomycin resistant strains), enterobacteriaceae (ESBL strains)
What is the MOA of Nitrofurantoin?
Nitroaromatic antibacterial, inhibits DNA and RNA functions through unclear mechanism
Is nitrofurantoin bactericidal or static?
Bactericidal in urine
What is the activity for nitrofurantoin?
Active against strep and staphylococcus, Enterococcus including VRE, E. coli, Klebsiella, Enterobacter (including ESBLS)
How is nitrofurantoin absorbed and eliminated?
Orally, no IV formulation, achieves therapeutic concentrations in bladder
Eliminated rapidly by kidney (20 min half life)
What are the two nitrofurantoin drugs and what are they used for?
Macrodantin, Macrobid (ER)
Used for prevention and treatment of UTIs
What are the ADEs of nitrofurantoin?
Pulmonary (hypersensitivity, interstitial pneumonitis, pulmonary fibrosis), hepatic necrosis, peripheral neuropathy, hematologic (agranulocytosis, anemia)
CI in renal impairment (<30 CrCl)
