A Wisp of Air: Review of Respiratory Medication

Kathy Tripepi-Bova MSN, RN, CCRN, CCNS

Keith Anderson PharmD

Disney wikia art

Functions

• provide oxygen to the blood stream and remove carbon dioxide

• enable sound production or vocalization as expired air passes over the vocal chords

• enable protective and reflexive non-breathing air movements such as coughing and sneezing, to keep the air passages clear

• control of Acid-Base balance in the blood and thus control the blood pH

One breath

• Normal respiratory rate is 10- 15 breaths per minute.

• For inspiration, the inspiratory center sends nerve impulses along the phrenic nerve to the diaphragm and along the intercostal nerves to the external intercostal muscles to stimulate inspiration (2 seconds)

• For expiration the inspiratory center stop firing for about 3 seconds which allows the muscle to relax and the lungs to recoil

Lower airways

•www.aduk.org.uk/ gfx/lungs.jpg

http://histology.med.umich.edu/medical/respiratorysystem&docid=JPBVlGa23XXLpM&w=850&h=562&ei=OhSCTv3yHqP-sQKQxuSbDw&zoom=1

Respiratory System – alveoli

http://www.livinghealthfully.com/2012-02/

Lining of the alveoli

• Type I cells or Type I alveolar cells

– Make up 97% of the alveolar surface

– Very thin components of the blood air barrier

– Coated by a thin layer of water

• Surfactant: a lipoprotein that is produced in the lungs Produced by Type II cells Cover the remaining 3% of the alveolar surface reduces the surface tension of fluid in the lungs and

prevents the alveoli from collapsing Production begins in utero at about 20 weeks gestation

• Macrophages

– important in removing any debris that escapes the mucus and cilia in the conducting portion of the system

– Also known as dust cells

http://quizlet.com/15237551/respiratory-system-flash-cards/

http://www.studydroid.com/index.php?page=viewPack&packId=539058

AIRWAY DISEASES

COPD and Asthma

Bronchitis

• Airway changes lead to hypersecretion of mucus and impaired cilia which lead to a chronic productive cough

• Bronchial wall thickening leads to progressive obstruction to air flow

“Blue bloater”

COPD-Emphysema

• A loss of elasticity in the walls of the small air sacs in your lungs. – Eventually, the walls stretch and break, creating larger, less

efficient air sacs that aren't able to handle the normal exchange of oxygen and carbon dioxide.

• When emphysema is advanced, the patient must work hard to expel air from their lungs

• Breathing can consume up to 20 percent of the resting energy.

Altered dynamics of breathing

• Diaphragm is pushed down

• Intercostal space enlarges as lung expands

• Must use neck muscles to aid in respiration

• “Purse lip breathing” on exhalation

Pink puffer

COPD-Emphysema

• Primary signs and symptoms

– shortness of breath

– or the feeling of not being able to get enough air

• Treatments focus on relieving symptoms and avoiding complications.

Asthma

Definition of asthma

• a chronic inflammatory disorder of the airways that involves many different cells, including mast cells, eosinophils, and T lymphocytes

• inflammation causes recurrent episodes of wheezing, dyspnea, and cough

Pathogenesis

• Airway inflammation with airway reactivity

– contraction of the airway smooth muscles

– microvascular leakage

– bronchial hyper-responsiveness

• Asthma differs from other airway diseases because of

– absence of bronchiolitis

– lack of fibrosis

– absence of granulation tissue

Early asthma response (EAR)

• With exposure to a trigger, there mobilization of histamines, prostaglandin and leukotrienes.

• This causes – Airway smooth muscle constriction

– Mucous hypersecretion

– Mucosal edema

Late asthma response (LAR)

• Includes mobilization of lymphokines and other chemotactic compounds that may cause lymphocytes, neutrophils and eosinophils to migrate to the site of airway hyperreactivity

LAR results in

• Damage to the respiratory epithelium

• Amplification of the inflammatory process

• Propagation of the inflammatory response along other airways

Goals of Asthma Therapy

• Prevent chronic symptoms such as cough and wheezing

• maintain near normal pulmonary function

• maintain normal activity levels-this includes exercise

• Prevent recurrent exacerbation

• Provide optimal pharmacotherapy with minimal side effects

• Meet patients and families expectations of satisfaction with asthma care

Prevent and decrease

symptoms

Reduce frequency and

severity of exacerbations

Improve health status

Improve exercise capacity

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014)

Stage Characteristics

I: Mild COPD FEV1 ≥ 80% predicted

II: Moderate COPD 50% ≤ FEV1 < 80% predicted

III: Severe COPD 30% ≤ FEV1 < 50%

IV: Very Severe COPD FEV1 < 30% predicted

In Patients with FEV1/FVC < 70%

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014)

Patient Characteristic Spirometric Classification

Exacerbations per year CAT mMRC

A Low Risk Less Symptoms

GOLD 1-2 ≤1 <10 0-1

B Low Risk More Symptoms

GOLD 1-2 ≤1 ≥10 ≥2

C High Risk Less Symptoms

GOLD 3-4 ≥2 <10 0-1

D High Risk More Symptoms

GOLD 3-4 ≥2 ≥10 ≥2

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014)

Patient Group

Recommended 1st Choice Alternative Choice Other Possible Treatments

A • SA anticholinergic prn or • SA β2-agonist prn

• LA anticholinergic or • LA β2-agonist or • SA anticholinergic and SA β2-agonist

• Theophylline

B • LA anticholinergic or • LA β2-agonist

• LA anticholinergic and LA β2-agonist • SA anticholinergic

and/or SA β2-agonist • Theophylline

C • ICS + LA β2-agonist or • LA anticholinergic

• LA β2-agonist and LA anticholinergic or • LA anticholinergic and PDE-4 Inhibitor or • LA β2-agonist and PDE-4 Inhibitor

• SA anticholinergic and/or SA β2-agonist

• Theophylline

D

• ICS + LA β2-agonist and/or LA anticholinergic

• ICS + LA β2-agonist and PDE-4 Inhibitors or • LA anticholinergic and LA β2-agonist or • LA anticholinergic and PDE-4 Inhibitor

• Carbocysteine • SA anticholinergic

and/or SA β2-agonist • Theophylline

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014)

SA=short acting LA=long acting ICS=inhaled corticosteroid PDE=phophodiesterase inhibitor

Short acting β2 agonists

Medication Usual dose Duration

Albuterol MDI: 2 puffs q4-6 hours Nebulization: 2.5mg q6-8 hours

4-6 hours

Levalbuterol MDI: 2 puffs q4-6 hours Nebulization: 0.63-1.25mg TID

6-8 hours

Long acting β2 agonists

Formoterol Foradil Aerolizer: 12mcg q12 hours Perforomist: 20mcg BID

12 hours

Arformoterol 15mcg BID 12 hours

Indacaterol 75-300mcg daily 24 hours

Olodaterol 5mcg daily 24 hours

Salmeterol 50mcg q12 hours 12 hours

Short acting anticholinergics

Medication Usual dose Duration

Ipratropium MDI: 2 puffs 4-6X daily Nebulization: 2.5mL 3-4X daily

6-8 hours

Long acting anticholinergics

Tiotropium Handihaler: 18mcg daily Respimat*: 5mcg daily

24 hours

Aclidinium 400mcg BID 12 hours

*Available 1/15

ICS + LA β2 agonists

Medication Usual Dose

Budesonide/salmeterol 160/4.5mcg BID

Fluticasone/salmeterol* 250/50mcg BID

Fluticasone/vilanterol 100/25mcg daily

Mometasone/formoterol** 10/200mcg-10/400mcg BID

SA anticholinergic + SA β2 agonists

Ipratropium/albuterol Respimat: 1 inhalation 4-6X daily Nebulization: 3mL 4-6X daily

LA anticholinergic + LA β2 agonists

Umeclidinium/vilanterol 62.5/25mcg daily

*DPI dose (MDI not approved for COPD) **Not FDA approved for COPD

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014) N Engl J Med. 2011; 365(8): 689–698

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014) Ann Pharmacother. 2012 Dec;46(12):1717-21

Global strategy for the diagnosis, management, and prevention of COPD: Revised 2014. Global initiative for Chronic obstructive lung disease (GOLD). http://www.goldcopd.org (Accessed October 25, 2014)

N Engl J Med. 1999;340(25):1941-7 Chest. 2007;132(6):1741-7 JAMA. 2010 Jun 16;303(23):2359-67 Am J Respir Crit Care Med. 2014;189(9):1052-64 JAMA. 2013;309(21):2223-31

Reduce impairment • Prevent chronic and

troublesome symptoms • Require infrequent use of

SA β2 agonists • Maintain normal lung

function • Maintain normal activity

levels

Reducing Risk • Prevent recurrent

exacerbations • Minimize need for ED

visits/hospitalizations • Prevent progressive loss of

lung function • Provide optimal therapy

with minimal or no adverse effects

Components of severity

Intermittent Persistent

Mild Moderate Severe

Symptoms ≤2 days/week >2 days/week but not daily

Daily Throughout the day

Nighttime awakenings

≤2x/month 3-4x/month 1x/week but not nightly

Often 7x/week

SA β2 agonist use ≤2 days/week >2 days/week, but not daily or >1x/day

Daily Several times per day

Interference with normal activity

None Minor limitation Some limitation Extremely limited

Lung function

• FEV1 > 80% predicted

• FEV1 /FVC normal

• FEV1 > 80% predicted

• FEV1 /FVC normal

• FEV1 > 60% but <80% predicted

• FEV1 /FVC reduced 5%

• FEV1 > 60% predicted

• FEV1 /FVC reduced >5%

Exacerbations requiring systemic corticosteroids

0-1/year ≥2/year

Recommended step for initiating treatment

Step 1 Step 2

Step 3 Step 4 or 5

And consider short course of oral systemic corticosteroids

National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Heart, Lung, and Blood Institute; Revised August 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed October 25, 2014

National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Heart, Lung, and Blood Institute; Revised August 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed October 25, 2014

Drug Low Daily Dose Medium Daily Dose High Daily Dose

Beclomethasone HFA 80-240mcg >240-480mcg >480mcg

Budesonide DPI 180-600mcg >600-1200mcg >1200mcg

Fluticasone HFA: 88-264mcg DPI: 100-300mcg

HFA: >264-440mcg DPI: >300-500mcg

HFA: >400mcg DPI: >500mcg

Mometasone DPI 200mcg 400mcg >400mcg

• Clinical effects – Decreased severity of symptoms

– Improved asthma control and quality of life

– Improved PEF and spirometry

– Diminished airway hyper-responsiveness

– Prevention of exacerbations

– Reduction in systemic corticosteroid courses, ED care, hospitalizations, and deaths due to asthma

Medication ICS dose Usual dose

Fluticasone/salmeterol DPI Low-medium dose 100/50mcg BID

Medium-high dose 250/50-500/50mcg BID

Fluticasone/salmeterol HFA Low-medium dose 45/21mcg BID

Medium-high dose 115/21-230/21mcg BID

Budesonide/formoterol Low-medium dose 160/9mcg BID

Medium-high dose 320/9mcg BID

Mometasone/formoterol Medium dose 200/10mcg BID

High dose 400/10mcg BID

*LA β2 agonists should not be used as monotherapy

Medication Dose

Albuterol

MDI: 4-8 puffs every 20 minutes up to 4 hours, then every 1-4 hours prn Nebulizer: 2.5-5mg every 20 minutes X3 doses, then 2.5mg every 1-4 hours prn, or 10-15mg/hr continuously

Levalbuterol 1.25-2.5mg every 20 minutes X3 doses, then 1.25-5mg every 1-4 hours prn

Ipratropium+albuterol 3mL every 20 minutes X3 doses, then as needed

Corticosteroids (methylprednisolone, prednisolone, prednisone)

40-80mg daily until PEF ≥70% of predicted personal best

• SA β2 agonists recommended for all patients – Mild-moderate exacerbations may use MDI or nebulizer

– Nebulizer for severe exacerbations

• Ipratropium – Recommended in ED for up to 3 hours for severe exacerbations

– Not recommended for hospitalized patients