Module 3: Drugs for Asthma + COPD Flashcards
Asthma Pathophysiology from Drug POV
Symptoms of asthma result from a combination
of inflammation and bronchoconstriction, so
treatment must address both components
COPD Pathophysiology from Drug POV
Symptoms of COPD result largely from two
pathologic processes: Chronic bronchitis and
emphysema
Both processes are caused by an exaggerated
inflammatory reaction to cigarette smoke
Chronic bronchitis, which is defined by a chronic
cough and excessive sputum production, results
from hypertrophy of mucus-secreting glands in
the epithelium of the larger airways
Overview of Drugs for
Asthma and COPD
Two main pharmacologic classes
Anti-inflammatory agents
* Glucocorticoids (prednisone)
Bronchodilators
* Beta2 agonists (albuterol)
Inhalation Drug Therapy
Three obvious advantages
Therapeutic effects are enhanced
Systemic effects are minimized
Relief of acute attacks is rapid
Three types
Metered-dose inhalers (MDIs)
Respimats
Dry-powder inhalers (DPIs)
Nebulizers
Anti-inflammatory Drugs
Foundation of asthma therapy
Taken daily for long-term control
Principal anti-inflammatory drugs are the
glucocorticoids (eg, budesonide, fluticasone)
Anti-inflammatory Drugs:
Glucocorticoids
Mechanism of action
Considered the most effective antiasthma drugs
available
Decrease synthesis and release of inflammatory
mediators
Reduce infiltration and activity of inflammatory cells
Decrease edema of the airway mucosa caused by
beta2 agonists
Usually administered by inhalation, but IV and
oral routes are also options
Mechanism of action = suppress inflammation
Reduce bronchial hyperreactivity and decrease
airway mucous production
May increase the number of bronchial beta2
receptors and their responsiveness to beta2
agonists
Use
Prophylaxis of chronic asthma
Dosing must be on a fixed schedule, not as needed
(PRN)
Not used to abort an ongoing attack because
beneficial effects develop slowly
Inhaled use
First-line therapy for management of inflammatory
component of asthma
Most patients with persistent asthma should use
these drugs daily
Inhaled glucocorticoids are very effective and much
safer than systemic glucocorticoids
Oral use
For patients with moderate to severe persistent
asthma or for management of acute exacerbations of
asthma or COPD
Potential for toxicity; should be used only when
symptoms cannot be controlled with safer
medications (inhaled glucocorticoids, inhaled beta2
agonists)
Treatment should be as brief as possible
Anti-inflammatory Drugs:
Glucocorticoids
Adverse Effects of Inhaled Forms
Adverse effects of inhaled forms
Adrenal suppression
Mechanism: Corticosteroids can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to reduced production of natural cortisol by the adrenal glands. This is more likely with higher doses of inhaled corticosteroids.
Implications: In situations of stress, such as surgery or severe illness, patients with adrenal suppression may require supplemental systemic corticosteroids to prevent adrenal crisis.
Oropharyngeal candidiasis
Description: Also known as oral thrush, this is a fungal infection caused by Candida species, commonly Candida albicans. The inhaled corticosteroid can disrupt the normal oral flora balance and depress local immune responses, creating an environment conducive to fungal overgrowth.
Prevention and Management: Rinsing the mouth with water and spitting it out after each inhalation can help reduce the risk. Antifungal treatments, such as nystatin or fluconazole, may be needed if an infection develops.
Dysphonia
Description: Dysphonia refers to difficulty speaking or changes in the voice, such as hoarseness. Inhaled corticosteroids can cause irritation and myopathy of the laryngeal muscles, leading to voice changes.
Management: Techniques such as using a spacer device with metered-dose inhalers, improving inhalation technique, and reducing the dose of inhaled corticosteroids (while maintaining asthma control) can help minimize this effect. Voice rest and hydration may also be beneficial.
Glucocorticoids can slow growth in children and
adolescents; however, these drugs do not decrease
adult height
Promotion of bone loss
Increased risk of cataracts
Increased risk of glaucoma
Anti-inflammatory Drugs:
Glucocorticoids
Adverse Effects of Oral Forms
Adverse effects of oral forms
Short-term therapy
Long-term therapy
Adrenal suppression
Osteoporosis
Hyperglycemia
Peptic ulcer disease
In young patients: Growth suppression initially, but
does not impact final adult height
Adrenal suppression
Prolonged glucocorticoid use can decrease the ability of the adrenal cortex to produce glucocorticoids of its own
Life-threatening at times of severe physiologic stress (eg, surgery, trauma, or systemic infection)
High levels of glucocorticoids are required to survive severe stress
Adrenal suppression prevents production of endogenous glucocorticoids
Patients must be given increased doses of oral or IV
glucocorticoids at times of stress
Failure to do so can prove fatal
D/C Gluticosteroid Treatment
Discontinuing treatment
* Must be done slowly
* Recovery of adrenocortical function takes several months
* Dosage of exogenous sources must be reduced gradually
* During this time, patients—including those switched to
inhaled glucocorticoids—must be given supplemental oral or IV glucocorticoids at times of severe stress
Anti-inflammatory Drugs:
Leukotriene Receptor Antagonists
Suppress effects of leukotrienes
Leukotrienes: Promote smooth muscle constriction,
blood vessel permeability, and inflammatory
responses through direct action and recruitment of
eosinophils and other inflammatory cells
In patients with asthma, leukotriene modifiers
can reduce bronchoconstriction and
inflammatory responses such as edema and
mucous secretion
Second-line agents
Generally well tolerated but can cause adverse
neuropsychiatric effects, including depression,
suicidal thinking, and suicidal behavior
Available agents
Zileuton [Zyflo]
Zafirlukast [Accolate]
Montelukast [Singulair
Zileuton [Zyflo]
Mechanism of Action
Leukotriene Inhibition: Zileuton works by inhibiting 5-lipoxygenase, an enzyme that is crucial in the leukotriene synthesis pathway. By blocking this enzyme, zileuton prevents the formation of leukotrienes, such as leukotriene B4 (LTB4), which is involved in inflammatory responses, and cysteinyl leukotrienes (LTC4, LTD4, LTE4), which are potent bronchoconstrictors and contribute to the pathophysiology of asthma.
Effect on Asthma: By reducing leukotriene production, zileuton decreases inflammation, bronchoconstriction, and mucus secretion in the airways, leading to improved asthma symptoms and lung function.
Adverse Effects
While zileuton can be effective in managing asthma, it can also have several adverse effects, some of which include:
Liver Enzyme Elevations: One of the most significant concerns with zileuton is its potential to cause liver injury. It can increase liver enzymes, indicating liver stress or damage. Patients taking zileuton require regular monitoring of liver function tests before and during treatment to detect any liver injury early.
Nausea and Dyspepsia: Gastrointestinal disturbances such as nausea, dyspepsia (indigestion), and abdominal pain can occur in patients taking zileuton.
Headache: Some patients may experience headaches while on zileuton therapy.
Neuropsychiatric Events: Although less common, neuropsychiatric events such as sleep disturbances, depression, and anxiety have been reported in patients taking leukotriene modifiers, including zileuton.
Given the potential for liver toxicity and other adverse effects, the use of zileuton is generally reserved for patients whose asthma is not adequately controlled with other medications, and who can adhere to the required monitoring. The decision to use zileuton should involve a careful assessment of the benefits and risks, considering the individual patient’s asthma severity, comorbid conditions, and response to other asthma therapies.
Montelukast [Singulair]
Mechanism of Action
Leukotriene Receptor Blockade: Montelukast works by selectively blocking leukotriene receptors, specifically the cysteinyl leukotriene type 1 (CysLT1) receptors found in the lungs and airways. Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory mediators produced by cells in the lungs, including mast cells and eosinophils, and are involved in the pathophysiology of asthma and allergic rhinitis.
Effect on Asthma and Allergies: By blocking the action of cysteinyl leukotrienes, montelukast reduces bronchoconstriction, airway inflammation, and mucus production, leading to improved control of asthma symptoms. It also reduces nasal congestion, sneezing, and itching in allergic rhinitis.
Adverse Effects
Montelukast is generally well-tolerated, but some individuals may experience side effects, including:
Psychiatric Events: There have been reports of neuropsychiatric events in patients taking montelukast, including mood changes, depression, suicidal thoughts or actions, agitation, aggressive behavior, hallucinations, and sleep disturbances. The U.S. Food and Drug Administration (FDA) has issued warnings about these potential risks, and patients and caregivers are advised to be alert to changes in behavior or mood.
Respiratory Symptoms: Although used to treat asthma, montelukast can sometimes cause or worsen respiratory symptoms like cough, wheezing, or shortness of breath in some individuals.
Gastrointestinal Issues: Some people may experience stomach pain, diarrhea, indigestion, or nausea.
Headaches: Headaches are among the more common side effects reported by patients taking montelukast.
Given the potential for neuropsychiatric side effects, healthcare providers are advised to weigh the risks and benefits of prescribing montelukast, particularly for mild conditions not adequately controlled by other treatments. Patients and caregivers should be informed about the signs and symptoms of potential psychiatric events. Montelukast is typically used when other treatments, such as inhaled corticosteroids for asthma, have not provided adequate control of symptoms, or in cases where patients have concurrent asthma and allergic rhinitis.
Mast Cell Stabilizer:
Cromolyn
Used for prophylaxis, not for quick relief
Suppresses inflammation; not a bronchodilator
Mechanism of action: Stabilizes cytoplasmic
membrane of mast cells, thereby preventing
release of histamine and other mediators; in
addition, inhibits eosinophils, macrophages, and
other inflammatory cells
Route: Inhalation
Nebulizer
Therapeutic use
Chronic asthma
Exercise-induced bronchospasm (EIB)
Allergic rhinitis
Adverse effects
Safest of all antiasthma medications
Cough
Bronchospasm
Monoclonal Antibody:
Omalizumab [Xolair]
Mechanism of action
Antagonism of immunoglobulin E (IgE), a type of
antibody
Therapeutic use
Patients age 12 years or older with moderate to
severe asthma that (1) is allergy related and (2)
cannot be controlled with an inhaled glucocorticoid
Adverse effects
Injection-site reactions
Viral infection
Upper respiratory infection
Sinusitis
Headache
Pharyngitis
Cardiovascular events
Malignancy
Life-threatening anaphylaxis
Interleukin-5 Receptor Antagonists: Benralizumab, Mepolizumab, Reslizumab
Benralizumab, mepolizumab, and reslizumab are monoclonal antibodies targeting the interleukin-5 (IL-5) pathway, which plays a crucial role in the maturation, activation, and survival of eosinophils.
Eosinophils are a type of white blood cell involved in the inflammatory process of certain types of asthma, particularly eosinophilic asthma, which is characterized by high levels of eosinophils in the blood, tissue, and sputum. These medications are part of a class known as interleukin-5 receptor antagonists and are used as add-on maintenance treatments for severe eosinophilic asthma in adults and some pediatric populations.
Actions and Uses
Benralizumab (Fasenra): Targets the IL-5 receptor alpha on eosinophils and basophils, leading to direct cell apoptosis (cell death). It is administered via subcutaneous injection.
Mepolizumab (Nucala): Binds to IL-5 itself, preventing it from interacting with its receptor on eosinophils. It reduces blood, tissue, and sputum eosinophil levels and is administered via subcutaneous injection.
Reslizumab (Cinqair): Also binds directly to IL-5, inhibiting its activity. It is indicated for intravenous use.
These agents are used in individuals with severe asthma that is not well controlled with standard treatments such as high-dose inhaled corticosteroids and long-acting beta-agonists. By targeting IL-5, they effectively reduce eosinophil counts, leading to fewer asthma exacerbations, improved lung function, and better asthma control.
Adverse Effects
Injection Site Reactions: Pain, erythema, and swelling at the injection site are common for subcutaneously administered drugs (benralizumab and mepolizumab).
Hypersensitivity Reactions: Although rare, hypersensitivity reactions, including anaphylaxis, can occur following administration of these medications.
Headache: A frequently reported side effect.
Respiratory Infections: There is an increased risk of common respiratory infections, such as nasopharyngitis and bronchitis.
Herpes Zoster: Some patients may have an increased risk of developing herpes zoster (shingles) while on these treatments.
Contraindications
Hypersensitivity: The primary contraindication for benralizumab, mepolizumab, and reslizumab is a known hypersensitivity to the active substance or any of the excipients. Patients with a history of hypersensitivity reactions to these drugs should not receive them.
**for severe asthma
