Currently available antitussives

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Abstract

Cough is among the most common complaints for which patients seek medical attention. Acute cough, usually due to a viral upper respiratory tract infection, generates a huge expenditure on prescription and over-the-counter cough and cold preparations worldwide. Most of these agents, however, have not been shown to be more effective than placebo in adequately performed clinical trials.

The goal of management in chronic cough is treatment of its underlying cause. However, certain situations will necessitate cough suppressant therapy for symptomatic relief. Unfortunately, currently available antitussives, such as the opioids, are not consistently effective, or achieve therapeutic effect at the expense of unpleasant or intolerable side effects.

Safer and more effective cough suppressants are desperately needed. Potential novel antitussives will need to be evaluated in properly formulated clinical trials, measuring relevant subjective and objective end points in appropriate subject populations.

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.

References (52)

  • P.V. Dicpinigaitis et al.

    Effect of guaifenesin on cough reflex sensitivity

    Chest

    (2003)
  • R.W. Bastian et al.

    Sensory neuropathic cough: a common and treatable cause of chronic cough

    Otolaryngol Head Neck Surg

    (2006)
  • P.V. Dicpinigaitis et al.

    Antitussive effect of the GABA-agonist baclofen

    Chest

    (1997)
  • P.V. Dicpinigaitis et al.

    Baclofen-induced cough suppression in cervical spinal cord injury

    Arch Phys Med Rehabil

    (2000)
  • P.V. Dicpinigaitis

    Potential new cough therapies

    Pulm Pharmacol Ther

    (2004)
  • C.W. Burt et al.

    Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1999–2000

    Vital Health Stat

    (2004)
  • K. Schroeder et al.

    Systematic review of randomised controlled trials of over-the-counter medicines for acute cough in adults

    Br Med J

    (2002)
  • K.F. Chung

    Currently available cough suppressants for chronic cough

    Lung

    (2008)
  • H. Sevelius et al.

    Objective assessment of antitussive agents in patients with chronic cough

    J New Drugs

    (1966)
  • H. Sevelius et al.

    Dose response to codeine in patients with chronic cough

    Clin Pharmacol Ther

    (1971)
  • M. Aylward et al.

    Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects

    Eur J Resp Dis

    (1984)
  • R. Eccles et al.

    Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection

    J Clin Pharm Ther

    (1992)
  • C. Freestone et al.

    Assessment of the antitussive efficacy of codeine in cough associated with common cold

    J Pharm Pharmacol

    (1997)
  • A.H. Morice et al.

    Opiate therapy in chronic cough

    Am J Respir Crit Care Med

    (2007)
  • H. Tukiainen et al.

    The treatment of acute transient cough: a placebo-controlled comparison of dextromethorphan and dextromethorphan-beta 2-sympathomimetic combination

    Eur J Respir Dis

    (1986)
  • M. Korppi et al.

    Antitussives in the treatment of acute transient cough in children

    Acta Paediatr Scand

    (1991)
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