Codeine, Dextromethorphan, Cloperastine and Levodropropizine

Mechanism

🧠 Codeine / Dextromethorphan

• Class: Central action cough suppressants.
• Mechanism: They selectively depress the cough center in the medulla oblongata.
• Codeine is a weak opioid agonist; Dextromethorphan is a non-opioid NMDA receptor antagonist with no analgesic effects.

⚡ Levodropropizine

• Class: Peripheral action cough suppressant.
• Mechanism: Inhibits the release of sensory neuropeptides from C Fibers.
• It does not cross the blood-brain barrier, lacking sedative or depressant effects on the respiratory center.

Mechanism of action

The cough reflex is initiated by the activation of rapidly adapting mechanoreceptors and chemoreceptors located in the laryngeal, tracheal and bronchial mucosa. Afferent impulses travel through the vagus nerve to the bulbar cough center.

Codeine: Acts as an agonist of the µ-type opioid receptors located in the gastric bulbar vomiting and cough center. It generally decreases the threshold of afferent response to mechanical or chemical stimuli.

Dextromethorphan: Left-handed enantiomer of an opioid derivative without relevant affinity for µ receptors. It acts centrally as an antagonist of NMDA-type glutamate receptors and as an agonist of brain Sigma-1 receptors, blocking reflex transmission in the cough center.

Levodropropizine: It is the levorotatory isomer of dropropizine. It exerts an inhibitory modulation on the release of inflammatory neuropeptides (substance P, neurokinin A) by the pulmonary nociceptive sensory C Fibers, attenuating the afferent transmission of cough purely peripherally.

Indicators and dose

Dosage and Clinical Adjustment

• Codeine phosphate (Syrup or tablets): 15 mg to 30 mg orally every 6 to 8 hours as needed.
• Dextromethorphan hydrobromide: 15 mg to 30 mg orally every 6 or 8 hours. Maximum daily dose of 120 mg.
• Levodropropizine: 60 mg orally three times a day on an empty stomach.

Security

Contraindications of central opioids

• Bronchial asthma and severe COPD: Codeine depresses the bulbar respiratory drive and inhibits the protective lung expectoration reflex, which can induce mucus retention and pulmonary atelectasis.
• Pediatric patients under 12 years of age (Codeine): It is strictly contraindicated due to the unpredictable risk of severe respiratory depression and death in patients presenting with the CYP2D6 ultra-rapid metabolizer genotype (which rapidly converts codeine to active morphine in plasma).