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Quinolone - Sulfonamides 2
Quinolone - Sulfonamides 2
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Quinolones
A. First quinolone, naladixic acid, was a byproduct of
chloroquine synthesis (an antimalarial drug)
B. Current drugs are fluorinated 4-quinolones
(Fluoroquinolones)
Effect on Microbes
spectrum of coverage
1. Broad (both G+ and G-)
2. Newer fluoroquinolones work against anaerobes
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Mechanism of action
Mechanism of resistance
1. mutations in chromosomal genes for gyrase and
topoisomerase IV that result in proteins with less binding
potential
2. active transport out of cell with efflux pumps
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Pharmacokinetics of Quinolones
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C. Excretion
1. Most are cleared by the kidney so adjust dosage
for renal patients
2. Exceptions are pefloxacin and moxifloxacin which
are metabolized by the liver; do not use in
patients with hepatic failure
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Pharmacology of Select Quinolones
1. Ciprofoxacin: 2nd
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Ciprofoxacin: 2nd generation
• It is the most potent of the fuoroquinolones for
Pseudomonas aeruginosa
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Ciprofloxacin-food interactions
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3. Levofloxacin: 3rd
• Is a broad spectrum
• It can be used in the treatment of
prostatitis due to E. coli and of STDs.
• It may be used in patients with gonorrhea.
• Utilized in a wide range of infections,
including: skin infections, pneumonia &
S. pneumoniae respiratory infections
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4. Moxifloxacin: 4th
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Therapeutic Uses of quinolones
A. Urinary tract infections
B. Prostatitis
C. STD’s
D. Gastrointestinal and abdominal infections
E. Respiratory tract infections
F. Bone, joint, and soft tissue infections
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Toxicity & Contraindications
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Sulfonamides
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Effect on Microbes
B. mechanism of action
1. competitive inhibitors of dihydropteroate synthase
2. bacteria cannot synthesize their own folic acid
3. bacteriostatic in most tissues, can be cidal in urine
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Pharmacokinetics of the Sulfonamides
A. Absorbance
70-100% of an oral dose is absorbed from the
gastrointestinal tract (mostly from small intestine, but also
from stomach)
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C. Excretion
1. eliminated mostly by the kidneys into the urine,
partially unchanged, partially metabolized
2. some drugs become insoluble in acid urine and
may precipitate
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Classes of Sulfonamides:
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B. Poorly absorbed sulfonamides (sulfasalazine)
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Toxicity & Contraindications
A. urinary tract
sulfamethoxazole and sulfadiazine can crystallize in acid
urine or in dehydrated patients causing urinary obstructions
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CO-TRIMOXAZOLE
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Resistance
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Urinary Tract Antiseptics/Antimicrobials
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• These infections may be treated with any one of a
group of agents called urinary tract antiseptics,
including:
– Methenamine
– Nitrofurantoin
– Nalidixic acid
• These drugs do not achieve antibacterial levels in the
circulation, but because they are concentrated in the
urine
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B. Nitrofurantoin
• It is less commonly employed for treating UTIs because of
its narrow antimicrobial spectrum and its toxicity.
• Sensitive bacteria reduce the drug to an active agent that
inhibits various enzymes and damages DNA.
• Spectrum:
– E. coli, but other common urinary tract gram-negative bacteria
may be resistant.
– Gram-positive cocci.
• Adverse effects include:
gastrointestinal disturbances
neurologic problems.
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