Are H1-blockers reversible or irreversible inhibitors?
Reversible
List three clinical uses of first-generation H1-blockers.
- To treat allergy
- To treat motion sickness
- As a sleep aid
List three toxicities of first-generation H1-blockers.
- Sedation
- Antimuscarinic
- Anti-α-adrenergic symptoms
Loratadine, fexofenadine, cetirizine, and desloratadine are examples of what class of drugs?
Second-generation H1-blockers
What is the clinical use of second-generation H1-blockers?
Allergies
What is the main difference between first- and second-generation H1-blockers with regard to their toxicities?
Second-generation H1-blockers are far less sedating because of decreased central nervous system entry
What are three first generation H1-blockers?
Diphenhydramine, dimenhydrinate, and chlorpheniramine
What are four second generation H1-blockers?
Loratadine, fexofenadine, cetirizine, and desloratadine
What two types of β-agonists are used to treat asthma?
Nonspecific β-agonists and β2-agonists
What is the mechanism of action of isoproterenol?
It relaxes bronchial smooth muscle through agonism of β2-adrenergic receptors
What is the adverse effect of isoproterenol?
Tachycardia
Isoproterenol induces tachycardia through its agonism of what receptors?
β1-Adrenergic receptors
What is the mechanism of action of albuterol?
Albuterol relaxes bronchial smooth muscle through its agonism of β2-adrenergic receptors
Is albuterol used as a controller medication or for relief of symptoms during exacerbations?
It is used for relief in acute asthma exacerbations
Salmeterol is a _____ (short/intermediate/long) -acting agent.
Long
List two adverse effects of salmeterol.
- Tremor
- Arrhythmia
What enzyme converts adenosine triphosphate to cAMP?
Adenylyl cyclase
What enzyme is inhibited by β-receptor agonists? What is the effect?
Adenylyl cyclase; it increases the amount of cAMP
Theophylline falls into which class of drugs?
Methylxanthines
caffeine is also a member of the class
Theophylline likely causes _____ by inhibiting phosphodiesterase and increasing what molecule?
Bronchodilation; cAMP
What is the effect on bronchial smooth muscle of increased cAMP concentration?
Decreased bronchial tone (ie, it causes bronchodilation)
The usage of what asthma drug is limited because of its narrow therapeutic index?
Theophylline
List two types of toxicity that theophylline can cause.
- Cardiotoxicity
- Neurotoxicity
In addition to inhibiting phosphodiesterase, theophylline also blocks endogenous _____ from inducing bronchoconstriction.
Adenosine
Ipratropium is an example of what class of drugs?
Muscarinic antagonists
Does ipratropium cause a competitive or a noncompetitive receptor blockade?
Competitive
By competitively blocking muscarinic receptors, ipratropium prevents endogenous _____ from inducing bronchoconstriction.
Acetylcholine
Cromolyn prevents what process from occurring?
The release of leukotrienes and histamine from mast cells
How is cromolyn used in the treatment of asthma?
Cromolyn is most effective when used as prophylaxis and cannot be used for acute symptoms
Name two corticosteroids commonly used to treat asthma.
- Beclomethasone
- Prednisone
What mechanisms of corticosteroids make them useful to treat asthma?
They inhibit the synthesis of almost all cytokines
Corticosteroids are useful in treating asthma by inactivating what transcription factor?
Nuclear factor κB
Nuclear factor κB induces the production of inflammatory agents including _____ _____ ____.
Tumor necrosis factor-α
What class of drugs is considered first-line therapy for chronic asthma?
Inhaled corticosteroids
Name three examples of antileukotriene drugs.
- Zileuton
- Zafirlukast
- Montelukast
Zileuton is an inhibitor of what pathway?
The 5-lipoxygenase pathway that produces leukotrienes from arachidonic acid
What is the mechanism of action of montelukast?
Montelukast blocks leukotriene receptors.
In the pathogenesis of asthma, antigens bind to _____ on _____ cells.
Immunoglobulin E; mast
In the pathogenesis of asthma, the binding of antigens to immunoglobulin E on mast cells results in what?
The release of mediators such as leukotrienes and histamine from mast cells
In the treatment of asthma, what are two drug types that prevent the binding of antigens to immunoglobulin E on mast cells from resulting in the release of mediators?
Cromolyn and steroids
In the pathogenesis of asthma, the release of mediators from mast cells results in what two responses?
Bronchoconstriction (early) and inflammation (late)
In asthma, the early response to the release of mediators is primarily _____ whereas the late response to the release of mediators is primarily _____ .
Bronchoconstriction; inflammation
In the treatment of asthma, what drug type prevents released mast cell mediators from inducing the late response of airway inflammation?
Steroids
Theophylline is metabolized by what enzyme system, making drug interactions possible?
Cytochrome P450
Name two clinical indications for the use of ipratropium.
Asthma and chronic obstructive pulmonary disease
Zafirlukast and montelukast block leukotriene receptors and are especially useful in the treatment of which type of asthma?
Aspirin-induced asthma
Bronchoconstriction is mediated by which two processes?
Inflammation and lack of sympathetic tone; these are targets for therapy
Guaifenesin is an expectorant. How does it work?
It removes excess sputum in large doses, but it does not reduce the cough reflex
N-Acetylcysteine is an expectorant. How does it work?
It is a mucolytic, which is used to dissolve mucus plugs (especially in patients with cystic fibrosis)
Which mucolytic is also used as an antidote for acetaminophen overdose?
N-Acetylcysteine
Bosentan is used primarily to treat what condition?
Pulmonary hypertension
By what mechanism does bosentan decrease pulmonary vascular resistance?
By competitively antagonizing endothelin-1 receptors
