Mucolytic agents

As a more sensitive detection method, MS can be very useful in amino acid determinations. For example, S-carboxymethyl-(R) cysteine or SCMC, is a mucolytic agent used in the treatment of respiratory diseases. The development of a method utilizing high performance IEC and atmospheric pressure ionization (API) mass spectrometry to quantify SCMC in plasma has been described.66 This method is simple (no derivatization needed), rapid (inn time 16 min.), sensitive (limit of quantification 200 ng/mL in human plasma), and has an overall throughput of more than 60 analyses per day. API-MS was used successfully with IEC to determine other sulfur-containing amino acids and their cyclic compounds in human urine.67 IEC has also been used as a cleanup step for amino acids prior to their derivatization and analysis by gas chromatography (GC), either alone or in conjunction with MS.68 69... 

Airway clearance therapy is usually accompanied by bron-chodilator treatment [albuterol (also known as salbutamol outside the United States) by nebulizer or metered-dose inhaler] to stimulate mucociliary clearance and prevent bronchospasm associated with other inhaled agents. A mucolytic agent may be administered to reduce sputum viscosity and enhance clearance. 

Dornase alfa (Pulmozyme ) is a recombinant human (rh) DNase that selectively cleaves extracellular deoxyribonucleic acid (DNA). This DNA is released during neutrophil degradation and contributes to the high viscosity of CF sputum. Nebulization of dornase alfa 2.5 mg once or twice daily improves daily pulmonary symptoms and function, reduces pulmonary exacerbations, and improves quality of life.16 N-acetylcysteine and hypertonic saline are other mucolytic agents that are occasionally used however, they are not preferred agents due to a greater incidence of bronchospasm and unpleasant odor and taste.5... 

Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. 

A molecular dissection of the alkaloid vasicine (52) ultimately resulted in the expectorant and mucolytic agent bromhexine (54). The synthesis starts with displacement of halogen on 2-nitrobenzyl-bromide (53) by N-methyl cyclohexylamine, followed by Raney nickel and hydrazine reduction of the nitro group. Bromination in acetic acid then affords bromhexine. 

Carbocisteine is a mucolytic agent that may be used in chesty cough. Antihistamines tend to have antimuscarinic properties, resulting in urinary retention and are therefore contraindicated in prostatic hypertrophy. 

Certain alkaloids such as vasicine obtained from plant Adhatoda vasica act as potent expectorant and mucolytic agent. Bromhexine, a derivative of vasicine depolymerises mucopolysaccharides directly and by liberating lysosomal enzymes. Another compound acetylcysteine opens disulfide bonds in mucoproteins present in sputum and decrease its viscosity. Carbocisteine acts in same manner. 

Bronchodilation/mucolytic agent Mudrane - mixture of phenobarbital, aminophylline, ephedrine... 

Iodinated glycerol is used as a mucolytic agent in respiratory disorders, but its efficacy is controversial. Organically bound iodine is changed to unbound iodide after absorption. 

Takatsuka, S., et al. 2006. Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant. Eur J Pharm Biopharm 62 52. 

Delivery device Mucolytic agents Enzyme inhibitors Mucoadhesives... 

Another condition where cell debris becomes life threatening is the obstruction of airways by viscous sputum in patients suffering from cystic fibrosis (CF). It has been shown that human plasma gelsolin can rapidly decreased the viscosity of CF sputum samples in vitro (Vasconcellos et al., 1994 Sheils et al., 1996 Davoodian et al., 1997 Ismailov et al., 1997), suggesting that in CF patients gelsolin may have therapeutic potential as a mucolytic agent. 

Decision/Solution. In addition to the neuromuscular facilitation activities, the physical therapist initiated a program of chest physical therapy including postural drainage and deep-breathing exercises. The physical therapist coordinated these activities with the respiratory therapist so that the patient first received a treatment of the mucolytic agent. Also, the physical therapist had the patient self-administer a dose of the inhaled beta-2 bronchodilator approximately 1 hour prior to the chest therapy session, thus allowing the bronchodilator to produce maximal airway dilation and permit optimal clearance of bronchial secretions. 

King M, Rubin BK Pharmacological approaches to discovery and development of new mucolytic agents. Adv Drug Deliv Rev. 2002 54 1475-1490. 

Poole PJ, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2003 CD001287. 

Bernkop-Schniirch, A., Valenta, C., and Daee, S. M. Peroral polypeptide delivery. A comparative in vitro study of mucolytic agents. Arzneimittel-Forsch. 49 799—803,... 

Strategies to overcome the mucus barrier focus mainly on the use of mucolytic agents such as dithiothreitol (DTT) and A-acetyl cysteine (NAC). So far, however, results were rather disappointing in improving accessibility to the intestinal crypts for somatic gene therapy (Sandberg et. al. 1994). 

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