Pathologic increase in the bronchoconstrictor response to antigens and irritants
Caused by bronchial inflammation
Bronchial hyperreactivity
Phosphodiesterase (PDE)
Enzymes that degrades cAMP (active) to AMP (inactive)
Tacyhphylaxis
Rapid loss of responsiveness to a stimulus (e.g. drug)
Asthma Diagnosis
- Airflow obstruction
- Reversibility of airflow obstruction
- Prolonged expiration and diffuse wheezes
- LIMITATION OF AIRFLOW on PFTs or bronchoprovocation challenge
What is drug therapy aimed to target?
- Narrow airway
- Tightened muscles
- Inflammation
What are the asthma treatment goals?
- Prevent bronchoconstriction-early phase, rescue
- Reduce inflammation- Late/Chronic phase, controller
- Prevent irritant reaction (IgE)- Late/Chronic phase
What drugs target early response phase (bronchoconstriction)?
- Beta agonists
- Theophylline
- Muscarinic antagonists
- Leukotriene antagonist
What drugs target late response phase (inflammation)?
- Steroids
- Cromolyn
- Leukotriene antagonists
What is the ultimate goal in drug therapy?
Relax bronchial tone
Beta Agonists MOA
Stimulate adenylyl cyclase (AC)
Increases cAMP in smooth muscle cells
Bronchodilator response
When would you use Albuterol (Short acting beta agonist )?
Acute asthma–>Rescue
When would you use Salmeterol (long acting beta agonist)?
Asthma proyphlaxis
COPD
Albuterol SEs
Tremor
Tachycardia
Salmeterol SEs
Tremor
Tachycardia
CV events
Lists antimuscarinic agents
Ipatropium
Tiotropium
antimuscarinic agents MOA
Competitively block muscarinic receptors
Prevent bronchoconstriction mediated by vagal discharge
When would you use antimuscarinic agents?
Asthma
COPD
antimuscarinic agents SEs
Dry mouth
Cough
What is unique about antimuscarinic agents?
REVERSE bronchoconstriction in some asthma pt’s (esp. children)
AND in COPD pt’s
Where can you find Methylxantines?
Plants:
- Caffeine
- Tea (Theophylline)
- Cocoa (Theobromine)
Methylxantines MOA
- Inhibits phosphodiesterase (PDE)
- increases cAMP–>Bronchodilation - Adenosine receptor antagonist
Who would we consider using Methylxantines in?
Prophylactic for nocturnal asthma attacks
Methylxantines effects
- Bronchodilation
- Cardiac stimulation
- CNS effect
- Increased muscle strength
Methylxantines SEs
- Insomnia
- Seizures
- Tremor
- Arrhythmias
- Anorexia
What drug can reverse Theophylline (Methylxantine) CV toxicity?
Beta blockers
What does Theophylline clearance depend on?
Age
Who is Theophylline clearance increased in?
- Young adolescents
2. Smokers
What is first line therapy for moderate-to-severe asthma?
ICS:
- Beclomethasone
- Fluticasone
- Mometasone
- Budesonide
ICS MOA
- Inhibition of phospholipase A2
- Inhibit expression of COX-2
- Increase B adrenoreceptor responsiveness
- Prevent full expression of inflammation and allergy
ICS SEs
- Pharyngeal candidiasis
- Minimal systemic steroid toxicity
- Mild growth retardation
Who would we consider using oral Prednisone in?
Severe refractory chronic asthma
Acute exacerbations
What is the number one cause of adrenal insufficiency?
Exogenously administered glucocorticoids (catabolic steroids)
What are important medications for status asthmaticus?
IV Prednisolone
IV Hydrocrotisone
What is the most potent systemic steroid?
Dexamethosone
List a leukotriene receptor blocker
Montelukast (singulair)
LTD4 receptor antagonist
What is Montelukast effective in preventing?
Exercise, antigen and ASA induced bronchospasm
Prophylaxis
List a Lipoxygenase inhibitor
Zileuton
what allergy is Zileuton effective against?
ASA
Zileuton MOA
selectively inhibits 5-lipoxygenase
reduces synthesis of leukotrienes
Zileuton drug toxicity
elevated liver enzymes
What drugs would we use prior to gardening?
Cromolyn and Nedocromil
Cromolyn and Nedocromil SEs
Cough
Omalizumab MOA
Antibody that binds to the IgE on sensitized mast cells
Omalizumab effects
Decreases inflammatory mediator release
Decrease allergic inflammation
Prevents exacerbation of asthma
Mepolizumab MOA
Monoclonal antibody to IL-5
Who would we use Mepolizumab in?
Severe eosinophilic asthma
What is there an increase in when we treat adults with Mepolizumab?
Herpes Zoster
What should we consider adding in adult house dust mites sensitive patients with allergic rhinitis who have exacerbations despite ICS tx provided FEV1 is 70% predicted?
Sublingual immunotherapy (SLIT)
