CVPR Week 5: Drugs used in the treatment of Asthma and COPD Flashcards
β2 adrenergic agonists to know
3 listed
- Albuterol
- Terbutaline
- Salmeterol
Muscarinic antagonists to know
2 listed
- Ipratropium
- Tiotropium
Phosphodiesterase inhibitors to know
2 listed
- Theophylline
- Roflumilast
Antileukotrienes to know
3 listed
- Ziluteon
- Zarfirlukast
- Motelukast
Corticosteroids to know
2 listed
- Beclomethasone
- Fluticasone
Anti-IgE Antibodies to know
Omalizumab
Mast cell degranulation inhibitors to know
Cromolyn sodium
Anti-IL5 receptor antibody to know
Benralizumab
Hallmarks of asthma
9 listed
Hallmarks of COPD
8 listed
Hyperreactivity and hypersensitivity
sensitive to less stimulus
vs
the amount of smooth muscle contraction in response
Both are in asthma to cause Hyperresponsiveness
Normal control of bronchial tone
Treatment of asthma for hyperresponsiveness of the trachea and bronchi to stimuli and smooth muscle contraction
5 listed
- β2-agonists
- PDEi - Theophylline
- Roflumilast
- Antimuscarinics
- Leukotriene modifiers
Treatment of asthma: Mucosal thickening from edema and mucus plug and cellular infiltration
6 listed
- Corticosteroids
- Leukotriene modulators
- Mast cell stabilizer
- Anti-IgE
- Anti-IL5R
- PDEi
Treatment of asthma: Short-term relief
bronchodilating agents to increase airway caliber by relaxing smooth muscles
- β-adrenoreceptor agonists
- Theophylline
- Antimuscarinics
Treatment of asthma: Long-term control
Antiinflammatory agents to reduce edema, mucus and infiltration
- Inhaled corticosteroids
- Antileukotrienes
- mast cell stabilizer (Cromolyn sodium)
- Anti-IgE
- β2 agonists
Bronchial tone
β2 adrenergic agonists properties
Effects of albuterol
Short-acting β2 agonists
Long-acting β2 agonists
What is the key to triggering the inflammatory cascade seen in asthma?
Anti-IL5 drugs
Benralizumab (Reslizumab and Mepolizumab bind IL-5
IL-5
Anti-IL-5 alpha chain receptor mAB IL-5 is a key cytokine in eosinophil maturation, activation, survival and proliferation
Benralizumab in severe asthma
In severe eosinophilic asthma, Benralizumab decreased eosinophils in the airways, sputum, bone marrow and peripheral blood
Benralizumab adverse effects
allergic hypersensitivity reactions (including anaphylaxis)
Benralizumab clinical use
- Add-on maintenance therapy
- approved in ages 12 and older
Antimuscarinics MOA in Asthma
Antimuscarinics MOA in Asthma
Antimuscarinic agents
Ipratropium bromide (Atrovent, atropine derivative) inhalation treatment for COPD
Tiotropium (Spiriva) a longer-lasting agent
Antimuscarinic clinical uses
- Inhibits bronchoconstriction
- Inhibits tracheobronchial secretions
- A weak bronchodilator
- Used in asthma patients intolerant to
Leukotriene antagonists and synthesis inhibitors
- CysLTX - a role in airway remodeling
- LTD4 and LTE4 - bronchial smooth muscle constriction
- LTD4 is 1000x more potent than histamine
- Zafirlukast and Montelukast are competitive antagonists
- Zileuton is an inhibitor of 5-Lipoxygenase
- Controlling drugs
Leukotriene antagonists MOA
Leukotriene modifying agents
Zafirlukast toxicities
Ziluteon warnings/precautions
Methylxanthines MOA
Methylxanthines
2 listed
- Theophylline
- Roflumilast
Methylxanthines clinical uses
Roflumilast MOA
Roflumilast specific MOA
PDE type 4 inhibitor
Roflumilast clinical uses
long acting PDE4 inhibitor (not considered a bronchodilator)
For severe COPD - controller not a rescue drug
Roflumilast Interactions
Avoid in combination with CYP3A4/5 inhibitors or inducers (carbamazapine, cimetidine, erythromycin, fluvomoxamine, ketoconazole, phenytoin, rifampicin and some oral contraceptives)
Roflumilast adverse effects
- Can cause tachycardia like other PDE inhibitors
- Some indication of depression
- can cause muscle spasm and uncontrollable shaking
Bronchodilators MOA
Therapeutic treatment for the inflammatory side of asthma
Corticosteroids Hx of Tx asthma
Used to treat asthma since 1950
Corticosteroids for asthma
4 listed
- Methylprednisone
- beclomethasone
- Fluticasone
- Mometasone
Corticosteroids clinical uses for asthma
5 listed
- reduces bronchial reactivity
- increases airway caliber
- Increases β2 receptors
- Inhibit production of LTX, PGs and PAF
- By repressing gene transcription - interferring with Nfkappa B transcriptional regulation of cytokine production, represses transcription of NOSi, COX-2, cytokine receptors
Corticosteroids MOA
Rate of death from Asthma to Corticosteroids used
Cromolyn sodium clinical uses
only valuable prophylactically
Inhibit antigen (seasonal or situational) and exercise induced asthma
No effect on airway smooth muscle tone
Does not reverse bronchospasm
Should not be used during an acute asthmatic episode
Cromolyn sodium MOA
- Cromolyn sodium alters chloride channel function which inhibits Ca2+ influx thus inhibiting mast cell function and airway nerves
- In the mast cell this prevents the release of histamine and LTX
- May also inhibit the function of other inflammatory cells
Omalizumab MOA
Omalizumab clinical use
- administered over 10 weeks for those with poorly controlled or severe asthma
- Reduces magnitude of early and late bronchospasms responses
Omalizumab adverse effects
Anaphylaxis
Omalizumab malignancies
breast
non-melanoma skin
prostate
melanoma
parotid
Omalizumab infections
geohelminthic infections (roundworm, hookworm, whipworm, threadworm)
Cromolyn sodium, benralizumab, omalizumab MOA
