Asthma/COPD Flashcards
Little Johnny comes to your office complaining of recurrent episodes of wheezing, chest tightness, and coughing (often at night). What do you suspect?
- asthma
- chronic inflammation of the airways
- variable airway obstruction that is usually completely reversible
Big Johnny comes to your office complaining of progressively feeling short of breath for the past year and half or so. He smoked a lot when he was younger. What do you suspect?
- COPD
- persistent airway limitation
- enhanced chronic inflammatory response in the airways and lungs to noxious particles and gases
- usually preventable and treatable
What are differences in the airway smooth muscle, basement membrane, and degree of fibrosis when comparing asthma with COPD?
- Asthma: airway SM is hypertrophic and basement membrane is thicker
- COPD: more fibrosis is present
What are two broad categories in use for therapy of COPD/asthma and name some classifications within each category
- Bronchodilators (acting on airways): short and long acting inhaled β agonists, anticholinergics, and theophylline
- Anti-inflammatory agents (acting on cells): inhaled corticosteroids, antileukotrienes, cromones, anti-immunoglobulin E
What are the intracellular effects of β2 agonists?
- stimulates Gs protein and increases adenylyl cyclase and cAMP, which raises PKA and induces bronchodilation
What are the intracellular effects of theophylline?
- prevents breakdown of cAMP, which raises PKA and induces bronchodilation
One of your patients has had well controlled asthma (with meditation) for years but has noticed that she tends to have a harder time breathing while exercising lately. You rule out any other cause besides her asthma - what can you prescribe her that she can use prior to beginning exercise to prevent these episodes? Tell me more about the drug.
- shorting acting β2 agonist (probably albuterol, but can use terbutaline, meoproterenol, or pirbutol)
- these drugs start working in 5 minutes and last about 6 hrs
- SE: tremor, tachycardia, hyperglycemia, hypokalemia, hypomagnesaemia, prolonged QTc, lactic acidosis, paradoxical bronchospasm
One of your patients is taking levalbuterol and claims that it isn’t working. What is unique about this drug? Upon further investigation, you realize that he’s taking the inhaler about 4 x’s/day. Why isn’t the drug working?
- Levalbuterol, a short acting β2 agonist, is the R isomer of albuterol which is supposed to be associated with fewer side effects
- however, clinically there is no significant difference between this drug and others in the class
- Tolerance has developed due to a downregulation of β2 receptors
You decide to prescribe your patient with COPD a long acting β2 agonist. What are your options?
- salmeterol, formoterol, or indacaterol (COPD only)
- these last 12-24 hrs, and are highly lipid soluble which causes binding to a secondary exosite
You decide to prescribe your patient with asthma a long acting β2 agonist. What must you remember to supplement with and why?
- always use in combo with inhaled corticosteroids in the setting of asthma!
- could be due to polymorphism in B-16 (arginine) locus of β receptor in some patients, increasing chance of death without steroid supplement
What receptor will anticholinergics ideally block, and accidental blockage of what receptor often causes side effects?
- aiming for blockage of M3 receptor
- if drugs are non selective and inhibit M2, more ACh is released and smooth muscle constricts
What are some characteristics of tiotropium, the first line antimuscarinic agent for COPD?
- long half life, with functional selectivity of M3 over M2
- anti-inflammatory: reduces neutrophil migration and airway remodeling
- decreases mucus production
How is aclidinium bromide different than the older antimuscarinics?
- metabolized in plasma, so short circulation half life –> less systemic/CNS side effects –> safe in higher doses
- M3>M2 affinity
What is the mechanism of action of the methylxanthines (theophylline, theobromine, and caffeine)?
- PDE 3, 4, and 5 inhibitor = bronchodilation
- enhances histone deacetylation and suppresses inflammatory genes
- improves contractility and reverses fatigue of diaphragm in COPD
What is the cornerstone treatment for persistent asthma?
- corticosteroids! (ex. prednisone, dexamethasone, ciclesonide)
- combining with β2 agonist has additive effect
- also, there is little proof of benefit (in fact, COPD is a steroid resistant inflammation!) but highly used in COPD
