T5 - IE3 - Pulmonology - Ostrom - Pathophysiology and Pharmacology of Chronic Obstructive Pulmonary Disease (COPD)

Asthma vs. COPD Chart

Asthma vs. COPD - treatment response: bronchodilators

Asthma: reversible

COPD: partially reversible

Asthma vs. COPD - treatment response: corticosteroids

Asthma: good

COPD: poor

Asthma vs. COPD - smoking status

Asthma: non-smokers affected

COPD: usually long smoking history

Asthma vs. COPD airway inflammation

Asthma: can normalize after resolution of each episode

COPD: cannot normalize - progressive deterioration with INCREASED age

In COPD - airway inflammation can ______ ____________, there is ____________ deterioration with increased age

- NOT normalize

- progressive (deterioration)

In COPD - airway inflammation: can NOT normalize, there is progressive ____________ with _________ age

- (progressive) deterioration

- INCREASED (age)

Asthma vs. COPD: Asthma is most often diagnosed in __________ or __________, while COPD is diagnosed ______ in life.

- childhood

- adolescence

- later (in life)

Asthma vs. COPD - smoking: Nearly all patients with COPD either _______ smoked or have a significant _____________ ________ ______ exposure, while asthma patients are more commonly non-smokers.

- (either) HAVE (smoked)

- (significant) environmental tobacco smoke (exposure)

Asthma vs. COPD - trigger signs: In general, asthma is acutely worsened by exposure to allergens, cold air and exercise.

COPD flare-ups are largely caused by _________ _______ ______ like pneumonia and influenza. COPD can also be made worse from exposure to ____________ _________.

- respiratory tract infections

- (exposure to) environmental pollutants

Asthma vs. COPD - trigger signs:

In general, asthma is acutely worsened by exposure to allergens, cold air and exercise.

COPD flare-ups are largely caused by respiratory tract infections like __________ and __________. COPD can also be made worse from exposure to environmental pollutants.

- pneumonia

- influenza

Asthma vs. COPD - trigger signs:

In general, asthma is acutely worsened by exposure to __________, ______ _____ and _________.

COPD flare-ups are largely caused by respiratory tract infections like pneumonia and influenza. COPD can also be made worse from exposure to environmental pollutants.

- allergens

- cold air

- exercise

Asthma vs. COPD - Treatment Goals: Different for each diseases. Asthma is treated to suppress __________ _________, whereas COPD is treated to reduce symptoms. Asthma pathology is ________, COPD is not.

- (to suppress) chronic inflammation

- reversible

Asthma vs. COPD - Treatment Goals: Different for each diseases. Asthma is treated to suppress chronic inflammation, whereas COPD is treated to __________ symptoms. Asthma pathology is reversible, COPD is _____ __________.

- reduce (symptoms)

- not reversible

ACOS

asthma-COPD overlap symdrome

Asthma-COPD Overlap Syndrome (ACOS): is a ____ of both diseases; ________ ________ than either alone, so more _________ therapy needed

- mix (of both)

- more serious (than either alone)

- aggressive (therapy needed)

ACOS is still poorly understood

Asthma-COPD Overlap Syndrome (ACOS): still _________ understood, diagnosis is still __________

- poorly (understood)

- (still) evolving

Asthma-COPD Overlap Syndrome (ACOS) diagram

COPD Pathophysiology - Progressive ____ of airflow in lungs resulting in ______________ that is not fully reversible. Primarily caused by chronic inflammation.

- (Progressive) loss

- bronchoconstriction

COPD Pathophysiology - Progressive loss of _______ in lungs resulting in bronchoconstriction that is _____ _______ reversible. Primarily caused by ________ inflammation.

- airflow (in lungs)

- not fully (reversible)

- chronic (inflammation)

COPD Pathophysiology - two common forms

Bronchitis

Emphysema

COPD Pathophysiology - two common forms: bronchitis

fixed obstruction of airways

- inflammation

- mucus production

conducting zone blocked

COPD Pathophysiology - two common forms: emphysema

destruction of alveolar architecture

loss of respiratory zone

COPD - bronchitis: _________ ______ of airways

- fixed obstruction (of airways)

Inflammation and/or mucus production

COPD - bronchitis: fixed obstruction of airways from the results of ___________ and/or _________ production

- inflammation

- (and/or) mucus (production)

COPD - emphysema: __________ of alveolar architecture

- destruction (of alveolar architecture)

Loss of respiratory zone

COPD - bronchitis: _____________ zone is blocked

- Conducting (zone)

COPD - emphysema: loss of __________ zone

- respiratory (zone)

Destruction and enlargement of air spaces

COPD - emphysema: __________ and ________ of air spaces

- destruction

- enlargement (of air spaces)

COPD - emphysema vs. normal lungs figure

COPD - chronic bronchitis: ___________ and ____________ changes

- inflammation

- structural (changes)

COPD - chronic bronchitis vs. normal lungs figure

COPD - Chronic Bronchitis and Emphysema Zone Figure

COPD Molecular / Cellular Pathophysiology Pathway Figure

COPD Molecular / Cellular Pathophysiology Pathway: smoke exposure

particulates

chemicals

reactive oxygen species

These lead to inflammation and progress to chronic inflammation

COPD Molecular / Cellular Pathophysiology Pathway:

Step 1: smoke exposure (particulates, chemicals, reactive oxygen species) leads to ___________

- (leads to) inflammation

Step 2: Inflammation will lead to chronic inflammation and activation of neutrophils.

COPD Molecular / Cellular Pathophysiology Pathway:

Step 1: smoke exposure (particulates, chemicals, reactive oxygen species) leads to inflammation

Step 2: Inflammation will lead to ________ __________ and activation of _________.

- chronic inflammation

- (and activation of) neutrophils

Activation of neutrophils lead to inactivation of antiproteases

COPD Molecular / Cellular Pathophysiology Pathway:

Step 2: Inflammation will lead to chronic inflammation and activation of neutrophils.

Step 3: Activation of neutrophils lead to ___________ of antiproteases

- inactivation (of antiproteases)

HDAC

Histone deacetylase.

Histone deactylase (HDACs)

An enzyme that removes acetyl groups from a histone tail, allowing histones to wrap the DNA more tightly promoting repression of gene transcription.

COPD Molecular / Cellular Pathophysiology Pathway:

Step 2: Inflammation will lead to chronic inflammation and activation of neutrophils.

Step 3: Activation of neutrophils lead to inactivation of ____________

- (inactivation of) antiproteases

Step 4: Inactivation of antiproteases cause increased elastase activity

COPD Molecular / Cellular Pathophysiology Pathway:

Step 3: Activation of neutrophils lead to inactivation of antiproteases

Step 4: Inactivation of antiproteases cause ___________ __________ activity

- increased elastase (activity)

This leads to destruction of alveoli, airways

COPD Molecular / Cellular Pathophysiology Pathway:

Step 4: Inactivation of antiproteases cause INCREASED elastase activity.

Hereditary deficiency of ___-_________ also causes INCREASED elastase activity

Step 5: Increased elastase activity causes DESTRUCTION of _________ and ____________

- α1-antitrypsin

- (causes DESTRUCTION of) alveoli

- airways

Smoking causes ________, but there is hope if you ________

- (causes) COPD

- (if you) quit

ALWAYs counsel on smoking cessation

Promoting tobacco cessation: advise patient to ____ / _______ second-hand smoke

- quit / avoid (second-hand smoke)

Promoting tobacco cessation: assess patient's willingness to quit

Stages:

Pre-contemplation

Contemplation

Preparation

Action

Maintenance

Relapse

Try to move patients along one stage

Promoting tobacco cessation: if ready to quit

establish a quit date

provide self-help materials

offer nicotine replacement therapy and/or non-nicotine medications

Promoting tobacco cessation - if ready to quit: offer _______ ________ therapy and/or ___-________ medications

- nicotine replacement

- non-nicotine

Promoting tobacco cessation - if ready to quit: recommending a smoking cessation program

Combination of medications plus a smoking cessation program is more effective than either alone

Algorithm for the treatment chart

Long Acting Inhaled Anticholinergics: improved selectivity through __________ application by ________ or _______ inhalation

- topical (application)

- nasal

- oral (inhalation)

Long Acting Inhaled Anticholinergics: __________ systemic adverse effects with recommended dosing regimen

- minimal (systemic adverse effects)

Increased risk of urinary retention, especially with BPH

Long Acting Inhaled Anticholinergics Drugs

Ipatropium

Tiotropium

Aclidinium

Umeclidinium

Ipatropium

ATROVENT

ATROVENT

ipatropium

tiotropium

SPIRIVA

aclidinium

TUDORZZA PRESSAIR

TUDORZZA PRESSAIR

aclidinium

umeclidinium

INCRUSE ELLIPTA

INCRUSE ELLIPTA

umeclidinium

Long Acting Inhaled Anticholinergics Chart

Counseling - anticholinergics: avoid activities requiring ________ alertness or __________ until drug effects are ____________

- mental (alertness)

- coordination

- realized

May cause dizziness, mydriasis, and blurred vision

Counseling - anticholinergics: may cause _________, __________, and _________ vision

- dizziness

- mydriasis

- blurred (vision)

Avoid medication contact with eyes

Counseling - anticholinergics: Inhalation form may cause...

headaches

dry mouth

respiratory tract infections (including bronchitis)

urinary retention,

urinary tract infections

sinusitis

Counseling - anticholinergics: Report symptoms of ___________ (anaphylaxis, rash, angioedema, urticaria), eye pain, blurred vision, excessively dry nasal passages, or nose bleeds

- hypersensitivity

Counseling - anticholinergics: advise patient on proper _________ technique, depending on __________ ______

- inhalation (technique)

- delivery device

SABAs for bronchodilation drugs

albuterol (VENTOLIN)

levalbuterol (XOPENEX)

pirbuterol (MAXAIR)

terbutaline

SABAs for bronchodilation: "____________" with _____ onset-intermediate duration

- "relievers"

- quick (onset-intermediate)

~6 hour

SABAs for bronchodilation: _________ smooth muscle

- relax (smooth muscle)

Stabilize mast cells preventing histamine release in response to allergen

SABAs for bronchodilation: stabilize ______ _______ preventing ___________ release in response to allergen

- (stabilize) mast cells

- histamine (release)

SABAs for bronchodilation: _________ route preferred

- inhaled (route preferred)

Also given PO, SC, IV

SABAs for bronchodilation - side effects

N/V

headache

Increased BP, HR

Arrhythmias

Convulsions

Coma

Respiratory & Vasomotor Collapse

Tremor via β2 receptors in skeletal muscle

Short-lived hyperglycemia

SABAs for bronchodilation: routine monitoring of ____________ function

- pulmonary (function)

LABA drugs for maintenance

Salmeterol (SEREVENT)

Formoterol (FORADIL)

Indacaterol (ARCAPTA NEOHALER)

salmeterol

SEREVENT

SEREVENT

salmeterol

formoterol

FORADIL

FORADIL

formoterol

LABAs for maintenance: ___________ _______ onset-long duration

- "preventers" slower (onset)

12+ hour duration

LABAs for maintenance: used for ____________ or _________-________ asthma

- nighttime

- exercise-induced (asthma)

Usually prescribed for 2x daily administration

LABAs for maintenance: usually prescribed for _____ daily administration

- 2x (daily administration)

Aerosol or powder

Counseling: β2AR Agonists - warn patient to report symptoms of ___________ _____________

- (symptoms of) paradoxical bronchospasm

Counseling: β2AR Agonists - instruct patent to report need for __________ _____ or _______ of drug to provide symptomatic relief

- increased frequency

- amounts (of drug)

Counseling: β2AR Agonists - advise patients to report symptoms of...

atrial fibrillation

supraventicular tachycardia

hypokalemia

Counseling: β2AR Agonists - side effects

Palpitations

Chest pain

Tremors

Headache

Dizziness

Nervousness

Combination LABA & Anticholinergic for COPD Figure

Parasympathetic: inhibits bronchoconstriction

Sympathetic: causes bronchodilation

ICS Corticosteroid Drugs

Beclomethasone dipropionate (BECLOVENT)

Budesonide (RHINOCORT)

Fluticasone propionate (FLOVENT)

Mometasone (NASONEX)

Ciclesonide (ALVESCO)

beclomethasone dipropionate

BECLOVENT

budesonide

RHINOCORT

fluticasone propionate

FLOVENT

ciclesonide

ALVESCO

ICS mono-therapy is _____ __________ for COPD

- NOT appropriate (for COPD)

Smokers can be resistant to _________________ therapy

- corticosteroid (therapy)

Oxidative / carbonyl stress from smoking may inhibit HDAC2 from unwinding thus increased inflammatory gene transcription and steroid resistance

Smokers: corticosteroid resistance

Oxidative / carbonyl stress from smoking may inhibit HDAC2 from unwinding thus increased inflammatory gene transcription and steroid resistance

Smokers - corticosteroid resistance: Oxidative / carbonyl stress from smoking may inhibit __________ from unwinding thus increased __________ gene transcription and steroid resistance

- HDAC2

- inflammatory (gene transcription)

This leads to inflammation in COPD

Combined corticosteroid & LABA drugs

Fluticasone / Salmeterol (ADVAIR DISCUS)

Budesonide / Formoterol (SYMBICORT)

Mometasone / Formeterol (DULERA)

fluticasone / Salmeterol

ADVAIR DISCUS

budesonide / formoterol

SYMBICORT

mometasone / formoterol

DULERA