Bronchodilators Flashcards
Asthma treatment: Step 1
Preferred: SABA PRN
Asthma treatment: Step 2
Preferred: Low-dose ICS
Alternatives: Cromolyn, LTRA, Nedocromil, or Theophylline
Asthma treatment: Step 3
Preferred: EITHER
Low-dose ICS + either LABA, LTRA, or Theophylline
OR
Medium-dose ICS
Asthma treatment: Step 4
Preferred: Medium-dose ICS + LABA
Alternative: Medium dose ICS + either LTRA or Theophylline
Asthma Treatment: Step 5
Preferred: High-dose ICS + LABA
Alternative: High-dose ICS + either LTRA or Theophylline
Asthma Treatment: Step 6
Preferred: High-dose ICS + LABA + oral systemic corticosteroid
Alternative: High-dose ICS + either LTRA or Theophylline + oral systemic corticosteroid
B-Adrenergic Agonists: Therapeutic Use in Asthma and COPD:
Drug of choice for rapid relief of bronchospasm.
Highly effective and safe for intermittent, prophylactic treatment of asthma.
B-Adrenergic Agonists: MOA
Stimulate B2-adrenergic receptor on bronchiolar SMCs.
B2-adrenergic receptor couples to Gs protein and activates adenylyl cyclase enzyme leading to increased cAMP.
cAMP stimulates phosphorylation cascade that leads to decreased intracellular calcium and smooth muscle relaxation.
Also inhibit mediator release from mast cells.
Rapid Acting-Short Duration B2-Adrenergic Agonists
Albuterol: onset<15 min duration: 2-4 hr
Levalbuterol, Pirbuterol, Terbutaline
These agents are used as “rescue inhalers”. They are relatively fast at relieving bronchospasm, but have a relatively short duration of action.
Long Acting B2-Selective Agonists (LABA)
Salmeterol & Formoterol:
slower onset
duration > 12 hours of useful bronchodilation
useful to control nighttime asthma attacks, also now used BID for prevention
not suitable for treatment of acute bronchospastic attacks because onset of action is too slow.
Less Selective or Nonselective B-Adrenergic Agonists
Epinephrine - Low-strength epinephrine inhalers sometimes prescribed for mild asthma
Isoproterenol
Metaproterenol
Isoetharine
Long-term Use of LABA
May cause down-regulation of b2 receptors with loss of the protective effect from rescue therapy with a short-acting agent.
“Stop use of a LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid.”
Oral Therapy with B-Adrenergic Agonists
Oral administration increases incidence of adverse side effects:
muscle tremor, cramps, cardiac tachyarrhythmias, metabolic disturbances, hypokalemia
Oral Therapy with B-Adrenergic Agonists: Appropriate situations for oral therapy
Brief therapy in children with upper respiratory tract infections who cannot manipulate inhaler
In severe asthma exacerbations where inhaler cannot be used or
when aerosol is irritating
Oral albuterol and terbutaline are available
Adverse Side Effects of B-Adrenergic Agonists
Pts with cardiovascular disease or diabetes are at higher risk of adverse effects.
Skeletal muscle tremor (most frequent side effect).
Tachycardia, dysrhythmias, hyper- or hypotension
Hypokalemia
Drug interactions with thyroid, digitalis, methylxanthines
Epinephrine: Emergency Use
Drug of choice for treatment of anaphylactic reactions.
Give SQ (or IM or IV with dextrose).
Bronchodilation (mediated by b2 receptors).
Vasoconstriction (mediated by a1 receptors).
maintains BP & decreases edema
Inhibition of mediator release (b2 receptors)
Anaphylaxis Treatments
Albuterol via nebulizer
IV fluids
Oxygen
Secondary therapy
Bronchodilators: Ipratropium bromide
A quaternary muscarinic receptor antagonist.
Given as inhaled aerosol:
few side effects, even when swallowed because is poorly absorbed from GI and does not cross into brain.
Poor diffusion across membranes.
Ipratropium bromide & Tiotropium: Therapeutic use
Bronchodilation develops more slowly and less intense than that produced by B-agonists.
Useful bronchodilation lasts up to 6 hours.
Principal use of ipratropium is in COPD.
Combined with albuterol = COMBIVENT
Used intranasally to reduce secretions in the upper and lower respiratory tract in allergic rhinitis and chronic postnasal drip syndrome.
Tiotropium: newer long-acting agent (QD dosing) used for maintenance therapy in chronic bronchitis and emphysema; dry powder inhaler device
Methylxanthine Bronchodilators
Theophylline, caffeine, theobromine
found in coffee, tea, chocolate, cocoa, colas
Theophylline
Bronchodilation is a clinically relevant effect of theophylline
Other effects include CNS stimulation, modest peripheral vasodilation, improved skeletal muscle contractility, and a thiazide-like diuresis
Theophylline: Therapeutic use
Formerly a first-line agent for treatment of asthma.
Now has a far less prominent role because: benefits are modest; narrow therapeutic window; considerable variation in absorption and elimination between different patients; monitoring of plasma concentrations is often required.
Nocturnal asthma
IV formulation = aminophylline
Corticosteroids: MOA
Steroid receptor agonists that bind to intracellular receptors that translocate to the cell nucleus and positively or negatively regulate gene transcription.
Inhibit the production and release of cytokines, vasoactive and chemoattractive factors, lipolytic and proteolytic enzymes, decrease mobilization of leukocytes to areas of injury, and decrease fibrosis.
Inhaled Corticosteroids
Beclomethasone dipropionate (Beclovent) Budesonide dipropionate (Pulmicort) Ciclesonide (Alvesco) Flunisolide (AeroBid) Fluticasone (Flovent) Mometasone (Asmanex Twisthaler) Triamcinolone acetonide (Azmacort)
Systemic Corticosteroids
IV or oral
Prednisone
Methylprednisolone
Hydrocortisone
Corticosteroids: Systemic Therapy
Used in severe asthmatic attacks requiring hospitalization.
For severe asthma, prednisone or methylprednisolone is given i.v., followed by oral doses and gradual tapering of the dose.
For acute, sever exacerbations, oral prednisone is administered for 1 -2 weeks.
Corticosteroids: Potential Side Effects
HPA suppression - low risks until high doses
Bone resorption - modest risks
Carbohydrate and lipid - minor risks
Cataracts and skin thinning - dose-related
Purpura - dose-related
Dysphonia - usually resolves
Candidiasis - use spacer device and rinse mouth
Growth retardation - of concern in children
Combination Products
Fluticasone propionate +Salmeterol (Advair Diskus, Advair HFA)
Budesonide + Formoterol (Symbicort HFA)
Mometasone + Formoterol (Dulera)
Not useful for acute bronchospastic attack
Cost Range: ~$145-$175/month
COPD Treatment
Inhaled ipratropium bromide or tiotropium.
Inhaled 2-adrenergic agonists
(beware overuse).
Cromolyn sodium (Intal)
An anti-inflammatory agent that indirectly inhibits antigen-induced bronchospasm and directly inhibits the release of histamine and other autocoids from sensitized mast cells.
May suppress the activating effects of chemoattractant peptides on eosinophils, neutrophils, and monocytes.
Cromolyn Compounds: Therapeutic Use
Do not directly relax smooth muscle, therefore they are not useful for control of acute bronchospasm.
Primarily prophylactic. When inhaled several times daily, they inhibit both the immediate and late asthmatic responses to antigenic challenge or exercise.
Leukotriene inhibitors: Montelukast
LTD4 receptor antagonist.
Alternative or adjunctive therapy to low-dose corticosteroids for mild persistent asthma.
Useful as oral prophylaxis in exercise-induced asthma.
