Asthma is a chronic inflammatory disease of the airways, that causes hyperresponsiveness, increased mucus production and mucosal oedema.
What this means is that Asthma is a long-term condition where the body has an extreme allergic reaction to environmental factors such as dust, pollen or animal dander. When triggered, this reaction causes inflammation in the airways which in turn causes excessive mucus production and swelling of the airways.
In these notes, we’ll be going over the Asthma Pharmacology, but before getting into that, make sure that you’ve understood the:
Introduction to Asthma Pharmacology
As we’ve discussed in the previous notes, the main concern in Asthmatic patients is the persistent and repetitive inflammation of the airways. To treat this, most medical providers will prescribe inhaled anti-inflammatory medication. This mode of administration will directly target the lungs and allow for a more effective treatment approach.
Keep in mind that asthmatic patients alternate between periods of exacerbations and longer periods of mild symptoms. Similarly, the medications for Asthma are split into two:
The Short-Acting Medications are indicated for exacerbations and severe asthmatic symptoms. As well as preventive in exercise-induced asthma
The Long-Acting Medications are indicated to control chronic Asthma symptoms.
Short-Acting Asthma Pharmacology
There are three main classes used for the quick relief of asthma symptoms, and these include:
Short-Acting Beta-2 Adrenergic Agonists (SABA)
Anticholinergics
Corticosteroids
The SABA and the Anticholinergics are typically both prescribed as inhalers, and both act as bronchodilators but their mechanisms are slightly different. SABAs will bind to the Beta-2 Adrenergic receptor and relax the smooth muscle, which in turn reduces bronchoconstriction. On the other hand, Anticholinergics inhibit the Muscarinic Cholinergic receptors and decrease the vagal tone of the airways. They also suppress the mucous gland secretion which helps to unplug the airways.
Corticosteroids however are typically prescribed as oral medication and act as Anti-Inflammatories. They stop the body’s reaction to the allergen decreasing the hyperresponsiveness, inhibiting cytokine production and revere the Beta-2 Receptor Downregulation. All together they reduce the inflammation and swelling of the airways.
Table 1: Short-Acting Asthma Pharmacology
Class | Generic Names | Side Effects | Drug Interactions |
Short-Acting Beta-2 Adrenergic Agonists | Albuterol Levabuterol HFA Metaprotenol Sulfate | Tachycardia Headache Muscle Tremor Paradoxical Bronchospasm Cardiovascular effects Hyperglycaemia Hypokalemia | Beta-Blockers Digoxin Non-Potassium Sparing Diuretics |
Anticholinergics | Ipratropium | Dry mouth Wheezing Cough Paradoxical Bronchospasm Ocular Effects Urinary Retention | No known drug interactions |
Corticosteroids | Methylprednisolone Prednisolone Prednisone | Weight-gain Fluid retention Hypertension Peptic ulcers Insomnia More susceptible to infections | Live vaccines Amphotericin B injection Potassium-Depleting Agents Antibiotics Antidiabetics |
Long-Acting Asthma Pharmacology
When it comes to the long-term treatment of Asthma there is a vast range of options and it all depends on the severity of the condition and the symptoms that it is presenting with. The most common long-term approach is Corticosteroids, this is because they are highly effective in treating the symptoms of Asthma, increasing airway function and reducing the peak flow variability.
Corticosteroids are usually prescribed as inhalers when managing chronic Asthma, but they are sometimes used in systemic ways (oral/intra-muscular) if the patient has severe and persistent symptoms, needs to quicken recovery or wants to prevent future exacerbations. Despite the number of advantages that corticosteroids have, several side effects work against their goal particularly the fact that they make patients more susceptible to acquiring respiratory infections.
Long-Acting Beta-2 Adrenergic Agonists (LABAs) are typically prescribed alongside anti-inflammatories to treat chronic asthmatic symptoms, especially symptoms that flare up during the night or exercise.
Leukotrienes are a group of Inflammatory Mediators, which are released by the body to block an allergen and fuel hyperresponsiveness. So Leukotriene Inhibitors do exactly the opposite, they block the production of Leukotrienes and in turn, stop bronchoconstriction. This class of medications can either be used instead of Corticosteroids or added along with inhaled corticosteroids if the patient’s condition is more advanced.
Phosphodiesterase Inhibitors affect the release of epinephrine, giving them mild anti-inflammatory properties, and they also act as bronchodilators. Theophylline is a type of phosphodiesterase inhibitor and it’s sometimes prescribed in addition to inhaled corticosteroids to treat asthmatic symptoms. However, it is used with high caution as it interacts with a lot of drugs and can cause severe side effects.
Lastly, if the patients do not respond well to treatment of high-dose inhaled corticosteroids even if given with a LABA, they would usually receive Immunomodulators either subcutaneously or intravenously. These Immunomodulators stop IgE from binding to receptors and in turn, they prevent bronchospasm, mucus hypersecretion and airway hyperresponsiveness.
So in total, we’ve mentioned 7 different medications that can be used to treat chronic asthma:
Inhaled Corticosteroids
Systemic Corticosteroids
Long-Acting Beta-2 Adrenergic Agonists
Phosphodiesterase Inhibitors
Leukotriene Modifiers
5-Lipoxygenase Inhibitor
Immunomodulators
Table 2: Long-Acting Asthma Pharmacology
Class | Generic Names | Side Effects | Drug Interactions |
Inhaled Corticosteroids | Beclomethasone Dipropionate Budesonide Ciclesonide Fluticasone | Cough Dyspnoea Headache Adrenal insufficiency Dermal thinning Paradoxical Bronchospasm Dental and oral damage | CYP3A4 Inhibitors Long-term Ketoconazole |
Systemic Corticosteroids | Methylprednisolone Prednisolone Prednisone | Adrenal axis suppression Dermal thinning Hypertension Diabetes Cushing’s syndrome Cataracts Muscle weakness Insomnia | Cyclosporin Aspirin Phenobarbital Phenytoin Rifampin |
Long-Acting Beta-2 Adrenergic Agonists (Inhaled) | Salmeterol Formoterol | Tachycardia Muscle tremor Hypokalemia Decreased protection against exercise induced bronchospasm | CYP450 3A4 Inhibitors Monoamine Oxidase Inhibitors Tricyclic Antidepressants Beta-Adrenergic Receptor Blocking Agents Non-Potassium Sparing Diuretics |
Phosphodiesterase Inhibitors | Theophylline | Insomnia Gastric upset GERD Peptic ulcers | Dipyridamole Febuxostat Riociguat (full list here.) |
Leukotriene Modifiers | Montelukast Zafirlukast | Headache Dizziness Upper respiratory infections Pharyngitis Sinusitis | Idelalisib Ivacaftor |
5- Lipoxygenase Inhibitor | Zileuton | Elevated liver enzymes | Theophylline Warfarin Propranolol |
Immunomodulators | Omalizumab Mepolizumab Reslizumab (IV) Dupilumab | Muscle aches Bruising Irritation of skin on injection sites | No formal drug interactions have been performed |