Mucolytics, Expectorants, and Mucokinetic Medications

Abstract

In health, the airways are lined by a layer of protective mucus gel that sits atop a watery periciliary fluid. Mucus is an adhesive, viscoelastic gel, the biophysical properties of which are largely determined by entanglements of long polymeric gel-forming mucins, MUC5AC and MUC5B. This layer entraps and clears bacteria and inhibits bacterial growth and biofilm formation. It also protects the airway from inhaled irritants and from fluid loss. In diseases such as cystic fibrosis there is almost no mucin (and thus no mucus) in the airway; secretions consist of inflammatory-cell derived DNA and filamentous actin polymers, which is similar to pus. Retention of this airway pus leads to ongoing inflammation and airway damage. Mucoactive medications include expectorants, mucolytics, and mucokinetic drugs. Expectorants are meant to increase the volume of airway water or secretion in order to increase the effectiveness of cough. Although expectorants, such as guaifenesin (eg, Robatussin or Mucinex), are sold over the counter, there is no evidence that they are effective for the therapy of any form of lung disease, and when administered in combination with a cough suppressant such as dextromethorphan (the “DM” in some medication names) there is a potential risk of increased airway obstruction. Hyperosmolar saline and mannitol powder are now being used as expectorants in cystic fibrosis. Mucolytics that depolymerize mucin, such as N-acetylcysteine, have no proven benefit and carry a risk of epithelial damage when administered via aerosol. DNA-active medications such as dornase alfa (Pulmozyme) and potentially actin-depolymerizing drugs such as thymosin β₄ may be of value in helping to break down airway pus. Mucokinetic agents can increase the effectiveness of cough, either by increasing expiratory cough airflow or by unsticking highly adhesive secretions from the airway walls. Aerosol surfactant is one of the most promising of this class of medications.