Chapter 12 Cough, Cold, and Allergy
Antitussives
Moa (Mechanism of Action)
Antitussives are cough suppressants. There are two ways to inhibit coughing: centrally and peripherally.
Cough is normally produced through the stimulation of sensory receptors of the glossopharyngeal and vagus nerves, innervating the mucous membranes of the lower pharynx, larynx, trachea, and smaller airways of the respiratory system. The receptors then transmit the signal to the cough center in the brain, which then triggers a reflex motor response that results in contraction of the muscles to close the glottis (vocal cords) and contraction of the muscles of expiration. The result is a sudden increase in intrathoracic pressure, followed by relaxation of the vocal cords, resulting in rapid expulsion of air (Figure 12-1).
Centrally acting agents such as dextromethorphan work by inhibiting the cough center in the brain, elevating the threshold for coughing. The exact mechanism by which they do this is still poorly understood. Dextromethorphan, for example, is an N-methyl-d-aspartate (NMDA) antagonist, although it is not known what contribution this has to its antitussive effects.
Important Notes
Dextromethorphan was developed in an attempt to create a cough suppressant with the efficacy of codeine but with none of the central nervous system (CNS) side effects such as euphoria. Dextromethorphan therefore has little or no ability to induce euphoria and therefore is available without a prescription and without pharmacist consultation in most jurisdictions.
However, very high doses of dextromethorphan can cause dissociative effects similar to those seen with phencyclidine (PCP). PCP and dextromethorphan are both NMDA antagonists, and this is believed to be why they share similar effects. The doses needed to achieve this effect with dextromethorphan are high enough to cause toxicities resulting in hypertension, tachycardia, and respiratory depression.
Codeine can be an effective antitussive at lower doses than required for analgesia. Therefore some of the more important side effects of codeine, such as respiratory depression, can generally be avoided at the antitussive dose. The exception appears to be young children (≤5 years of age) who may be more sensitive to the respiratory depression. Codeine is therefore not recommended for children under the age of 2 and should be used with caution in children 2 to 5 years old.
The use of cough and cold preparations in children, particularly combination products, has come under close scrutiny owing to concerns over deaths attributed to overdose. The use of multiple combination products facilitates overdose, as parents can be easily confused by the duplication of ingredients among products. In addition, the lack of clear evidence of efficacy of these products in young children has prompted many to question why they are used at all.
Evidence
Over-the-Counter Preparations for Acute Cough
A 2008 Cochrane review (25 trials, N = 3492 participants) assessed the effects of over-the-counter (OTC) cough preparations for acute cough. Six trials in adults had variable results for antitussives versus placebo. Of the two trials involving expectorants, one showed benefit versus placebo whereas the other did not. In children, antitussives (two trials), antihistamines (two trials), antihistamine-decongestant combinations (two trials), and antitussive-bronchodilator combinations were no more effective than placebo. No trials were found of expectorants, but one trial showed benefit of a mucolytic versus placebo.
Expectorants
Moa (Mechanism of Action)
Mucus serves as an airway lubricant and functions as a first level of immune defense. When mucus becomes thickened and/or dried out by infections, the functions of the mucus, including the clearing of infections, becomes impaired.
Important Notes
There has been a longstanding controversy over the use of expectorants. This is partly because of the limited data demonstrating their efficacy.
The use of cough and cold preparations in children, particularly combination products, has come under close scrutiny because of concerns over deaths attributed to overdose. The use of multiple combination products facilitates overdose, as parents can be easily confused by the duplication of ingredients among products. In addition, the lack of clear evidence of efficacy of these products in young children has prompted many to question why they are used at all.
Guaifenesin is the most widely used expectorant. Other agents that have been used as expectorants include ammonium chloride, which can cause acidosis in patients with renal failure; terpin hydrate, which can cause nausea and vomiting; potassium iodide, which has several side effects; and iodinated glycerol.
Evidence
Over-the-Counter Preparations for Acute Cough
A 2008 Cochrane review (25 trials, N = 3492 participants) assessed the effects of OTC cough preparations for acute cough. Of the two trials involving expectorants, one showed benefit versus placebo whereas the other did not. In children, no trials were found of expectorants, but one trial showed benefit of a mucolytic versus placebo.
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