Treatment of Obstructive Lung Disease Flashcards
(20 cards)
Goals of asthma therapy
- Reduce the frequency and intensity of asthma symptoms
- Cough, chest tightness, wheezing, dyspnea
- Decease use of rescue short acting beta agonists
- Reduce night-time symptoms and awakenings
- Prevent exacerbations
- Prevent long term consequences of poorly controlled asthma
Well controlled asthma characteristisc
- sx = (less than or equal to) 2x/wk
- nighttime sx = 2x/mo
- SABA use =2x/wk except for exercise
- peak flow near normal
- oral steroid = 1x/yr
- urgent care visit = 1x/yr
Long-term control medications for asthma
- Inhaled glucocorticoids – preferred long-term control medication for the treatment forpersistent asthma
- Long-acting inhaled beta2-agonists –preferred supplementary long-term control agent for use with inhaled glucocorticoids
- Leukotriene modifiers
- Omalizumab (anti-IgE) –biologic response modifier
Short-term relief in Asthma
- Short acting beta2-agonists – preferred treatment to relieve symptoms and to prevent exercise-induced asthma.
- Anticholinergics – approved for use in COPD but not asthma; used as secondary reliever for significant asthma exacerbations.
- Systemic glucocorticoids – used to manage severe acute asthma exacerbations and occasionally for continued use in managing severe asthma.
B-adrenergic agonist pharmacokinetics
- •Clinical pharmacology: albuterol, terbutaline, salmeterol, formoterol. Used to treat asthma and COPD.
- Route: inhaled, injectable and oral
- rapid onset of action: minutes for albuterol and formoterol (slightly longer for salmeterol)
- duration of action:
- •quick relievers: 4 - 6 hours (albuterol)
- •long-term controllers: long acting ß-agonists last ~12 hours (salmeterol, formoterol)
B-adrenergic agonsits MOA/benefit
- mechanism of action: ß-adrenergic receptor stimulation
- beneficial effect: bronchodilation via smooth muscle relaxation; inhibits production of respiratory secretions
Anticholinergics MOA/pharmacokinetics
- mechanism of action: cholinergic receptor inhibition
- beneficial effect - bronchodilation via smooth muscle relaxation –inhibits production of respiratory secretions
- Clinical pharmacology: atropine, ipratropium, tiotropium; approved for use in COPD but not in asthma
–Route: inhaled
–rapid onset of action: minutes
•duration of action: –Quick relievers: up to 6 hours (ipratropium) –Long-term controllers: up to 12 hours (tiotropium)
Systemic glucocorticoids MOA/benefits
- mechanism of action: phospholipase inhibition; inhibition of cytokine synthesis
- beneficial effect :
- anti-inflammatory - reduces cellular infiltration, particularly eosinophils, mast cells, lymphocytes
- vasoconstrictor - reduces edema
Systemic glucocorticoids pharmacokinetics
Clinical pharmacology: hydrocortisone, prednisone, prednisolone, methylprednisolone. Used to treat acute exacerbations of asthma.
- Route: oral or parenteral
- onset of action: 30 - 60 minutes
- metabolism: half-life 2 -3 hours
- peak of action: approximately 8 hours
- duration of action: hydrocortisone=12-24 hrs & prednisolone=36-48
Inhaled glucocorticoids MOA/pharmacokinetics
- Used as the preferred long-acting control agent to treat asthma and for the treatment of COPD, if repeated COPD exacerbations noted.
- Route: inhaled
- duration of action: requires once to twice daily administration to maintain effect •mechanism of action: phospholipase inhibition; inhibition of cytokine synthesis •beneficial effect
–anti-inflammatory - reduces cellular infiltration, particularly eosinophils, mast cells, lymphocytes;
–vasoconstrictor - reduces edema
Asthmatic combination therapy
- Inhaled products are now available that combine an inhaled corticosteroid plus long acting ß-adrenergic agonist for benefits of both in the same delivery device.
Leukotriene modifiers MOA/pharmacokinetics
• mechanism of action:
leukotriene D4 antagonist – montelukast,
zafirlukast
5-lipoxygenase inhibition – zileuton
• beneficial effect
bronchodilator effect
anti-inflammatory effect due to leukotriene
blocking effect
attenuates exercise-induced asthma
- administered by the oral route
- onset of action: 30 - 60 minutes
- metabolism: half-life 6 hours; hepatic metabolism
- duration of action: 12-24 hours
Immunomodulator (omalizumab)
- Anti-IgE
- Approved for allergic asthma, requires parenteral (subcutaneous) administration
- binds to IgE to reduce likelihood of allergic response by inhibiting binding of IgE to mast cells.
- An adverse effect associated with anti-IgE is anaphylaxis which may occur shortly after or several hours after administration.
Cromolyn/nedocromil MOA/pharmacokinetics
- Route: inhaled route
- half-life: 20 minutes; excreted unchanged
- mechanism of action: inhibition of mast cell mediator release
- beneficial effect: preventative therapy for exercise-induced asthma can prevent allergen-induced pulmonary response
Theophyllines MOA/benefits
- mechanism of action: inhibition of phosphodiesterase
- beneficial effect: bronchodilator effect and some anti-inflammatory activity
Theophylline: pharmacokinetics
• Route: oral or IV
• metabolism: half-life 7 hours; hepatic
metabolism
• duration of action: 12 - 24 hours after single dose
Theophylline adverse effects
- caffeine-like effects such as irritability, gastrointestinal distress
- very narrow therapeutic range and requires blood level monitoring to individualize dose.
- Significant adverse effects can include seizures and irreversible neurologic damage
- multiple drug interactions
COPD therapeutic options
- Smoking cessation has the greatest capacity to influence the natural history of COPD.
- Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates.
- All COPD patients benefit from regular physical activity
COPD medications (6 + subtypes + combos)
First-line tx for each category of COPD severity (A –> D)
- A ==> SAMA (SAmuscarinic antagonist) prn or SABA prn
- B ==> LAMA or LABA
- C ==> ICS + LABA or LAMA
- D ==> ICS + LABA or LAMA
