Asthma and COPD

Asthma
Reversible chronic airway inflammation. It involves obstruction, ↑ airway
responsiveness, episodic asthma symptoms. Pathologic changes are not permanent.

It may be: mild intermittent, and persistent (mild, moderate, severe)

And caused by allergens (pollen, dust mite, animal dander, mold, food), occupational
exposures (chemicals, flour, wood, textile dust), viral respiratory infections, exercise,
emotions (anxiety, laughter, stress, crying), irritant exposure (odors, chemicals,
irritants), environmental exposure (weather change, cold air, smoke, sulfer dioxide),
drugs (hypersensitivity, aspirin, NSAID, cholinergics (bethanechol), anti-adrenergics
(B blockers)).

Allergic rhinitis is twice as common in asthmatics.

Inflammatory cells: such as mast cells, eosinophils, activated T cells, macrophages,

epithelial cells
secrete mediators.

Autonomic neutral control: ↑ cholinergic sensi)vity
↑ parasympathe)c tone,

reflex bronchoconstriction.

Sequencing of events in asthma

Triggering: exposure to trigger (allergen, aspirin, virus, etc)
antigen binds to IgE

attach to activated mast cells.

Early response: begins in < 30 min and resolves in < 2hr, blocked by beta agonist or
cromolyns.

Late response: begins 6 hr after trigger, persistent airway obstruction, inflammation,

hyper-responsiveness, occurs in 50% of cases, may last several days, blocked by
corticosteroids or cromolyns.

Signaling: inflammatory cells (mast cells, lymphocytes, eosinophils, macrophages,

epithelial cells) release chemical signals (cytokines, chemokines, eicosanoids,
leukotrienes)
attract more inflammatory cells.

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Signs of respiratory distress: cyanosis (↓ PaO2 / ↑ PaCO2), use of accessory
muscles, inability to speak in sentences, ↓ mental status, PEFR < 50% of normal.

Diagnostic tests
1)Pulmonary function tests: determine degree of obstruction, may be normal
between exacerbations.

2) Forced expiratory volume in 1 second (FEV1): ↓ during exacerba)on. Air trapping

and lung hyperventilation
↑ residual volume (RV), ↑ total lung capacity (TLC).

3) Peak expiratory flow rate (PEFR): correlates with FEV1, used to monitor therapy,
triggers, need for emergency care. Measure PEFR in early morning before
medications, and may be again midday. Diurnal variation > 20% in PEFR indicate ↑
responsiveness, and poor control.

4)Blood analysis: ↑ WBC count during acute exacerba)on, eosinophilia, leukocytosis

(due to WBC demargination due to corticosteroids).

5)Sputum analysis: may reveal eosinophils, clumps of epithelial cells, bacterial if

infected, mucous in small airways.

6)Pulse oximetry It measures oxygen saturation in arterial blood (SaO2) and pulse.

7)Arterial blood gas: help gauge the severity of exacerbations. Early stages
hyper-
ventilation
↓ PaCO2
fatigue of respiratory muscles. Respiratory acidosis: poor
prognostic sign
respiratory fatigue
↓ respiratory rate
↑ PaCO2.

8) ECG: may show sinus tachycardia, especially in the elderly.

9)Chest radiograph: may show pneumonia, hyperinflation.

10)Allergy skin and radioallergosorbent test: identify possible allergic triggers.

Complications
1)Status asthmaticus

2)Pneumothorax: acute exacerbation with air accumulation in the pleural space.

3)Atelectasis: airway obstruction
↓ gas exchange during respira)on
collapsed

lung.

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Exercise-induced bronchospasm (EIB):cortisone is ineffective
Warm-up period helps prevent EIB. Prevent EIB by using short acting beta agonist
(albuterol) 15 min before exercise, long acting beta agonist (salmeterol) 45 min
before exercise, or cromolyn sodium 1 hr before exercise. Keep albuterol handy.

Chronic asthma (NIH guidelines)

Severe persistent: ↑ dose inhaled steroid + ↓ dose oral steroid + long ac)ng
bronchodilator (inhaled or oral salmeterol, SR theophylline).

Moderate persistent: inhaled steroid + long acting bronchodilator for nigh time
symptoms (inhaled or oral salmeterol, SR theophylline) (drop oral steroid).

Mild persistent: only one of the following: ↓ dose inhaled steroid, inhaled cromolyn,
SR theophylline, leukotriene modifier.

Mild intermittent: no daily medications. Albuterol for attacks.

Therapeutic agents

1)Beta agonists
Short acting: albuterol (R- and S- isomers), levalbuterol (only active R-enantiomer),
metaproterenol, pirbuterol, for acute exacerbation and EIB prophylaxis.

Long acting: salmeterol, formoterol for asthma maintenance, EIB prophylaxis,

nocturnal symptoms, ↑↑ albuterol use, COPD.

Mechanism: stimulate beta 2 receptors
↑ adenyl cyclase
↑ cAMP

bronchodilation, ↑ mucociliary clearance, ↓ inflammatory cell mediator release.

SE: tremors (due to B2 activation in skeletal muscles), gluconeogenesis (↑ glucose),

activation of Na K ATPase, cardiac stimulation (due to partial B1 stimulation:
palpitation, tachycardia), nervousness, headache.

Administration: inhalation ↓ systemic SE (preferred over oral). Always use

salmeterol with inhaled steroid, except for EIB prophylaxis. May combine long and
short acting.

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Tachyphylaxis: occurs due to regular use. It’s due to down-regulation due to moving
of beta receptors from cell surface to inside the cell. Effect may be reversed with
steroids.

Paradoxical bronchoconstriction: due to cold-Freon effect or use of adjuvants.

↑ bronchial hyperac2vity: due to irritants such as methacholine and histamine. May

be due to albuterol’s S-isomer.

Drug interactions: hypertensive crisis with MAO inhibitors, TCA and methyldopa.
Beta blockers (e.g. propranolol)
bronchospasm. Combined with
sympathomimetics
↑ heart effect, vasoconstric)on (prevent by alpha blockers,
phenolamine).

2)Corticosteroids
Mechanism: Bind to glucocorticoid receptors in the cell cytoplasm
alter gene
transcription
↓ inflammatory response, ↓ airway hyper-responsiveness, ↓
mucus.

Use: in case of allergic component. Added only when anticholinergic / beta agonist
combo is ineffective.

Systemic steroids: used for rapid response during acute exacerbations (few hours).

IV steroids: hydrocortisone and methylprednisone. Alternative to oral steroids to

prevent respiratory arrest in hospitals. Switch to oral steroids after stabilization.

Oral steroids: prednisone, prednisolone. Used in emergencies if possible when there

is no risk of respiratory arrest. Used in burst doses for a week. Dose tapering may be
required.

Inhaled steroids: fluticasone, flunisolide, triamcinolone, beclomethasone,

budesonide. Used for chronic treatment, not for acute exacerbations. Less SE and
less efficacy. ↑ steroid penetra)on into bronchial tree by giving bronchodilator
several minutes prior.

Systemic steroids SE: hyperglycemia, ↑ BP, CHF, pep)c ulcer, immunosuppression,

chronic infections, osteoporosis, glaucoma, depression, psychosis, cataract, skin
changes. If long term, minimize SE by giving morning dose or alternate day dosing.

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Inhaled steroids SE: fungal infection, voice hoarseness, dry mouth. May ↓ children
growth velocity, but uncontrolled asthma also retards growth. Systemic SE with large
doses. Gargle and wash mouth after use to ↓ fungal infec)ons, systemic absorp)on.

Interactions: enzyme inducers (rifampin, barbiturates, hydantoins)
↑ steroid

metabolism. Oral contraceptives, estrogens, enzyme inhibitors
↓ steroid
clearance. ↑↑ hypokalemia with thiazide and loop diure)cs, amphoterecin
↑
digitalis toxicity. Cyclosporine
↑ steroid concentra)on.

3)Leukotriene modifiers
Leukotrienes: derivatives of fatty acids formed by lipoxygenase. No ring structure.
Covalently linked to 2-3 amino acids. Slow reacting substances of anaphylaxis.
↑
eosinophil and neutrophil migration, ↑ leukocyte adhesion, ↑ neutrophil and
monocyte aggregation, ↑ capillary permeability, ↑ smooth muscle contrac)on, ↑
mucous secretion, bronchoconstriction, .

Effect: anti-inflammatory and bronchodilation
↓ steroid dose.

Leukotriene receptor antagonists (x-lukast)

Examples: zafirlukast, montelukast

Mechanism: prevent interaction of leukotrienes with receptors by ↓ cysteinyl

leukotriene-1
block effect of histamine in asthma and allergy reactions.

Take zafirlukast on empty stomach (max absorption).

SE: ↓↓, can be used in children. GI upset, dizziness.

Churg-Strauss syndrome: eosinophilic vasculitis angiitus when steroids are d/c or ↓.

DI: enzyme inhibitor, ↑ effect of warfarin / theophylline.

Lipoxygenase inhibitor (Zileuton)

Mechanism: blocks 5-lipoxygenase
↓ leukotrienes synthesis from arachidonic
acid.

SE: liver dysfunction and ↑ ALT (monitor, esp in alcoholics). Others (mild): headache,
GI upset, myalgia.

DI: ↑ effect of warfarin, theophylline, propranolol.

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4)Mast cell stabilizers (Cromolyn, nedocromil Na)
Effects: Nonsteroidal anti-inflammatory. Less effective than steroids. Used only for
asthma maintenance, EIB prevention.

Mechanism: ↓ mast cell degranula)on, ↓ inflammatory cells.

SE: ↓↓, used in children. Wheezing, coughing, nasal congestion, throat irritation /
dryness.

5)Methyl xanthines (theophylline)

Use: alternative to B-agonists and steroids in acute attacks and to long acting B-
agonist in persistent asthma. Combine with inhaled steroids
control night or early
morning symptoms.

Effects: ↓ mucus, ↑ mucociliary transport, ↑ respiration, anti-inflammatory, ↑

renal diuresis.

Mechanism: ↓ phosphodiesterase
↑ cAMP, antagonize adenosine receptors.

Less bronchodilation than B-agonists.

Oral (SR): ↑ compliance. ↓ fat )ssue distribu)on, calculate dose based on lean
body weight. Gradually titrate dose upward.

IV: rare. Start with loading dose, then maintenance infusion.

Theophylline anhydrous
oral solids, theophylline monohydrate
oral solutions.

Aminophylline
IV.

SE: palpitations, restlessness, nervousness, insomnia, seizures, GI upset, diarrhea,

dizziness. Do not use in pregnancy.

Therapeutic drug monitoring: monitor SE, serum level, other drugs use. Clearance is
age and condition specific.

Interactions: multiple drug and other interactions. ↑ clearance (↓ level) with

smoking, ↑ protein. ↓ clearance (↑ level) with age (↑↑ or ↓↓) , fats and
carbohydrates, CHF.

CI: peptic ulcer or uncontrolled seizure.

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6)Anticholinergics
Postganglionic muscarinic block
bronchodilation.

Use: more effective in COPD than in asthma.

Ipratropium sodium: quaternary ammonium compound. Used with or as an

alternative to beta agonist in acute attacks. Slow onset and long duration compared
to beta agonists
give regularly. SE: ↑ intraocular pressure if touches the eye, ↓
anticholinergic.

Atropine aerosols, glycopyrrolate (quaternary ammonium compound): rarely used

due to ↑ SE and ↓ efficacy. Used in nebulizers

7)Other drugs
Antihistamines: if patient has allergic rhinitis. Prevent release of histamine mediated
response that influence asthma.

Antibiotics: used to treat infections (change in volume, color, viscosity of sputum).

Sputum cultures are useless because COPD are chronically seeded. Chronic antibiotic
preventative used can be considered in case of frequent exacerbations. M.
pneumoniae or Legionella pneumophilia
macrolide . C. pneumoniae
oral
doxycycline. Pneumonia in the hospital
2nd or 3rd generation cephalosporin or
beta-lactam with b-lactamase inhibitor.

Magnesium sulfate (IV): cause little bronchodilation, ↑ respiratory muscle strength

in hypomagnesemic patients.

Immunotherapy: may ↑ lung func)on, ↓ symptoms.

Non-pharmacologic
Humidified O2: ↓ flow rate helps reverse hypoxemia (use if PaO2 < 55 mmHg), esp.
at night/during exercise. Goal: SaO2 > 90%.

Heliox: helium / oxygen mixture that is less dense than air
↑ ven)la)on during
acute attack.

IV fluids: and electrolytes are given if volume is depleted.

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Environmental control: avoid allergens and triggers. Use allergen-resistant
mattresses / pillow encasements, ↑ filtra)on vacuum cleaners, avoid ferry pets,
carpets and draperies.

Vaccines: used to prevent infections that may trigger asthma (e.g. influenza and
polyvalent pneumococcals).

Drug delivery options

1)MDIs: accurate with good technique and a spacer. A facemask may be needed for
children. Wait 1 min between buffs.

2)Spacers and holding chambers: ↓ drug deposition in the upper airway, ↓ oral
absorption, ↓ local / systemic SE. Spacers are important for ↑ dose steroids or if
hand-lung coordination is poor.

3)Nebulizers: require ↓ pa)ent coordina)on. Disadvantages: cost, )me consuming,

↑ size, inconsistent drug delivery. Used in ↑ dose beta agonists, an)cholinergics,
cromolyn in children.

4)Dry powder inhalers: more common, avoid the use of Freon propellants, easier to
use. First load the dose, and then inhale rapidly. No spacers. Keep away from
moisture.

COPD
1)Chronic bronchitis
Definition: excessive mucus production by the tracheo-bronchial tree
edema and
bronchial inflammation
airway obstruction.

Pathophysiology: respiratory tissue inflammation
vasodilation, congestion,

mucosal edema
↑ mucus. Neutrophils infiltra)on. Cilia impairment. Car)lage
atrophy. Airways become blocked by thick, tenacious mucus secretions
sputum
rich productive cough. Normally sterile airways become colonized by Strept
pneumoniae, H influenza, Mycoplasma. Recurrent viral / bacterial infections
↓
body defenses, ↑ mucus accumula)on, ↓ ciliary ac)vity. Airway degenera)on
↓
gas exchange
exertional dyspnea. Hypoximia, ↑ PaCO2 (hypercapnia).

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Physical findings: chronic productive cough after age 45 (first in winter, worse in the
morning). Progressive exertional dyspnea, obesity, wheezing, prolonged expiration,
right ventricular failure, cyanosis (called “blue bloater”)

Diagnostic tests: hypoxemia
↑ erythropoiesis
polycythemia (↑ RBCs). ↑ WBC

due to infections. Sputum: thick, colored (if infected), ↑ neutrophils,
microorganisms. Arterial blood gas: ↓ PaO2 (hypoxemia), ↑ PaCO2 (hypercapnia).
↓ FEV1. Right ventricular hypertrophy and cor pulmonale in ECG.

2)Emphysema
Definition: permanent alveolar enlargement and destruction of the alveolar walls, ↓
alveolar surface area.

Pathophysiology: Inflammation, ↑ mucus secre)on
alveoli air trapping.
tissue

damage
↓ space into which normal lung tissue expands.. Alveoli merge
↑
space for air trapping. Alveolar wall destruction
small airways collapse.
Hypercapnia and respiratory acidosis are uncommon because of compensatory ↑ in
respiratory rate.

Physical findings: cough is chronic but less productive than in chronic bronchitis,
starts at age 55. Exertional dyspnea is progressive, constant, more severe than in
bronchitis. Other findings: weight loss, tachypnea, prolonged expiration, ↓ breath
sounds. Patient usually maintain good oxygenation through tachypnea
“pink
buffer”.

Diagnostic tests: small chance of ↓ AAT in blood or infec)ons in sputum. ↓ PaO2

and ↑ PaCO2 in arterial blood gas, ↓ FEV1.

Etiology
Smoking: causes pulmonary hyperactivity and persistent airway obstruction.↑ risk of
COPD when smoking is combined with genetic ATT(alpha one antitrypsin) deficiency.

Complications
Pulmonary hypertension and infection

Acute respiratory failure: advanced emphysema
brain respiratory center damage

↓ cerebral oxygena)on
↑ PaCO2
hypoxia, respiratory acidosis

respiratory failure.

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Polycythemia: ↑ in RBCs
hypercoagulate state, embolism, stroke.

Therapy
Anticholinergics: First line treatment for COPD.

Beta blockers, corticosteroids, theophylline, O2, etc (see above)

Mucolytics: such as acetylcysteine
↑ sputum clearance, ↓ mucus plugs. May

cause bronchospasm.

Expectorants: such as guaifenesin. Avoid potassium iodide.

Chest physiotherapy: loosens secretions, re-expand lungs, ↑ efficacy of respiratory

muscle. More important in outpatient.

Physical rehabilitation: ↑ exercise tolerance and ↑ diaphragm and abdominal

muscle tone.

Smoking cessation: and avoidance of irritants. Use drugs with behavior intervention
for maximum success.

Surgery: lung volume reduction therapy

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