Centrally Active Antitussive Agents

Cough is a useful physiological mechanism that serves to clear the respiratory passages of foreign material and excess secretions and should not be suppressed indiscriminately. Chronic cough sometimes can prevent rest or sleep or contribute to fatigue, especially in elderly patients. In such situations, the physician should use a drug that will reduce the frequency or intensity of the coughing. The cough reflex is complex, involving the central and peripheral nervous systems and the smooth muscle of the bronchial tree. It has been suggested that irritation of the bronchial mucosa causes bronchoconstriction, which, in turn, stimulates cough receptors (which probably represent a specialized type of stretch receptor) located in tracheobronchial passages. Afferent conduction from these receptors is via the vagus nerve; central components of the reflex probably include several mechanisms or centers that are distinct from the mechanisms involved in the regulation of respiration.

The opioid analgesics discussed earlier (codeine and hydrocodone are the opioids most commonly used to suppress cough), as well as a number of nonopioid agents reduce cough as a result of their central actions. Cough suppression often occurs with lower doses of opioids than those needed for analgesia. A 10- or 20-mg oral dose of codeine, although ineffective for analgesia, produces a demonstrable antitussive effect, and higher doses produce even more suppression of chronic cough.

DEXTROMETHORPHAN Dextromethorphan (D-3-methoxy-N-methylmorphinan) is the D-isomer of the codeine analog methorphan; unlike the L-isomer, it has no analgesic or addictive properties and does not act through opioid receptors. The drug acts centrally to elevate the threshold for coughing; its potency is nearly equal to that of codeine, but it produces fewer subjective and GI side effects. In therapeutic dosages, the drug does not inhibit ciliary activity, and its antitussive effects persist for 5-6 hours. Its toxicity is low, but extremely high doses may produce CNS depression.

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