COPD Update: It takes my breath away!

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 C...
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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

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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

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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

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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.

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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).

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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?

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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

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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

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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

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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