[약] Bromhexin

Mucolytics

 

Relevant Pathophysiology

 

The viscosity of pulmonary mucus secretions depends on the concentrations of mucoproteins and deoxyribonucleic acid (DNA). While mucoprotein is the main determinant of viscosity in normal mucus, in purulent inflammation the mucoid concentration of DNA increases (due to increased cellular debris) and so does its contribution to mucoid viscosity.

 

Clinical Indications

 

In a proportion of patients with respiratory tract disease, significant bronchial inflammation will be associated with the presence of large amounts of relatively viscous, inflammatory exudate and mucus which is firmly attached to the lining of bronchioles and bronchii. By effectively increasing bronchial wall thickness, this thick adherent mucus can exacerbate the "lumen-narrowing" effects of bronchial constriction, enhance the overall inflammatory process as well potentiating persistent coughing. In this situation mucolytic therapy may have some value in facilitating resolution of the inflammatory airway disease.

 

The two most frequently prescribed mucolytics in veterinary practice are described below. In man, guaifenesin has been proposed as an oral expectorant or mucolytic. However, evidence for its efficacy in this role is lacking in animals and currently its use in veterinary practice is confined to its significant muscle relaxant activity. It is also worth remembering that normal saline, directly administered to the airways by effective nebulisation therapy, is an extremely effective mucolytic and expectorant.

 

Bromhexine Hydrochloride

 

Bromhexine increases mucus viscosity by increasing lysosomal activity. This increased lysosomal activity enhances hydrolysis of acid mucopolysaccharide polymers, which significantly contribute to normal mucus viscosity. It should be remembered that in purulent bronchial inflammation, bronchial mucus viscosity is more dependent upon the large amount of DNA fibres present. As bromhexine does not effect these DNA fibres, its mucolytic action is limited in these situations.

 

It has also been suggested that bromhexine increases the permeability of the alveolar/capillary barrier resulting in increased concentrations of certain antibiotics in luminal secretions. Furthermore over time (2-3days) bromhexine results in a significant increase in γ-globulin concentrations and a decline in albumin and γ-globulin concentrations in respiratory secretions. The increased g-globulins are IgA and IgG while IgM levels remain unchanged. It has been hypothesized that because of these effects concurrent administration of bromhexine and an antimicrobial agent will facilitate treatment of infectious tracheobronchitis.

 

The mucolytic dose of bromhexine hydrochloride in dogs and cats is 2mg/kg/12h orally for 7 to 10 days then 1mg/kg/12h for a further 7-10 days.

 

Acetylcysteine

 

When administered directly into airways, acetylcysteine reduces viscosity of both purulent and nonpurulent secretions. This effect is thought to be a result of the free sulphydryl group on acetylcysteine reducing the disulphide linkages in mucoproteins which are thought to be at least partly responsible for the particularly viscoid nature of respiratory mucus. The mucolytic activity of acetylcysteine is unaltered by the presence of DNA and increase with increasing pH.

 

For effective mucolytic activity, an acetylcysteine solution should be nebulised and administered directly to the respiratory mucosa as an aerosol. The dose rate in dogs and cats is 50ml/kg for 30 minutes every 12 hours.

 

Acetylcysteine is available as 10% and 20% solutions of the sodium salt in various sized vials. This solution can be readily used in a nebuliser undiluted although dilution with sterile saline will reduce the risk of reactive bronchospasm.