W14 COPD And Smoking Cessation Flashcards
COPD learning objectives
● For treatment of COPD, list the
major classes of drugs, examples of
drugs within those classes, and their
common adverse effects.
● Based on GOLD guidelines,
recommend medication therapy for a
COPD patient on initial diagnosis, as
well as for treatment escalation.
● Be familiar with the different types
of inhalers and their advantages and
disadvantages.
● Recommend pharmacologic agents to
facilitate smoking cessation based on
patient-specific factors.
COPD symptoms and diagnosis
—dyspnea that is persistent and/or progressing
—chronic cough +/- wheezing
—chronic sputum production
—recurrent lower respiratory tract infections
—risk factors, incl family history
—spirometry :
FEV1«FVC
post- bronchodilator
FEV1/FVC<0.7 indicates irreversible airflow limitation, more likely COPD than asthma
COPD
Goals of treatment
Preventative measures
ANS: PNS vs SNS : how do you achieve bronchodilation?
⭐️
symptom reduction
● relieve symptoms
● improve exercise tolerance
● improve health status
risk reduction
● prevent disease progression
● prevent/treat exacerbations
● reduce mortality
No medication has conclusively shown to slow lung function decline or prolong survival in COPD.
Preventative measures
these should be addressed and optimized at every follow-up visit
—⭐️smoking cessation and avoidance of environmental exacerbants
—⭐️vaccination: influenza, pneumonia, pertussis, COVID-19
—physical activity (incl cardiovascular health)
—pulmonary rehab if group B-D
⭐️this is especially important in COPD, since no medication has conclusively shown to slow lung function decline or prolong survival in COPD
Autonomic Nervous System
—parasympathetic (ACh, cholinergic) → bronchoconstriction
—sympathetic (NE, a,ß receptors) → bronchodilation
⭐️thus, to achieve bronchodilation:⭐️
● enhance the sympathetic system (β2-agonist), and/or
● block the parasympathetic system (anticholinergic, aka
antimuscarinic)
How do you achieve bronchodilation?
What is bronchodilation?
to achieve bronchodilation (↓bronchial tone):
● enhance the sympathetic system (β2- agonist),
and/or
● block the parasympathetic system (anticholinergic, aka antimuscarinic)
What should you be cautious about with BB and COPD patients?
Which are non-selective
Which are non-selective + alpha blocker ?
caution giving beta-blockers to patients w/ asthma, COPD,
etc. particularly agents that are not β1-selective and can cause β2 blockade (propranolol, carvedilol, labetalol)
β1,β2 non-selective: O → Z
—ex: propranolol, timolol:
—avoid in bronchospastic disease non-selective β-blockade
Non-selective BB AND ɑ1 blockade
—carvedilol, labetalol
ɑ1 blockade adds vasodilation
-olol = no ɑ activity
-ilol or -alol = ɑ activity
c
short-acting β2-selective agonists (SABA)
Which 2 agents?
⭐️albuterol (VentolinTM, ProventilTM)
● rescue inhaler of choice for most patients!
Anyone with COPD should have this (or other
SABA or SAMA) and ideally carry it with them
at all times.
● adverse effects/limitations
○ cardiovascular: tachycardia
○ neurologic: headache, jittery
● caution/avoid if patient has
○ uncontrolled HTN / CVD
levalbuterol (Xopenex)
● pure (R)-isomer of albuterol which is responsible for the bronchodilation effect
● theoretically more efficacy and less tachycardia, but $$ and benefits over albuterol are not well proven
terbutaline
—oral or injectable agent, rarely used chronically, utility in acute exacerbations in addition to albuterol
long-acting β2-selective agonists (LABA)
● ⭐️ formoterol
● ⭐️ salmeterol
● ⭐️ vilanterol
● arformoterol
● olodaterol
generally considered equivalent/interchangeable often coformulated with an inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)
adverse effects / limitations
—fewer than albuterolcompared to LAMAs
—lesser efficacy in reducing exacerbations and hospitalizations
⭐️only for chronic control - never use for rescue!
short-acting muscarinic antagonists (SAMA)
(see notebook)
⭐️ipratropium (AtroventTM)
adverse effects
● dry mouth
● nausea
● metallic taste
muscarinic receptors exist throughout the rest of the body!caution/avoid if patient has
● narrow-angle glaucoma
● urinary obstruction, including BPH
compared to SABAs
● similar efficacy and characteristics; ipratropium
technically takes longer to work (15-20min, vs
5min for albuterol)
● often combined (albuterol-ipratropium inhaler or
neb), especially for COPD
● in general, short-acting bronchodilators (SABA and
SAMA) do not reduce frequency or severity of COPD
exacerbations the way long-acting bronchodilators
do
don’t get it mixed up w/ tiotropium (a LAMA)!
“i” for immediate (short-acting)?
long-acting muscarinic antagonists (LAMA)
compared to ipratropium, more selective for muscarinic receptors and dissociate slower
adverse effects/limitations and precautions - similar to ipratropium
● ⭐️tiotropium
● aclidinium
● umeclidinium
● glycopyrrolate / glycopyrronium
● revefenacin
—generally considered equivalent/interchangeable
—often coformulated with a LABA
⭐️only for chronic control - never use for rescue!
—⭐️ compared to LABAs, greater efficacy in reducing exacerbations and hospitalizations — it is the sole agent in group C ⭐️
Summary of inhaled bronchodilators
⭐️ know them well
B2 agonists
SABA
LABA
Muscarinic antagonists, anti-cholinergics
SAMA
LAMA
Characteristics and usage
Recognise B2 agonists first
Ipratropium = think “immediate”
inhaled corticosteroids (ICS)
Place in therapy
Used in combo with?
Initial therapy criteria
Step up therapy criteria
ADRs
When should it not be used
What are the 4 meds?
Place in therapy
● ⭐️do not use as monotherapy
COPD isn’t as steroid-responsive as asthma, so only use when benefits > risk
○ must combine w/ LABA, or LABA+LAMA
○ no evidence for just ICS+LAMA
● for initial therapy, only for Group D (sickest, most symptomatic) patients if
○ h/o asthma, or
○ ⭐️blood eosinophils ≥300 cells/µL
● for step-up therapy, use if
○ blood eosinophils ≥300 cells/µL, or
○ blood eosinophils ≥100 cells/µL AND ≥2 exacerbations or ≥1 requiring hospitalization
● as with LABAs and LAMAs, ❌ should NOT be used for
rescue during acute exacerbation
adverse effects / monitoring
❌ avoid if patient has recurrent pneumonia or h/o mycobacterial lung disease
● candida/thrush (oral, if used improperly)
● osteoporosis (orthopedic, w/ long-term use)
● cataracts (ophthalmic, w/ long-term use)
memorization tip: -son or -sone = corticosteroid
💊 budesonide
💊 fluticasone
💊 mometasone
💊 beclomethasone
Know the combination inhalers for COPD
—SABA + SAMA
—LAMA + LABA
—ICS + LABA
—ICS + LAMA + LABA
Inhaler terminology
FYI
And technique
MMRC and CAT
MMRC is a dyspnea scale
CAT is a bit more comprehensive, includes coughing, mucous, fatigue etc
The refined ABCD assessment tool
What are the steps?
What are the grades GOLD 1-4
This is for initiating treatment
What is the initial treatment approach for A, B, C D?
Bronchodilator first SABA/SAMA
Then LAMA is a mainstay of therapy
LAMA/LABA is also appropriate, especially if D
Make it a triple therapy with ICS if really sick
Follow up
notes on the f/u pathway
● ABCD only applies to initial tx
● remember to always assess compliance and technique
● COPD meds are usually fixed dosing (dose isn’t titrated like w/ asthma) general step-up/escalation approach:
● + LAMA or LABA if not already taking
● + ICS only if patient qualifies (and 🔺stop ICS if patient has pneumonia or doesn’t respond)
● if maximized on inhaled therapy, considering roflumilast or azithromycin
if patient experiences exacerbations despite optimized inhaler therapy,
or is unable to optimize inhaler therapy
Which two adjunctive agents?
roflumilast (DalirespTM)
● oral PDE-4 inhibitor, relaxes airway smooth muscles, decreases activity of inflammatory cells and mediators
● consider for severe airflow limitation (FEV1 <50%of predicted), chronic bronchitis, and recurrent exacerbations
● use w/ LABA+LAMA +/-ICS
● ADRs: GI, headache, neuropsychiatric (later-line treatment, like ranolazine is for Angina, or ivabradine is for HF)
azithromycin
● oral macrolide, has some anti-inflammatory effects
● reduces exacerbation rates and improves quality-of-life scores
● consider in former smokers (no utility for active smokers)
● dosing (off-label): 250 or 500mg 3 times weekly, or 250mg daily
● ADRs: ↑QTc, macrolide resistance
COPD
Agents for special case scenarios
**methylxanthines (ie, oral theophylline)*(
● slight bronchodilatory effect (inhibits PDE, thus don’t mix w/ roflumilast), reduces airway responsiveness to histamine, adenosine, and allergens
● old-school med; typically reserved for patients unable to optimize inhaler therapy, rarely initiated nowadays
● disadvantages: very narrow therapeutic index, interpatient variability, drug interactions, requires level monitoring
● s/sxs of toxicity: dyspepsia, N/V/D, headache, dizziness, tachycardia, arrhythmias, seizures
mucolytics (ie, N-acetylcysteine)
● may be considered if not on ICS, esp w/ chronic bronchitis
● if nebulized, administer after bronchodilator
● smells like rotten eggs :(
alpha-1 antitrypsin augmentation therapy
● inhibition of alpha-1 proteinases
● may slow progression of emphysema if due to AAT deficiency
❌what’s NOT recommended in the guidelines ❌:
—oral bronchodilators (inhaled prefered)
—oral long-term corticosteroids
—statins
—antitussives (cough suppressants)
—vasodilators
COPD
managing exacerbations
4 steps
1️⃣ SABAs +/- SAMAs
—(ie, albuterol +/- ipratropium) every 4-6 hours until resolution
—definitely use in combination for severe exacerbations
—switch to long-acting bronchodilators once stable (or continue home dose)
2️⃣ Oral or IV corticosteroids (ie, prednisone)
—typically for 5-7 days
3️⃣ Antibiotics?
only if increased sputum purulence, in addition to increased dyspnea and/or sputum volume
—procalcitonin could come into play here, if it’s low, probably not a bacterial infection
—similar organisms and treatments as CAP - azithromycin or clarithromycin, doxycycline, 2nd or 3rd-gen cephalosporins, amox-clav, respiratory fluoroquinolones
—treat for no more than 5-7 days
4️⃣ Oxygen and ventilatory support
Smoking — quitting
What is a measure of nicotine dependence? And a determinant of nicotine replacement therapy (NRT)
measures of nicotine dependence:
—amount of daily smoking
—and smoking within 30 minutes of waking
= predictor of difficulty quitting
= determines dosing of nicotine replacement therapy (NRT)
What are the 5 A’s for tobacco cessation?
—Ask about tobacco use from all patients at every visit
—Advise all tobacco users to quit
—Assess willingness and motivation for tobacco user to make a quit attempt
● motivational interviewing to address ambivalence to change
● if patient isn’t motivated, no treatment plan is going to make them quit
—Assist in the quit attempt
—Arrange for follow-up
What are the physiologic effects of nicotine on:
CNS
CV
GI
Safety concerns w/ NRT
CNS:
—respiratory excitation
—vomiting
—release of dopamine, etc.
—tremors (high doses)
safety concerns w/ NRT
—insomnia and sleep disturbance (esp if taken overnight or close to bedtime)
CV
—stimulates sympathetic ganglia and the adrenal medulla, stimulates release of catecholamines from sympathetic nerve endings → vasoconstriction, tachycardia, elevated blood pressure
safety concerns w/ NRT
—increased cardiac oxygen demand, hence avoid with active cardiovascular disease
GI
increased bowel tone and activity → nausea, vomiting, diarrhea
safety concerns w/ NRT
—dyspepsia
—nausea
nicotine replacement therapy (NRT)
What is the most common approach/treatment?
How often, dose, for how many cigarettes/day
Precautions: which two groups should avoid?
Caution with nasal spray, and patch?
When could toxicity occur?
most common approach:
—transdermal patch - start at highest dose (21 mg/day) for those who smoke over a half-pack pack per day
—put on a new patch every morning
—PLUS PRN lozenge or gum for cravings
less-used (Rx-only):
—nasal spray or oral inhaler for cravings
realize the limitations w/ PK:
—patch takes 2-8hr to peak, and short-term craving options take up to 30min to peak;
—for comparison, remember that smoking a cigarette kicks in with seconds
Precautions
—serious cardiovascular dz (recent MI, serious underlying
arrhythmia, serious/worsening angina)
—pregnancy, breastfeeding
—nasal spray - avoid w/ ENT conditions, requires prescription
—patch - avoid w/ dermatologic conditions
Toxicity
GI upset, palpitations, dizzinessfrom NRT is actually rare
—typically arises when patient smokes on top of taking NRT (ie, patch), which is an indication that their controller medication (nicotine patch, varenicline, or bupropion) could be better optimized
—some experts even recommend two 21mg patches to start for patients with high degree of dependence
Smoking cessation: varenicline (ChantixTM)
How should it be taken?
MOA?
Dosing
*most effective agent when used as monotherapy and most strongly recommended by guidelines
MOA: reference only:
—partial agonist of ɑ4 β2 nicotinic receptor; prevents
nicotine stimulation of mesolimbic dopamine system; also
stimulates dopamine activity, decreasing craving and withdrawal symptoms
Dosing: not tested, just know it’s stepwise
● 0.5mg once daily on day 1-3
● then twice daily on day 4-7,
● then 1 mg twice daily
● labeled for 12-week course; guideline recommends taking
for at least 4 months for best success, studies have gone
on as long as a year
—doubles the chances of a person abstaining even if they
weren’t ready to quit when they first start it
—30% success at achieving abstinence for 6 months when
used in combination with NRT
Smoking cessation: varenicline (ChantixTM)
Approaches to treatment?
ADRs
Warnings/precautions
● ⭐️start at least 1 week prior to quit date
● choose a fixed quit date (ie, start varenicline, aim to quit on day 8)
● flexible quit date
● gradual quit date (ie, reduce smoking by 50% by week 4 of treatment, additional 50% by week 8, and so on)
● if patient successfully quits at end of 12 weeks, an additional course can increase likelihood of long-term success the 2020 ATS guidelines even recommend starting varenicline in patients who are NOT ready to quit, rather than waiting for them to be ready to quit
🔺ADRs 🔺
common:
—nausea (up to 40%)
—headache (up to 20%)
—insomnia (up to 20%)
—abnormal dreams,
—irritability, suicidal ideation, depression
hence why dose should be increased gradually
Warnings/Precautions
● CNS depression
● hypersensitivity reactions
● nausea
● neuropsychiatric effects
● somnambulism
● risk of cardiovascular events (less than NRT)
● seizures
Smoking cessation: Bupropion (Wellbutrin)
MOA
Approach to therapy
Precautions
C/I
MOA:
—nicotinic antagonist, which lessens the stimulant effect of nicotine use;
—inhibits dopamine reuptake in the synaptic cleft, which helps w/ nicotine withdrawal symptoms
start 1-2 weeks prior to quit date:
—150mg daily for 3 days
—then twice daily for up to 12 weeks,
—consider maintenance for up to 6 months benefits
● antidepressant (originally created for this purpose)
● weight loss - may be desirable since weight gain often accompanies smoking cessation
precautions
● ⭐️lowers seizure threshold
● pregnancy and breastfeeding
● neuropsychiatric symptoms (treatment-emergent)
contraindications
● ⭐️ seizure disorder, or simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines
● h/o bulimia or anorexia nervosa
● MAO inhibitors (within 14 days)
Psychiatric concerns with varenicline or bupropion
key FDA decisions:
● in 2006, the FDA added a BBW to both varenicline and bupropion about increased risk
neuropsychiatric events (suicidal thoughts, agitation, hostility)
● in 2016, the BBW was removed based on findings from the EAGLES trial that showed NO
significant increase in “neuropsychiatric adverse events attributable to varenicline or
bupropion relative to nicotine patch or placebo”
key takeaway:
—well-managed psychiatric history is not a contraindication to varenicline or bupropion, but ensure patients get close follow-up as they transition through the quitting process
COPD, bronchodilator treatment
Escalating therapy
*need to check answers with Dr. Chu
