3/23/2016
Chronic Obstructive Pulmonary Disease (COPD)
COPD Update: It takes my breath away!!
2014 Global Gl b l IInitiative iti ti for f Chronic Ch i Obstructive Lung Disease (GOLD) A report by NHLBI and WHO to define, diagnose, treat COPD
Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates
www.goldcopd.org/
Global Strategy for Diagnosis, Management and Prevention of COPD
COPD and Asthma
Definition of COPD
n
n
COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases Exacerbations and comorbidities contribute to the overall severity in individual patients
COPD • Onset in mid-life • Symptoms slowly progressive
•
Long smoking history
ASTHMA • Onset early in life (often childhood)
• Symptoms vary from day to day
• Symptoms worse at
night/early morning
• Allergy, rhinitis, and/or eczema also present
© 2015 Global Initiative for Chronic Obstructive Lung Disease
• Family history of asthma
Mechanisms Underlying Airflow Limitation in COPD
Mechanisms Underlying Airflow Limitation in COPD
COPD “signature” is small airway disease:
Parenchymal Destruction:
Airway inflammation Airway fibrosis, luminal plugs Increased airway resistance
Loss of alveolar attachments Decrease of elastic recoil
1
3/23/2016
Global Strategy for Diagnosis, Management and Prevention of COPD
GOLD Staging System
The Global Initiative for COPD
Symptoms of COPD
Characteristic symptoms: chronic and progressive dyspnea, cough, and sputum production that can be variable from day-to-day
D Dyspnea: P Progressive, i persistent i t t and d characteristically worse with exercise
Chronic cough: May be intermittent, unproductive
Chronic sputum production: common © 2015 Global Initiative for Chronic Obstructive Lung Disease
Follow up COPD • Patient questionnaires COPD Assessment Test (CAT) every 2-3 months to identify trends (change in med, worsening symptoms) • www.catestonline.org • With new ne treatment, treatment ASK: ASK Are you less breathless? Can you do more? Can you sleep better? SPIROMETRY: Perform at least annually © 2015 Global Initiative for Chronic Obstructive Lung Disease
Chronic Obstructive Pulmonary Disease (COPD) Pharmacologic Management
www.goldcopd.org/
Therapeutic Options:
COPD Medications Beta2-agonists Short-acting beta2-agonists Long-acting beta2-agonists Anticholinergics Short-acting anticholinergics Long-acting anticholinergics Combination short-acting beta2-agonists + anticholinergic in one inhaler Combination long-acting beta2-agonist + anticholinergic in one inhaler Methylxanthines Inhaled corticosteroids Combination long-acting beta2-agonists + corticosteroids in one inhaler Systemic corticosteroids Phosphodiesterase-4 inhibitors www.goldcopd.org/ © 2015 Global Initiative for Chronic Obstructive Lung Disease
Chronic Obstructive Pulmonary Disease (COPD) Pharmacologic Management
Bronchodilators
Bronchodilators
Beta agonists (cause bronchodilation):
SABAs
• Short acting beta agonists (SABAs)
Albuterol ProAir HFA, Proventil HFA, Ventolin HFA, Levalbuterol (Xopenex), ProAir RespiClick (inhalation powder)
• Example: albuterol • Suffix is “terol” • “Rescue med” (works immediately and effects last for about 4 hours)
$42 - $56 per inhaler
2
3/23/2016
Quiz
What are the implications?
Pharmacologic Management
Pharmacologic Management
Short acting bronchodilator use is associated with greater risk of arrhythmias y in new users. Which arrhythmia(s)?
Compare the ß-2s Drug
Brand
Form
Duration in hrs
Albuterol
ProAir HFA
MDI
3-6
ProAir RespiClick
DPI
Proventil HFA
MDI
Ventolin HFA
MDI
Xopenex HFA
MDI
Levalbutero l
• Must manage cardiovascular risks aggressively! • Get patient in good control to decrease times that SABAs are used!
What’s the difference between the ß-2s? Drug
ß-2 potency
Onset in minutes
Duration in hrs
Albuterol
2
Within 5
3-6
Levalbuterol
???
Within 5
8
8
What’s the relationship between levalbuterol (Xopenex®) and albuterol?
R isomer ===> bronchodilation S isomer ===> tachycardia,etc. • Albuterol is a mixture of R and S isomers • Levalbuterol is R-isomer of albuterol
Albuterol is a mixture of R and S isomers
RS R S SR R S R R R S S
R R R R R R RR R
Albuterol
Xopenex
3
3/23/2016
Levalbuterol (Xopenex®)
True or False Pharmacologic Management
• R-isomer of albuterol • Albuterol is a mixture of R and S isomers
Levalbuterol is more g effective at relieving shortness of breath than albuterol.
Chronic Obstructive Pulmonary Disease (COPD)
Levalbuterol (Xopenex®) • Inconclusive whether there are fewer side effects for the degree of bronchodilation • Older adults: inconclusive
Pharmacologic Management
Long acting beta agonists (LABAs) (First available in Late 1990s) •
Stimulate B2 B2-adrenergic adrenergic receptors which produces relaxation of smooth muscle (prevents bronchoconstriction)
•
Stimulation increases intracellular messenger cAMP (which controls smooth muscle tone)
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (updated 2016). http://www.goldcopd.org/uploads/users/files/GOLD_Report%202016.pdf. (Accessed March 8, 2016).
Chronic Obstructive Pulmonary Disease (COPD)
Chronic Obstructive Pulmonary Disease (COPD)
Pharmacologic Management
Long acting beta agonists (LABAs) (First available in Late 1990s) •
Reduce air trapping
•
Improve emptying of the lungs (reduces lung volume)decreases breathlessness and increases exercise capacity
Pharmacologic Management
Long acting beta agonists (LABAs) •
Salmeterol (Serevent®), formoterol ( (*** Foradil®): Twice Daily
•
Suffix is “terol”
•
Not a rescue med (takes 10-20 mins to work) but works for 12-24 hours
***Formoterol leaving market about January, 2016 Cooper C: Airflow obstruction and exercise. Respir Med 2009;103:325–34.
4
3/23/2016
Chronic Obstructive Pulmonary Disease (COPD) Pharmacologic Management
Long acting beta agonists (LABAs) •
NEWER---- ONCE DAILY
•
I d Indaca t terol l (Arcapta (A t Neohaler) N h l )
•
Olodaterol (Striverdi Respimat)
•
Vilanterol (in combo with fluticasone, in combo with umeclidinium)
Indacaterol Long acting beta agonists (LABAs)
Stimulates beta 2 adrenergic receptors, relaxes airway smooth muscle
•
Once daily, 75 mcg/cap DPI
•
Rapid onset and long duration
•
US approved dose 75 mg; in Canada and Europe: 150-300 mg daily
•
3A4 substrate; P-glycoprotein transporter: ??? Is it safer in lower doses????
Olodaterol Long acting beta agonists (LABAs) Pharmacologic Management •
Stimulates beta 2 adrenergic receptors, relaxes airway smooth muscle
•
Once daily daily, 2 puffs; 2.5 2 5 mcg/actuation MDI (soft mist inhaler)
•
Rapid onset and long duration
How do we get the Pharmacologic drug to theManagement place it needs to work? It has to commute from the mouth to the lungs!!!!!
Pharmacologic Management
•
Vilanterol Long acting beta agonists (LABAs) Pharmacologic Management •
Once daily, NOT A LONE AGENT
•
In combination with umeclidinium (Anoro Ellipta)
•
In combination with fluticasone (Breo Ellipta)
MDI vs DPI Pharmacologic Management DPI MDI • Solution/suspension • Uses a propellant to move drug into lungs • Small, portable • Hand: breath coordination (technique/coordination req’d); spacer, chamber helps • Less expensive (than DPI)
• Solid particles • Breath actuated (No propellants so, depends on force of inhalation) • Portable, quick to use • No spacer needed • Needs adequate lung volume • Dose counters • No SABA in US
Geller, D.E. 2007. Comparing clinical features of the nebulizer, metered dose inhaler, and dry powder inhaler.respcare vol 50(10).
5
3/23/2016
DPI Quiz
Dry Powder Inhaler
What simple way can you use to make sure a patient has enough inspiratory effort to use a DPI inhaler?
Chronic Obstructive Pulmonary Disease (COPD) Pharmacologic Management
LABA
Dosing Frequency
Cost
Formoterol (DPI) (Foradil)
BID
$221.07
Salmeterol (MDI) (Serevent)
BID
$221.76
Indacaterol (DPI) (Arcapta Neohaler) Olodaterol (MDI) (Striverdi Respimat)
Daily
$183.37
Daily
$155.70
• Single dose capsules, multidose devices • Inhalation de-aggregates the powder into smaller particles • Can induce a cough • Must have good inspiratory flow/effort (kids, COPD, asthma) • Must have adequate lung volume • Fewer irritant effects
Chronic Obstructive Pulmonary Disease (COPD) Pharmacologic Management
LABAs
• More convenient and more effective for symptom relief • Reduce exacerbations and hospitalizations • Improve symptoms • Improve health status www.goldcopd.org/
Quiz Is it considered safe practice to prescribe a LABA (as the lone daily agent) for a patient who has COPD? 1. Yes 2. No
Chronic Obstructive Pulmonary Disease (COPD) Bronchodilators Pharmacologic Management Inhaled Anticholinergic (Long acting muscarinic agents-LAMAs) Muscarinic antagonists facilitate bronchodilation by competing with acetylcholine for muscarinic receptors By inhibiting acetylcholine at receptor sites in lung, smooth muscle contraction is inhibited
Is it considered safe for a patient who has asthma?
6
3/23/2016
Chronic Obstructive Pulmonary Disease (COPD)
Chronic Obstructive Pulmonary Disease (COPD)
Bronchodilators Pharmacologic Management
Bronchodilators Pharmacologic Management
Inhaled Anticholinergic (Long acting muscarinic agents-LAMAs)
Inhaled Anticholinergic (Long acting muscarinic agents-LAMAs)
•
Works by preventing bronchoconstriction
•
Examples: Ipratropium (Atrovent), tiotropium
(yeah, ok it bronchodilates a little)
(Spiriva), aclidinium (Tudorza Pressair), Umeclidinium (Incruse Ellipta), Glycopyrrolate (Seebri Neohaler)
•
Suffix is “tropium”, “clidinium”
•
C Combos: b with i h SABA SABA, LABA, LABA
•
May cause constipation, increased IOP
Chronic Obstructive Pulmonary Disease (COPD)
Quiz
Inhaled Anticholinergic (Long acting muscarinic agentsPharmacologic Management LAMAs)
•
Head to head comparison (7 trials)
•
No significant N i ifi t difference diff in i outcomes t or QOL
•
No statistically significant differences in mortality or hospitalizations
Depends • Data is not overwhelmingly supportive of either intervention • Either choice is acceptable! • Initial selection should depend on availability, co-morbidities, and side effects
www.goldcopd.org/
Which long-acting medication class is preferred first line for a patient with COPD who complains p of frequent q SOB? 1. LABA? 2. LAMA?
Chronic Obstructive Pulmonary Disease (COPD) Dosing Frequency Cost Pharmacologic Management
Long Acting Anticholinergic (LAAC, LAMA)
Aclidinium (DPI) (Turdoza Pressair)
BID
$256.05
Tiotropium Spiriva Handihaler (DPI) Spiriva Respimat (MDI) Umeclidinium (DPI) (Incruse Ellipta)
Daily
$297.81
Daily
$224.76
Seebri Neohaler (glycopyrrolate)
BID
$300
7
3/23/2016
Anticholinergic Medications Anti-cholinergic Side Effects Memory impairment, confusion, hallucinations, dry mouth, blurred vision, ii urinary i retention, i constipation, i i tachycardia, acute angle glaucoma
Mr. Boudreaux is a 60 year old patient who has COPD and uses tiotropium daily. He has had steady worsening of his symptoms over the past several months. He is using albuterol 4-5 times daily. What next?
Incomplete resolution of symptoms: 1. Add theophylline 2. Add a LABA 3. Add a steroid 4. Punt?
“An Ode to an Anticholinergic Med” Oh this drug, it makes me pink, Sometimes, I can’t think or even blink. I can’t see, I can’t pee, I can’t spit, I can’t (**it) (“defecate”).
Therapeutic Options:
Theophylline
Theophylline is less effective and less well tolerated than inhaled l long-acting ti bronchodilators b h dil t Not recommended if LABAs are available and affordable www.goldcopd.org/ © 2015 Global Initiative for Chronic Obstructive Lung Disease
Therapeutic Options:
Theophylline
Modest bronchodilator effect, some symptomatic benefit compared with placebo in stable COPD Diminished respiratory fatigue compared to LABAs Theophylline plus salmeterol produces a greater increase in FEV1 and breathlessness than salmeterol alone www.goldcopd.org/
© 2015 Global Initiative for Chronic Obstructive Lung Disease
Therapeutic Options:
Theophylline
Low dose theophylline reduces exacerbations but does not improve post-bronchodilator lung function
www.goldcopd.org/ © 2015 Global Initiative for Chronic Obstructive Lung Disease
8
3/23/2016
Mr. Boudreaux is a 60 year old patient who has COPD and uses tiotropium daily. He has had steady worsening of his symptoms over the past several months. He is using albuterol 4-5 times daily. What next?
Incomplete resolution of symptoms: 1. Add theophylline 2. Add a LABA 3. Add a steroid 4. Punt?
Are 2 better than one? • Data from controlled trials are conflicting • 5 trials found only slightly better QOL, small increase in post-bronchodilator p FEV1 with combo (compared to LAMA alone)
Long acting Beta Agonist? Pharmacologic Management LABA
Dosing Frequency
Cost
Formoterol (Foradil)
BID
$221.07
Salmeterol (Serevent)
BID
$221 76 $221.76
Indacaterol (DPI) (Arcapta Neohaler) Olodaterol (MDI) (Striverdi Respimat)
Daily
$183.37
Daily
$155.70
Combo LABA and LAMA Pharmacologic Management
Combo
Dosing Frequency
Cost
Olodaterol/Tiotro prium (Stiolto Respimat)
Daily
$315.68
Vilanterol/Umecli dinium (Anoro Ellipta) Indacaterol/glyco pyrrolate
Daily
$280.95
BID
$300
www.goldcopd.org/
Mr. Boudreaux is a 60 year old patient who has COPD and uses tiotropium daily. He has had steady worsening of his symptoms over the past several months. He is using albuterol 4-5 times daily. What next?
Therapeutic Options:
Inhaled Corticosteroids Regular treatment with inhaled corticosteroids:
Improves p symptoms, y p , lung g Incomplete resolution of symptoms: 1. Add theophylline 2. Add a LABA 3. Add a steroid 4. Punt?
function and quality of life
Reduces frequency of
exacerbations for COPD patients who have an FEV1 < 60% predicted www.goldcopd.org/ © 2015 Global Initiative for Chronic Obstructive Lung Disease
9
3/23/2016
Therapeutic Options:
Therapeutic Options:
Combination Therapy
Inhaled Corticosteroids
Inhaled corticosteroid plus LABA is more effective than the individual components:
Inhaled corticosteroid therapy is associated with an increased risk of pneumonia
Improving lung function Improving health status Reducing exacerbations in
moderate to very severe COPD www.goldcopd.org/
www.goldcopd.org/
© 2015 Global Initiative for Chronic Obstructive Lung Disease
Therapeutic Options:
Inhaled Corticosteroids Withdrawal from treatment with
inhaled corticosteroids may lead to exacerbations in some p patients
© 2015 Global Initiative for Chronic Obstructive Lung Disease
Mr. Boudreaux is a 60 year old patient who has COPD and uses tiotropium daily. He has had steady worsening of his symptoms over the past several months. He is using albuterol 4-5 times daily. What next? What is his FEV1?
Incomplete resolution of symptoms: 1. Add theophylline 2. Add a LABA 3. Add a steroid 4. Punt?
www.goldcopd.org/ © 2015 Global Initiative for Chronic Obstructive Lung Disease
Chronic Obstructive Pulmonary Disease (COPD):
Chronic Obstructive Pulmonary Disease (COPD)
Inhaled Steroids
Pharmacologic Management
Pharmacologic Steroid Combos Management
• Best in COPDers with FEV1