COPD packet 2

what are the two goals for treatment of stable copd?

• reduce symptoms

• reduce risk of exacerbations

what are the pharmacotherapy options for stable copd?

SABA, LABA, SAMA, LAMA, LABA/ICS, LABA/LAMA/ICS, PDE inhibitors, biologics, antibiotics

beta 2 agonists moa

increase cAMP

how do SABAs treat copd?

improve FEV1, decrease symptoms

how do LABAs treat copd?

• improve FEV1, lung volumes, and health status

• decrease dyspnea, exacerbations, hospitalizations

• no effect on mortality

beta-2 agonists ADRs

tachycardia, cardiac rhythm disturbances, tremor, hypokalemia

SAMAs

• block M2 and M3

• better at improving FEV1 than SABAs

• decreases the need for oral steroids

LAMAs

• prolonged binding to M3

• improved symptoms (cough, sputum)

• decreased exacerbations, hospitalizations

• better at decreasing exacerbation rates than LAMAs

• no effect on mortality

muscarinic antagonists ADRs

dry mouth, bitter/metallic taste, small increased risk of cardiac events

methylxanthine drug

theophylline

how do methylxanthines work?

non-selective PDE inhibitor

what are some benefits from theopylline?

• modest bronchodilator in stable COPD

• improved FEV1 and dyspnea when added to salmeterol

what are some cons of theophylline?

• no consistent improvement in risk of exacerbations

• metabolized by CYP450 enzymes

• requires careful monitoring

theophylline ADRs

HA, insomnia, nausea, seizures, arrhythmias

when is theophylline recommended in treatment algorithm?

only recommended if other agents aren’t available / affordable

what is the response of ICS to copd?

copd inflammation has less response to ICS

can ICS be used as monotherapy for copd?

no

when is ICS beneficial in copd?

• reducing exacerbations in pts with exacerbations in the past year

• linked to blood eosinophil count

when does ICS have the greatest benefit in copd?

if eosinophil count > 300

ICS ADRs

oral candidiasis, hoarseness, bruising, pneumonia

what should be assessed before concluding that current Tx needs modification?

inhaler technique and adherence

what plays a role in choosing inhalers for patients?

• insurance, cost

• patient’s ability/preference

what are some other medications that can be used in copd management?

roflumilast, antibiotics, ensifentrine, dupilumab, mepolizumab

what is Tx for group A of copd?

LABA or LAMA (bronchodilator - long acting is preferred)

what is Tx for group B of copd?

LABA + LAMA

what is Tx for group E in copd?

LABA + LAMA; consider triple treatment that includes ICS (only when eosinophils > 300)

what are tx recommendations for dyspnea?

LABA/LAMA combo

what should not be used in treating dyspnea?

ICS

how does ensifentrine work?

dual PDE3 and PDE4 inhibitor

what did the ENHANCE trials show?

use of ICS and long-acting bronchodilators should be limited

ensifentrine dose

3 mg bid nebulized

what is a safety precaution for ensifentrine?

psychiatric events including suicide

what are the recommendations for exacerbations?

• LABA/LAMA combo

• LABA/ICS = not recommended

• ICS added if elevated eosinophil count

when should ICS be considered in exacerbations?

• Eos > 300

• Eos > 100 with at least two moderate exacerbations OR 1 hospitalization

• concurrent asthma

when are biologics (dupilumab or mepolizumab) added?

if two moderate or one severe exacerbation AND eos > 300

what symptoms should be monitored with copd/Tx?

dyspnea, cough/sputum, fatigue, ADLs, sleep

what exacerbations should be monitored with copd/Tx?

frequency, severity, causes

when and how should adherence be monitored with copd/Tx?

“mandatory at each visit;” assess doses, effectiveness, side effects

what should be monitored when evaluating smoking status?

current smoking status and exposure

what is measured with copd/Tx?

FEV1 at least annually

risk factors for pneumonia with ICS in copd pts

• current smokers

• 55 and older

• history of prior pneumonia

• BMI < 25

• increased mMRC score

• severe airflow limitation

what are additional treatments for exacerbations?

• roflumilast

• azithromycin

• biologic therapy (-mabs)

when is roflumilast used in exacerbations?

if FEV1 < 50% & chronic bronchitis

when is azithromycin used in exacerbations?

preferentially in former smokers

roflumilast moa

inhibits metabolism of cAMP; decreases eosinophils/neutrophils

roflumilast dosing

250 mcg daily x 4 weeks; then 500 mcg once daily

roflumilast use

a patient with copd

• severe copd (FEV1<50%)

• chronic bronchitis

• history of exacerbations

roflumilast ADRs

• weight loss

• psychiatric effects (depression, anxiety, suicidal thoughts)

roflumilast warnings

• underweight patient

• depression

roflumilast DDI

metabolized by 3A4 and 1A2

benefits of macrolides in exacerbation prevention

• decrease exacerbations per year

• decrease percentage of patients with exacerbations

  • improve quality of life

what is the harm of macrolides?

hearing loss, prolonged QT arrhythmias

when are macrolides recommended in exacerbation prevention?

patients with moderate-very severe copd and exacerbations despite optimal inhaler Tx

when is azithromycin most effective in exacerbation prevention?

more effective for previous smokers & less effective in current smokers

IL4 and IL3 function

• increase FeNO

• promote eosinophil