Asthma/COPD Flashcards
Salmeterol (Serevent)
Class: Bronchodilator - long-acting β2 agonist
Mech: Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability (BMMM)
Thera: used for long-term control of asthma symptoms (always in comination with inhaled steroids)
Important SE’s: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia
Other SE’s: Tolerance with chronic use, Prolonged QTc, lactic acidosis, paradoxical bronchospasm
Misc: 10-15 minutes to take action, 6-12 hours (max) of duration; nebulizer delivers more, but greater side effects; oral is least effective (requires more dose –> side effects); can be used night symptoms, but not ideal
Asthma is
- chronic inflamm of airways
- recurrent episodes of wheezing, SOB, chest tightness (SEC)
- Variable airway obstruction, often completely reversible
COPD is a
- persistent airway limitation
- progressive (not fully reversible)
- enhanced chronic inflamm responses (cough, SOB, increased sputum)
Some key similarities and differences b/w COPD and asthma:
Sim: both inflamm; Diff: 1. TH2 dom in astham, TH1 in COPD 2. IgE producing in asthma 3. reversible in asthma, fixed in COPD 4. Bronchial hyperreactivity in asthma 5. Smoking risk factor for COPD; genetics, environment in asthma
Some epidemiology:
- Females > males for percent asthma
- Females more likely to get asthma as we get older, and more AA pop mortality
- Men with greater death rate by COPD than females, but more females die of it
- Could be underdiagnosing COPD and hence undertreating
In asthma and the ____ model, what helps mediate early inflamm? Late inflamm?
allergen;
leads to IgE coating mast cells and degranulation, and also T lymphocyte activity (both with IL4, IL5; mast cells with leukotriens, prostaglandin D, platelet activating factor);
late: eosinophils and neutrophils with their mediators (e.g. MBP for eosinophils) and this leads to more bronchospasm
Rather than think of the allergen model of asthma, what is a viable model to think of?
Bronchial hyper-reactivity model (cold air or maybe exercise)
What three things does COPD help cause? Why?
- fibrosis (small airways)
- Alveolar wall destruction (emphysema)
- Mucus hypersecretion (hypertrophy of mucous glands0;
Imbalance of proteases and antiproteases
FAM
Important mech of action of bronchodilators (beta 2 agonist)?
increases cAMP through G-protein receptor interaction and activation of AC;
Albuterol, terbutaline, metoproterenol, pirbutol:
Class: Bronchodilator - short-acting β2 agonist)
Mech: Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability
Thera: Prevent or reduce exercise-induced bronhospasms; mild asthma & acute exacerbations
Important SE’s: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia; Tolerance with chronic use (downregulate beta 2 receptors), Prolonged QTc, lactic acidosis, paradoxical bronchospasm
Misc: 5 minutes to take action, 4-6 hours duration; nebulizer delivers more, but greater side effects. Note: Levalbuterol is R-isomer of albuterol.
Levalbuterol:
- R isomer of albuterol
- Just beta agonist effects
- No inflamm or SE’s like tachy due to no S isomer
- No significant difference in clinical or pharmacological outcome
Salmeterol, formoterol, indacaterol:
S: partial agonist; F: full agonist; I: ultra long acting (only in COPD);
Onset: 10-30 min; duration: 12 hrs or more;
Highly lipid soluble and binds to secondary exosite;
USED IN COMBO WITH INHALED CS IN ASTHMA!!!!!
Comparison of tiotropium and ipratropium bromide:
- Half life of tio is longer at M3 receptor (can dose 1x/day);
- Tio will dissociate faster from M2 receptor and keep its M3 activity longer
Ipratropium (Atrovent); Tiotropium; Atropine
Class: Quarternary amine antimuscarinic
Mech: Blocks vagal pathways and decreases vagal tone to bronchial smooth muscle; also blocks the reflex bronchoconstriction caused by inhaled irritants
Thera: First-line agent for chronic COPD; status asthmaticus (w/ nebulized β2-agonists); no role in chronic stable asthma
SE’s: Typical antimuscarinic effects; acute angle glaucoma; paradoxical bronchospasm GAP (inhibition of vagal induced bronchoconstriction would require high dose than current therapeutic doses); consider receptor selectivity;
Misc: Note: tiotropium has anti-inflammatory properties and decreases mucus secretion.
Aclidinium bromide:
Class: Quarternary amine antimuscarinic
Mech: Blocks vagal pathways and decreases vagal tone to bronchial smooth muscle; also blocks the reflex bronchoconstriction caused by inhaled irritants
Thera: Functionally similar to tiotropium
1. structurally and functionally similar to tio
2. M3>M2 affinity
3. Half life at M3: 29 hours
4. Short circulation half life: 2.4 min (Less systemic & CNS side effects than other antimuscarinics due to extremely short circulation half-life)
5. Higher dose can be given safely;
same SE’s as antimuscarainics
Theophylline, theobromine, caffein:
Class: relatively weak bronchodilator
Mech: non-selective PDE inhibitors (PDE 3, 4, 5): Phosphodiesterase inhibition and enhanced signalling via increased cAMP and cGMP; relax bronchial smooth muscle to get bronchodilation; improve contractility and reverse fatigue of diaphragm in COPD patients; can restore CS sens at low dose!!! Get him a PR Contract
Thera: Reduce inflammation (suppress inflamm genes) and bronchospasm in moderate to severe asthma, night symptoms
SE’s: CNS stimulation or seizures, tachycardia/arrythmias, anorexia, nausea STAN; serum level doesn’t correlate with symptoms in chronic users of theophylline; drug interactions because it’s metabolized by ctyp450 system
Misc: Low therapeutic index! Metabolized by liver; cimetidine and quinoline increase blood levels
Roflumilast:
Class: selective PDE4 inhibitor (methylxanthine)
Mech: anti-inflamm (prevents neutrophil migration by inhibiting PDE4 isoforms); improvement in lung function secondary to anti-inflamm more so than bronchodilation;
Thera: COPD
SE’s: same as other the methyxanthines
Corticosteroids (Budesonide; Fluticasone propionate; beclomethasone):
Class: Corticosteroid - anti-inflammatory agent
Mech: 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 Luis Vasquez can’t hit into the GAP No More
Thera: Cornerstone treatment of persistent asthma; beneficial combination with beta-2 agonist; limited role in COPD (restore steroid sens with low dose theophylline);
Important SE’s: Inhaled has thrush, hoarseness, dry cough, mild adrenal suppression (higher doses) CHAT; oral has mood-swings, increased appetite, and suppression of adrenocorticotropic hormone secretion (Cushing’s Syndrome) AMA
Misc: combine with beta 2 agonist (one helps with transcription of B2 receptor gene; other helps with translocation of glucocorticoid receptor from cytoplasm to nucleus)
Ciclesonide (CS):
Class: Corticosteroid - anti-inflammatory agent
Mech: Same as other corticosteroids, but is a prodrug and only activated by airway esterase.
Thera: Cornerstone treatment of persistent asthma; beneficial comination with beta-2 agonist; limited role in COPD
Important SE’s: Less side effects than other corticosteroids (on site activation required);
3. less systemic absorption
4. less systemic side effects
About how large should particles be for inhaled therapies?
1-5 micrometers;
solution or suspension: metered dose inhaler;
solid particles: dry powder inhaler;
latter, patient can control inhalation and it’s patient actuated, but requires faster inspiratory flow than MDI
Leukotriene inhibitor: Montelukast (Singulair); Pranlukast (Azlaire); Zafirlukast (Accolate)
Class: Leukotriene inhibitor Mech: Leukotriene receptor antagonist Thera: Add-on therapy in mild persistent asthma; aspirin-induced asthma; prophylaxis for exercise-induced bronchospasm Important SE's: Well tolerated Misc: Must monitor liver function test.
Na cromoglycate and Nedocromil Na:
Class: Anti-inflammatory agent
Mech: Prevent mast cell degranulation and mediator release from mast cells
Thera: Prophylaxis for inhibiting both early and late phase reactions (maybe preventive treatment before exercise or exposure to known allergens); best results in mild and allergic asthma
Important SE’s: Minimal local side effect (cough & throat irritation)
Omalizumab (Xolair)
Class: anti-IgE MAB
Mech: Blocks IgE function.
Thera: Poorly controlled severe asthma
Misc: Administered by subQ injection every 3 weeks
To deal with intermittent asthma, what is step 1? What can you do for step 2?
1: short acting B2 agonist as needed
2. Can use low-dose ICS (by now persistent asthma)
When do you use ICS for COPD?
Only as the risk increases to around C or D
Treatment of exacerbation of asthma and COPD
- differences disappear b/w two with exacerbations
- systemic CS for short period (5-7 days)
- Short acting beta 2 agonist and short acting antiCh via nebulizer (albuterol or ipratropium)
- Antibiotics usually prescribed in COPD exacerbation
- No role of long acting beta agonist and long acting antiCh
Zileuton (Zyflo)
Class: Leukotriene inhibitor
Mech: Inhibits 5-lipoxygenase and blocks leukotriene synthesis
Thera: Add-on therapy in mild persistent asthma; aspirin-induced asthma; prophylaxis for exercise-induced bronchospasm
Important SE’s: Liver toxicity
