Currently available antitussives
Introduction
Cough is among the most common complaints for which medical attention is sought [1]. Acute cough, most frequently due to viral upper respiratory tract infection (URTI), generates huge financial expenditure on prescription and over-the-counter (OTC) cough and cold preparations worldwide. Unfortunately, most currently available cough suppressants have not demonstrated antitussive efficacy in adequately performed clinical trials of acute cough. This includes non-prescription (OTC) products [2] as well as central cough suppressants such as codeine [3].
The goal of management of chronic cough is to address its underlying cause. Multiple prospective studies have shown that adequate treatment of the specific aetiologies of chronic cough (upper airway cough syndrome [formerly known as post-nasal drip syndrome]; asthma; non-asthmatic eosinophilic bronchitis; and, gastroesophageal reflux disease) is successful in the vast majority of cases [4]. However, in certain circumstances, the underlying cause of chronic cough is known but not treatable (i.e. endobronchial lung cancer, pulmonary fibrosis). Nonspecific (symptomatic) cough suppressant therapy would be appropriate in such situations but, alas, presently available antitussives are often inadequate due to limited efficacy, intolerable side effects or both [5].
The aim of this review is to list and evaluate antitussive agents currently available to practitioners. To structure the discussion, drugs have been classified as those approved as antitussives, and those approved for other indications, but that may also have cough suppressant action. Within each group, agents have been distinguished as those thought to act by a central mechanism or a peripheral mechanism (Table 1).
Section snippets
Centrally acting
Centrally acting antitussives include the narcotic opioids (codeine, hydrocodone, morphine); the non-narcotic opioid dextromethorphan; and, the older-generation antihistamines.
Although the narcotic opioids, especially codeine, are often thought of as the gold standard of cough suppressant therapy, their antitussive effect compared with placebo, as demonstrated in clinical trials of varying size and quality, has been unpredictable and inconsistent (Table 2). Adequate cough suppression, when
Centrally acting
Recently, two small studies have suggested an antitussive effect of the tricyclic antidepressant amitriptyline. In a prospective, randomized trial of subjects with chronic cough thought due to “postviral vagal neuropathy,” amitriptyline demonstrated a significantly greater likelihood of achieving a complete elimination or greater than 50% improvement in cough, compared to a combination of codeine and guaifenesin [41]. In a report of 12 patients whose chronic cough was described as due to
Theobromine
Theobromine is a methylxanthine derivative found in cocoa. In a recent study, theobromine was shown to inhibit citric acid-induced cough in guinea pigs, as well as to inhibit capsaicin-induced cough in healthy human subjects [49]. In the same study, theobromine directly inhibited capsaicin-induced sensory nerve depolarization of guinea pig and human vagus nerve, suggesting that its antitussive action is peripherally mediated [49]. Given these preliminary data, clinical trials of theobromine in
Conclusion
Better cough suppressants, in terms of efficacy, safety and tolerability, are desperately needed. Fortunately, in recent years we have witnessed a significant increase in cough-related research, with many potential antitussives currently being developed [50], [51], [52]. Novel cough suppressants will need to be evaluated in properly conducted clinical trials, testing appropriately chosen subject populations, and measuring relevant subjective and objective end points.
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