Asthma & COPD Flashcards
drugs useful for treating asthma
- B2 –agonists (albuterol, terbutaline, pirbuterol, levalbuterol, metaproterenol, bitolterol, formoterol, salmeterol)
- Corticosteroids (beclomethasone, triamcinolone, flunisolide, fluticasone, budesonide, mometasone)
- Cromolyn and Nedocromil
- Muscarinic antagonists: ipratropium and tiotropium
- Theophylline
- Leukotriene antagonists (zafirlukast, montelukast, zileuton)
- Omalizumab
B2 agonists drugs
short-acting (SABA): albuterol, levalbuterol, terbutaline, pirbuterol, bitolterol, metaproterenol
long-acting (LABA): salmeterol, formoterol
B2 agonists use
SABAs are the drugs of choice for mild asthma; these drugs have no anti-inflammatory effects and should never be used as the sole therapy for patients with chronic asthma; they are used for symptomatic relief from asthma but long-term 2 agonist use is controversial
B2 agonists moa
directly relax bronchial smooth muscle by acting on 2 receptors in the lungs; stimulation of this receptor activates adenylyl cyclase and increases cAMP, which in turn activates PKA which phosphorylates the MLCK and causes muscle relaxation; stabilizes mast cell membranes
B2 agonists kinetics
the short-acting agents have a rapid onset of action (5-15 min. inhaled, 15-30 min. oral) and provide relief for 4-6 hours; LABAs have a slower onset of action (about 1 hour) but provides relief for at least 12 hours; LABAs are not used for acute asthmatic attacks; given usually as metered-dose inhalers (MDI) and also by nebulizer; these drugs are not catecholamines so are not destroyed by catechol-O-methyl-transferase (COMT)
B2 agonists adverse
as selective 2 –agonists given in the form of inhalers, these drugs have few adverse effects; excessive doses can cause skeletal muscle tremor and cardiac stimulation; unnecessary use has been associated with the increase in asthma mortality
The use of orally administered 2 –agonists …
has not gained wide acceptance due to the risk of systemic side effects such as muscle cramps, cardiac tachyarrhythmias, and metabolic disturbances; there are two situations where oral 2 –agonists are used frequently: in young children (<5 years old) who cannot manipulate a metered dose inhaler oral therapy with albuterol or metaproterenol syrups are well tolerated and effective, and second, oral therapy is effective in patients who experience irritation or enhanced cough or bronchospasms when using the inhaler
CORTICOSTEROIDSs drug
Inhaled: beclomethasone, triamcinolone, flunisolide, fluticasone, budesonide, mometasone
Systemic: methylprednisolone, prednisolone, prednisone
CORTICOSTEROIDS use
moderate to severe asthma; asthmatic patients who require inhaled 2 -agonists four or more times weekly are reviewed as candidates for inhaled corticosteroids; severe asthmatics may require systemic glucocorticoids for a short term
CORTICOSTEROIDS moa
act on cytoplasmic glucocorticoid receptors and stimulate protein synthesis (4-12 hours before clinical response is seen); are anti-inflammatory; to be effective in controlling inflammation, these drugs must be taken continuously; these steroids have no direct effect on the airway smooth muscle; three main benefits from corticosteroids are 1) inhibition of inflammation at all levels, 2) reducing mucous production and hypersecretion, 3) increasing 2 receptor levels
CORTICOSTEROIDS kinetics
a. the development of inhaled steroids have greatly reduced the need for systemic corticosteroid treatment;a large fraction (80-90%) of the inhaled dose is deposited in the mouth and pharynx, or is swallowed, and these steroids are absorbed from the gut and enter the systemic circulation through the liver
b. most inhaled corticosteroids undergo extensive first- pass metabolism so only a small portion of the drug reaches the systemic circulation; the 10-20% that is
not swallowed is deposited in the lungs
systemic corticosteroids
used in patients with severe exacerbation of asthma (status asthmaticus) and are given IV as methylprednisolone (Solu-Medrol) or orally; once the patient has improved, the dose of drug is gradually decreased leading to discontinuance in 1-2 weeks
spacer
a spacer is a large volume chamber that is attached to the metered-dose inhaler and is used to decrease the deposition of drug in the mouth; the chamber reduces the velocity of the injected aerosol and also serves as a type of filter to allow mainly small drug particles to be deposited in the mouth; the small particles are more likely to reach the target airway tissue
rinsing the mouth after inhalation can also decrease systemic absorption and the possibility of oropharyngeal candidiasis (thrush)
CORTICOSTEROIDS adverse
in the inhaled form, thrush may be a problem; when given orally or parenterally a number of adverse effects can be observed
Cromolyn and Nedocromil use
Are effective as prophylactic antiinflammatory agents, but are not useful in managing an acute asthma attack because they are not direct bronchodilators
Therapeutic use: mild to moderate asthma; pretreatment with either drug prevents exercise-induced and allergen-induced asthma; especially useful in children due to effectiveness and few side effects (better than corticosteroids)
Cromolyn and Nedocromil moa
these drugs inhibit pulmonary mast cell degranulation in response to a variety of stimuli which, in turn, prevents the release of histamine and other granular contents
Cromolyn and Nedocromil kinetics & adverse
Pharmacokinetics: both drugs are given by inhalation (MDI)
Adverse effects: usually infrequent and minor; rare instances of anaphylaxis, laryngeal edema, headache, rash, and nausea have been reported (cromolyn is touted as the “least toxic drug” used to treat asthma; adverse effects in 0.01% of patients)
