Quinolones-Antibacterial Activity

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ANTIBACTERIAL ACTIVITY

• Wide spectrum of activity vs aerobic bacteria.
• Newer 3rd and 4th generation FQs have very good
  activity against gram-positive organisms.
• Inactive against most anaerobic bacteria.

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MECHANISM

• In gram- bacteria, DNA gyrase is the primary
  target.
• In gram bacteria, topoisomerase IV is the
  primary target (newer quinolones).

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PHARMACOKINETICS

• Rapidly absorbed from the GI tract.
• Widely distributed in body tissues (except CNS).
• Excreted via the kidney both unchanged and as
  metabolites.

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PHARMACOKINETICS

• Newer FQs have longer serum half-lives than
  ciprofloxacin allowing for once daily dosing.

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THERAPEUTIC USES
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http/kidneyfound.
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Strept. pneumoniae
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THERAPEUTIC USES

• Gastrointestinal infections.

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CONTRAINDICATIONS

• Children less than 18 years old and pregnant or
  nursing women.

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DRUG INTERACTIONS

• Quinolones divalent and trivalent cations

IMPAIRED ABSORPTION OF QUINOLONES
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COMPARISON OF 2ND GEN.VS 3TH AND 4 TH GEN. FQS
Mechanism of action Therapeutic uses Adverse Effects
Ciprofloxacin- Inhibits DNA Gyrase predominantly UTIs, Bone, joint and soft tissue infections GI, CNS, Photosensitivity
Gatifloxacin-Inhibits Topoisomerase IV predominantly Community acquired pneumonia GI, CNS Phototoxicity and EKG
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MECHANISM OF ACTION

• Bactericidal.
• Inhibit DNA gyrase (topoisomerase II).
• Inhibition of topoisomerase IV (newer FQs).

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MECHANISM

• DNA gyrase is the primary target. It is
  responsible for the continuous introduction of
  negative supercoils into DNA. This is an
  ATP-dependent enzyme requiring that both strands
  of the DNA be cut to permit passage of a segment
  of DNA thru a break, which is then resealed.

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ADVERSE EFFECTS

• GI effects are common (mild nausea, upper GI
  discomfort).

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ADVERSE EFFECTS

• CNS effects such as headache, restlessness, and
  dizziness. High doses may produce convulsions.

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ADVERSE EFFECTS

• Hypersensitivity reactions---rashes including
  photosensitivity reactions.

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ADVERSE EFFECTS

• Prolongation of the QT interval with possible
  serious arrhythmias.
• Hypoglycemia and hyperglycemia.

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His/Purk. Ventricle
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Prolong QT Interval
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