Although inhaled corticosteroids and oral corticosteroids have similar mechanisms of action, they have different indications for use, side effects, and drug interactions.

Mechanisms of Action

Corticosteroids are man-made drugs that mimic the action of the stress hormone cortisol. Cortisol is the hormone secreted by the adrenal glands and has potent anti-inflammatory effects.

At times of physical or emotional stress, cortisol can slow the rate at which lymphocytes and other white blood cells replicate. Though these cells are central to the body’s defense, increased numbers trigger the release of inflammatory proteins known as cytokines, causing redness, swelling, pain, and increased sensitivity in affected tissues.

This action is important in controlling a disease like asthma in which persistent inflammation can increase airway hyperresponsiveness (sensitivity to asthma triggers like allergens, temperature, and environmental irritants). By tempering inflammation, hyperresponsiveness is reduced along with the risk of acute attacks.

Though inhaled and oral corticosteroids work in more or less the same way, they differ in how they are used to treat asthma:

Inhaled corticosteroids: Because they are delivered directly to the lungs, inhaled steroids require smaller doses (measured in micrograms—mcg), have fewer side effects, and are safer for long-term use. They are considered the first-line controller medication for people with asthma.  Oral corticosteroids: Because they are delivered systemically (via the bloodstream), oral steroids require larger doses (measured in milligrams—mg), have more side effects, and pose greater harms with long-term use. They are reserved for more severe cases.

There are different types of inhaled and oral steroids approved to treat asthma in the United States.

Indications for Use

Inhaled and oral corticosteroids differ in when they are introduced into an asthma treatment plan.

Inhaled Corticosteroids

Inhaled corticosteroids are indicated for asthma that is not well controlled with a short-acting beta-agonist (SABA), also known as a rescue inhaler. They are used on a long-term basis and regularly—usually daily or several times a day—although based on updated guidelines from the National Institutes of Health (NIH) for asthma management issued in December 2020, some people with mild persistent asthma may not need to use an inhaler every day.

If you use an inhaler every day, talk to your healthcare provider about the NIH guidelines to find out if they might apply to your asthma treatment.

Persistent asthma is classified in stages (mild, moderate, severe) and can be diagnosed when you have:

Acute asthma symptoms more than two days a week More than two nighttime awakenings per month due to asthma More than twice-weekly use of a rescue inhaler Limitations to normal activities due to asthma

Inhaled corticosteroids can be used in all stages of persistent asthma. As the severity of the disease increases, the steroid dose will also increase.

Oral Corticosteroids

Oral corticosteroids are used either to treat a severe asthma attack or to provide long-term control of severe persistent asthma.

Severe asthma attacks (requiring hospitalization or emergency care) are typically treated with an intravenous dose of a corticosteroid drug to bring down the acute inflammation. This will be followed by a short course of oral corticosteroids to help normalize lung function and prevent a repeat attack. Severe persistent asthma is a stage of the disease when your lung function is severely impaired and other asthma medications fail to control your symptoms. In cases like these, oral steroids are prescribed on a daily basis in combination with other medications.

Severe persistent asthma is diagnosed when you meet some or all of certain criteria, such as frequent use of a rescue inhaler throughout the day and severely reduced lung function (as measured by an FEV1 value of under 60% of your expected range).

Dosages

Inhaled and oral corticosteroids differ by the amount of drug a person is exposed to with each dose and the duration of treatment.

Inhaled Corticosteroids

Because inhaled corticosteroid doses are relatively small, people with asthma can use these treatments on an ongoing basis with relative safety. Depending on the drug used—as well as the user’s age and the severity of symptoms—inhaled steroids may be used once or twice daily.

Different inhaled steroids use different delivery systems:

Metered-dosed inhalers (MDIs) use an aerosolized propellant to deliver the steroids into the lungs. Dry powder inhalers (DPIs) require you to suck in the dose with your breath. Nebulizers transform the drug into an aerosolized mist for inhalation and are ideal for babies, younger children, or those with severe breathing problems.

When used for asthma emergencies, oral corticosteroids are typically prescribed for no longer than five to 10 days. The dose can vary by the drug used but is typically calculated as 1 milligram per kilogram of body weight (mg/kg) with a maximum daily dose of around 50 mg.

When oral corticosteroids are used for the long-term treatment of severe persistent asthma, the dose and duration of treatment can vary by the combination of drugs used.

For example, when an oral corticosteroid is used with a biologic drug such as Xolair (omalizumab), it can often be administered at a lower dose and for a longer period of time. Similarly, a daily inhaled steroid reduces the amount of oral steroid you need to control asthma symptoms.

Depending on the dose and how long you’ve used the oral steroid, the tapering process may take weeks or months.

Side Effects

There are generally fewer and less severe side effects associated with inhaled corticosteroids than with oral corticosteroids. But, this is not always the case.

Common

Side effects of inhaled steroids are generally limited to the upper respiratory tract, although systemic side effects can occur as well. Oral steroids can cause a diverse range of side effects impacting multiple organ systems.

Severe

Although inhaled steroids pose a lesser risk of side effects than oral ones, this does not mean they pose no risks.

Inhaled and oral corticosteroids can cause immune suppression, increasing your risk for common and uncommon infections. They can also cause hormonal imbalances by impairing the function of the adrenal glands.

Prolonged exposure to corticosteroids, whether inhaled or oral, can also inhibit bone growth and cause irreversible changes in your vision.

Drug Interactions

Both inhaled and oral steroids are metabolized by a liver enzyme called cytochrome P450 (CYP450). Other drugs that are also metabolized by CYP450 can interact with corticosteroids as they compete for the available enzyme. This can cause adverse increases or decreases of one or both drugs in the bloodstream.

Some of the more significant CYP450 interactions involve certain classes of drugs:

Anti-arrhythmia drugs like Pacerone (amiodarone) Anticonvulsants like Tegretol (carbamazepine) Antifungals like Nizoral (ketoconazole) Anticoagulants like Coumadin (warfarin) Calcium channel blockers like Verelan (verapamil) Chemotherapy drugs like cyclophosphamide HIV protease inhibitors like Crixivan (indinavir) Hormonal contraceptives like Ethinyl estradiol Immunosuppressant drugs like Sandimmune (cyclosporine) Macrolide antibiotics like clarithromycin Opioid drugs like Oxycontin (oxycodone) Tuberculosis drugs like rifampin

By contrast, oral steroids are more likely to cause significant interactions due to their higher doses. These interactions may require a dose adjustment, a drug substitution, or a separation of doses by one or several hours.

Oral corticosteroids can also interact with specific drugs that are less commonly affected by inhaled corticosteroids, including:

Digoxin (digitalis) Fluoroquinolone antibiotics Nonsteroidal anti-inflammatory drugs (NSAIDs) Seroquel (quetiapine) Thalomid (thalidomide) Vaccines

To avoid interactions, always advise your healthcare provider about any drugs you are taking, whether they are prescription, over-the-counter, herbal, or recreational.

A Word From Verywell

Corticosteroid drugs can be highly effective for treating asthma if used as prescribed. Always keep to a strict schedule when taking a steroid, spacing your doses equally to ensure you neither have too little or too much of the drug in your system at one time.

Never increase or decrease a corticosteroid dose without first speaking to your healthcare provider. Larger doses don’t always afford better results, and lower doses may end up causing withdrawal symptoms and other harmful effects.

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