Corticosteroids, Inhaled

Definition

Inhaled corticosteroids are glucocorticoids (a class of steroid hormones that are synthesized by the adrenal cortex and have anti-inflammatory activity) formulated to be used in the respiratory tract and lungs.

Purpose

Inhaled corticosteroids are glucocorticoid compounds designed to be applied directly to the tissues of the respiratory tract. There are two types. The intranasal are deposited into the nasal passages and may be used to treat nasal polyps, perennial allergic rhinitis, seasonal allergic rhinitis, and recurrent chronic sinusitis.

The second type is used when the steroids are designed for deposition further into the respiratory tract. These are used for treatment of chronic asthma and prevention of asthmatic attacks.

Because they have anti-inflammatory effects, corticosteroids are invaluable in treatment of asthma and other respiratory conditions which are associated with an allergic reaction. In many cases, the corticosteroids are life saving. But systemic corticosteroids affect all parts of the body and may cause very severe adverse effects, particularly with long-term use. These reactions include inhibitions of the adrenal glands and weakening of bones. By administering these drugs by inhalation, it is possible to target the areas that require treatment and reduce the amount of drug that reaches other parts of the body. Some patients may be able to do without systemic steroids entirely, while others can reduce their doses of systemic steroids and thereby reduce the risk and severity of unwanted effects.

The drugs used as inhaled steroids are all anti-inflammatory corticosteroids and are very similar to each other in action and use. The way they are formulated, the size of the particles, the design of the inhaler, and whether the drugs are inhaled by the mouth or nose determine how far into the respiratory tract the steroids go. The formulations designed for nasal inhalation are only effective for nasal polyps or rhinitis because the steroid does not penetrate deeply into the respiratory tract. Oral inhalations, containing the same drug but in different particle size and inhaler design, deposit medication deeply into the lungs and are of value in treatment of asthma.

Description

As of 2005, there are five corticosteroids designed for inhalation:

• beclomethasone dipropionate (Qvar)
• budesonide (Pulmicort)
• flunisolide (AeroBID)
• fluticasone propionate (Flovent)
• triamcinolone acetonide (Azmacort)

Although the different products vary in potency and duration of action, once dose size and frequency have been adjusted to offer comparable results, there do not appear to be significant differences between the drugs. The design of the inhalers, their ease of use, and the training each patient receives in the proper use of the inhaler may be of greater significance than the drug itself.

Recommended dosage

Although the different products vary in milligram potency, for practical purposes, doses are measured in puffs on the inhaler. For example, beclomethasone will deliver 40 micrograms each time the inhaler is used, while triamcinolone delivers 100 micrograms with each inhalation. However, the effects are essentially equal.

The appropriate dose of inhaled corticosteroids depends on the severity of the case, and in some instances, on what treatment has been used prior to starting inhaled steroid therapy. The doses listed are typical of the inhaled steroids used for asthma therapy but do not represent all possible cases:

• beclomethasone: one to two puffs two times a day
• budesonide: one to two puffs two times a day
• flunisolide: two puffs two times a day
• fluticasone propionate: available in forms that deliver either 50 or 100 micrograms of fluticase in each puff; typical initial dose, 100 micrograms two times a day, representing either one puff of the 100 microgram product or two puffs of the 50 microgram product
• triamcinolone acetonide: two puffs three or four times a day or four puffs twice a day, not to exceed 16 puffs daily

Precautions

Particular care is essential for patients who are transferred from systemic corticosteroids to inhaled steroids. Because the long-term use of oral steroids lowers the output of these compounds from the adrenal gland and normal production does not recur for several months, patients who have their oral doses reduced are at risk of adrenal insufficiency. This condition may become particularly serious in the event of trauma, surgery, or infections. While inhaled steroids may provide adequate control of asthma during these periods, the inhaled drugs do not replace the systemic compounds. In the event of stress or a severe asthma attack, oral therapy must immediately begin. Regular testing for cortisol levels is essential until the normal levels have been resumed.

For patients who had been on systemic therapy and are being switched to corticosteroid inhalation, the immediate period during which the oral dose is reduced may cause symptoms, including joint or muscle pain, tiredness, and depression. Continuous monitoring is required until normal functions have been resumed.

It is essential that patients learn proper use of inhalers. If inhalers are not used properly, the corticosteroids may not reach their intended site of action. Instead, they may be left in the mouth or swallowed and be deposited in the digestive tract. This situation may increase the risk of adverse effects, while reducing the protection from asthmatic attacks.

Inhaled corticosteroids are not for treatment of acute asthmatic attacks or rapid relief of bronchospasm.

Inhaled corticosteroids are designated as pregnancy category C. This designation means one of two levels of knowledge concerning the drugs adverse effects. In one instance, studies on animals show adverse fetal effects but there are no controlled studies on women. In the other instance, no studies on animals and women are not available.

Side effects

It can be difficult to evaluate the side effects of inhaled corticosteroids because many of the reported adverse effects are closely associated with dose reduction or discontinuation of systemic steroids. Not all of the adverse reactions listed have been associated with all of the marketed inhaled steroids, but because of the similarities between these drugs, an adverse reaction reported with one must be considered possible for the others.

The most common severe problem is white patches in the mouth due to localized infection. Additional common side effects are:

• cough
• general aches and pains or general feeling of illness

• greenish-yellow mucus in nose
• headache
• hoarseness or other voice changes
• loss of appetite
• runny, sore, or stuffy nose
• unusual tiredness
• weakness

Very rare but severe adverse effects include the following:

• blindness, blurred vision, eye pain
• large hives
• bone fractures
• diabetes mellitus (increased hunger, thirst, or urination)
• excess facial hair in women
• fullness or roundness of face, neck, and trunk
• growth reduction in children or adolescents
• heart problems
• high blood pressure
• hives and skin rash
• impotence in males
• lack of menstrual periods
• muscle wasting
• numbness and weakness of hands and feet
• weakness
• swelling of face, lips, or eyelids
• tightness in chest, troubled breathing, or wheezing

Interactions

Because inhaled steroids do not reach therapeutic levels in the blood stream, there are no serious interactions. Ketoconazole (Nizoral), an antifungal agent, has been reported to increase blood levels of budesonide and fluticasone, but it is unclear whether this has any importance when the steroids are administered by inhalation.

Resources

BOOKS

Austen, K. Frank, ed. Samter's Immunological Diseases. Baltimore, MD: Lippincott Williams & Wilkens, 2001.

Beers, Mark H., ed. Merck Manual of Medical Information: Home Edition. Riverside, NJ: Simon & Schuster, 2004.

Physicians' Desk Reference 2005. Montvale, NJ: Thomson Healthcare, 2004.

KEY TERMS

Adrenal glands— The two glands that are located on top of the kidneys. These glands secrete several hormones, including the glucocorticoids which, among other things, influence the way the immune system works, and the mineralocorticoids, which affect retention of water and sodium.

Glucocorticoid— A class of steroid hormones that are synthesized by the adrenal cortex and have anti-inflammatory activity.

Perennial— Present at all seasons of the year.

Polyp— A small vascular growth on the surface of a mucous membrane.

Respiratory tract— The air passages from the nose to the air sacs of the lungs, including the pharynx, larynx, trachea, and bronchi.

Rhinitis— Inflammation of the mucous membranes of the nose.