Category:Mucolytics

A mucolytic is a medicine that thins or breaks down respiratory or other body-secretion mucus, making it easier to clear by ciliary action, by coughing, or by suctioning. The category is used principally in cystic fibrosis (where airway mucus is the dominant pathophysiologic problem), in chronic obstructive pulmonary disease (where mucus hypersecretion contributes to airway obstruction and recurrent infection), in bronchiectasis, in selected severe acute bronchitis and pneumonia (where retained secretions impair gas exchange), and in paracetamol poisoning (the unrelated antidotal use of N-acetylcysteine).

The mucolytic category divides by mechanism. The thiol-disulfide-exchange agents (N-acetylcysteine, the related carbocysteine and erdosteine) reduce the disulfide cross-links between mucin molecules in mucus, lowering its viscosity and elasticity. The recombinant deoxyribonuclease dornase alfa cleaves the extracellular DNA released from neutrophils in the inflammatory mucus of cystic fibrosis, reducing its viscosity by a quite different mechanism. The hyperosmotic agents (hypertonic saline and mannitol inhaled) hydrate the airway surface and produce a thinner periciliary fluid layer that improves mucociliary clearance. The ambroxol-bromhexine group enhances surfactant production and modifies mucus viscoelasticity by mechanisms incompletely characterised.

The most clinically significant mucolytic medicine in absolute outcome terms is dornase alfa. Dornase alfa (Pulmozyme, Genentech 1993) is a recombinant human deoxyribonuclease I expressed in CHO cells; it is administered by nebuliser to patients with cystic fibrosis and cleaves the polymerised DNA that is the principal contributor to the unusual viscosity of CF mucus.^[1] The 1994 Fuchs trial demonstrated reduced exacerbation rate and improved lung function with daily dornase alfa, and the medicine has been a foundation of CF pulmonary care since. The introduction of the CFTR modulators (ivacaftor 2012, ivacaftor-lumacaftor 2015, ivacaftor-tezacaftor 2018, the highly transformative elexacaftor-tezacaftor-ivacaftor Trikafta 2019) has substantially reduced the role of dornase alfa in CFTR-modulator-eligible patients, although the medicine retains a place in the CF pharmacopoeia.

The other major CF mucolytic, hypertonic saline (7 percent saline, inhaled by nebuliser twice daily), was shown in the 2006 Donaldson and Boucher trials to improve mucociliary clearance and to reduce exacerbations in CF.^[2] Hypertonic saline produces airway-surface hydration; the resulting expansion of the periciliary fluid layer improves cilia function and the gel-layer mucus is mobilised more easily. Inhaled mannitol (Bronchitol, Pharmaxis 2020 in U.S.) works by the same hyperosmotic mechanism and is an alternative for patients intolerant of hypertonic-saline-induced cough.

N-acetylcysteine (NAC; Mucomyst as nebuliser; Acetadote intravenous) is the prototype thiol mucolytic. Its acetylated sulfhydryl group reduces the disulfide bonds of mucus glycoproteins, lowering viscosity. The medicine has been used by nebuliser since the 1960s for retained secretions in COPD, post-operative atelectasis, and selected bronchiectasis; the clinical evidence for routine COPD mucolytic use is mixed and current guidelines recommend it only for patients with frequent exacerbations on optimal bronchodilator therapy. The oral preparation, much less effective for respiratory secretions because of substantial first-pass metabolism, has small evidence-base utility in idiopathic pulmonary fibrosis (the PANTHER-IPF and IFIGENIA trials) and remains in selected use as antioxidant therapy in IPF. The dominant clinical use of N-acetylcysteine is, in contrast to its mucolytic indication, the antidotal treatment of paracetamol overdose (replenishment of hepatic glutathione consumed by the reactive paracetamol metabolite NAPQI), described under acetaminophen.

The carbocysteine, erdosteine, and bromhexine class are widely used in European and Asian practice but not approved in the United States. Carbocysteine (S-carboxymethyl-L-cysteine, Mucodyne in U.K.) is an oral thiol mucolytic with mixed evidence for COPD; erdosteine has antioxidant and mucolytic properties; ambroxol and its prodrug bromhexine enhance surfactant production and have been used widely in Europe and Asia for acute and chronic bronchitis.

The expectorants (the largest of which is guaifenesin, available over-the-counter in many cough-and-cold preparations) are conventionally considered alongside mucolytics, although they act by a slightly different mechanism: guaifenesin increases the volume and reduces the viscosity of respiratory secretions by enhancing vagal-mediated reflex bronchial secretion. The clinical evidence for expectorant efficacy in routine acute bronchitis is limited.

By mechanism:

• Thiol mucolytics (disulfide-bond reduction):
  • N-acetylcysteine (NAC; Mucomyst nebulised; Acetadote and Cetylev oral/IV for paracetamol overdose)
  • Carbocysteine (Mucodyne; European)
  • Erdosteine, fudosteine
• Recombinant DNase:
  • Dornase alfa (Pulmozyme; for cystic fibrosis)
• Hyperosmotic (airway-surface hydration):
  • Hypertonic saline (3%, 7%, 10% nebulised)
  • Inhaled mannitol (Bronchitol)
• Surfactant modifiers / mucokinetic:
  • Ambroxol, bromhexine (European, Asian use)
• Expectorants (cross-indexed; enhance reflex bronchial secretion):
  • Guaifenesin (Mucinex; OTC and prescription)
  • Potassium iodide (older expectorant; uncommon current use)
• Other:
  • Inhaled isotonic saline (less established; some bronchiectasis use)
  • Antibody-targeted MUC5AC modulators in trial

The boundary of this category is "medicine that reduces the viscosity or volume of respiratory mucus to improve clearance." The bronchodilators indirectly improve clearance by enlarging the airway lumen but are not mucolytics in mechanism and are listed under bronchodilators separately. The mucus-blocking medicines used in COPD with predominant cough-and-mucus phenotype (the inhaled corticosteroids in combination with LABA) are listed under antiasthmatic agents and bronchodilators. The medicines for selected non-airway mucus indications (the saline irrigations for chronic rhinosinusitis; the meibum-targeted medicines for dry eye; the cervical-mucus modulators of selected reproductive-medicine indications) are listed under their primary system categories. The non-mucolytic antitussives (the central-acting dextromethorphan, codeine, and benzonatate; the peripheral-acting menthol and camphor) are conventionally listed alongside mucolytics in cough-and-cold OTC categories but act by suppression of cough rather than mucus modification.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.