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Main Asthma Medications:
The main medications used to treat chronic asthma are easiest to remember using the following mnemonic.
I like lazy Saturdays!
I is for inhaled corticosteroids because I come first to help you remember that they are the first line of treatment in asthma! Like is for leukotriene modifiers, Lazy is for long acting beta-2 agonist (these are used even on a lazy day!) Saturdays is for short acting beta-2 agonist because on Saturday college football players may require a short acting beta-2 agonist. Let’s dive into each of these further.
Treatment Goal:
The goals of asthma treatment are to prevent chronic symptoms that can interfere with daily living, and decrease the need for rescue inhalers, maintain pulmonary function and activity level, and prevent exacerbations.
Inhaled Corticosteroids:
Inhaled corticosteroids are considered the key controller medications that work by reducing inflammation specifically in the lungs. They do this by binding onto glucocorticoid receptors which go on to inhibit the transcription of inflammatory genes such as cytokines as well as the activation of esoinophils and the release of inflammatory mediators. Cytokines are like your messenger proteins that alerts other immune system cells to the site of inflammation. Eosinophils are a type of white blood cell that can cause inflammation and swelling. The inflammatory mediators like leukotrienes, histamine, or prostalgandins directly lead to the symptoms of inflammation. By inhibiting them, this reduces the hyperinflammatory cascade that leads to bronchial hyperreactivity, swelling and mucus production, making it easier to breath and preventing future asthma attacks.
It is the preferred medication for controlling asthma over the long term since hyperinflammation is the main cause of asthma. Examples include:
- Budesonide (Pulmicort)
- Beclomethasone (QVAR)
- Fluticasone (Flovent),
- Mometasone (Asmanex)
- Clicosenide (Alvesco)
Steroids often end in the suffix ‘onide’ or ‘-asone’ similar to prednisone or cortisone (naturally occurring corticosteroid).
Luckily, Inhaled corticosteroids work locally and have relatively few side effects compared to oral corticosteroids. The common side effects of inhaled corticosteroids can be remembered using the mnemonic HOCUS:
- Hoarseness
- Oral thrush/candidiasis (Be sure to counsel patients to rinse their mouth and throat with warm water and spit to prevent this from occuring)
- Cough
- Upper respiratory tract infections (is rare and often occurs with high doses or long-term use)
- Sore throat
Inhaled Beta-2 Agonists:
Beta-2 agonists are bronchodilators that work to relax the smooth muscle bands that tighten around the airways and are divided into two forms, short-acting and long-acting beta-2 agonists. These forms differ by their duration of action with short acting beta-2 agonists working rapidly within 5 minutes to reverse bronchoconstriction and relieve or stop asthma symptoms which makes this a great rescue inhaler. Long-acting beta-2 agonists help keep the airways open for 12 hours or longer and are used on a daily basis to prevent asthma attacks.
Beta-2 agonists work by binding on to beta-2 receptors located on smooth muscles of the airways in the lungs. If you can recall, beta-2 receptors are commonly located on the lungs while beta-1 receptors are mainly located on cardiac muscles. Remember, we have 2 lungs (beta-2) and 1 heart (beta-1).
Activation of beta-2 receptors causes an increase in cyclic AMP which leads to a decrease in calcium release. Since calcium plays a big role contraction, a decrease in calcium leads to a decrease in contraction of airway smooth muscles and bronchodilation.
Beta-2 agonists can cause some unwanted side effects with the heart at high doses such as increased heart rate, palpitations, blood pressure, and anxiety. You can remember this as the beta symbol also looks like a heart turned sideways. Other side effects include tremors, hyperglycemia, hypokalemia, and cough.
It is important to monitor how often patients are using their rescue inhaler as frequent use can indicate that their asthma is not under control. Other things to monitor include BP, HR, blood glucose and potassium. Also, since this class of medications works quickly, they are often used prior to exercise or in exercise induced asthma. They can be taken 5-15 minutes before exercise and last 2-3 hours. Remember back to how the football player may need this on the sidelines at his Saturday game?
Activation of beta-2 receptors causes an increase in cyclic AMP which leads to a decrease in calcium release. Since calcium plays a big role contraction, a decrease in calcium leads to a decrease in contraction of airway smooth muscles and bronchodilation.
Beta-2 agonists can cause some unwanted side effects with the heart at high doses such as increased heart rate, palpitations, blood pressure, and anxiety. You can remember this as the beta symbol also looks like a heart turned sideways. Other side effects include tremors, hyperglycemia, hypokalemia, and cough.
It is important to monitor how often patients are using their rescue inhaler as frequent use can indicate that their asthma is not under control. Other things to monitor include BP, HR, blood glucose and potassium. Also, since this class of medications works quickly, they are often used prior to exercise or in exercise induced asthma. They can be taken 5-15 minutes before exercise and last 2-3 hours. Remember back to how the football player may need this on the sidelines at his Saturday game?
Long-acting beta-2 agonist or LABA works just like a SABA, it just lasts longer with a duration of action of 12 hours and are used with a twice daily dosing regimen. Examples include salmeterol and formoterol.
You can remember this because they contain words similar to metro in their names. Metro trains run long distances, so these are long-acting.
Because they have no anti-inflammatory action, these medications should not be used alone in asthma due to increased risk of asthma-related deaths. That is why they are often found in combination with an inhaled corticosteroid like Symbicort which includes budesonide and formoterol or Advair including salmeterol and fluticasone.
Side effects are similar to short-acting beta2 agonist. Remember, long-acting beta-2 agonists with inhaled corticosteroids are considered controller medications and should be taken daily even on a lazy day to prevent asthma exacerbations.
Now that we have talked about specific counseling points about the different types of inhaled medications, let’s review how to counsel a patient on using their metered dose inhaler using the mnemonic: SPORTT
- Shake well before each use
- Prime before first use by shaking well for 5 seconds and then spraying into the air 3 times. This should be repeated if the inhaler has not been use for more than 7 days.
- Out. Take a deep breath and breathe out all the way
- Rest the inhaler in the mouth and close your lips around it.
- Take a deep breath in as you press all the way down on the inhaler to release the medication.
- Ten seconds. Hold your breath for as long as you can up to 10 seconds
Spacers should be used for children as they help to ensure proper delivery of the medication
There are several different types of inhalers that deliver medications in a slightly different way such as dry powder inhalers, respimats, accuhalers, elliptas and more. Always double check the package inserts when educating patients on how to use their new inhaler.
Leukotriene Modifiers:
Leukotriene modifiers are a great add on therapy in patients with allergies since they block the action of leukotrienes. If you can recall, leukotrienes are a type of proinflammatory chemicals that cause bronchiole smooth muscle contraction as well as recruit other proinflammatory mediators such as histamine and prostaglandin into tissues. By inhibiting leukotrienes, we can see a reduction in airway swelling, smooth muscle contraction, inflammation and nasal congestion often associated with allergies.
Examples include:
- Montelukast
- Zafirlukast
- Zileuton
They all have the suffix “-luk” in the name reminding you that it is a Leuk-otriene modifier.
Clinical pearl! This class of medications is dosed based on age not weight. Other side effects include headache, dizziness, abdominal pain, increased LFTs, upper respiratory infections, sinusitis, and pharyngitis. Behavior and mood changes are rare side effects that include aggressive behavior, agitation, hostility, depression and/or suicidal thoughts and is an important counsel point for patients. Though this may all sound like a lot, they are relatively well tolerated.
Theophylline:
Theophylline is an oral bronchodilator medication that you may see in the treatment of asthma. Its use has declined due to the greater efficacy of inhaled corticosteroids and beta-2 agonists as well as the numerous drug interactions and side effects associated with it (nausea, headache, tachycardia, insomnia, tremor, and nervousness, arrhythmias, confusion, seizures).
It has a narrow therapeutic index of 10-20 mcg/mL and requires frequent lab draws to monitor drug levels. It’s mechanism of action is not fully known but it is believed to block phosphodiesterase resulting in bronchodilation and mild anti-inflammatory effects.
Inhaled Anticholinergics:
Short-acting inhaled anticholinergics such as ipratropium can commonly be used with beta-2 agonists in acute asthma exacerbations. They inhibit acetylcholine from binding onto muscarinic receptors on airway smooth muscle cells (hence why they are called anti-cholinergics) leading to bronchodilation. They have few side effects (mainly just dry mouth that is common with tiotropium) due to the fact that they are inhaled locally and are poorly absorbed into the circulation. Long-acting inhaled anticholinergics (Spiriva or tiotropium) provide modest improvements in asthma exacerbations and are reserved in patients with uncontrolled asthma despite being on an ICS-LABA.
Omalizumab (Xolair):
Omalizumab (Xolair) is a subcutaneous injection made of IgG monoclonal antibodies that inhibit IgE binding to mast cells. If you can recall, IgE is one the main culprits that lead to asthma symptoms. Omalizumab is indicated in patients with moderate to severe persistent allergic asthma despite being on max doses of ICS-LABA. It has a box warning for anaphylaxis and requires that it be administered in a healthcare setting where patients can be monitored. Other side effects include injection site reactions, muscle pain, dizziness, fatigue, and dermatitis.
Wrapping it up:
To wrap it up, when initiating medications in a newly diagnosed asthma patient, assess their symptoms and start them on a rescue inhaler such as a short-acting beta2 agonist as needed. If their symptoms worsen, they can escalate therapy using higher doses of their controller medications. Lastly, if a patient has allergies and is not responding to other therapies, they may benefit from an add-on medication such as a leukotriene modifier.