Mucokinetics RC 195

Mucokinetics – drugs that increase and aid clearance of respiratory tract secretions Hypoviscosity agents (Wetting agents) Mucolytics Expectorants (Bronchomucotropics)

Muco-ciliary Blanket 95% water, 2% glycoproteins Gel layer-high viscosity from goblet cells Sol layer – low viscosity from submucosal bronchial glands

Both goblet cells and bronchial sub-mucosal glands increase secretion when irritated. Vagal stimulation will also increase bronchial sub-mucosal gland secretion. Increased goblet cell secretion = increased sputum viscosity. Increased bronchial sub-mucosal gland secretion = decreased sputum viscosity

Mucokinetics are needed when secretions increase in amount and/or viscosity

Hypoviscosity/Wetting Agents: Water Systemic administration, eg P.O. or IV, decreases viscosity by increasing the sol layer Aerosol may decrease viscosity by diluting the gel layer Limitations of aerosol Nebulizer output Bronchospasm Hypotonicity and mucosal swelling

Hypoviscosity/Wetting Agents: Saline solutions Normal Saline (.9%) Isotonic and good diluent for drugs Half-normal Saline (.45%) Hypotonic, good diluent, and can be administered via USN Aerosol solutions tend to increase in tonicity as they go deeper into the lung because of evaporation!

Hypoviscosity/Wetting Agents: Saline solutions (cont.) Hypertonic Saline (usually 10%) Wetting agent Bronchorrhea (draws fluid from mucosa to dilute gel) May also help break up mucoprotein-DNA bonds in mucus (mucolytic effect!) Limitations: Bronchospasm Hypernatremia

Hypoviscosity/Wetting Agents: Sodium Bicarb Usually 2 – 7.5% solution Wetting agent and bronchorrhea Also alkaline pH breaks up hydrogen bonds Also breaks up calcium bonds Like hypertonic saline, it is both a wetting agent and a mucolytic Can usually NOT be used as a diluent for drugs Has same side effects as hypertonic saline

Aid mucokinesis by breaking up bonds in mucus Mucolytics Aid mucokinesis by breaking up bonds in mucus

Mucolytics: Mucomyst (N-Acetylcysteine) 10 or 20% solution (hypertonic and alkaline pH) Breaks disulfide bonds (most effective form of mucolysis) Also breaks mucoprotein bonds and hydrogen bonds Bronchorrhea

Mucolytics: Mucomyst (N-Acetylcysteine) cont. Aerosol dose is 2-5ml of 10% 10% is as effective as 20% when aerosolized and is not as irritating Side effects/Pre-cautions: Bronchospasm May need a concurrent bronchodilator Decreased ciliary activity Patient may need to be suctioned if he can’t cough effectively Nausea/rhinorrhea Reacts with metal and rubber Shelf life is 96 hours after opening Should be refrigerated Purple streaks when too old Inactivates some antibiotics if they are aerosolized with Mucomyst

Mucolytics: Pulmozyme (Dornase Alpha or DNAse) Excellent aerosol mucolytic for cystic fibrosis patients Lyses the DNA bonds in the sputum of cystic fibrosis patients These patients have a lot of these bonds!

Expectorants (Bronchomucotropics) Usually stimulate sol layer production by direct irritation or indirect through vagal stimulation Remember, increased sol means decreased viscosity! Smoke is a bronchomucotropic! Unfortunately, it’s irritation stimulates the bronchial submcosal glands AND the goblet cells so mucus production increases as well as viscosity Spicy food causes increased sol due to vagal stimulation!

Vagal Stimulation and Mucokinesis

Expectorants (Bronchomucotropics): SSKI Vagal stimulation and irritation when administered orally Also stimulates proteolytic enzymes for a slight mucolytic effect Side effects/Precautions: Tastes like hell! Excess vagal stimulation N &V, diarrhea, bradycardia Anaphylaxis

Expectorants (Bronchomucotropics): Guaifenesin Vagal stimulation like SSKI but not as foul tasting or severe side effects Active ingredient in many “cough” medicines, eg Robitussin Prescription version is Humibid (pills) Guaifenesin is a very effective expectorant for chronic bronchitis

Expectorants (Bronchomucotropics): Ammonium Chloride Vagal stimulation only Found in many children’s “cough” syrups because it is easy to flavor Side effects are like SSKI and Guaifenesin Also may cause metabolic acidosis

One more case study!

This is the end of this course. But….