Quinolones & Folic Acid Antagonists Flashcards

Flashcards covering Quinolones, Folic Acid Antagonists, and related antimicrobials.

Quinolones Mechanism of Action

Inhibit DNA gyrase (topoisomerase II) → inhibit DNA replication → cell death. Also inhibits topoisomerase IV → ↓bacterial division.

Quinolones Spectrum

Effective against both Gram (-) and Gram (+) bacteria.

1st Generation Quinolones

Non-fluorinated; used only in urinary tract infections with G-ve bacilli. Rapid resistance limits use.

2nd-4th Generation Quinolones

Newer Fluorinated derivatives achieving systemic levels→ used in systemic infections. More potent, broader spectrum, better safety profile.

Ciprofloxacin Spectrum

Gram-ve (including Pseudomonas species), Some G +ve, Chlamydia & Mycoplasma pneumoniae.

Levofloxacin Spectrum

Effective against G -ve, Effective on G +ve (including Strept pneumoniae), Chlamydia & Mycoplasma pneumoniae.

Moxifloxacin Spectrum

Same as 3rd generation (but not effective on Pseudomonas), Anaerobes.

Fluoroquinolones Absorption Interference

↓ absorption if administrated with: Sucralfate, antacids (Al or Mg), Dietary supplements with Fe, zn or Ca.

Fluoroquinolones Distribution & Elimination

High levels in bone, urine and kidney. Excreted renally (Except Moxifloxacin in bile).

Fluoroquinolones Adverse Reactions

Gastrointestinal issues, Central nervous system effects, Phototoxicity, Connective tissue issues.

Fluoroquinolones Contraindications

Pregnancy & lactating female, Children < 18 years, Elderly >60 yrs.

Folate Antagonists Mechanism (Sulfonamides)

Structural analogs of PABA, compete with it for the enzyme (dihydropteroate synthetase) → inhibition of bacterial dihydrofolic acid synthesis → inhibition of DNA & RNA synthesis.

Folate Antagonists Mechanism (Trimethoprim)

In bacteria & human Dihydro- folate Reductase.

Sulfonamides Pharmacokinetics

Well absorbed orally (Except Sulfasalazine), cross the placenta & BBB. They are acetylated in the liver → toxic metabolite → precipitate at neutral or acidic pH → crystalluria → “stone formation ” in kidneys. Renal elimination.

Sulfonamides Adverse Reactions

Crystalluria, Hypersensitivity, Hemopoietic disturbance, Kernicterus, Drug interaction.

Trimethoprim Adverse Effects

Produce manifestations of folic acid deficiency as megaloblastic anemia, especially in pregnant women.

Cotrimoxazole Advantages

Synergistic combination, Less and delayed bacterial resistance, More potent (Bactericidal) & wider-spectrum.

Metronidazole Mechanism of Action

• Inhibits proteins and DNA, resulting in cell death.

Metronidazole Adverse Effects

Nausea, vomiting, epigastric distress and abdominal cramps, Metallic Taste (Unpleasant), disulfiram-like effect with alcohol.

Clostridium difficile-induced diarrhea Associations

Associated with Clindamycin and tetracycline use. Treat with oral Vancomycin.

Red Man Syndrome

Caused by rapid IV infusion of vancomycin. Avoid by slow infusion.