Drug-mucus actions and interactions.

Although it has generally been accepted that the main structural component of mucus secretions is the high molecular weight glycoprotein it has now been established that other macromolecules are co-secreted. For example, lysozyme, lactoferrin and albumin are known to be secreted by the serous cells within the sub-mucosal respiratory glands: significantly the albumin is synthesised within the cell and is not derived from serum. The various cells within the gland respond differently to agonists and since goblet cells, apart from when they are in the crypts within the gastro-intestinal tract, do not appear to be innervated, they cannot respond to any agonist as yet identified. It is therefore probable that the changes which occur during disease may result from changes in the sensitivity of a particular cell type to an agonist as this can markedly affect the type of secretion that is produced. Since the products of the serous cell form part of the natural defence system then the reduction in their number which is observed in chronic obstructive airways disease could also be significant in the disease process. Within the gastro-intestinal tract, it has now been established that substances which reduce the mucus structure can produce damage to the underlying membrane. The endogenous surfactants produced in bile are good examples and co-secretion of phosphatidylcholine provides a defence against self-digestion within the gut by the formation of mixed micelles. The importance of the mucus layer in the access of drug molecules to the absorbing epithelium has also been identified. The diffusion of water molecules is hindered even at concentrations below the gelling point (approximately 10-20 mg ml-1) and above this concentration a precipitate fall in diffusion coefficient is followed by a levelling off. This pattern is followed by low molecular weight drug molecules and a reasonable correlation between drug absorption and binding to mucus glycoproteins can be demonstrated. The agents which have been claimed to affect the quality and quantity of mucus secreted by the respiratory epithelium during conditions like chronic obstructive airways disease have been poorly understood. Recent studies have shown that compounds like bromhexine and S-carboxymethylcysteine can block the activity of mucus secretagogues in the rat. Furthermore, it has also been demonstrated that such compounds can prevent the inflammatory response to cigarette smoke. However, their activity is not restricted to the respiratory epithelium and the cervical mucus barrier has also been shown to be compromised following systemic administration.