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Mucolytics

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Mucolytics

Introduction

Mucolytics are part of mucoactive agents that are used to manage the hypersecretion of

mucus and its associated conditions which are majorly COPD, bronchiectasis and cystic fibrosis.

They function by breaking down the molecular cross-linking bonds of mucus to reduce their

viscosity and enable easier expectoration of the mucus. Mucus production is meditated by the

mucous membrane lining that control its production and clearance. The aforementioned

conditions disrupt this regulatory mechanism and also predispose the patient to frequent

infections or they exacerbate the respiratory symptoms of the patient.

Indications for Mucolytics

Depending on the pathological mechanisms of the mucus producing respiratory

conditions, specific mucolytics are indicated to assist in the breakdown and clearance of mucus

or mucoid discharges from the respiratory tracts (Calverley et al., 2020). Firstly, classic

mucolytics such as N-acetylcysteine are effective in conditions such as COPD and bronchiectasis

because their mucous lining hyper secretes mucous in copious amounts more than it can be

cleared and it leads to the formation of mucous plugs that increase the viscosity and further

impairs their clearance (Calverley et al., 2020).

In contrast, peptide mucolytics are effective in conditions such as cystic fibrosis. Such

conditions are unique in the molecular composition of mucus and other mucoid discharges, in

that, the compose largely of filamentous actin polymers and inflammatory cell derived DNA

(Calverley et al., 2020). These molecular compounds make the mucous thicker and more viscous
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compared to other hypersecretory conditions and predispose these cadre of patients to recurrent

bacterial infections that are difficult to eradicate (Calverley et al., 2020).

Therapeutic Actions of Mucolytics

Mucolytics are categorized into two distinct groups namely: Classic and Peptide

Mucolytics. Classic mucolytics work by disrupting the disuphide bonds that maintains the three-

dimensional structure of mucus. N-acetyl L-cysteine (NAC) which is the active pharmacologic

agent in classic mucolytics acts through hydrolyzation of the disulphide bonds to sulfhydryl

bonds and cysteine residues and it reduces the anchoring of the protein complex (Poole et al.,

2019). Subgroups of classic mucolytics exist which are Carbocysteine, Erdosteine and

Fudosteine (Poole et al., 2019). Carbocysteine is more effective in producing more mucus and

aids in the amount of bacterial inoculum in mucus. This fact makes it ideal for patients with an

acute exacerbation of COPD. Erdosteine and Fudosteine are new variants of NAC, they possess

additional properties such as an anti-oxidant and anti-tussive effects. Additionally, it has

antibiotic potentiating effects and hence is ideal for all forms of COPD (Poole et al., 2019).

Conversely, peptide mucolytics tend to preserver the protective function of mucus and

the mucus lining (Aldini et al., 2018). Peptide mucolytics breakdown DNA polymers and F-actin

links in mucous that are responsible in promoting purulent mucous discharges classically seen in

cystic fibrosis (Aldini et al., 2018). The subgroups under this categories are Dornase Alfa and

Thymosin β4. Dornase Alfa’s action involves the depolymerization of DNA polymers. Its vital

for cystic fibrosis patients because it mildly increases the FEV1 (forced expiratory volume after

1 second) (Aldini et al., 2018). Moreover, Thymosin β4 depolymerizes F-actin which produces a

large quantity of purulent mucus and therefore it is useful in lysing airway pus and provide

symptomatic relief (Aldini et al., 2018).

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Considerations for Use of Mucolytics

The use of NAC is associated with an increase in incidences of vomiting and diarrhea.

The incidences approach to almost 50% when used for more than two to three weeks (O’Neill et

al., 2019). Therefore, patients should use titrated doses in conjunction with antiemetics if

prolonged use of the medication is expected. Additionally, patients with peptic ulcers,

esophageal varices and Mallory-Weiss tears should be given alternative medications that do not

contain NAC because of their propensity of precipitating vomiting episodes (O’Neill et al.,

2019). The use of Dornase alfa should be considered because of its propensity to cause laryngitis

and pharyngitis therefore its use should be monitored closely. Its use is contraindicated in

patients with hypersensitivity to the drug in the past as well as Chinese hamster ovary cell

products (O’Neill et al., 2019).

Conclusion

Mucolytics are essential in relieving chest congestion in conjunction with other

mucoactive agents. The development of these drugs has influenced therapy in chronic conditions

such as COPD and cystic fibrosis. Furthermore, newer drugs such as Erdosteine and Fudosteine

have added benefits to the use of NAC, where its use was controlled due to the adverse effects

and further development in this class is promising.

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References

Aldini, G., Altomare, A., Baron, G., Vistoli, G., Carini, M., Borsani, L., & Sergio, F. (2018). N-

Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free

Radical Research, 52(7), 751–762. https://doi.org/10.1080/10715762.2018.1468564

Calverley, P., Rogliani, P., & Papi, A. (2020). Safety of N-Acetylcysteine at High Doses in

Chronic Respiratory Diseases: A Review. Drug Safety, 44(3), 273–290.

https://doi.org/10.1007/s40264-020-01026-y

O’Neill, K., O’Donnell, A. E., & Bradley, J. M. (2019). Airway clearance, mucoactive therapies

and pulmonary rehabilitation in bronchiectasis. Respirology.

https://doi.org/10.1111/resp.13459

Poole, P., Sathananthan, K., & Fortescue, R. (2019). Mucolytic agents versus placebo for chronic

bronchitis or chronic obstructive pulmonary disease. Cochrane Database of Systematic

Reviews. https://doi.org/10.1002/14651858.cd001287.pub6