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

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….