1. Antimicrobials - Quinolones & Fluoroquinolones Antimicrobials - Quinolones & Fluoroquinolones Pharmacology -1 DSX 215 DSX 215 Dr/ Abdulaziz Saeedan Pharmacy College Pharmacy College 1

2. Quinolones and Fluoroquinolones The quinolones are a family of synthetic antibiotics. nalidixic acid The parent of this group is nalidixic acid. Nalidixic acid Nalidixic acid is a synthetic narrow spectrum antibiotic. pseudomonas ► Active against gram-negative bacteria except pseudomonas species. the fluoroquinolones The addition of fluorine atom to the original quinolone antibiotics produced a new class of drugs, the fluoroquinolones Fluoroquinolones are synthetic broad-spectrum antibiotics. pseudomonas ► Active against gram-negative bacteria, especially pseudomonas species in addition to gram-positive bacteria. Due to the excellent activity and safety of fluoroquinolones, they become alternatives to penicillin in the treatment of various infections. 2

3. Fluoroquinolones - Antimicrobial Spectrum Fluoroquinolones are broad-spectrum antibiotics. ► They are effective against many different types of bacteria, both Gram-negative including pseudomonas and Gram-positive.  Pharmacokinetics: 1- Absorption 1- Absorption. Well absorbed after oral administration (50% to >95%). ► This degree of absorption result in high blood levels comparable to their intravenous preparations. ► Thus, oral preparations should be used if the patient is able to take oral medications. 3

4. 2- Distribution 2- Distribution. Distributed into urine, kidney, prostate tissue, lung, stool, skin. ► So fluoroquinolones are very useful for treatment of infections in these areas of the body. 3- Elimination 3- Elimination. The kidneys are an important route of elimination. Fluoroquinolones – Advantages Ease of administration Excellent oral absorption Prolonged half-lives ► daily or twice daily dosing Excellent tissue penetration ► widely distributed 4

5. Fluoroquinolones - Classification  First Generation. ► Nalidixic acid Antimicrobial Spectrum: Antimicrobial Spectrum: Gram-negative bacteria (but not Pseudomonas species) Used only for uncomplicated urinary tract infections. Nalidixic acid require more frequent dosing than the newer quinolones.  Second Generation. ► Norfloxacin, Lomefloxacin, Ciprofloxacin, Ofloxacin Ciprofloxacin and ofloxacin are the most widely used second-generation quinolones because of their availability in oral and intravenous formulations Antimicrobial Spectrum: Antimicrobial Spectrum: Gram-negative bacteria (including Pseudomonas species), some gram-positive bacteria (including Staphylococcus aureus but not Streptococcus pneumoniae). Ciprofloxacin is the most potent fluoroquinolone against Pseudomonas. Used for uncomplicated and complicated urinary tract infections, pyelonephritis, prostatitis, skin and soft tissue infections. 5

6.  Third Generation. ► Levofloxacin, Gatifloxacin, Sparfloxacin, Moxifloxacin. Antimicrobial Spectrum: Antimicrobial Spectrum: The same as second-generation agents plus expanded activity against gram-positive bacteria (Streptococcus pneumoniae). Used for bronchitis and pneumonia  Fourth Generation. ► Trovafloxacin Antimicrobial Spectrum: Antimicrobial Spectrum: Same as for third-generation agents plus anaerobic bacteria. The same uses of first-, second- and third-generation agents. 6

7. Fluoroquinolones– Action & Mechanism of Action  Action: Quinolones and fluoroquinolones are bacteriocidal drugs, meaning that they kill bacteria.  MOA: Quinolones and fluoroquinolones inhibit bacterial DNA-gyrase enzyme which is necessary for supercoiling and replication of DNA. This action results in damage of bacterial DNA and bacterial cell death. Thus, fluoroquinolones are bactericidal agents.  NOTE: Fluoroquinolones are the only class of antimicrobial agents that are direct inhibitors of bacterial DNA synthesis. Gyrase is an essential enzyme in prokaryotes but it is not found in eukaryotes, So fluoroquinolones do not interfere with human DNA.. 7

8. Fluoroquinolones - Side Effects/Precautions 1- The most common adverse effects of fluoroquinolones are nausea, vomiting and diarrhea, which occur in 3 -6 % of patients. 2- Other more serious but less common side effects are CNS effects (headache, confusion and dizziness). 3- Fluoroquinolones are not recommended for use in patients younger than 18 years. ► They can affect the growth of bones, teeth, and cartilage. 4- Fluoroquinolones are not recommended for pregnant or feeding women. ► They have the potential to cause embryocidal effects. ► These agents are also excreted in breast milk. 8

9. Fluoroquinolones - indications All of the fluoroquinolones are effective in treating urinary tract infections caused by susceptible organisms. Prostatitis ► They are the first-line treatment of uncomplicated or complicated cystitis. Lower respiratory tract infections ► bronchitis, pneumonia Acute sinusitis Diarrhoea due to E.coli, Salmonellosis, Shiegellae, Skin and soft tissue infections 9