Classification and Structure-Activity Relationship
The quinolone derivative group is divided into two major subgroups based on chemical structure—specifically, the presence or absence of a fluorine atom. This structural feature directly determines the spectrum of antibacterial action and the pharmacokinetics of the drugs.
Structure-activity relationship (SAR) analysis shows that maximum antibacterial efficacy is achieved with a piperazine ring (substituted or unsubstituted) at position 7 of the quinolone core, and a fluorine atom at position 6. Compounds lacking a fluorine atom at position 6 are classified as non-fluorinated (classic) quinolones.
The first-generation drugs of this group include:
- Nalidixic acid (trade names: Negram) — the prototype of the group.
- Oxolinic acid and pipemidic acid (such as Palin) — structural analogues with higher pharmacological activity compared to nalidixic acid.
Mechanism and Spectrum of Antibacterial Action
All drugs in this group are characterized by a bactericidal mechanism of action. Their primary pharmacological target is the bacterial enzyme DNA gyrase. Inhibition of this enzyme disrupts bacterial DNA replication, leading to microbial cell death.
The spectrum of activity of classic quinolones is relatively narrow and covers predominantly Gram-negative (Gr-) flora. These drugs are effective against:
- Escherichia coli;
- Shigella and Salmonella species;
- Klebsiella species (including Klebsiella pneumoniae);
- Proteus species.
Important clinical exception: non-fluorinated quinolones have absolutely no activity against Pseudomonas aeruginosa. Furthermore, a significant disadvantage of the entire class is the rapid development of secondary microbial resistance during therapy.
Pharmacokinetics and Clinical Application
The prototype of the group—nalidixic acid—is well absorbed from the gastrointestinal tract when administered orally (per os). Absorption is particularly efficient when the drug is taken on an empty stomach.
A key feature of the distribution of non-fluorinated quinolones is their inability to accumulate in body tissues (such as lung tissue or cerebrospinal fluid). High therapeutic concentrations are achieved exclusively in urine. Approximately 80% of the administered dose is excreted unchanged by the kidneys. Due to rapid elimination, these drugs require a frequent dosing regimen—4 times daily.
Indications for use are strictly limited by their pharmacokinetics:
- Genitourinary tract infections (cystitis, pyelitis, pyelonephritis, urethritis, prostatitis);
- Prophylaxis of infectious complications during surgical procedures on the kidneys, ureters, and urinary bladder;
- Intestinal infections.
Safety Profile and Adverse Effects
Despite their narrow scope of application, first-generation drugs can cause a range of adverse effects across various body systems. In clinical practice, it is important to consider the following adverse reactions:
- Gastrointestinal tract: dyspeptic symptoms, and in rare cases, bleeding.
- Central nervous system: psychomotor agitation, seizures.
- Special senses: specific visual disturbances, including altered color perception.
- Hepatobiliary system: liver dysfunction, development of cholestatic jaundice and hepatitis.
- Blood and lymphatic system: hematological shifts such as thrombocytopenia and leukopenia.
- Skin and immune system: allergic reactions and photosensitization.