Asthma therapy – 2 goals

• (1) Remove airway obstruction
• b agonists
• methylxanthines
• anticholinergics
• (2) Preventing it from reoccurring
• steroids
• Cromolyn and Nedocromil
• Leukotriene inhibitors

b-Adrenergic stimulants – catecholamines, resorcinols, saligenins

• b₁ receptors: heart Þ Ý heart rate and contractility
• b₂ receptors: relax smooth muscle bronchi, blood vessels, uterus
• Action:
• (1) airway dilatation through stimulation of b₂ receptors
• (2) ß release of mediators and improve mucocilliary transport
• Mechanism: directly relax airway smooth muscle by Ý activity of adenyl cyclase (Ý cyclic AMP)
• (1) Catecholamine: epinephrine, isoproterenol, isoetharine, rimiterol, hexoprenaline
• Metabolism: short-acting
• Administration: inhalation, parentral
• Epi and isoproterenol are not b ₂ selective and have chronotropic and inotropic cardiac effects
• Epi has a stimulating effects, 0.3-0.5ml administered subcu
• Isoproterenol: no a activity, most potent agent administered inhalation
• Isoetharine: most b ₂ selective, relatively weak bronchodilator, administered as aerosol
• Hexoprenaline, rimiterol: similar to isoetharine
• (2) Resorcinol: metaproterenol, terbutaline, fenoterol
• Duration of action: 4 hours
• Side effects: affects striated muscles as well as smooth muscle Þ tremor; does not affect hear function directly (dilate blood vessels Þ ß BP Þ Ý Hr
• (3) Saligenin: albuterol, salbutamol
• Action: Highly selective for the respiratory tract and virtually devoid of significant cardiac effects except in high doses.
• Major side effect: tremor
• Duration of action: 6 hr
• Administration: inhalation - Ý bronchial selectivity, ß side effects (superior administration over IV)
• (4) Long acting b agonists: Salmeterol , formaterol
• 4-200x more potent than albuterol
• Duration of action: 10 hours
• Usage: nocturnal asthma – inhibits early and late asthmatic reaction to antigen induced increase in activity
• Action: bronchodilation, interferes with mediator release

• Action: bronchodilator, Ý strength and ß fatigue of respiratory muscles, accelerates mucocilliary transport, ß late reaction to antigen ß mediator release from mast cells
• Mechanism: Ý cyclic AMP by the inhibition of phosphodiesterase (however not proven)
• Therapeutic range: 10-20m g/ml - very close to toxic range
• Disadvantages: Narrow therapeutic window
• Cardiac and CNS effects (arrythmias and seizures),
• Metabolism and elimination kinetics vary from person to person
• Clearance ß in: children and elderly, hepatic dysfunction, cardiac decompensation, cor pulmonale, erythromycin troleandomycin allopurinal cimetidine propranolol
• Clearance Ý with: cigarettes, marijuana, phenobarbital

• Action: NOT bronchodilators, reduce airway inflammation
• Usage: acute illness when severe airway obstruction is not resolving, chronic disease
• Dosage: acute: 4mg/kg of hydrocortisone loading dose IV, infusion 3mg/kg / 6hr
• Effects: NOT immediate may not be seen for 6hr after administration
• Inhaled steroids
• Action: reduce airway reactivity, alternative to oral glucocorticoids, effects are dose dependent
• Side effects: Oral thrush (candida), dysphonia, adrenal suppression, cataracts ß growth, interference with bone metabolism, purpura

• Action: NOT bronchodilators; inhib. degranulation of mast cells Þ prevents release of chemical mediators of anaphylaxis
• Effects: improve lung function, reduce symptoms, lower airway reactivity, can block the acute obstructive effects of exposure to antigen, industrial chemicals, exercise, and cold air. With antigen, can abolish the late response.
• Delivery: inhalation Þ use before exposure if can
• Who: atopic patients with seasonal disease

• Action: produce bronchodilation, usage limited by side effects
• Who: asthma with coexistent heart disease
• Metabolism: SLOW (60-90 min), modest potency
• Disadvantages: atropine crosses BBB Þ mild psychosis and fever. Only ipratropium bromide in use today because does not cross BBB

• Action: bronchodilators
• Mechanism: block lipoxygenase, Lt receptor antagonists
• Who: exercise induced asthma
• Metabolism: requires 2 weeks to work
• Disadvantage: only effective in 20% of patients

• Emergency situations: presence of paradoxical pulse, use of accessory muscles, hyperinflation
• Acute episodes: aerosolized b ₂ agonists
• Benefits: 3-4x more relief than IV aminophylline, can give every 20 minutes
• Direct correlation between severity of obstruction with time it takes to resolve obstruction:
• FIV1 < 20% of predicted
• Chronic treatment
• Goal: achieve stable, asymptomatic state with best pulmonary function possible
• 1^st line treatment: b₂ agonist by inhalation
• If symptoms persist: inhaled steroids and/or mast cell stabilizing agents