IgE on mast cells bind allergens, release histamine, tryptase, prostaglandins, and leukotrienes, causing contraction of the smooth muscle, fall in FEV.

Release cytokines that attract eosinophils and neutrophils that cause edema, mucous, smooth muscle contraction, and bronchial hyperreactivity

1-5 um

Dry powder, metered dose, and nebulizers

2-10% to lungs, rest is swallowed

Anti-inflammatory and bronchodilators

(control/prevent and acute symptoms, respectively)

relax smooth muscle

inhibit release of bronchocontricters from mast cell

may inhibit vascular leakage

may increase mucocilliary transport

Nonselective B-adrenoreceptor agonist:

SQ or inhaled.

Max effect: 15 min; lasts: 60-90 min

Also stimulate B1 = cardiac effects

Nonselective B-adrenoreceptor agonist:

Orally effective

Lasts longer than epinepherine

Not used often

Nonselective B-adrenoreceptor agonist:

Potent

Max effect: 5 min; lasts 60-90 min

Lots of cardiac arrhythmia deaths

Short acting B2-selective agonists:

All the same

Max effect: 15 minutes; lasts: 3-4 hours

Inhaler: All

Nebulizer: Albuterol and Metaproterenol

(Preferred) 

Oral: Albuterol, Terbutaline, Metaproterenol

(Children under 5, severe asthma where inhaled is too irritating)

SQ: Terbutaline

(Emergent; when inhaled is irritating; long lasting with cumulative effects)

Long acting B2 selective agonist:

Metered dose or powder

Lasts: 12+ hours

Slow, not for acute bronchospasm

Lipid soluble = high conc in SMC

"Slow release depot"

Not a one drug solution; work well with steroids

Long acting B2 selective agonist:

Long duration, rapid onset

FDA approved for rapid, not acute

Nebulizer

Methylxanthine drugs: Mechanism unknown

? Inhibits cell surface Adenosine, phosphodiesterases

Orally or parenterally

Theophylline: Potent for acute bronchospasm

Made as salts to improve solubility

Measure serum levels - low TI and many side effects: 5-20, 20-40, 40+

Side effects: 20-40: anorexia/n/v, anxiety: increase in gastric secretions and HR/BP

40+: nervousness, insomnia, tremors, convulsions

Improves contractility of skeletal muscle and helps with COPD fatigue

Anticholinergic:

Low doses - bronchodilation w/o cardiac effect

Lasts: 5 hours

Adverse effects: Urinary retention, tachycardia, loss of accommodation, agitation 

Anticholinergic 

Quad ammonium of atropine

Given in high doses, poorly absorbed, does not enter CNS

Given with B2 for enhanced effect

Better for COPD then a B agonist

Corticosteroids

Do not relax SMC directly

Anti-inflammatory: Modulate chemokine/cytokine production, inhibit eicosanoid synthesis, inhibit accumulation of basophils/eosinophils/leukotrienes

Work if given chronically, but side effects make them reserved for acute treatment.

Lipid soluble aerosol best

Must have attack 4+ times per week to get steroids

When taking inhaled, taper oral to prevent adrenal insufficiency

Side effects: Thrush, hoarseness, growth retardation in children

Chromone drugs:

Pretreatment prevents antigen, aspirin, or exercise asthma (5-60 min before, lasts 3-4 hr).

Taken 2-4x daily, reduces need for bronchodilators.

Nasal/eye drops, reduces allergies in nose/eyes

Nedocromil + cortocosteroid = best effect.

Works by: inhibits masts, eosinophils, and nerves

Side effects: Cough, throat irritation, dermatitis, GI problems

Antileukotrienes:

Prevent mucous secretion, bronchoconstriction, and edema.

Zileuton = 5-lipooxygenase inhibitor; others = LTD4 receptor antagonist

Taken orally

Side effects:

Zileuton: dyspepsia, hep that clears when drug stops, drug interaction, 4x daily

Zafirlukast: GI/headache, drug interactions

Montelukast: Does not inhibit cyp450s

Anti IgE

Humanized marine monoclonal antibody

Binds free IgE and inhibits its binding to mast cells

SQ makes IgE serum undetectable

High cost off set by 88% reduction in attacks

Some anaphylaxis and malignant neoplasm