Lehne's Ch 62 Drugs for Asthma COPD Chapter Outline

Ch 62 – Drugs for Asthma and Chronic Obstructive Pulmonary Disease

Inhaled Glucocorticoids Leukotriene Receptor Antagonists
Budesonide Montelukast
Fluticasone
Immunoglobin E Antagonist Short Beta-Adrenergic Agonists
Omalizumab Albuterol
Anticholinergics Long-Acting Beta-Adrenergic Agonists
Ipratropium Salmeterol
Phosphodiesterase-4 Inhibitor
Roflumilast

BASIC CONSIDERATIONS

 Classic S/S are sense of breathlessness and chest tightness paired with wheezing, dyspnea, and
cough
 Underlying cause is immune-mediated airway inflammation
 COPD is a chronic progressive largely irreversible disorder characterized by airflow restrictions and
inflammation
 COPD is mostly preventable with a primary cause of cigarette smoking
 COPD S/S include chronic cough, excessive sputum production, wheezing, dyspnea, and poor
exercise tolerance

Pathophysiology of Asthma

 Asthma is a chronic inflammatory disorder of the airways; 50% due to immune response to known
allergens
 Inflammatory process begins with binding of allergen molecules to IgE antibodies on mast cells;
mast cells then release mediators such as histamine, leukotrienes, prostaglandins, and interleukins
 Mediators act immediately causing bronchoconstriction; mediators also promote infiltration and
activation of inflammatory cells – eosinophils, leukocytes, macrophages which release mediators of
their own
 The end result is airway inflammation, presenting as edema, mucus plugging, smooth muscle
hypertrophy obstructing airflow
 Inflammation also produces a state of bronchial hyperreactivity, allowing mild triggers like cold air,
exercise, smoke to cause intense bronchoconstriction

Pathophysiology of COPD

 COPD is the result of chronic bronchitis and emphysema
 Chronic bronchitis is defined by chronic cough and excessive sputum production and results from
hypertrophy of mucus-secreting glands in the epithelium of the larger airways
 Emphysema is defined as enlargement of the air space within the bronchioles and alveoli due to
deterioration of the walls of these air spaces
 Diagnosed by spirometry testing which measures the degree of airway obstruction
 Irritants, like cigarette smoking, initiate an inflammatory response in the airways; the frequent and
recurrent irritation and subsequent response by leukocytes and inflammatory mediators cause
changes resulting in bronchial edema and increase in mucus secretion typical of chronic bronchitis
 The continuous inflammation inhibits protease inhibitors that normally protect alveolar integrity,
resulting in the breakdown of elastin by protease enzymes leading to destruction of alveolar walls
and decrease in elastic recoil that characterizes emphysema
 Uncommonly, emphysema results from genetic a1 antitrypsin deficiency; a1 antitrypsin is a
protease inhibitor that protects the lungs from enzymatic destruction by proteases

Overview of Drugs for Asthma and COPD

 Two main classes are anti-inflammatory agents (glucocorticoids) and bronchodilators (b2 agonists)

,  Glucocorticoids are given on a fixed schedule usually via inhalation for chronic asthma and stable
COPD; b2 agonists usually inhaled and can be given long term on a fixed schedule or PRN for an
acute attack

Administering Drugs by Inhalation

 Most antiasthma drugs are inhaled
 Inhalation enhances therapeutic effects by delivering drugs to their site of action, minimizes
systemic effects, provides rapid relief of acute attacks
 Devices delivering meds via inhalation are metered dose inhalers (MDIs), dry-powder inhalers
(DPIs), and nebulizers

MDIs

 Small hand-held pressurized device that delivers a measured dose of drug with each actuation
 Dosing accomplished with one or two inhalations
 For two inhalations, separate by at least one minute
 Pt should begin inhaling before activating device; requires hand-breath coordination making them
difficult to use correctly
 Even with optimal use only 10% of the dose reaches lungs, where the remaining affects the
oropharynx and is swallowed
 Spacers can attach to the MDI to increase delivery to the lungs and decrease deposit of drug on
oropharyngeal mucosa; some have one way valve that activates on inhalation obviating the need
for good hand-breath coordination; some have an alarm whistle to notify of breath that is too rapid;
can also reduce bronchospasm that can occur from sudden inhalation of drug

DPIs

 Deliver drugs in dry micronized powder directly to lungs
 Breath-activated, unlike MDIs; Much easier to use
 Deliver more drug to lungs (20% of dose)
 No need for spacers

Nebulizers

 Small machine that converts drug solution into a mist
 Mist is much more fine that inhalers so less drug deposits on oropharynx and more goes to lungs
 Via face mask or mouthpiece delivering med with each breath so several minutes are needed to
deliver the same amount of drug contained in 1 inhalation from an inhaler; could still be more
effective than an inhaler for some pt

ANTIINFLAMMATORY DRUGS

Glucocorticoids – budesonide and fluticasone

 Most effective drugs for long-term control of airway inflammation
 Administered via inhalation but can be IV or oral
 Adverse reactions minor, as are reactions to systemic glucocorticoids taken acutely
 Long term systemic glucocorticoids however more likely for severe adverse effects

MOA

 Glucocorticoids reduce respiratory symptoms by suppressing inflammation which reduces bronchial
hyperreactivity and decreases airway mucus production
 Effects include
o Decreased synthesis and release of inflammatory mediators (leukotrienes, histamine,
prostaglandins)
o Decreased infiltration and activity of inflammatory cells (eosinophils, leukocytes)
o Decreased edema of the airway mucosa (second to decreased vascular permeability)