Antibiotics IV: Inhibitors of Nucleic Acid Synthesis and Plasma Membrane Disruptors Flashcards
MOA: bactericidal agent that inhibits one of two topoisomerase II enzymes (DNA gyrase or topoisomerase IV)
ciprofloxacin
fluoroquinolones
ciprofloxacin
widely used to treat common urogenital, respiratory and GI infections; prophylaxis for anthrax
ciprofloxacin
Adverse effects: tendon rupture; prolongation of Q-T interval; confusion, somnolence, visual disturbances in elderly
ciprofloxacin
causes CDAD
ciprofloxacin (and clindamycin)
Interactions: theophylline, warfarin; multivalent cations
ciprofloxacin
prodrug - reduced in anaerobes by pyruvate-ferredoxin oxidoreductase or nitroreductase
metronidazole
MOA: bactericidal in anaerobic bacteria, sensitive protozoa; cause DNA strands to break and lose helical structure
metronidazole
Drug of choice for CDAD
metronidazole (vancomycin is 2nd)
Used in combo w/ tetracycline and bismuth subsalicylate to eradicate H. pylori
metronidazole
antiparasitic agent
metronidazole
Adverse reactions: dark red-brown urine; N/V when combined w/ ethanol
metronidazole
MOA: bacteriostatic; analog of PABA; ultimately prevents DNA replication
sulfamethoxazole
resistance due to synthesis of sufficient PABA, mutation in active site results in reduced drug affinity, and/or decreased drug uptake
sulfamethoxazole
Therapeutic uses: G+/G- infections; UTIs
sulfamethoxazole (in combo with trimethoprim)
Adverse reactions: kernicterus in newborns, Stevens-Johnson syndrome, hemolytic anemia
sulfamethoxazole
MOA: competitive inhibitor of dihydrofolate reductase
trimethoprim
Resistance due synthesis of increase amount of DHFR, production of mutated DHFR w/ lower drug affinity, and reduced drug uptake
trimethoprim
Uses: alone for initial therapy of uncomplicated UTIs
trimethoprim
Adverse reactions: bone marrow suppression in folate-deficient patients; fetal malformations in high doses
trimethoprim
fixed-dose combination of TMP/SMX
co-trimoxazole
Therapeutic uses: UTIs, Pneumocystis jirovicii pneumonia, otitis media
co-trimoxazole
MOA: bactericidal combo that results from inhibition of sequential steps of folate biosynthesis
co-trimoxazole
MOA: inhibition of bacterial RNA polymerase; bactericidal against G+
fidaxomicin
Therapeutic uses: C. difficile colitis (minimally disruptive to normal flora)
fidaxomicin
cyclic lipopeptides
daptomycin
MOA: Ca-dependent insertion of lipophilic tail into plasma membrane that permits efflux of intracellular K+
daptomycin
inhibits DNA, RNA, and protein synthesis
daptomycin
causes membrane depolarization - loss of membrane potential
daptomycin
inactivated by surfactant; not effective against pneumonia
daptomycin
Therapeutic Uses: MRSA, VRSA; bacteremia and right-sided endocarditis (MRSA)
daptomycin
Adverse reaction - myopathy (monitor CPK)
daptomycin
polymyxins
colistin
polymyxin B
MOA: binds to neg-charged LPS in outer membrane of G- bacteria
polymixins
hydrophobic tail disrupts both outer and plasma membranes; increases membrane permeability
polymixins
polymyxin formulation for topical and oral use
colistin sulfate
polymyxin formulation for parenteral use
colistimethate (prodrug of colistin)
treatment of last resort for serious MDR G- bacterial infections (ESCAPE pathogens)
colistimethate
topical for infections of skin, mucous membranes, eye and ear
colistin sulfate, polymyxin B
