Treatment of Asthma & COPD Flashcards
Short acting bronchodilator B2-agonist?
Albuterol, Terbutaline, Metoproterenol, Pirbutol
MOA of short acting B2 agonists? Uses? Effective in COPD? Side effects? Timing? Taken as? With isomer exerts beta agonistic effects?
MOA: Increase cAMP!! Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability. Uses: Prevent or reduce exercise-induced
bronhospasms; mild asthma & acute exacerbations. Less effective in COPD. Side effects: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia, Tolerance with chronic use, Prolonged QTc, lactic acidosis, paradoxical bronchospasm. Timing: 5 minutes to take action, 30-60 minutes for peak, 4-6 hours duration. Given as inhaler, nebulizer, oral, subcutaneous (terbutaline) – nebulizer delivers more, but greater side effects. The R isomer exerts effects – the R isomer of albuterol is lebalbuterol.
Mainstay of treatment in asthma?
Short-acting agonist on an as-needed basis. Long-acting agents for long-term control – ALWAYS used in combination with inhaled steroids (FDA Black Box warning to do so). These drugs are less effective in COPD.
Long acting B2 agonists? Whih one is a partial agonist? Which is full? Which is ultra-long acting and thus only used in COPD? What is the duration of action of these? What about the onset of action?
Salmeterol (partial agonist), Formoterol (full agonist), Indacaterol (ultra long activity – only in COPD). Duration 12+ hours (salmeterol > formoterol), Onset 10-30 minutes (formeterol > salmeterol).
MOA of long acting B2 agonists? Uses? Side effects? Timing? Most effectively taken as? Can these be taken at night?
MOA: Increase cAMP!! Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability. Uses: Long-term control of asthma
symptoms (always in combination with inhaled steroids) Side effects: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia, Tolerance with chronic use, Prolonged QTc, lactic acidosis, paradoxical bronchospasm. nebulizer delivers more, but greater side effects; oral is least effective (requires more dose –> side effects); can be used night symptoms, but not ideal.
Antimuscarinics used?
Atropine, Ipratropium, Tiotropium, Aclidinium bromide
MOA of antimuscarinics? Tiotropium is used for? Aclidinium is functionally similar to? Ipratropium is used for? Side effects?
MOA: Blocks vagal pathways and decreases vagal tone to bronchial smooth muscle; also blocks the reflex bronchoconstriction caused by inhaled irritants. Blockage of M3 is most important.Tiotropium also has antiinflammatory properties and decreases mucus secretion. Tiotropium: First line agent for chronic stable COPD (long half-life of 34 hrs, functionally selective for M3 over M2 receptors). Also used for chronic asthma. Not effective in acute exacerbation of asthma or COPD. Ipratropium is also for chronic COPD but is less preferred (need more frequent dosing, variable bronchodilator response), additive effect to nebulized albuterol in acute severe asthma, no role in chronic stable asthma. Aclidinium is functionally similar to tiotropium. Side effects: Typical antimuscarinic effects; acute angle glaucoma; paradoxical bronchospasm; Aclidinium has less systemic & CNS side effects than other antimuscarinics due to extremely short circulation half-life.
Methylxanthines?
Theophylline, Theobromine, Caffeine, Roflumilast
MOA of methylxanthines? How is roflumilast unique? Uses? What about roflumilast? Side effects? Why is use of these drugs waning? How are these drugs metabolized?
MOA: Phosphodiesterase inhibition and enhanced
signalling via increased cAMP and cGMP; relax bronchial smooth muscle. Roflumilast is a specific PDE4 inhibitor. Use: antiinflammatory (suppress inflammatory genes via histone deacetylation), improve contractility and reverse fatigue of diaphragm in COPD, restore corticosteroid sensitivity at low doses. Roflumilast is more of an antiinflammatory (improvement in lung function is secondary to antiinflamation rather than bronchodilation, which is very weak). Approved for COPD. All of these can also be used for night symptoms. Side effects: (at lower doses) anorexia, nausea, headache, insomnia GERD + (at higher doses) cardiac arrythmia, seizure. Use is waning because these drugs have a low therapeutic window and require frequent monitoring of blood level. Metabolized by liver P450.
Corticosteroid antiinflammatory agents?
Budesonide, Fluticasone, Propionate, Beclomethasone, Ciclesonide. (“Becler cicles, Bud props flutes”)
MOA of corticosteroids? How is ciclesonide unique? Uses? What inflammation is considered “resistant?” How can sensitivity be restored? Side effects?
MOA: Anti-inflammatory effects: inhibition of growth factor secretion, inhibition of arachidonic acid metabolites and platelet activation factor, inhibition of leukocyte accumulation, decreased vascular permeability, inhibition of neuropeptide- mediated responses, inhibition of mucous glycoprotein secretion. Ciclesonide is the same, but it is a pro-drug and is activated on-site via esterase. Uses: Cornerstone treatment of persistent asthma!! Beneficial combination with beta-2 agonist (increases transcription of B2 receptor gene + B2 agonist increases translocation of glucocorticoid receptor from cytoplasm to the nucleus). Limited proven role but highly used in COPD (especially in those with severe disease & frequent exacerbations). “Resistant inflammation:” COPD, severe asthma, asthamtics who smoke. Sensitivity restored with low dose theophylline. Side effects: (Inhaled) thrush, hoarseness, dry cough, mild adrenal suppression (higher doses); (oral) mood-swings, increased appetite, and suppression of adrenocorticotropic hormone secretion (Cushing’s Syndrome). Ciclesonide has less side effects.
Anti-inflammatory agents used mostly for prophylaxis? MOA? Side effects? Role in COPD?
Sodium cromoglycate & Nedocromil sodium. MOA: Prevent mast cell degranulation and mediator release from mast cells (at the molecular level, these alter the function of the delayed chloride channel). Side effects: mild and local (cough, throat irritation). NO role in COPD.
Leukotriene inhibitors?
Montelukast (Singulair), Pranlukast, Zafirlukast, Zileotun.
Uses of leukotriene inhibitors? Role in COPD? Side effects?
Uses: DOC for aspirin-intolerant asthma. Add on therapy for mild asthma (though less effective than doubling dose of inhaled corticosteroid or adding B2 agonist), prophylazis for exercise induced bronchospasm. NO role in COPD Oral or tablet. Side effects: Mostly well tolerated, although zileuton has liver toxicity. Coincidental Churgg-Strauss?
Anti-IgE monoclonal antibody? Uses? Administered how?
Omalizumab. Used in patients with very severe asthma who are poorly controlled on oral corticosteroids + reduces the requirement for oral and inhaled corticosteroids and markedly reduces asthma exacerbations. Given SQ every 2-4 weeks.
