Effects of drugs on mucus clearance

Abstract

Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side‐effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back‐up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S‐carboxymethylcysteine, sodium 2‐mercapto‐ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5′‐triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N‐acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N‐acetylcysteine, S‐carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit. Eur Respir J 1999; 14: 452–467.

Oral l-cysteine ethyl ester (LCEE) reduces amoebic gill disease (AGD) in Atlantic salmon Salmo salar

“…Since Sheffner (1963) measured viscosity at 37°C and shear rate was not mentioned, direct comparisons of the results between studies cannot be made. NAC, along with other cysteine compounds including LCEE, possess a free sulfhydryl group that reacts with and ruptures the disulfide bridges of mucoproteins leading to a decreased mucus viscosity (Walters et al 1985, Holdiness 1991, Houtmeyers et al 1999. When ingested by humans and canines, NAC has also been shown to decrease the production and secretion of mucus by mucous cells (Aylward et al 1980, Martin et al 1980).…”

“…N-acetylcysteine (NAC) is a widely used mucolytic agent that by virtue of its free sulfhydryl group reacts with and ruptures the disulfide bridges of mucoproteins leading to a decreased mucus viscosity (Walters et al 1985, Holdiness 1991, Houtmeyers et al 1999. The NAC analogue, L-cysteine ethyl ester (LCEE), was successfully tested as an in-feed additive to protect coho salmon Oncorhynchus kisutch against the harmful phytoplankter Chaetoceros concavicornis (Yang & Albright 1994).…”

The Influence of Purulence on Ciliary and Cough Transport in Bronchiectasis

“…According to Houtmeyers et al, 18 it is not known whether or not age affects the transport properties of respiratory secretions. Our results from our without-lung-disease group are comparable to those presented by Jeanneret-Grosjean, with ages ranging from 19 to 50 years.…”

“…A review by Houtmeyers et al 18 suggests that the relative transport velocity is within the normal range and the rheological properties are unchanged after anesthesia.…”

Enhanced Bioavailability of Ambroxol by Transdermal Administration of the EVA Matrix Containing Penetration Enhancer in Rats

“…It is known to have a high affinity to lung tissue. Ambroxol is used as a mucolytic drug that lowers sputum viscosity by normalizing secretion from bronchiolar glands and increases mucociliary clearance (Nagaoka and Kase, 1981;Houtmeyers et al, 1999), provides anti-oxidative (Nowak et al, 1994a, b) as well as anti-inflammatory capacity (Yang et al, 2002). Ambroxol, an expectoration improver and mucolytic agent, has been widely used in the treatment of acute and chronic disorders characterized by the production of excess or thick mucus (Seki et al, 1977;Nowak et al, 1994a, b).…”