Flashcards in L58 – Drugs Used in the Treatment of Airway Diseases Deck (74):
What test distinguishes Asthma from COPD?
Spirometry test: pre- and post- bronchodilator
Airflow limitation in asthma is completely reversible by
Compare the inflammatory cells in airway between Asthma and COPD?
1. CD4+ T-lymphocytes
1. CD8+ T-lymphocytes
Compare the inflammatory consequences in airway between Asthma and COPD?
Asthma = Airway remodeling
COPD = Parenchymal destruction
Loss of alveolar wall and capillaries
Compare the thickness of basal membrane in airway between asthma and COPD?
Asthma = Thickened reticular basal membrane
COPD = normal BM
Compare the change in airway epithelia in airway between asthma and COPD?
Asthma = Epithelial loss
COPD = Epithelial metaplasia
What is atopy?
genetic tendency to develop allergic diseases
What are some risk factors that that are unique to Asthma but not COPD?
What are the inflammatory cells involved in Asthma- COPD overlap syndrome? (ACOS)
What can be used to present a bronchial challenge to trigger asthma?
Whole allergen extract (e.g. methacholine)
Used as non-specific bronchoconstrictor stimuli
After an allergen provocation test, what are the differences between an early response and late response?
Drop in FEV1:
Early response: due to rapid bronchoconstriction
Late response: due to inflammation and hyperreactivity
What is used as a control in an allergen provocation test?
Negative control = normal saline
What changes in FEV1 after bronchodilator distinguish asthma from COPD?
Post-bronchodilator FEV1/FVC <70% confirms airflow limitation:
1) Positive response = Increase FEV1 from baseline of >200mL and >=15% of prebronchodilator value = asthma
2) Not fully reversible = COPD
What assessments are included in the Combined assessment of COPD ?
Assessment of :
Lung function test
>> give 4 groups: A,B,C,D
Which group in the combined assessment of COPD is the most severe?
What are the 2 therapy goals of asthma treatment?
1. Induce bronchodilation (relieves bronchoconstriction)
2. Decrease inflammatory response (targets chronic airway inflammation)
4 classes of drugs for treatment of asthma? BLAC
2) Leukotirene pathway modifiers
3) Anti-inflammatory drugs
4) Cytokine targeted asthma therapies (monoclonal antibodies)
What is the first line drug in asthma therapy and what are the 2 kinds?
Short acting and Long acting (LABA)
Name some short and long term B2 agonists?
Short-acting agents: e.g. Salbutamol (Albuterol), Terbutaline
Long-acting agents (LABA): e.g. Salmeterol, Formoterol
What is the second line of drug in asthma therapy? Give 2 examples
e.g. theophylline, aminophylline
Apart from B2 agonists and Methylxanthines, what is the 3rd bronchodilator drug for asthma?
Muscarinic receptor antagonists (anticholinergics)
When are Muscarinic receptor antagonists (anticholinergics used?
Not for 1st/2nd line for asthma, but useful for COPD
What are the 2 types of Muscarinic receptor antagonists? Give 1 example of each?
a) Short-acting agent: e.g. ipratropium (Atrovent®)
b) Long-acting agent (LAMA) e.g. tiotropium bromide
Why is Methyxanthines used as second line and not first line asthma drug?
Drug action takes longer time than B2 agonist
What are some pharmacological effects of B2 agonists in asthma patients?
(think cilia, smooth muscle, vascular)
1) relax smooth muscle = relief bronchoconstriction
2) Decrease vascular permeability and oedema
3) Increase ciliary beat frequency > Increase mucus clearance
4) Marked protection against non-specific bronchoconstrictor stimuli
Compare the duration of action between short acting and long acting B2 agonists in asthma drugs?
Short acting = 4-6 hours
Long = > 12 hours
Compare the administration of B2 agonist in acute vs chronic asthma attacks?
Acute = IV
Chronic = inhalation
Name some benefits of long term B2 agonists asthma drug?
Improved lung function
Less nocturnal asthma
Improved quality of life
What are some common adverse effects of B2 agonist in treating asthma?
What are some Long term adverse effects of B2 Agonist usage in asthmatic patients?
Due to decoupling of G protein to B2AR surface receptor > low receptor responsiveness
Low receptor number due o internalization and degradation
What drug is used with long term B2 agonists to combat long term desensitization and down-regulation?
How does Methylxanthines relieve asthma? (think PDE- Phosphodiesterase- and adenosine)
1. PDE inhibitors (less degradation) > increase intracellular cAMP > smooth muscle relaxation
*PDE usually degrades cAMP to AMP*
2. Block adenosine receptors:
a) On airway smooth muscle to decrease contraction
b) On mast cells to decrease histamine release
What are some adverse effects of Methylxanthines?
chronotropic and inotropic
Nausea and vomiting
Why are side effects of Methyxanthines common?
narrow therapeutic range >>
difficult to adjust dose
What is the action of Muscarinic receptor antagonists to relive asthma?
Bind to all parasympathetic muscarinic (M1, M3)receptors >> decrease vagal cholinergic tone
1) decrease mucus secretion
2) Decrease airway SM contraction
Side effects of Muscarinic receptor antagonists?
Inhalation: few adverse effects
What are the specific targets of the 2 types of muscarinic receptor antagonists?
Short acting: ipratropium (Atrovent®) targets parasympathetic nerves
Long- acting (LAMA): tiotropium bromide targets M1 and M3 receptors
What chemicals can counteract the effects of Muscarinic receptor antagonist and Methylxanthines?
Muscarinic - countered by Ach (Ach- mediated bronchospasm)
Methylxanthines - countered by Adenosine (methyxanthine is an adenosine receptor blocker)
What is the role of Leukotrienes in body normally?
What are the 2 classes of Leukotriene pathway modifiers?
Cysteinyl leukotriene (LT) receptor antagonists
Name some Leukotriene pathway modifiers?
Cysteinyl leukotriene (LT) receptor antagonists (e.g.
Montelukast (Singulair), Zafirlukast
5-lipoxygenase inhibitor (e.g. Zileuton)
What is the action of Cysteinyl leukotriene receptor antagonists?
Bind to LTC4 and LTD4 receptors >> inhibit LTC4
and LTD4-mediated bronchospasm
What is the action of 5-lipoxygenase inhibitor ?
arachidonic acid (AA) turns to cyclooxygenase pathway instead > make lipid inflammatory mediators
>> inhibit production of Leukotrienes from arachidonic acid
Route of admin for leukotriene pathway modifiers? Is it first line?
Use as an add on therapy, not first line
What are the ways that Glucocorticoids can suppress inflammation?
Decrease synthesis and release of inflammatory mediators
Decrease infiltration and activity of inflammatory cells
Decrease airway mucus production
How does glucocorticoid counteract the downregulation effect of Long term B2 agonists?
Increase the number of bronchial B2-receptors and their responsiveness to
B2-agonists (prevent down-regulation)
Explain the action of glucocorticoids on modifying gene expression of a cell? (remember it has to enter a cell)
Glucocorticoids enter cell >
Bind to cytoplasmic glucocorticoid receptors (GR)
> enter nucleolus > bind to
glucocorticoid response element (GRE) > regulate gene expression
Name some inhaled glucocorticoids for chronic asthma?
Name some oral/ systemic IV glucocorticoids for severe acute attacks / exacerbation
Which route of administration of glucocorticoids can cause many adverse effect? Name some?
Name one anti-allergic drug, its route of admin, when it is used and adverse effects?
Mast cell stabilisers e.g. cromolyn sodium
Adverse effects: dry mouth, irritating cough
What is the action of cromolyn sodium?
Inhibit mast cell degranulation (e.g. histamine) and activation
Depress the exaggerated neuronal reflexes triggered by irritant receptors in airways
Anti-IgE antibodies are used for which patients?
Prophylactic treatment for patients with severe uncontrolled asthma only (e.g. no response to steroids) or very high IgE in circulation
Name an Anti-IgE antibody drug for asthma treatment?
e.g. Omalizumab (Xolair)
What is the action of Anti-IgE antibodies?
Decrease circulating levels of IgE >> reduce IgE receptors (FceRI) expression on mast cells, basophils and dendritic cells
>> Prevent release of inflammatory mediators
Route of administration of Anti-IgE antibodies?
Subcutaneous injection every 2-4 weeks
Side effects of Anti-IgE antibodies to treat asthma?
What cytokine targeted therapies are there for asthma patients except for Anti-IgE antibodies?
IL-5 specific Abs
monoclonal antibodies made against which interleukin has failed?
Anti-IL-13-mAb has failed
Name some Anti-IL-5 Abs?
Name a Anti-IL-4 mAb
fully human mAb against IL-4
Which of the drugs for treating asthma are RELIEVERS?
-Short acting B2 agonists
-Muscarinic receptor antagonists (anticholinergics)
What drugs stop antigen on IgE and mast cells from inflammatory mediator release?
Cromolyn sodium (Anti-allergic drugs, Mast cell stabilizers)
Glucocorticoids - Decrease synthesis and release of inflammatory mediators
What drugs block the action of inflammatory mediators from inflicting late response in asthma
What drugs stop Inflammatory mediators from inflicting early response bronchoconstriction in asthma?
B2 agonist > SM relax
Methyxanthines > block adenosine receptor > SM relax
Antichollinergics > decrease vagal cholinergic tone > SM relax
Leukotrienes antagonists > stop LTC4 and LTD4 mediated bronchospasm
Asthma ' controllers' are taken how frequently?
Daily on a long term basis
What are some goals of treating COPD?
Prevent disease progression (difficult to achieve)
Prevent and treat exacerbations, complications
What are the classes of drugs used to treat COPD?
+ many combo therapies
What are the combo therapies used to treat COPD?
1) B2 agonist/antichollinergics:
SABA + SAMuscarinicA
LABA + LAMA
2) Glucocorticoids/ B2 agonists (ICS + LABA)
3) Glucorticoids + B2 agonist + Antichollinergics (ICS + LABA + LAMA)
Combo therapies for COPD are all given in what form?
Dry powder inhaler
Are glucocorticoids usedful against all COPD patients?
What are some anti-inflammatory drugs used for COPD?
-Selective PDE4 inhibitors = Methylxanthines
What are the bronchodilators used for COPD?
Name one B2 agonist that is used only for COPD?