Martin Bronchodilator DSA Flashcards
Corticosteroids
Inhaled
Budesonide
Fluticasone
(anti-inflammatory)
corticosteroids- oral
prednisone
methylprednisolone
prednisolone
(anti-inflammatory)
Cromolyn compounds
cromolyn sodium
anti-inflammatory
Leukotriene Inhibitors
Montelukast
anti-inflammatory
Bronchodilators- beta 2 selective adrenergic agonists
Short-Acting beta 2-selective adrenergic agonists
Albuterol
Long-Acting beta 2-selective adrenergic agonists
Salmeterol
Formoterol
Others:
Epinephrine
Racemic Epinephrine
Muscarinic antagonists
Ipratropium bromide
Tiotropium
Combinations
Albuterol + Ipratropium bromide (Combivent)
Bronchodilators:
Methylxanthines
Theophylline
Decongestants
Sympathomimetic Agents
(alpha-agonists)
Phenylephrine
Oxymetazoline
Asthma
currently viewed primarily as an inflammatory illness that results in bronchial hyperreactivity and bronchospasm. The recommendations for prevention and treatment of asthma emphasize control of the inflammatory component as the underlying problem and reserving bronchodilators primarily for symptomatic use. The inflammatory component and the airway narrowing of asthma are largely reversible, and thus, drug therapy plays a significant role in the management of the disease.
chronic obstructive pulmonary disease (COPD)
disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. Drug therapy is useful in addressing the reversible component of COPD to induce bronchodilation, decrease inflammatory reaction, and facilitate expectoration.
Allergen-specific IgE binds to
Fc receptors on mast cell.
When allergen comes in contact with IgE, the mast cell is activated and releases a large number of mediators.
t an enormous variety of mediators is released, each having more than one potent effect on airway inflammation. Thus, a pharmacological blocker of any one mediator, e.g. antihistamine, is ineffective in alleviating the symptoms or progression of asthma or the inflammatory component of other respiratory diseases. Corticosteroids, which can block many of the key steps in the inflammatory process, come closest to this ideal therapy.
KEY FEATURES OF ASTHMA
- Mast cell activation associated with early bronchospasm
- Inflammatory cell infiltration with subsequently mediator release
- Epithelial cell damage
- Increased responsiveness of the airways to a variety of non specific stimuli
Benefits of Aerosol Delivery
Consider Ipratroprium *
The pathophysiology of asthma appears to involve the respiratory tract alone. So, ideally, effective treatment could be achieved if drug administration was restricted to the lungs.
- Aerosol application of drugs to the lungs can produce a high local concentration in the lungs with a low systemic absorption, thereby significantly improving the therapeutic ratio by minimizing side effects.
- Both 2-agonists and corticosteroids have potentially serious side effects when delivered systemically.
- Probably more than 90% of asthmatic patients who are capable of manipulating inhaler devices can be managed by aerosol treatments alone.
- Factors that determine effective deposition of drug in the lung
a. Particle size: >10 m deposit in mouth and oropharynx; <0.5 m are inhaled and then exhaled; 1-5 m deposit in small airway and are most effective.
b. Rate of breathing and breath holding are important.
c. The recommendation technique is that a slow, deep breath be taken and held for 5 - 10 sec. - Even under ideal conditions only 2 - 10 % of drug is deposited in lungs; most of the remainder is swallowed. Therefore, to have minimal systemic side effects, an aerosolized drug should be either poorly absorbed from the GI tract or be rapidly inactivated by first-pass liver metabolism. Consider Ipratropium
Devices for Aerosol Delivery
Metered-dose inhalers (MDI)- Advantages of MDIs are low cost and portability; disadvantages include need for hand-lung coordination making it more difficult for young children and the elderly to use. Spacer devices that attach to the MDI markedly improve the ratio of inhaled to swallowed drug and reduce need for coordination.
Nebulizers: preferred for severe asthma exacerbations with poor inspiratory ability; do not require hand-lung coordination.
Dry powder inhalers: require relatively high air flow to suspend the powder and can be irritating when inhaled.
Use of beta agonists in asthma
preferred therapy for bronchoconstriction per se. These are the only agents shown to be immediately effective for relieving bronchoconstriction during acute, severe asthma. Beta 2-selective agonists are more potent at Beta 2 compared to Beta-11-adrenergic receptors.
Inhalation usually produces excellent bronchodilation
Mechanism of Action of beta-Adrenergic Agonists
stimulate adenylyl cyclase and an increase in intracellular cyclic AMP.
–> decreased intracellular calcium, bronchial smooth muscle relaxation, and inhibition of mediator release from mast cells
beta 2 selective
albuterol
nonselective
epinephrine
Epinephrine is the drug of choice for the emergency treatment of anaphylactic reactions in general. Typically, epinephrine is administered by SQ injection
LABA
Salmeterol is useful for prevention of nighttime asthma attacks and prophylactic bronchodilation.
Formoterol (Foradil Aerolizer) is a long-acting, dry powder inhaler for maintenance therapy of asthma or prevention of bronchospasm in COPD and exercise-induced asthma. It was recently approved as a solution for nebulization (Perforomist). Not for treatment of acute attacks***
LABA recommendation
“Stop use of the LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid.”
Adverse Effects of beta-Adrenergic Agonists
Skeletal muscle tremor is the most common adverse effect.
Corticosteroids
In asthma (and some COPD) an inflammatory response is responsible for the underlying disease process. So many inflammatory mediators are involved that a blocker of any given autocoid or cytokine, e.g., antihistamine, is ineffective in alleviating the symptoms of asthma. Corticosteroids block many of the steps involved in the inflammatory cascade.
Mechanism of Action
corticosteroids are steroid receptor agonists that bind to intracellular receptors that translocate to the cell nucleus and positively or negatively regulate gene transcription. This takes time.*
corticosteroids inhibit the production and release of cytokines, vasoactive and chemoattractive factors, lipolytic and proteolytic enzymes, decrease mobilization of leukocytes to areas of injury, and decrease fibrosis.
***General anti-inflammatory response.
Anticholinergic Agents
The principal clinical use of ipratropium and tiotropium is in the treatment of COPD.
Ipratropium is used exclusively as an inhaled aerosol.
less intense than that produced by beta -agonists.
A useful bronchodilation response may last up to 6 hours with ipratropium while tiotropium is usually dosed once-per-day.
Combined treatment with ipratropium and beta 2-adrenergic agonists results in a slightly greater and more prolonged bronchodilation than therapy with either agent alone. Combined therapy can be considered if severe asthma or COPD exacerbations exist.
Albuterol + ipratropium bromide combination = Combivent and is a treatment of choice for COPD patients.
Ipratropium is also used intranasally to reduce secretion in both the upper and lower respiratory tract in allergic rhinitis and chronic postnasal drip syndrome (vasomotor rhinitis).
