Exam III Asthma COPD Flashcards
Asthma VS COPD
Asthma
- Allergen based irritation
- Smooth muscle thickening-> bronchoconstriction
- Episodic SOB, wheeze, cough, chest tightness
- Often reversible lung fxn w/ meds
COPD
- Inflammation-based irritation
- Cellular damage by external irritants
- Chronic cough, sputum production, Dyspnea on Exertion
- Often irreversible lung fxn w/ meds
Treatment approaches for Asthma
Short-acting B agonists (SABA)
Long-acting B agonists (LABA)
Inhaled corticosteroids (ICS) – oral too
Mast cell stabilizers
Leukotriene antagonists
Methylxanthine derivatives
Immunotherapy
Long acting antimuscarinics (LAMA)
Treatment approaches for COPD
Smoking cessation
Short-acting B agonists (SABA)
Long-acting B agonists (LABA)
Short-acting antimuscarinics (SAMA)
Long-acting antimuscarinics (LAMA)
Inhaled corticosteroids (ICS) – oral too
Methylxanthine derivatives
Phosphodiesterase 4 (PDE-4) inhibitors
Notes on Delivery systems
Aerosolized delivery systems preferred
-+: small particles size, delivered directly to leading to reduced systemic exposure, doses usually lower, usually quicker onset
–: requires proper technique for effective therapy, expensive, variability in devices that require different techniques
Multiple delivery systems including metered dose inhaler (MDI), dry powder inhaler (DPI), soft mist inhaler, nebulizer.
Aerosolized delivery systems - Metered dose inhaler (MDI)
Advantages
- Small, compact, portable, Easy to use (<1 minute)
- Can be used with spacer
- No drug prep
Disadvantages
- Needs proper technique / coordination with breath (requires breath hold)
- Expensive
Aerosolized delivery systems – Dry powder inhaler (DPI)
Advantages
- Small, compact, portable
- Easy to use (<1 minute)
- Usually cheaper vs MDI
- Less coordination needed
Disadvantages
- PT must prepare the dose
- Requires fast, deep inhalation (requires breath hold)
- Moisture sensitive
Aerosolized delivery systems – Soft Mist inhaler
Advantages
- Compact, portable
- Multi-dose device
- High lung deposition
- Does not contain propellants
Disadvantages
- Complicated process for first dose
- Slow moving mist
- Cannot use a spacer
- Expensive
Aerosolized delivery systems – Nebulizer
Advantages
- Minimal technique required
- PT is not required to Hold breath
Disadvantage
- Expensive, requires dose prep
- Bulky (not portable)
- Administration time 5-15 minutes
- Needs a power source
- Cleaning needed
Considerations for device selection
PT related factors
-Age, physical and cognitive abilities
PT preference
Availability of the drug
-Combination products
Convenience
-Portability, maintenance, cleaning
Cost / reimbursement
Bronchodilators
SABA
LABA
Muscarinic antagonists
Methylxanthine derivatives
PDE-4 inhibitors
Short-Acting B2 Agonists (SABA)
MOA: Stimulate adenylyl cyclase at B2. Inc cAMp. Dilation
Selective for B2
Drug of choice for Acute Asthma Attacks and exercise-induced Asthma
- Onset 5 minutes
- Duration 3-4 Hours
Route: Inhalation
Well tolerated for PRN use
ADR:
- Mouth Irritation and Cough
- At high doses
–Skeletal muscle tremor
– Tachycardia/palpations
–Arrhythmia
–Tolerance with excessive use
—Decreased responsiveness and decrease in number of B receptors
SABA Agents
Albuterol
-Racemic mixture of (S)-albuterol and (R)-albuterol
–(R)-albuterol (levalbuterol) is therapeutically active
–(S)-albuterol is clinically inert but has unwanted side effects
Levalbuterol
- Developed to minimize side effects
- In acute asthma (&COPD) attacks, no sig Diff in efficacy
- No Diff in HR
Long Acting B2 Agonists (LABA)
MOA: Same as SABA
- Slower onset (~30 min)
- Longer duration (12-24 Hrs)
Not for rescue therapy
Cannot be used as MONOTHERAPY
-Ok in COPD
ADEs same as SABA
LABA Agents
Long-acting
- Salmeterol
- Formoterol
Ultra-long acting
- Indacaterol
- Olodaterol
- Vilanterol
Antimuscarinics
MoA: Competitively block muscarinic receptors (M1, M2, M3) and the effects of ACh in airway-> Prevent vasoconstriction mediated by vagal discharge
No effects on Chronic inflammation
Bronchodilation effect last longer than B agonists
Antimuscarinic ADEs
Minimally absorbed, generally well tolerated
Potential for:
- Dry mouth, eyes
- Bitter, metallic taste
- Constipation
- Urinary retention
No tremors or arrhythmias
Antimuscarinic Agents
Ipratropium
Tiotropium
Aclidinium
Umeclidinium
Glycopyrolate
Methylxanthine derivative
Theophylline – oral
MoA: (1) Non-selectively inhibits phosphodiesterase (PDE)-> increases cAMP-> broncodilation (2) Block adenosine receptors-> bronchodilation
Duration: ~12 Hrs
Requires high concentration
Narrow therapeutic index
Theophylline
Metabolized via CYP450, 1A2 enzyme system
-Many DDIs – febuxostat, bupropion, carbamazepine, macrolide antibiotics, etc.
Clearance mediated by age, smoking status, and other drugs
Requires monitor
-Therapeutic range 10-20 mcg/mL
–Levels correlate with efficacy
Smoking will reduce drug levels as smoking is a 1A2 inducer.
Theophylline ADEs
GI distress (enhanced gastric acid secretion)
Tremor
Insomnia
In overdose, severe nausea and vomiting, hypotension, agitation, arrhythmias, cardiac arrest, seizures
PDE-4 inhibitors
Roflumilast – oral
MoA: Not fully elucidates; selectively inhibits PDE-4-> increases cAMP-> bronchodilation
Used for severe or very severe COPD
-should be given in combination with at least 1 other long-acting bronchodilator for COPD
Given by mouth once daily
-Duration of action > 10-20 Hrs
Roflumilast ADE/DDI
Partially metabolized by CYP450 3A4
-DDIs with rifampin, phenobarbital, phenytoin, carbamazepine
ADEs:
- Diarrhea, nausea, vomiting, abdominal pain, HA, dyspepsia
- Psychiatric events
- Weight loss
Corticosteroids
MoA: Binds glucocorticoid receptor to:
- Inhibit inflammatory cell migration/activation
- Inhibit cytokine and mediator release
- Up regulate B2 receptors
- Inhibit IgE synthesis
Drug of choice for persistent asthma
-Prophylaxis
May take 4-6 weeks for effect
Multiple dosing
Do not abruptly D/C – Taper
Corticosteroid (inhaled) ADEs
Inhaled
Thrush (oral candidiasis)
-Counsel PTs to rinse mouth after use
Dysphonia
Sore throat
Cough
Corticosteroid (oral/IV) ADEs
Adrenal suppression
Cushing Syndrome
Growth retardation
Osteoporosis
Glucose intolerance
Infection risk
Mood changes
Weight gain
Edema
Corticosteroid agents
Inhaled
- Beclomethasone
- Budesonide
- Fluticasone propionate
- Fluticasone furoate
- Mometasone
- Flunisolide
- Ciclesonide
Oral/IV
- Prednisone
- Prednisolone
- Methylprednisolone
- Hydrocortisone
Corticosteroids in kids
Potential growth stunting in children
Still preferred DOC (drug of choice) in children
Leukotriene antagonists – Lipoxygenase inhibitor
Zileuton – Oral
MoA: Inhibits actions of 5-lipoxygenase to inhibit the synthesis of Leukotrienes
ADEs:
HA
Insomnia
Somnolence
GI Upset
Hepatotoxicity
-Do not administer if LFTs >3x ULN
-Females > 65 Yrs of age and those with preexisting LFT elevations are highest-risk -> monitor!
Leukotriene Receptor Antagonists
Montelukast - Oral
Zafirlukast - Oral
MOA: Competitively block actions of Leukotrienes at the LTD receptor
Can be used for asthma, allergic symptoms, exercise-induced bronchospasm, urticaria
Leukotriene receptor antagonists
DDIs:
Zafirlukast + warfarin -> may increase risk of bleed
ADEs:
Generally well tolerated
HA
Hepatoxicity (Zafirlukast)
Neuropsychiatric events
-Abnormal Dreams, hostility, aggression, suicidality, agitation, hallucinations, etc.
–2008: Reports to FDA MedWatch
–2009: Labeling change on all leukotrienes
Mast cell stabilizers
Indicated for mild asthma cases
-Not used much in clin practice
Not for rescue use
Require multiple daily doses
Clin improvement may take 2-6 weeks
Well tolerated
-Mild throat irritation, cough abnormal taste
No DDIs
Immunotherapy - Anti IgE agents
Omalizumab
MOA: Monoclonal IgE antibody -> inhibits binding of IgE to surface of mast cells & basophils -> inhibits release of inflammatory mediators
Indicated for allergic asthma not relieved with corticosteroid therapy
-Must have evidence of allergic sensitization
Dose based on IgE levels and body weight
-Sub Q injection every 2-4 weeks
Omalizumab - ADEs/DDIs
Indicated for > 12 Y/O
Clin improvement delayed - Takes up to 12 weeks
ADEs:
- Injection site RXN (45%)
- Anaphylaxis -> 1.5-2 hours post-dose (watch for RXN)
- Arthralgia, HA
- Pharyngitis, sinusitis
- Malignancies?
DDI-None
IL-5 Antagonists
Mepolizumab
Reslizumab
IL-5 MOA
Humanized IL-5 monoclonal antibody antagonist to reduce the amount of circulating eosinophils
Used for the maintenance of severe asthma for PTs who continue to have attacks despite therapy
Admin:
SubQ (mepolizumab)
IV (reslizumab)
q4w by HCP
IL-5 ADEs
Not recommended monotherapy
-Must be > 18 Y/O with eosinophilic phenotype
ADEs:
-Injection site RXN
-HA
-Hypersensitivity RXNs ->Anaphylaxis
-Malignancy?
-Muscle/Face pain
