Pharm Wk6 - Asthma Flashcards
What is asthma?
A chronic inflammatory disease of the airways
What mediators are released by mast cell activation in asthma?
Bronchoconstrictor mediators such as:
* Histamine
* Leukotriene D4
* Prostaglandin D2
What are the consequences of bronchoconstrictor mediator release?
Leads to:
* Smooth muscle contraction
* Vasodilation
* Microvascular leakage
* Plasma exudation
* Mucus hypersecretion
* Activation of sensory nerves
What is the long-term effect of chronic inflammation in asthma?
Irreversible fibrosis
At what age is asthma typically diagnosed?
In childhood
Is adult-onset asthma a possibility?
Yes, adult-onset asthma does exist
How have pharmaceutical standards for asthma treatment changed?
They have been converging for children and adults
What is the goal of asthma therapy for infants and children?
To prevent cough, wheeze, or shortness of breath that interferes with:
* Daytime activities
* Exercise
* School attendance
* Growth and development
* Sleep
What is a key goal regarding exacerbations for infants and children with asthma?
Prevent exacerbations requiring emergency room visits, hospitalizations, or systemic corticosteroids
What is the target for the use of short-acting beta2-agonists (SABAs) in children?
To reduce to ≤2 doses/week
What pulmonary function measure should be achieved in children capable of performing tests?
Normal measures of pulmonary function, e.g., forced expiratory volume in 1 second (FEV1)
What should be avoided to minimize medication side effects in children?
Interference with normal growth
What is a primary goal of asthma therapy for adults?
Prevent asthma-related mortality
What should be maintained for adults with asthma?
Asthma control and normal activity levels
What is the goal for daytime symptoms in adults with asthma?
Goal: ≤twice/week for symptoms such as cough, wheeze, dyspnea
What is the goal for nocturnal symptoms in adults with asthma?
Goal: none for night waking
What is the goal for the need for reliever therapy in adults?
Goal: ≤twice/week
What is essential for optimal asthma management in adults?
Provide optimal pharmacotherapy and avoid adverse effects
What are inhaled corticosteroids primarily used for?
Long-term asthma control
Inhaled corticosteroids are the mainstay for managing asthma over the long term.
How do inhaled corticosteroids work at the genetic level?
They alter the transcription of many genes
This includes increasing transcription of β2 adrenergic receptor and anti-inflammatory cytokines while decreasing proinflammatory cytokines.
What effect do inhaled corticosteroids have on proinflammatory cells?
Induce apoptosis
This helps reduce inflammation in the airways.
Do inhaled corticosteroids directly affect mast cells?
No
Many mast cell mediators are performed, so the effect is indirect over time due to overall muting of the inflammatory response.
What is the effect of inhaled corticosteroids on vascular permeability?
Reduce it
This leads to decreased airway edema.
What modification is commonly made to inhaled corticosteroids to reduce systemic exposure?
Increasing susceptibility to first-pass effect or using a prodrug version
For example, ciclesonide is activated by lung esterases.
What is an example of an inhaled corticosteroid that is extensively metabolized?
Budesonide
It has a bioavailability of around 10% due to metabolism by CYP3A4.
What are common adverse effects of inhaled corticosteroids?
Sore mouth, sore throat, dysphonia, oral thrush
Risk of oral thrush can be reduced by rinsing the mouth after use or using a spacer.
How does long-term use of high doses of inhaled corticosteroids affect children?
Associated with an initial decrease in growth rate
This minimally affects adult height, resulting in a 1-2.5 cm reduction.
What is recommended for adults using high doses of inhaled corticosteroids?
Bone densitometry
This is suggested for those with risk factors for osteoporosis.
What is the mechanism of action for inhaled beta2-agonists?
Activate β2 adrenergic receptors to increase cAMP
cAMP activates protein kinase A, leading to muscle relaxation.
What distinguishes short-acting from long-acting beta2-agonists?
Duration of bronchodilator effect
Short-acting options are for immediate relief, while long-acting options provide prolonged control.
What is the recommendation for using short-acting beta2-agonists?
Only as reliever therapy in combination with low-dose daily inhaled corticosteroid
Monotherapy is no longer recommended due to increased risks.
What should long-acting beta2-agonists be used in conjunction with?
Inhaled corticosteroids
They should not be used alone due to safety concerns.
Which long-acting beta2-agonist has a slow onset and should not be used for immediate relief?
Salmeterol
It is important to note the difference in onset times between long-acting options.
What can indicate suboptimal long-term control in asthma management?
Use of short-acting options more than 2 times per week
This suggests that the underlying asthma is not adequately controlled.
How can short-acting agents help prevent exercise-induced bronchospasm?
Used 5-10 minutes before exercise
They can provide protection for up to 2-4 hours.
What are common adverse effects of beta2-agonists?
Tachycardia, palpitations, nervousness, tremor, hypokalemia, restlessness, dizziness, headache, nausea
These effects can vary based on the agent used.
Fill in the blank: Long-acting options are not to be used as _______.
monotherapy
This is critical to ensure safety and efficacy in asthma management.
What do anticholinergics bind to and block?
M3 receptors and block cholinergic stimulation from the vagus nerve
What is the primary mechanism of action for anticholinergics?
Blocks the rise in intracellular calcium and prevents bronchoconstriction
What type of antagonist is Ipratropium?
Short-acting muscarinic antagonist
How can Ipratropium be used in asthma management?
As an add-on therapy to beta2-agonists for management of acute asthma exacerbations
What is a useful alternative for patients susceptible to tremor or tachycardia from beta2-agonists?
Anticholinergics
How does the onset of action for anticholinergics compare to beta2-agonists?
Delayed onset of action, but the bronchodilator effect lasts longer
In what situation may anticholinergics be useful?
In beta-blocker–induced bronchospasm
What type of antagonist is Tiotropium?
Long-acting muscarinic antagonist
What is the dosing frequency for Tiotropium?
Once-daily
What benefit does Tiotropium provide in asthma therapy?
Improves lung function and decreases exacerbations as an add-on therapy
What is Ipratropium considered in pediatric patients with severe acute exacerbations?
Adjunctive therapy
Is Tiotropium approved for use in children in Canada?
No, but sometimes used as add-on therapy in children over age 6 with a history of exacerbations
What are common adverse effects of anticholinergics?
Dry mouth, metallic taste
What ocular side effects can occur if anticholinergics are released into the eye?
Mydriasis and glaucoma
What triggers the release of arachidonic acid in asthma?
Asthma triggers such as antigens, cold air, exercise, cytokines
What enzyme converts arachidonic acid to leukotriene A4 (LTA4)?
5-lipoxygenase
What is Montelukast classified as in asthma therapy?
Second-line add-on therapy
What combination is more effective than combining an inhaled corticosteroid and a leukotriene receptor antagonist?
Inhaled corticosteroid/long-acting beta-agonist combination
When may leukotriene receptor antagonists be used in children?
When corticosteroids fail to control symptoms or cannot be used
What are the common adverse effects of leukotriene receptor antagonists?
Headache, abdominal pain, flu-like symptoms, hepatotoxicity (rare)
What warning has been issued regarding leukotriene receptor antagonists?
Boxed warning for neuropsychiatric effects
What are biologics used for in asthma treatment?
As an adjunct in the treatment of severe, uncontrolled asthma
What improvements may biologics provide in asthma patients?
Symptom control, FEV1, frequency of exacerbations, and/or reduce oral corticosteroid exposure
What is the consensus regarding the use of biologics in pediatric patients?
More studies are needed to indicate the benefit, especially in those <12 years of age
What is Omalizumab indicated for?
Children ≥6 years and adults with moderate to severe asthma inadequately controlled with inhaled corticosteroids and evidence of allergic IgE-mediated asthma
Evidence includes a positive skin prick test or other objective determination.
What are the common adverse effects of Omalizumab?
- Injection site reactions (45%)
- Viral infections (24%)
- Upper respiratory tract infections (19%)
- Headache (15%)
- Sinusitis (16%)
- Pharyngitis (10%)
These percentages represent the frequency of reported adverse effects.
What role does IL5 play in allergic disease?
IL5 plays a key role in the generation and survival of eosinophils
Eosinophils are important in the pathophysiology of allergic diseases.
Who is Mepolizumab indicated for?
Patients ≥6 years with severe eosinophilic asthma inadequately controlled with medium-to-high-dose inhaled corticosteroids and additional asthma controllers
Patients must have a blood eosinophil count ≥300 cells/µL in the past 12 months for children and adolescents or ≥150 cells/µL in adults.
What are the adverse effects of Mepolizumab?
- Headache
- Nasal congestion
- Pharyngitis
- Injection site reactions (pain, erythema, swelling, itching)
- Malignancy (rare)
- Hypersensitivity reactions (rare)
Hypersensitivity reactions can occur within hours or days of treatment.
What symptoms may indicate hypersensitivity reactions to Mepolizumab?
- Swelling of the face, mouth, and tongue
- Fainting
- Dizziness
- Hives
- Breathing problems
- Rash
These symptoms require immediate medical attention.
What is Dupilumab indicated for?
Add-on therapy in patients ≥6 years with severe asthma or atopic dermatitis
Dupilumab targets IL4 and IL13, which are involved in allergic inflammation.
What are the common adverse effects of Dupilumab?
- Injection site reactions (14–18%)
- Oropharyngeal pain (2%)
- Eosinophilia (2%)
- Arthralgia
- Hypersensitivity
These percentages reflect the frequency of adverse effects associated with Dupilumab.
What is the first step in using a metered-dose inhaler?
Shake the inhaler for 10 seconds
What should you do before putting the inhaler mouthpiece in your mouth?
Take the cap off the inhaler and make sure it is clean and there is nothing inside of the mouthpiece
What is the correct way to breathe while using a metered-dose inhaler?
Breathe in deep and steady
How long should you hold your breath after inhaling from the inhaler?
10 seconds
What should you do if you need another puff of medicine after using the inhaler?
Wait 1 minute and repeat steps 3-6
What should you do after using the inhaler?
Rinse with water and spit it out
Does pregnancy affect asthma in a predictable manner?
No, pregnancy does not affect asthma in any predictable manner
What are some outcomes associated with inadequate control of asthma during pregnancy?
- Preterm birth
- Low birth weight
- Congenital anomalies
- Pre-eclampsia
- Placenta previa
What is associated with a normal outcome for asthma during pregnancy?
Good control of asthma
What types of medications are considered safe for use in pregnancy?
- Inhaled corticosteroids
- Beta2-adrenergic receptor agonists
- LABAs
What has not shown adverse effects when used during pregnancy?
LABAs
Is there a lot of published data on the effectiveness and safety of biologic therapies during pregnancy?
No, there is little published data
Does breastfeeding have any known effect on the severity of asthma?
No, breastfeeding has no known effect
What types of asthma medications are considered safe for breastfeeding patients?
- Bronchodilators (short- and long-acting beta2-agonists and muscarinic antagonists)
- Inhaled corticosteroids
- Oral corticosteroids
Is there published data on the effectiveness and safety of biologic therapies in breastfeeding?
No, there is a lack of published data
