Mechanism of Action and Rational Drug Design
The influenza virus attaches to respiratory epithelial cells via hemagglutinin, which binds to sialic acid on the cell surface. After new viral particles assemble inside the cell, the enzyme neuraminidase comes into play. It cleaves terminal sialic acids, allowing virions to detach from the membrane, penetrate the mucus layer, and infect neighboring cells.
Drugs in this class (Oseltamivirum, Zanamivirum) were developed using rational drug design. By studying the structure of the enzyme-sialic acid complex, scientists synthesized chemical analogs of sialic acid. These analogs bind to the active site of neuraminidase more tightly than the natural substrate and alter its conformation.
As a result, enzyme function is blocked:
- The release of new virions from the infected cell is impaired.
- The virus cannot penetrate the mucus barrier.
- The spread of infection through the respiratory tract is halted.
Outcome: Viral replication is limited to a single cycle, stopping the development of a full-scale infection. Furthermore, these drugs exhibit high selectivity—they inhibit viral neuraminidase at concentrations 100 times lower than those required to inhibit mammalian homologous enzymes.
Pharmacological Profile of Zanamivir
Zanamivir (trade name Relenza) is the first representative of this class, active against influenza A and B viruses. It is used for the prevention and treatment of influenza in adults and children aged 5 years and older.
Its primary pharmacokinetic feature is extremely low oral bioavailability (less than 5%). Consequently, it is administered exclusively via local inhalation. With this route of administration:
- About 80% of the drug is deposited in the oral cavity and pharynx.
- Approximately 15% reaches the lower respiratory tract.
- Only 5–20% of the dose is absorbed into the systemic circulation.
Elimination occurs via the kidneys, with the drug excreted unchanged.
Safety Profile: Inhalation can trigger adverse respiratory effects, ranging from breathing difficulties to bronchospasm. Allergic reactions (urticaria, laryngeal edema) occur very rarely. Due to the risk of bronchospasm, zanamivir is not recommended for patients with chronic respiratory diseases, primarily bronchial asthma and COPD.
Pharmacokinetics and Administration of Oseltamivir
Oseltamivir is a second-generation drug with improved pharmacokinetics. It is a prodrug and is well absorbed when taken orally (the bioavailability of the active moiety is approximately 80%).
In the body, bioactivation occurs via hepatic and intestinal esterases, converting the drug into its active metabolite (oseltamivir carboxylate). It is excreted unchanged by the kidneys, with a half-life of 6–10 hours.
The drug is indicated for the treatment and prevention of influenza A and B in adults and children over 1 year of age (for children under 12, the dosage is calculated based on body weight). A key condition for efficacy is initiating therapy within the first 48 hours after symptom onset.
Side Effects:
- Dyspepsia: Nausea, vomiting, abdominal pain. These are related to the local irritant effect on the gastrointestinal mucosa. Symptoms are usually transient and resolve spontaneously within 1–2 days. To reduce their severity, the drug should be taken with food.
- Neurological disorders: Headache, dizziness, and insomnia may occur.