Page 2 of 3

Mediator Modifiers

Prostaglandins Prostaglandins are synthesized in all tissues, and the three that are of substantial interest in respiratory therapy are PGE1, PGE2, and PGF2A. The first two because they cause relaxation of bronchial smooth muscle, and the latter because it causes contraction of bronchial muscle. Protaglandins, unlike adrenergic or anticholinergic drugs, act directly on smooth muscle.

Prostaglandins are used for vasodilation of the pulmonary vascular bed in patent ductus arteriosus (PDA). Increased pulmonary vascular resistance in PDA helps maintain a shunt through the patent ductus, and lowered resistance allows more blood to flow through the pulmonary system and less through the ductus. It is important to release the prostaglandin via a line located distal to the ductus, otherwise the ductus becomes dilated and the problem is worsened.

Anticholinergic bronchodilators

Anticholinergics or parasympatholytic bronchodilators, which are also often referred to as antimuscarinics because they act at the muscarinic receptors of the parasympathetic nervous system, achieve bronchodilation through a different pathway in the autonomic nervous system. As a result, anticholinergics can be used either alone or in combination with beta adrenergics.

Because they tend to decrease secretion production, drying of the airways can be a problem if significant doses are administered. Additional side-effects can include: drying of the mouth and skin, blurred vision, and an increase in speech, swallowing, and micturition problems. Among these drugs, the most common include:

Atropine sulfate which has traditionally been the model antimuscarinic bronchodilator agent used in the treatment of airway disease. It has an additive effect to the Beta adrenergic agonists when given together. However, the development and increased use of adrenergic drugs has tended to gradually displace atropine as a bronchodilator.

Atropine is available as a nebulized solution administered via injection or aerosol (Dey-Dose). Because it is a tertiary ammonium compound, atropine is readily absorbed by aerosol, and side effects are seen in the dosages required for effective bronchodilation. Duration and incidence of side effects are therefore dose dependent. Normal inhaled dose for atropine is around 0.025 mg/kg for adults (2.5 mg per 24 hours maximum), with onset in 15 minutes, peak at .5-1.0 hour, and duration 3-4 hours. Atropine is also available in tablets and elixirs.

Ipratropium Bromide (Atrovent) is approved specifically for the maintenance treatment of airflow obstruction in COPD. It is considered a first-line medication for COPD patients, particularly those with chronic bronchitis. It is currently available in two formulations for bronchodilator use: an MDI with 18 mcg per puff, and a nebulizer solution of 0.02% concentration in a 2.5 ml vial, providing a 500 mcg dose per treatment. Usual adult dose is 2 puffs QID via MDI (12 puffs per 24 hours maximum).