Asthma:

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Asthma Pharmacologic Treatment
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Clinical
manifestations Wheezing Coughing Shortness of
breath Reversible airway obstruction resulting
from Contraction of airway smooth
muscle Excessive mucus secretion Edema
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Predominantly an Inflammatory Illness
Increased inflammatory cells Eosinophils
Macrophages Lymphocytes Increased IgE
levels

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Macrophage
IL3,4,5,6,8 GM-CSF TNF-alpha Eosinophil
peroxidase Many others
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Major stimuli inciting
attack Allergens Pharmacologic agents - ex.
Aspirin, b antagonists Pollutants Occupational
factors Infections Exercise Emotional factors GERD

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Diurnal Variation of Lung Function
Diurnal variability Approx.. 29
400
350
Distribution of Peak Flow
300
400 800 1200 1600 2000 2400 400
Time (Hours)
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Drug Therapy Bronchodilators Glucocor
ticoids Cromones Cysteinyl leukotriene inhibitors

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Highlights Classes Mechanism of
action Route of administration Onset of
action Side effects
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UNIQUE DELIVERY AEROSOL TYPES
Metered dose inhaler Nebulizer Dry
powder inhaler (doesnt rely on CFC) BENEFIT
Minimizes systemic side effects Majority can be
managed on aerosols alone Requires patient
education and a degree of coordination
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Drug Therapy Bronchodilators I
Adrenomimetic Amines II Anticholinergics III
Theophylline Glucocorticoids Cromolyn/Nedocromil
Cysteinyl Leukotriene Inhibitors
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Adrenomimetics
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Adrenomimetic amines
Classes a/b Epinephrine - severe attacks
(SC) Rapid onset - 5-15 min Potential for
serious S.E. (Hypertension, CVA, arrhythmias,
etc) Pulmonary vasoconstriction (useful
with pulmonary edema) b1 2 Isoproterenol
b 2 Albuterol, terbutaline - short acting
(class most often used) Salmeterol,
formoterol - long acting
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Adrenomimetic Mechanism
Activate adenylyl cyclase -increase cAMP
causing Bronchial smooth muscle -
bronchodilation Mast cells - decrease mediator
release Bronchial epithelium - improve
cilliary transport Vascular endothelium -
maintain integrity
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Adrenomimetic routes of administration
- Inhalation (INH) - Oral (? Chronic
use leads to tachyphylaxis) Useful
with Coordination impaired Aerosol
irritation - Subcutaneous (sc) Severe
episodes of asthma
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Adrenomimetic Onset Minutes
-Inhalation (standard forms) and sc Hours - Oral
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Adrenomimetic Side Effects - INH
- minor unless overusage - Oral and sc
nervousness tachycardia dizziness arr
hythmias metabolic disturbances muscle
tremor
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Bronchodilators II
Anticholinergics (Antimuscarinics)
Efferent autonomic nerves mainly cholinergic
Vagal stimulation Bronchoconstriction I
ncreased mucus secretion
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Belladonna Alkaloids
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Anticholinergics Ipratropium (Atrovent) Mechanis
m - block inhibition of adenylyl cyclase -
decrease mucus secretions - decrease bronchial
vasodilation Route - INH Onset - 1-2 hours
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Anticholinergic Side Effects - dry mouth -
nervousness - cough - headache - dizziness -
nausea
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Anticholinergics -
As effective as b2 agonists in COPD, not
asthma - Asthma treatment Usually given
with a b2 agonist Solo tx - psychogenic
exacerbations or concomitant with b2 antagonists
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Bronchodilators III
MethylxanthineTheophylline Mechanism -
inhibit phosphodiesterase - antagonize
adenosine receptors - reduce respiratory muscle
fatigue - inhibition of mediator release -
increase sympathetic activity - alter immune
cell function Route - oral or IV Onset -
hours to days
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Theophylline Side
Effects - CNS excitation (from mild to
seizures) - weak diuretic - cardiac
stimulation increased heart rate increased
contractile force decreased preload (high
conc. can cause arrhythmias) - nausea and
vomiting
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Theophylline Other Information - 90
metabolized by liver - large variation in
t1/2 - narrow therapeutic index -
therapeutic concentration 10-20 mg/ml
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Glucocorticoids
Mechanism - Affect transcription of many genes,
leading to Decrease - inflammatory
mediator release - IgE synthesis -
vascular permeability - inflammatory cell
influx - mucus secretion Increase - b
adrenoceptors
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Glucocorticoid Routes - INH, oral,
parenteral Onset - Hours to days Side
Effects Systemic Glucocorticoids With
brief tx (5-10 d), relatively few Mood
disturbances Increased appetite Loss of BS
control in diabetics Candidiasis
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Side Effects Glucocorticoid
Aerosols -Mainly seen at high doses -Adrenal
suppression -Bone resorption -Increase blood
glucose -Cataracts -Purpura -Dysphonia/Candi
diasis -Growth retardation
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Glucocorticoids - INH forms - front line
controller therapy - Not used alone as acute
treatment - Amount of drug per inhalation varies
greatly among formulations
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Cromones Cromolyn/Nedocromil
Mechanism Inhibits Mast cell mediator
release Irritant receptors Plasma
exudation Inflammatory cell influx
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Cromones Route - Inhalation Onset - Weeks (up to
6 weeks) BUT in exercise induced
asthma, prophylactic use may be effective
after 1 dose
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Cromones Side Effects - (rare) - bronchospasm,
coughing, wheezing - laryngeal edema - joint
swelling - angioedema - rash - nausea -
anaphylaxis (very rare) Other info - effective
in 60-70 of children and adolescents
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Cysteinyl Leukotriene
Inhibitors Classes Competitive receptor
antagonist Zafirlukast (Accolate), Montelukast
(Singulair) 5-lipoxygenase inhibitor
Zileuton (Zyflo)
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PG and Tbx
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Mechanism - Inhibit synthesis or action of
cysteinyl leukotrienes Route - Oral
Onset of action- Days Efficacy - Approx.
cromolyn
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Zafirlukast S.E. Increased frequency of mild
to moderate infections in 55 yo. Slight
increased incidence of hepatitis and
elevated liver enzymes Other info. Many
drug ix (inhibits P450 cyp3A4 and
2C9) (warfarin, theophylline, aspirin,
erythromycin, etc) Use in adults and children
6 yo.
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Zileuton S.E. Elevation of hepatic
enzymes (monitor liver function tests)
Other info. Contraindicated with liver
disease Pregnancy category C - birth defects in
animals Use in adults and children 12 yo
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Drug Therapy Bronchodilators Glucocorticoids Cro
molyn/Nedocromil Cysteinyl leukotriene
inhibitors Other agents ex. Gold salts, TAO,
methotrexate

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MAJOR POINTS Asthma- predominantly an
inflammatory illness. All but the mildest
intermittant forms are treated with a drug that
decreases the inflammatory process (
Corticosteroid, cromolyn/ nedecromyl,
leukotriene inhibitor or theophylline). Main two
classes of drugs - b2 agonists and
glucocorticoids Others frequently used -
Cromolyn type, theophylline, anticholinergics
Two categories of drugs - long term controllers
and quick relievers With proper education, most
patients can be managed on aerosols The role of
leukotriene inhibitors is currently not
established