Quinolones: Exploring the Mechanism of Action and Generations

Quinolones: Exploring the Mechanism of Action and Generations

Quinolones are a group of broad-spectrum antibiotics used to treat various infections. This group was developed based on the basic structure of Nalidixic acid, the first drug discovered within the Quinolone family.

Mechanism of Action:

• Inhibition of DNA gyrase (Topoisomerase II) in Gram-negative bacteria and Topoisomerase IV in Gram-positive bacteria: This is the primary mechanism of Quinolones, preventing bacterial DNA replication.

Classification and Generations of Quinolones:

• Generation I:

• Nalidixic acid: The first drug in the Quinolone family, with a narrow antibacterial spectrum.

• Generation II:

• Ciprofloxacin, Ofloxacin, Norfloxacin: Wider antibacterial spectrum compared to the first generation.

• Generation III:

• Levofloxacin, Sparfloxacin, Gatifloxacin, Gemifloxacin: More effective, broader antibacterial spectrum, and longer duration of action.

• Generation IV:

• Moxifloxacin, Trovafloxacin,…: Broadest antibacterial spectrum, particularly effective against aerobic Gram-negative bacteria.

Structure and Effects of Quinolones:

• C=O group at position 4 and COOH at position 3: These two functional groups create the primary effect of Quinolones, which also contribute to side effects.

• Position 1 replaced with short alkyl (methyl, ethyl, cyclopropyl): Modifications at position 1 enhance antibacterial activity.

• R1: piperazin R2: C2H5-: Quinolone efficacy is enhanced with the structure shown in the R1 and R2 substituents.

Precautions When Using Quinolones:

• Not to be used in newborns and children under 16 years old.

• Possible interactions with other drugs:

• Antacids, multivitamins, Fe, Zn, Ca: Form chelates with Quinolones, reducing absorption.

• Anticancer drugs: Decrease Quinolone concentration in plasma.

• Ciprofloxacin: Can reduce metabolism and increase the half-life of Diazepam, decrease liver detoxification of caffeine and theophylline.

• Foscarnet (anti-VR drug): Using Foscarnet with Ciprofloxacin increases the risk of seizures.

Newer Generations of Quinolones:

• Broader antibacterial spectrum: Newer generations of Quinolones are developed with a broader antibacterial spectrum, particularly against aerobic Gram-negative bacteria.

• Reduced side effects: Newer generations have fewer side effects and also reduce bacterial resistance.

Conclusion:

Quinolones are an important group of antibiotics with diverse applications in treating infections. Understanding the mechanism of action, classification, structure, and precautions when using them will lead to more effective and safer treatment.