Bronchodilators

Question 1

Asthma treatment: Step 1

Answer 1

Preferred: SABA PRN

Question 2

Asthma treatment: Step 2

Answer 2

Preferred: Low-dose ICS

Alternatives: Cromolyn, LTRA, Nedocromil, or Theophylline

Question 3

Asthma treatment: Step 3

Answer 3

Preferred: EITHER
Low-dose ICS + either LABA, LTRA, or Theophylline
OR
Medium-dose ICS

Question 4

Asthma treatment: Step 4

Answer 4

Preferred: Medium-dose ICS + LABA

Alternative: Medium dose ICS + either LTRA or Theophylline

Question 5

Asthma Treatment: Step 5

Answer 5

Preferred: High-dose ICS + LABA

Alternative: High-dose ICS + either LTRA or Theophylline

Question 6

Asthma Treatment: Step 6

Answer 6

Preferred: High-dose ICS + LABA + oral systemic corticosteroid

Alternative: High-dose ICS + either LTRA or Theophylline + oral systemic corticosteroid

Question 7

B-Adrenergic Agonists: Therapeutic Use in Asthma and COPD:

Answer 7

Drug of choice for rapid relief of bronchospasm.

Highly effective and safe for intermittent, prophylactic treatment of asthma.

Question 8

B-Adrenergic Agonists: MOA

Answer 8

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.

Question 9

Rapid Acting-Short Duration B2-Adrenergic Agonists

Answer 9

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.

Question 10

Long Acting B2-Selective Agonists (LABA)

Answer 10

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.

Question 11

Less Selective or Nonselective B-Adrenergic Agonists

Answer 11

Epinephrine - Low-strength epinephrine inhalers sometimes prescribed for mild asthma

Isoproterenol
Metaproterenol
Isoetharine

Question 12

Long-term Use of LABA

Answer 12

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.”

Question 13

Oral Therapy with B-Adrenergic Agonists

Answer 13

Oral administration increases incidence of adverse side effects:
muscle tremor, cramps, cardiac tachyarrhythmias, metabolic disturbances, hypokalemia

Question 14

Oral Therapy with B-Adrenergic Agonists: Appropriate situations for oral therapy

Answer 14

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

Question 15

Adverse Side Effects of B-Adrenergic Agonists

Answer 15

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

Question 16

Epinephrine: Emergency Use

Answer 16

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)

Question 17

Anaphylaxis Treatments

Answer 17

Albuterol via nebulizer
IV fluids
Oxygen
Secondary therapy

Question 18

Bronchodilators: Ipratropium bromide

Answer 18

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.

Question 19

Ipratropium bromide & Tiotropium: Therapeutic use

Answer 19

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

Question 20

Methylxanthine Bronchodilators

Answer 20

Theophylline, caffeine, theobromine

found in coffee, tea, chocolate, cocoa, colas

Question 21

Theophylline

Answer 21

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

Question 22

Theophylline: Therapeutic use

Answer 22

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

Question 23

Corticosteroids: MOA

Answer 23

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.

Question 24

Inhaled Corticosteroids

Answer 24

Beclomethasone dipropionate (Beclovent)
Budesonide dipropionate (Pulmicort)
Ciclesonide (Alvesco)
Flunisolide (AeroBid)
Fluticasone (Flovent) 
Mometasone (Asmanex Twisthaler)
Triamcinolone acetonide (Azmacort)

Question 25

Systemic Corticosteroids

Answer 25

IV or oral
Prednisone
Methylprednisolone
Hydrocortisone

Question 26

Corticosteroids: Systemic Therapy

Answer 26

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.

Question 27

Corticosteroids: Potential Side Effects

Answer 27

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

Question 28

Combination Products

Answer 28

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

Question 29

COPD Treatment

Answer 29

Inhaled ipratropium bromide or tiotropium.
Inhaled 2-adrenergic agonists
(beware overuse).

Question 30

Cromolyn sodium (Intal)

Answer 30

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.

Question 31

Cromolyn Compounds: Therapeutic Use

Answer 31

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.

Question 32

Leukotriene inhibitors: Montelukast

Answer 32

LTD4 receptor antagonist.
Alternative or adjunctive therapy to low-dose corticosteroids for mild persistent asthma.
Useful as oral prophylaxis in exercise-induced asthma.