Physiology of the Cough and Therapeutic Strategy
Coughing is an essential protective reflex triggered in response to irritation of the respiratory tract mucosa. Its physiological purpose is to expel irritating agents, whether excessive bronchial secretions (sputum) or foreign bodies.
To understand the pharmacodynamics of antitussives, it is important to know the structure of the reflex arc:
- Afferent pathway (input): Begins with sensory receptors. Impulses from the larynx travel via glossopharyngeal nerve fibers (n. glossopharyngeus), and from the bronchi via sensory fibers of the vagus nerve (n. vagus).
- Central component: The signal reaches the medulla oblongata, stimulating the cough center.
- Efferent pathway (output): Impulses travel via somatic motor fibers from the brain to the respiratory muscles (diaphragm and intercostal muscles). Their abrupt contraction results in a forced expiration.
Pharmacotherapeutic strategy depends strictly on the clinical presentation:
- Productive ("wet") cough: Accompanies inflammatory conditions with hypersecretion (bronchitis, tracheitis). It serves a protective function by draining the bronchi and accelerating recovery. Suppressing this type of cough is contraindicated; expectorants should be used instead.
- Non-productive ("dry") cough: Characteristic of pleurisy, neoplasms, and chronic inflammation. The protective function is lost; the symptom merely exhausts the patient and disrupts nocturnal sleep. In this case, antitussives are indicated.
Classification of Drugs
Based on their site and mechanism of action, antitussives are divided into two major groups:
- Centrally acting agents (suppress the cough center in the brain):
- Narcotic (opioid) agents: codeine, ethylmorphine.
- Non-narcotic agents: glaucine, oxeladin.
- Peripherally acting agents (reduce the sensitivity of respiratory tract receptors):
- Representative agent: prenoxdiazine.
Centrally Acting Agents
Narcotic Antitussives These include opium alkaloids and their derivatives. Their mechanism of action involves stimulation of opioid receptors in the medulla oblongata, leading to decreased excitability of the cough center.
- Codeine (methylmorphine). Available as a base or phosphate. It exhibits pronounced antitussive and analgesic effects. In therapeutic doses, respiratory center depression is minimal (there is no direct correlation between cough suppression and respiratory depression). It is frequently included in combination medications.
- Ethylmorphine (dionine). A semi-synthetic morphine derivative. Administered orally for dry, exhausting coughs.
Risks: Stimulation of opioid receptors in the mesolimbic and mesocortical systems induces euphoria, resulting in a high abuse potential (risk of dependence). Systematic use leads to constipation. Dispensing of these agents is strictly regulated.
Non-Narcotic Antitussives These also directly suppress the cough center but do not activate the opioidergic system. Consequently, they do not cause dependence and have a lesser effect on respiration.
- Glaucine (Glauvent). A plant alkaloid derived from Glaucium flavum. Well absorbed, with an onset of action in 30 minutes and a duration of about 8 hours. Side effects include hypotension, dizziness, and nausea.
- Oxeladin (Tusuprex). A synthetic agent with a profile similar to glaucine. Rapidly and completely absorbed, with peak plasma concentrations reached in 4–6 hours.
Peripherally Acting Agents
These agents operate outside the central nervous system, acting directly on the respiratory tract.
- Prenoxdiazine (Libexin). Possesses a triple mechanism:
- Local anesthetic effect: Reduces the sensitivity of bronchial mucosal receptors, preventing reflex initiation.
- Bronchodilatory effect: Causes bronchodilation.
- Anti-inflammatory effect.
The drug does not affect the CNS, and its duration of action is 3–4 hours. Due to its local anesthetic property, a specific side effect is tongue numbness. Dry mouth and diarrhea are also possible.