Anti-Asthmatics Flashcards
Asthma
a common disease characterized by airway inflammation and episodic, reversible bronchospasm with severe shortness of breath. Subsets of clinical asthma may reflect differently
pathogenic factors and different responsiveness to currently
available therapies
Drugs useful in classic allergic asthma include (Bronchodilators)
Beta agonist
Muscarinic agonist
Methylxanthines
Anti-inflammatory agents
inflammatory release inhibitorsSteroids
Slow-antiinflammatory drugs, Antibodies
leukotriene antagonists
Lipoxygenase inhibitors, Receptor inhibitors
COPD drugs
bronchodilators, Steroids, and antibiotics
Bronchial hyperreactivity
Pathologic increase in the bronchoconstrictor response to antigens and irritants; caused by
bronchial inflammation
IgE-mediated disease
Disease caused by excessive or misdirected immune response mediated by IgE antibodies.
Example: asthma
Mast cell degranulation
Exocytosis of granules (vesicles) from mast cells with a release of mediators of inflammation and bronchoconstriction
Phosphodiesterase (PDE)
Family of enzymes that degrade cyclic nucleotides to nucleotides, for example, second messenger
cAMP (active) converted to AMP (inactive) or cGMP to GMP
Tachyphylaxis
Rapid loss of responsiveness to a stimulus (eg, a bronchodilator drug)
PATHOPHYSIOLOGY OF ASTHMA (immunologic causes)
The immediate cause of asthmatic bronchoconstriction is the release
of several mediators from IgE-sensitized mast cells and other cells
involved in immunologic response
mediators involved in asthma
leukotrienes LTC4 and LTD4, tryptase, histamine, and
prostaglandin D2. These substances bring about the “early response”
consisting of bronchoconstriction and increased secretions
“late response” of asthma
chemotactic mediators such as LTB4 attract inflammatory cells
to the airways and several cytokines, and some enzymes are released,
resulting in the “late response” leading to inflammation
Chronic inflammation leads to
Hyperreactivity y to various inhaled substances, including antigens, histamine, muscarinic agonists, and irritants such as sulfur dioxide (SO2) and cold air. This
reactivity is partially mediated by vagal reflexes
STRATEGIES OF ASTHMA THERAPY
Acute bronchospasm must be treated promptly and effectively with bronchodilators (“reliever” drugs). Beta2 agonists, muscarinic antagonists, and theophylline and its derivatives are available for this indication.
How is asthma treated long term
The most important anti-inflammatory drugs in the treatment of chronic asthma are corticosteroids. Long-acting β2 agonists can improve the response to corticosteroids. Anti-IgE antibodies also appear promising for chronic therapy. The leukotriene
antagonists
mechanisms of Beta agonist
stimulate Adenylyl cyclase, cAMP activity increases- relaxation of bronchial smooth muscle
MOA of Methylxanthines (found in tea, coffee, and cocoa)
inhibits Phosphodiesterase activity (degrades cAMP to AMP)- to increase cAMP levels, in turn, cause vasodilation and relaxing bronchial smooth muscle.
Methylxanthines also inhibits adenosine receptors (which leads to constriction)
MOA of Leukotriene antagonist
`inhibit LTE4 receptor, prevents exercise-induced asthma and aspirin induced bronchospasm
MOA of Musc. antagonists
block Ach receptors, preventing bronchoconstriction
MOA of corticosteroids
reduce the synthesis of PA2 and inhibits COX-2, reduced levels of PGs and Leukotrienes
CROMOLYN & NEDOCROMIL
Cromolyn (disodium cromoglycate) and nedocromil are unusually insoluble chemicals; so even massive doses given orally or by the aerosol result in minimal systemic blood levels.
MOA of Cromolyn and Nedocromil
The mechanism of action of these drugs is poorly understood
but may involve a decrease in the release of mediators (such as
leukotrienes and histamine) from mast cells. The drugs have
no bronchodilator action but can prevent bronchoconstriction
caused by a challenge with antigen to which the patient is allergic.
Cromolyn and nedocromil are capable of preventing both early
and late responses to challenge
ANTI-IgE ANTIBODIES
Omalizumab is a humanized murine monoclonal antibody to
human IgE. It binds to the IgE on sensitized mast cells and prevents activation by asthma trigger antigens and subsequent release
of inflammatory mediators. Although approved in 2003 for the
prophylactic management of severe asthma, experience with this
drug is limited because it is very expensive and must be administered parenterally
