Airflow Obstruction Pharmacotherapy

Question 1

What are the classes of “rescue” or quick-relief medications for AFO?

Answer 1

Beta-agonists and anticholinergics; both have short-acting and long-acting forms

Question 2

What are the classes of controller medications for AFO?

Answer 2

corticosteroids (systemic and inhaled), leukotriene modifiers, methylxanthines or phosphodiesterase inhibitors, and anti-IgE antibodies

Question 3

Beta-agonists

Answer 3

stimulate the Beta-2 receptor (a G-protein coupled transmembrane receptor) which leads to increase in cyclic AMP promoting smooth muscle relaxation; short-acting forms are albuterol and levalbuterol; long-acting forms as formoterol and salmeterol

Short-acting beta agonists are used for rescued therapy during an acute asthma attack

Long-acting beta-ag’s are NOT for acute tx, but used in asthma when controller meds (like inhaled corticosteroids) not satisfactory; also can use LABA alone in COPD

Question 4

Short-acting Beta agonists

Answer 4

Albuterol and levalbuterol; used as rescue tx for acute asthma attacks

Question 5

Albuterol

Answer 5

short-acting beta2 agonist; used as rescue tx for acute asthma

rapid onset, 3-4 hr duration, better efficacy/less toxicity if inhaled (vs IV or PO)

Question 6

Levalbuterol

Answer 6

short-acting beta2 agonist; used as rescue tx for acute asthma

R-isomer of albuterol; less proinflammatory effects but not any better than albuterol; more $

Question 7

Long-acting Beta agonists

Answer 7

Formoterol and Salmeterol; inhaled BID; improve pulm fxn, asthma sxs, and reduce need for rescue inhaler; but may be associated with asthma mortality, increased exacerbations, and increased cardiac toxicity.

LABA should only be used to address sxs not well controlled with controller agents; should only be used as maintenance tx (stop during acute asthma exacerbation); and never us as mono-therapy for asthma. Reassess need for LABA once stable or if not helping.

In COPD, LABA’s can be used alone or in conjunction with another long-acting drug like tiotropium.

Question 8

Formoterol

Answer 8

a LABA; has lipophilic side chains (prolonged effect), administered via inhalation BID; NOT for acute asthma tx, but used as a maintenance drug.

Question 9

Salmeterol

Answer 9

a LABA; has lipophilic side chains (prolonged effect), administered via inhalation BID; NOT for acute asthma tx, but used as a maintenance drug.

Question 10

Anticholinergics

Answer 10

target the increased cholinergic tone seen in asthma and COPD; improve FEV1

short-acting formulation: ipratropium bromide
long-acting formulation: tiotropium bromide

Question 11

Ipratropium

Answer 11

a short-acting anticholinergic that improves FEV1 and sxs associated with asthma and COPD; slower onset than B2-agonist, so not a rescue drug; inhaled as single agent or combined with albuterol; 2-4 puffs 4x/day for mild/mod COPD

Question 12

Tiotropium

Answer 12

a long-acting anticholinergic that improves FEV1, reduces exacerbations, improves health, and decreases hyperinflation; used to tx asthma and COPD. Inhaled once daily as a dry powder only; most commonly used anticholinergic for AFO.

Question 13

Long-term controller agents

Answer 13

Not used to acute AFO, but taken as maintenance drug to help decrease inflammation associated with asthma and COPD. Includes corticosteroids, leukotriene modifiers, methylxanthines (Phosphodiesterase inhibs), and anti-IgE.

Question 14

Corticosteroids

Answer 14

The most potent and consistently effective controlled medication for asthma; broad spectrum anti-inflamm. mechanisms; inhibit transcription factors like NF-KB; suppress cytokine production effects, inhibit inflammatory mediator release/cell recruitment

Oral/IV forms used for short courses, have significant side effects with long-term use

Inhaled form BEST option; first line tx for all forms of asthma except mild-intermittent sxs (less than twice wkly)

Question 15

Prednisone

Answer 15

oral corticosteroid; used in 5-10 day courses (w/ taper); chronic use with significant side effects

Question 16

Dexamethasone and methylprednisone

Answer 16

IV corticosteroids; little advantage after 1st dose, so best to switch to a PO or inhaled form after; chronic used associated with significant side effects.

Question 17

Inhaled corticosteroids

Answer 17

Beclamethasone, triamcinolone, flunisolide, fluticasone, budesonide, mometasone

Mainstay of asthma tx, potent anti-inflammatory properties, prevent asthma exacerbations, reduces COPD exacerabtion frequency, safe for chronic use

PK: takes 6-12 months to achieve maximal benefit, take in dry powder prep 1-2 puffs 1-2x/day.

Toxicity: at stnd dose: include oral thrush and dysphonia; high dose SE’s include osteoporosis, growth suppression, adrenal suppression, and cataracts.

Question 18

Leukotriene modifiers

Answer 18

Zafirlukast and montelukast (Singulair); potent LT D4 receptor antagonists; block bronchoconstriction effects of leukotriene D4; other LT modifiers inhibit LT synthesis.

Shown to improve spirometry, reduce sx, reduce Beta agonist use

PO formula

Toxicity: elevated liver enzymes, Churg-Strause syndrome (vasculitis), altered metabolism of drugs (like Warfarin)

Question 19

Methyxanthines

Answer 19

Theophylline and aminophylline; mild long-acting bronchodilators and possible anti-inflammatory effects; unclear MOA but thought to inhibit phosphodiesterase and increase cAMP.

Significant side effects: tremor, atrial dysrythmia, N/V, insomnia, diuresis, seizures; significant drug interactions

Rarely used now!