Pulmonology – Memory Pharm

Inhaled Corticosteroid Combinations

Leave a Comment / Pulmonology / Marlene Hernandez

🧠Memory tips for inhaled corticosteroid combinations!⁠
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🌬️Inhaled corticosteroids are first-line options for treating patients with asthma. But many of these inhalers are brand-name only and some come in combination with long-acting beta 2 agonists or inhaled anticholinergics. ⁠
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🫁Inhaled corticosteroids work by reducing inflammation and swelling in the airways. Reducing inflammation makes it easier to breathe, which minimizes asthma attacks. But these medications have to be taken daily, and it may take several weeks before they’re fully effective.⁠
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🧠Some of these brands are often used on exams and it is helpful to know what their combinations are: ⁠
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TIP – we would never put two corticosteroids together so for example if the question asks about Symbicort – the answer should be ✅️budesonide with formoterol (ICS + LABA) NOT ❌️budesonide with fluticasone (ICS + ICS). ⁠

⁠👉🏻Quiz yourself on how well you know the combinations and some of my memory tips on remembering them!

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Asthma 1: What is asthma?

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Think of yourself as a visual learner? Check out our video above that uses graphics and animation to discuss the material below!

Definition:

Asthma is often defined as a chronic inflammatory disorder of the airways.

So what does that mean? Well normally, our body has an amazing filtering system for the air we breathe that starts at our nose. Our nose secretes this thick and sticky substance called mucus that traps unwanted particles like dirt, pollen, or smoke. Small hairs called cilia move in wave like motions pushing the mucus to the back of our throat where it either gets swallowed or spit out. Have you ever noticed a lot of post-nasal drip during pollen season? As irritating as it can be, that is your nose is working overtime to clear out the pollen before it reaches your lungs. This is completely normal and our body’s way of protecting us from particles that may contain bacteria or viruses that can lead illnesses.

Pathophysiology:

In asthma, the body’s inflammatory process goes into overdrive! This occurs when the immune system is exposed to something called an allergen or trigger such as pollen, pet dander, smoke, or mold. It mistakenly tags it as something bad by producing antibodies to it called IgE.

Upon reexposure to the same allergen, the body’s hyperinflammatory system remembers the allergen and causes the release of IgE antibodies that bind to and activate mast cells. Mast cells are a type of immune cell that function as the body’s first line of defense against harmful allergens preventing them from entering the body. They do this by releasing granules that contain such as histamine, prostaglandin and leukotriene. These granules sound fancy but they are just names for types of mediators of anaphylaxis. These mediators go on to cause constriction of the airway smooth muscle and increase mucous production. This process is something called the ‘early asthmatic response. This is followed 3-6 hours later by a ‘late asthmatic response’ where proinflammatory cytokine proteins recruit and activate additional immune cells such as eosinophils that contribute to continued and sustained bronchoconstriction and mucous production.

Symptoms:

These series of events lead to the symptoms of asthma including:

Wheezing
Breathlessness
Chest tightness
Coughing

In asthma, the smooth muscles around the airways tighten and shrink making them narrower leading to chest tightness. In addition, overproduction of mucous produces mucous plugs throughout the lining of the airway that can cause coughing. This makes it tough to move air through and almost causes a whistling sound as air passes through the narrow space. This is known as wheezing. The narrow and inflamed airways not only lead to decrease oxygenation but also decrease ventilation as air gets trapped inside the lungs. The increase work of breathing to get air in and out can lead to exhaustion and breathlessness as seen in patients with asthma.

Diagnosis:

In addition to the patient’s symptoms, medical history and physical exam, physicians commonly use a spirometer to diagnose asthma. A spirometer is a device used to measure the volume of air inspired and expired by the lungs. A physician will have a patient use the spirometer after administering a medication called a beta agonist. If there is an improvement in the spirometry readings after using the beta agonist, this is a good indication of asthma since it is reversible with medications, unlike COPD. Once the diagnosis is confirmed, initial asthma management depends on how often they have symptoms such as nighttime awakenings, the need for a rescue inhaler to control symptoms, activity limitations due to asthma and daytime symptoms.

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Asthma 2: Asthma Medications Made Simple

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Think of yourself as a visual learner? Check out our video above that uses graphics and animations to discuss the material below!

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?

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.

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Asthma, Management of

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📖 Asthma is a common airway disease and has a range of severity, from a very mild, occasional wheeze to acute, life-threatening airway closure. It usually presents in childhood and is associated with other features of atopy, such as eczema and hayfever.⁠ ⁠ 💊 Medical management includes bronchodilators like beta-2 agonists and muscarinic antagonists (salbutamol and ipratropium bromide respectively) and anti-inflammatories such as oral or nebulized steroids. Theophylline was once popular but is rarely used due to its narrow therapeutic index and side effect profile. However, it is still important to note as there are patients still treated with it. ⁠ ⁠ 💊 Patients with life-threatening asthma are managed with high flow oxygen inhalation, systemic steroids, back-to-back nebulizations with short-acting beta 2 agonists, and short-acting muscarinic antagonists, and intravenous magnesium sulfate.⁠ ⁠ 💊 Antibiotics should only be used if an infection is suspected (positive CXR, symptoms of cough and purulent sputum production, fever, high WBC, etc.) and should be withheld if not, to reduce the rise of antimicrobial resistance. ⁠

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Corticosteroid Side Effects

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Ever been on corticosteroids before? Due to the activation of the sympathetic system (“fight or flight”), your body responds with an increase in blood pressure, blood sugar, mood changes, and blood volume. With short term use, side effects are minor but can vary depending on their dose and how long they are taken.

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Short-Acting Beta-2 Agonists

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Singular (Montelukast)

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💊 Montelukast is an oral leukotriene modifier that reduces the proinflammatory and bronchoconstriction effects of leukotrienes that occur in asthma patients or allergies. ⁠⠀
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⭐ They are not used to treat acute exacerbations and must be taken on a regular basis, even during symptom-free periods. ⁠⠀
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This medication is dosed based on age not weight and is often dosed once daily! ⁠⠀
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🧠 Memory tip: When you hear the brand name Singulair, think of the word ‘singular’ which refers to one person or thing or in this case, once a day!⁠⠀

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