Pharmacy staff are expected to be the experts on coughs. Alan Nathan summarises the relevant information on this common minor ailment

Pharmacists are usually asked for advice and treatment for coughs associated with upper respiratory tract infections. These can be classified into three general types:

• ‘Dry’ (irritating and non-productive)
• ‘Chesty’ (with production of mucus)
• ‘Chesty, non-productive’ (no mucus is produced but there is a feeling of tightness or wheezing resulting from congestion of the bronchial airways).

The active constituents of cough remedies fall into four main categories:

• Suppressants (antitussives) to treat dry, irritating coughs
• Expectorants for chesty, productive coughs
• Decongestants for chesty, non-productive coughs
• Demulcents to soothe any kind of cough.

Around 60 branded products are available, most containing combinations of two or more ingredients. Choice should be made carefully to try to ensure that the product selected is suitable for the symptoms and that the combination of ingredients is rational.

Suppressants

Two classes of compounds are used: opioids and sedating antihistamines.

Opioids

• Compounds used: codeine, dextromethorphan, pholcodine.
• Mode of action: opium alkaloids act on the medullary cough centre in the brain to depress the cough reflex. Both dextro and laevo isomers of opioid compounds possess antitussive activity, but only the laevo isomers have liability for dependence. Dextromethorphan, a dextro isomer developed as an orally active antitussive with little or no dependence liability, is the most widely used opioid constituent.
• Side effects: codeine is partially demethylated in the body to morphine. This may contribute to its antitussive activity but also accounts for its liability to cause sedation, respiratory depression (although this is not normally a problem at OTC doses), constipation and addiction. Pholcodine has a generally lower side effect profile than codeine, and dextromethorphan is claimed to be virtually free from side effects. At antitussive doses, opioids have no significant interactions with other drugs.

Sedating antihistamines

• Compounds used: diphenhydramine, triprolidine.
• Mode of action: these compounds exert a central and peripheral inhibitory action on neuronal pathways involved in the cough reflex. Their sedative properties may be useful in helping to induce sleep if taken near bedtime. They also exert anticholinergic side effects, including the drying up of bronchial and nasal secretions, which may be helpful in some situations.
• Side effects include sedation and anticholinergic effects such as dry mouth, urinary retention, constipation and blurring of vision. Elderly patients are more susceptible to these side effects, and they hould not be recommended to patients with glaucoma or prostate problems.
• Interactions: the sedative effects of antidepressants, anxiolytics and hypnotics are likely to be enhanced by antihistamines, as are the antimuscarinic actions and side effects of drugs such as trihexyphenidyl, orphenadrine, tricyclic antidepressants and phenothiazines.

Expectorants

• Constituents used: guaifenesin, ammonium chloride, ipecacuanha, squill.
• Mode of action: in a productive cough, mucus produced in the bronchial passages as a result of infection is moved upwards towards the pharynx by ciliary action and is then expelled by coughing. Expectorants are used to assist mucus removal. In large doses they are emetic, acting through vagal stimulation of the gastric mucosa to produce a reflex response from the vomiting centre in the brain. The same mechanism stimulates the bronchial glands and cilia, and it is postulated that this stimulation still occurs at sub-emetic doses.
• At doses used in OTC formulations there is little risk of adverse effects, and expectorants do not interact with other drugs.

DECONGESTANTS

Compounds used: pseudoephedrine, phenylephrine.

• Mode of action: Pseudoephedrine is a sympathomimetic. It mimics the action of noradrenaline, the principal neurotransmitter between the nerve endings of the sympathetic nervous system and the adrenergic receptors of the innervated tissues. It stimulates both alpha adrenoceptors, causing constriction of smooth muscle and blood vessels, and beta adrenoceptors, producing bronchodilation. It is indicated in coughs where the tissues of the upper respiratory tract are congested, as it shrinks swollen mucosae and opens up the airways.
• Phenylephrine is a selective alpha adrenergic agonist, causing vasoconstriction alone. It is considered to be not very effective orally, due to irregular absorption and first-pass metabolism in the liver. It is included in two proprietary ‘cough and cold’ products, with legal classification GSL, while pseudoephedrine preparations are P.
• Cautions: because of their pressor effects and because they can also increase heart rate, sympathomimetic decongestants should be avoided by patients with any kind of cardiovascular condition or glaucoma. These drugs also interfere with metabolism, including glucose metabolism, and should not be taken by patients with diabetes or thyroid problems. As they are CNS stimulants, doses should not be taken near bedtime.

Interactions:

• Administration of sympathomimetics in conjunction with MAOIs increases the level of adrenergic transmitter substances, potentially resulting in a lethal hypertensive crisis. Sympathomimetic decongestants must therefore not be given to patients taking MAOIs.
• Blockade of beta adrenoceptors by beta blockers allows unopposed alpha- adrenoceptor-mediated vasoconstriction, which can lead to a potentially hazardous rise in blood pressure. Co-administration should therefore be avoided.

DEMULCENTS

• Constituents used: glycerol, liquid glucose, syrup, honey, treacle.
• Mode of action: demulcents act mechanically by coating the mucosa of the pharynx and providing short-term relief from the irritation that provokes reflex coughing.
• Caution: demulcents are generally safe to be taken by anyone. The only drawback is the high sugar content of some preparations; these should be used with caution in patients with diabetes and in children because of their cariogenic potential.

RESTRICTIONS IN CHILDREN

Cough preparations containing any of the constituents above, except for demulcents, are generally not licensed for use in children under 12 years. A few products containing low doses of diphenhydramine, pholcodine and expectorants are licensed for children aged between six and 12.

EFFICACY

• In clinical trials OTC cough medicines were perceived to be effective, although up to 85 per cent of the efficacy could be attributed to a placebo effect.¹ The conclusion of a Cochrane systematic review was that there was no good evidence for or against the effectiveness of OTC medicines in acute cough.²
• The sweet taste of cough syrups may modulate cough at the level of the nucleus tractus solitarius in the brain, possibly by influencing the production of endogenous opioids.³
• Recent evidence as to whether codeine, pholcodine and dextromethorphan are effective is conflicting, and most trials rate them as little or no better than placebo.^4-9
• Little research has been published on the antitussive effects of antihistamines, but trials that have been performed show that they are effective.^10,11
                                                           

References available on request