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Mucus-controlling drug therapy

The mucociliary protective system

The self-renewing, self-cleansing mucociliary escalator is one of the major defense mechanisms of the lung.

Many respiratory diseases are associated with an impaired function of the mucociliary system.

Regardless of its location, mucus is a protective factor, including lubrication, waterproofing and protection against osmotic or inflammatory changes.

The term "mucolytic" has been replaced with "mucoactive agents".

Clinical indication

To prevent and reduce accumulation of airway secretions, thus improving pulmonary function and gas exchange.

To prevent repeated infection and airway damage.

Some diseases in which MA therapy is indicated are cystic fibrosis, bronchiectasis, acute and chronic bronchitis and pneumonia (mucus hypersecretion and poor clearance are common factors).

Nevertheless, the best mucus thinner is water.

Factors affecting mucociliary transport

Transport rates are slower in:

COPD

Parasympatholytics (atropine)

Narcotics

Endotracheal suctioning and tracheostomy

Cigarette smoking

Atmospheric pollutants

Hyperoxia and hypoxia

Milk doesnt increase phlegm production or

congestion in the respiratory tract.

Nature of the mucus secretion

Mucus hypersecretion (bronchorrhea) is the production of watery sputum of 100 ml or more per day.

Mucus is a threadlike strand consisting of a protein backbone to which carbohydrate side chains are attached.

Mucus is transparent; a green-yellow sputum means infection (cellular breakdown caused by the action of the enzyme myeloperoxidase).

Therapeutic options for controlling mucus hypersecretion

Remove causative factors whenever possible:

- Treat infections

- Stop smoking

- Avoid pollution and allergens

Optimize tracheobronchial clearance:

- Use of bronchodilators

- Bronchial hygiene measures (deep breathing, cough and postural drainage)

- Airflow improvement by exercise and proper nutrition.

           Reduce inflammation:

- Treat infection

- Use of corticosteroids

Use mucoactive agents (N-Acetyl L-Cysteine and Dornase alfa) as specifically indicated.

N-Acetyl L-Cysteine

Clinical indications:

- Treatment of conditions associated with viscous mucus secretions.

- As an antidote (antioxidant) for acetaminophen overdose.

Mode of action:

Acetylcisteine disrupts the structure of the mucus molecule by substituting its own sulfhydryl groups for the disulfide bonds in the mucus molecule. (Figure 9.9, p. 179)

N-Acetyl L-Cysteine

Brand name: Mucomyst

Dosage forms Administration

SVN 20% 3-5 ml tid-qid

SVN 10% 6-10 ml tid-qid*

either % 1-2 ml via direct instillation

*not efficiently nebulized by the typical gas- powered, hand-held disposable nebulizer.

Hazards:

Bronchospasm. It is more frequent in patients with

hyperreactive airways (ex. asthma) and can be

lessened by using the 10% solution and by

concomitant use of a bronchodilator, either mixed or

previously administered.

Other side effects include stomatitis, nausea or

vomiting and rhinorrhea. Highly concentrated

residues by the end of the nebulization should be

avoided by rediluting with sterile water.

          Incompatibility with antibiotics in mixture:

Ampicillin

Amphotericin B

Erythromycin

Tetracyclines

Aminoglycosides

Other clinical uses:

Antidote for Acetaminophen overdose

Antioxidant for ARDS and lung cancer prevention

Dornase alfa

Dornase alfa is a clone of the natural

human DNAse I enzyme, which digests

extracellular DNA.

Clinical indication:

Management of cystic fibrosis, to reduce the

frequency of infections and to improve or

preserve pulmonary function.

Mode of action:

DA breaks down DNA molecules found in infected

mucus. It has no action in uninfected mucus.

Dosage and administration:

DA is available as an ampule containing 2.5 mg in

2.5 ml. Daily dosing schedule is 2.5 mg a day. The

solution is to be refrigerated and protected from light.

Only approved nebulizers should be used for DA

Side effects:

Voice alteration

Pharyngitis

Laryngitis

Rash

Chest pain

Conjunctivitis

Other side effects are less common

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