Therapeutic approaches to mucus hypersecretion

Abstract

Mucolytic and related agents have been in use since prehistoric times. Although widely prescribed and used extensively in over-the-counter preparations, their efficacy and mechanisms of action remain in doubt. These agents belong to several distinct chemical classes. Mucolytic agents such as N-acetyl-cysteine are thiols with a free-sulfhydryl group. They are assumed to break disulfide bonds between gel-forming mucins and thus reduce mucus viscosity. Mucokinetic agents are thiols with a blocked sulfhydryl group. Expectorants such as guaifenesin increase mucus secretion. They may act as irritants to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing. The roles of anticholinergic agents, DNase, and other drugs are also discussed with regard to their roles in reducing mucus production in rhinitis and other airway diseases.

In Vitro Activity and Durability of a Combination of an Antibiofilm and an Antibiotic against Vascular Catheter Colonization

“…NAC also adversely affects bacterial growth and polysaccharide production and disrupts disulfide bonds in mucus, reducing the viscosity of secretions. These properties may contribute to the prevention and disruption of biofilm around different polymeric and metallic surfaces (9,(19)(20)(21). Not only does NAC diminish the formation of biofilm by common pathogens (19,22,23), it also possesses some in vitro intrinsic antimicrobial activity against both Gram-positive and Gram-negative bacteria (24).…”

Guaifenesin in rhinitis

“…However, few data on effi cacy are available for any in this category; indeed, mucoactive agents are not included in current guidelines and practice parameters for treating (allergic) rhinitis [2,3]. Nonetheless, documented use of such therapy dates back more than 3000 years [7].…”

“…The mechanism of action is not completely understood, but expectorants reduce the viscosity of airway secretions and/or increase their volume, thereby enhancing their removal [18•]. Parasympathetic refl exes involving the irritation of gastric vagal receptors and subsequent glandular exocytosis in the airways are proposed [1,7] but not accepted by all [18•]. Regardless of mechanism, the clinical outcome is a transient and paradoxical increase in mucus secretion and drainage-with associated coughing/expectoration-that may help to dislodge tenacious mucus from the airways.…”

“…Few studies have evaluated the effi cacy of guaifenesin for symptoms relating to mucus congestion in patients suffering from acute respiratory conditions [1,7]. The lack of clinical data from randomized clinical trials has limited recommendations for use in current treatment guidelines other than for sinusitis and cough [4,5].…”

“…Guaifenesin is the only expectorant considered effective by the US Food and Drug Administration [9]. The recommended doses range from 400 to 1200 mg/d, but doses up to 2400 mg/d may be needed for some patients [7]. This paper reviews the use of guaifenesin as an adjunctive therapy for rhinitis, including the limited clinical data available in the literature, anecdotal evidence, and one of the authors' experiences.…”