Antibacterial Agents IV: DNA Function Inhibitors Flashcards
What drugs interact with Metronidazole?
inhibitors and inducers of CYP450
Tx for Giardia lamblia giardiasis?
Metronidazole
Give an example of resistance due to escape.
Sulfonamides are noncompetitively antagonized by methionine, homocysteine, serine, purines, and thymine
What are the adverse rxns for Nitrofurantoin use?
GI upset, occasionally hypersensitivity rxns, neuropathy, birth defects
Tx of Pseudomonas aeruginosa burn infections?
topical silver sulfadiazine
Why are Sulfonamides selectively toxic?
humans don’t synthesize their own folic acid
Tx of Plasmodium (resistant) malaria?
sulfadoxine + pyrimethamime
How do the Sulfonamides work?
they’re analogs of PABA that competitively inhibit dihydropteroate synthetase (enzyme used to synthesize folic acid)
What drug can predispose neonates to kernicterus? Why?
Sulfonamides; its protein binding displaces bilirubin
Tx of MRSA skin infections?
TMP/SMX
Name the Abx that inhibit DNA function (4).
- fluoroquinolones (-floxacin) 2. Nitrofurantoin 3. Metronidazole 4. Sulfonamides (Sulfa-)
Sulfonamides have synergy with _____, which inhibits dihydrofolate reductase (DHFR).
trimethoprim (TMP)
What is the tx for Staph. aureus (MSSA) skin infections?
levofloxacin, moxifloxacin, gemifloxacin (respiratory quinolones)
Inhibitors of _____ have increased potential for human toxicity.
dihydrofolic acid reductase
Tx for Entamoeba histolytica amebiasis?
Metronidazole
Tx for C. diff diarrhea, pseudomembranous colitis?
Metronidazole
Sulfonamides have synergy with trimethoprim (TMP), which inhibits _____.
dihydrofolate reductase (DHFR)
Name the 4 fluoroquinolones.
- ciprofloxacin 2. levofloxacin 3. gemifloxacin 4. moxifloxacin
Name 3 methods of resistance that Sulfonamides use?
- acquired (increased PABA or altered DHPS) 2. escape (end products from pus) 3. natural (no folic acid req = not susceptible)
Tx for Clost. perfringens gas gangrene, food poisoning?
Metronidazole
Tx for Trichomonas vaginalis trichomoniasis?
Metronidazole
What is the mechanism of action of the fluoroquinolones?
inhibits DNA gyrase and topo IV
Tx for Helicobacter pylori gastritis, peptic ulcers?
Metronidazole
Tx of U.C.?
sulfasalazine
Tx of Moraxella catarrhalis otitis media?
TMP/SMX
What are the adverse rxns for the fluoroquinolones?
GI upset, CNS issues, QT elongation, skin rashes, abn glucose, tendon rupture, arthropathies
What is TMX/SMX?
trimethoprim/sulfamethoxazole combo drug (sulfonamide class)
Tx of Norcardia nocardiosis?
sulfisoxazole, sulfadiazine
What is the tx for Moraxella catarrhalis sinusitis, bronchitis?
levofloxacin
What is the tx for Chlamydia trachoma, C.A. pneumonia, urethritis?
moxifloxacin, gemifloxacin
Why do antacids negatively affect fluoroquinolones?
they reduce oral absorption of cipro
What is the tx for Myco. pneumoniae C.A. pneumonia?
moxifloxacin, gemifloxacin
Why do Sulfonamides have a delayed onset of action?
the folate stores have to be depleted
How is Metronidazole absorbed, distributed, and metabolized?
GI not affected by food; good dist including CSF and bone; hepatic metabolism
What is the tx for Bacilllis anthracis anthrax?
ciprofloxacin
Sulfonamides are ____ spectrum Abx.
broad
How are fluoroquinolones absorbed, distributed, metabolized, and excreted?
A: orally or parenterally D: into most tissues, including bone, fat, muscle, prostate, repro organs, and urine M: minimal E: kidney
____ should cease until 24-48 hours post Metronidazole therapy because _____.
Breast feeding; it can be carcinogenic
Is Metronidazole bactericidal or bacteriostatic?
bactericidal
Combination use of Sulfonamides + trimethoprim (TMP) is BACTERIOSTATIC/BACTERICIDAL.
BACTERICIDAL
Trimethoprim (TMP), used with sulfonamides, is also used in combination with _____.
sulfamethoxazole
What is Nitrofurantoin used for?
URIs
Are Sulfonamides bacteriostatic or bactericidal?
bacteriostatic
What is the tx for Strep. pneumoniae pneumonia, chronic bronchitis, acute sinusitis?
levofloxacin, moxifloxacin, gemifloxacin (respiratory quinolones)
Which drug is contraindicated in pregnancy and in children under 18yo?
fluoroquinolones
Why is Nitrofurantoin selectively toxic?
mammalian enzymes don’t reduce Nitrofurantoin as rapidly
What are the adverse rxns for Metronidazole?
nausea, dry mouth, headache, metallic taste, candida superinfections
Where do bacteria obtain methionine, homocysteine, serine, purines, and thymine used to escape (resistance)?
from pus
How does resistance to fluoroquinolones occur, and how often?
point mutations in the binding site on DNA gyrase, or a change in drug permeability- plasma mediated; 10^7-10^9 organisms
What is the absorption, distribution, metabolism, and excretion of the sulfonamides?
well absorbed from the GI tract on an empty stomach but with plenty of fluids; distributed widely in body water including pleural, ocular, synovial fluid, and CSF- crosses placenta; N-acetylated to inactive compound; excreted by kidney with increasing pH and in breast milk
Which drugs interact with the fluoroquinolones?
theophylline (esp with ciprofloxacin), antacids (with cipro)
Tx of Shigella diarrhea?
TMP/SMX (preferred over quinolones in children)
What is the mechanism of action for Metronidazole?
transformed into a reactive nitro radical anion that breaks DNA and inhibits replication
What happens to the urine in Nitrofurantoin use?
it turns brown
Tx of Klebsiella, Proteus, Enterobacter UTIs?
TMP/SMX
What is the tx for Pseudomonas aeruginosa, E. coli, Klebsiella, Serratia, Proteus, Enterobacter, Shigella, Salmonella UTIs and traveler’s diarrhea?
ciprofloxacin, levofloxacin
How does Nitrofurantoin work?
reduced by bacterial enzymes to intermediates that damage bacterial DNA
Is Nitrofurantoin bacteriostatic or bactericidal?
both, depending on the conc
What is the tx for Richettsia rocky mountain spotted fever, Q fever?
moxifloxacin, gemifloxacin
What are the 6 adverse rxns with Sulfonamides?
- sensitization rxns 2. renal damage 3. hemolytic anemia in G6PD pts 4. GI upset 5. category C in pregnancy 6. drug interactions (bilirubin, oral anticoagulants, sulfonylurea hypoglycemic agents)
______ have synergy with trimethoprim (TMP), which inhibits dihydrofolate reductase (DHFR).
Sulfonamides
Tx for Bacteriodes fragilis intraabd and brain abscesses?
Metronidazole
How is Nitrofurantoin absorbed and excreted?
complete from GI tract; into urine via filtration and excretion
What is the tx for H. influenzae lower RI, pneumonia?
moxifloxacin, levofloxacin
Tx of Staph. aureus conjunctivitis?
sulfacetamide
What should be avoided during Metronidazole therapy?
alcohol, pregnancy, breast-feeding
Tx of Chlamydia trachoma, C.A. pneumonia, urethritis?
TMP/SMX
Choose: Fluoroquinolones are BACTERICIDAL/BACTERIOSTATIC.
bactericidal
Tx of Pneumocystis carinii pneumonia?
TMP/SMX