DRUGS FOR ASTHMA
What are the classifications of asthma severity?
Mild intermittent; mild persistent; moderate persistent; severe persistent
What are the main classifications of drugs for asthma?
Bronchodilators; anti-inflammatory agents
Name the drug class for each of the following medications:
Albuterol
Short-acting β2-adrenergic agonist
Epinephrine
Short-acting β2-adrenergic agonist
Terbutaline
Short-acting β2-adrenergic agonist
Salmeterol
Long-acting β2-adrenergic agonist
Formoterol
Long-acting β2-adrenergic agonist
Isoproterenol
Short-acting β-adrenergic agonist
Metaproterenol
Short-acting β-adrenergic agonist
Fluticasone
Inhaled corticosteroid
Flunisolide
Inhaled corticosteroid
Beclomethasone
Inhaled corticosteroid
Triamcinolone
Inhaled corticosteroid
Budesonide
Inhaled corticosteroid
Methylprednisolone
Systemic corticosteroid
Prednisone
Systemic corticosteroid
Cromolyn
Mast cell stabilizer
Nedocromil
Mast cell stabilizer
Ipratropium
Inhaled anticholinergic
Tiotropium
Inhaled anticholinergic
Theophylline
Phosphodiesterase inhibitor; adenosine antagonist; methylxanthine
Zileuton
5-Lipoxygenase inhibitor
Zafirlukast
Leukotriene receptor antagonist
Montelukast
Leukotriene receptor antagonist
How do β2-agonists help treat asthma?
Bronchodilation via β2-adrenoceptor-mediated smooth muscle relaxation
How do corticosteroids help treat asthma?
Decrease production and release of proinflammatory cytokines; decrease inflammatory cell activation, recruitment, and infiltration; decrease vascular permeability; decrease mucous production; increase number and sensitivity of β2-adrenergic receptors
How do mast cell stabilizers help treat asthma?
Prevent mast cell degranulation, thereby decreasing release of histamine, platelet activating factor, leukotrienes, and other mediators that cause bronchoconstriction. Therefore only useful before exposure to allergen.
How do inhaled anticholinergics help treat asthma?
Competitively inhibit muscarinic receptors, thereby inhibiting vagal-mediated bronchoconstriction; reduce mucous production
How do phosphodiesterase inhibitors help treat asthma?
Increase cAMP which causes bronchodilation
How do 5-lipoxygenase inhibitors help treat asthma?
Inhibits production of leukotrienes (LTC4, LTD4, LTE4) from arachidonic acid, thereby preventing bronchoconstriction
What β2-adrenergic agonist is commonly used as a tocolytic agent (stops premature labor by relaxing uterine smooth muscle)?
Terbutaline
What cation can be used as a tocolytic agent?
Mg2+ (Magnesium ion)
Is cromolyn used for treatment or prevention of an asthma attack?
Prevention
Is nedocromil effective during an acute asthma attack?
No
What are the side effects of mast cell stabilizers?
Bitter taste; throat irritation
What are the side effects of β2-adrenergic agonists?
Tachycardia; muscle tremors; anxiety; arrhythmias; hyperglycemia; hypokalemia; hypomagnesemia (systemic side effects are minimized when drug is delivered via inhalation)
What are the side effects of 5-lipoxygenase inhibitors and leukotriene antagonists?
Increased liver function tests (LFTs); headache; Churg-Strauss syndrome
What is the main nonsystemic side effect of inhaled corticosteroids?
Thrush
What is thrush?
Oropharyngeal candidiasis
How can you prevent thrush when using inhaled corticosteroids?
Use of a spacer device; rinse mouth with water after medication use
What is a possible systemic side effect of inhaled corticosteroids in children?
Decreased growth of long bones
If using an inhaled corticosteroid and β2-adrenergic agonist together, which do you use first?
β2-adrenergic agonist (bronchodilates the airways, thereby increasing amount of corticosteroid that is delivered to its site of action)
What are the side effects of theophylline?
Tachycardia; arrhythmias; nausea; diarrhea; central nervous system (CNS) excitation (narrow therapeutic index)
Give an example of a methylxanthine other than theophylline:
Caffeine; theobromine; aminophylline
Why do inhaled anticholinergics have a minimal side effect profile?
Quaternary ammonium derivatives of atropine, therefore, do not leave the pulmonary system and cannot cross the blood-brain barrier
What are examples of systemic anticholinergic side effects?
Dry mouth; dry eyes; constipation; urinary retention; blurred vision; mydriasis; drowsiness; tachycardia
How do you treat β-blocker-induced bronchospasm?
With anticholinergics such as ipratropium and tiotropium
Name two drugs used to treat an acute asthma attack:
What is the IV form of theophylline called?
Aminophylline (2:1 complex of theophylline and ethylenediamine)
What is the term used to describe a severe asthma attack that does not respond to usual asthma therapy?
Status asthmaticus
How is status asthmaticus treated?
Oxygen; inhaled albuterol; intravenous or oral corticosteroids; inhaled anticholinergics
What is the drug of choice for mild asthma?
Short-acting α2-adrenergic agonist
What is the maintenance drug of choice for chronic asthma?
Inhaled glucocorticoid
How is theophylline primarily metabolized?
Hepatic cytochrome P-450 enzymes (CYP 1A2 and CYP 3A4)
Give examples of medications that can lead to increased theophylline levels when used concomitantly:
Cimetidine; erythromycin; fluoroquinolones
What drug can cause asthma, nasal polyps, and rhinitis?
Aspirin (“aspirin triad”); seen in the rare case of aspirin sensitivity where inhibition of cyclooxygenase (COX) leads to a buildup of leukotrienes
CHRONIC OBSTRUCTIVE PULMONARY DISEASE AGENTS
What disease processes fall under the category of chronic obstructive pulmonary disease (COPD)?
Asthma; chronic bronchitis; emphysema
State whether the following pulmonary function tests (PFTs) will be increased, decreased, or remain unchanged in patients with COPD:
Forced expiratory volume in 1 second (FEV1)
Decreased
Forced vital capacity (FVC)
Unchanged or increased
FEV1/FVC
Decreased (<75%)
Total lung capacity (TLC)
Unchanged or increased
What agents are used to treat COPD?
Inhaled anticholinergics; α2-adrenergic agonists; theophylline; inhaled corticosteroids
What are the first-line agents for treatment of COPD?
Inhaled anticholinergics (ipratropium)
ANTITUSSIVE AGENTS
Give examples of drugs that can suppress the CNS cough reflex:
Morphine; codeine; hydrocodone; hydromorphone; dextromethorphan
Which has greater antitussive (anticough) action, morphine or codeine?
codeine
When using opioids for cough suppression, are the doses required less than, equal to, or greater than the doses required for analgesic activity?
Less than
Which opioid is the drug of choice for cough suppression?
Dextromethorphan (no analgesic activity, no addiction risk)
What is a cough expectorant?
An agent that thins respiratory tract mucus and promotes its expulsion from the tracheobronchial system
Give an example of a cough expectorant:
Guaifenesin
AGENTS FOR ALLERGIC RHINITIS
What is/are the signs and symptoms of allergic rhinitis?
Inflammation of the nasal mucous membrane which is characterized by nasal itching, sneezing, rhinorrhea, and congestion
What causes allergic rhinitis?
Allergens interacting with IgE-coated mast cells leading to release of histamine, leukotrienes, and chemotactic factors
How do you treat allergic rhinitis?
Antihistamines; α-adrenergic agonists; intranasal corticosteroids; intranasal cromolyn; 5-lipoxygenase inhibitors; leukotriene antagonists
Give examples of antihistamines used in the treatment of allergic rhinitis:
Diphenhydramine; chlorpheniramine; loratadine; desloratadine; fexofenadine; cetirizine; astemizole
Name three nonsedating antihistamines:
Why are loratadine, desloratadine, and fexofenadine nonsedating?
No CNS entry
Where are H1 histamine receptors located?
Smooth muscle; endothelial cells; heart; CNS
Histamine acting at H1 receptors does what to the following?
Bronchiolar smooth muscle
Contraction
Capillaries
Dilation; increased permeability
Peripheral nociceptive receptors
Activation which leads to increased pruritus and pain
What are the major side effects of diphenhydramine?
Anticholinergic side effects, such as sedation, dry mouth, dry eyes, constipation, urinary retention, blurred vision, mydriasis, and tachycardia
Give examples of α-adrenergic agonists (nasal decongestants) used in the treatment of allergic rhinitis:
Phenylephrine; pseudoephedrine; oxymetazoline
How do α-adrenergic agonists help relieve signs and symptoms of allergic rhinitis?
Vasoconstriction of dilated arterioles in nasal mucosa; decrease airway resistance
What can happen when you discontinue use of long-term intranasal decongestants?
Rebound nasal congestion (only use these types of medications for short-term relief)
AGENTS FOR RESPIRATORY DISTRESS SYNDROME
What causes neonatal respiratory distress syndrome?
Insufficient maturation of type II pneumocytes leading to decreased production of surfactant
What is the purpose of lung surfactant?
Reduce alveolar surface tension which allows alveoli to remain open for proper gas exchange
What medications can be used to accelerate fetal lung maturation?
Glucocorticoids; thyrotropin-releasing-hormone (TRH)
What is a marker of fetal lung maturity?
Lecithin to sphingomyelin ratio of at least 1.5:1
What pharmacologic options are available for treating neonatal respiratory distress syndrome?
Surfactant replacement therapy; nitric oxide (NO)
AGENTS FOR CYSTIC FIBROSIS
What can be used to reduce small airway accumulation of viscous mucus in cystic fibrosis patients?
N-acetylcysteine; DNase
How does N-acetylcysteine work in cystic fibrosis?
Acts as a mucolytic agent through its free sulfhydryl group which breaks disulfide bonds in mucoproteins, thereby lowering mucus viscosity
How does DNase work in cystic fibrosis?
Deoxyribonuclease that selectively cleaves polymerized DNA in pulmonary secretions, thereby reducing mucus viscosity
Patients receiving which radiologic enhancing compound can be given concomitant N-acetylcysteine to protect renal function?
Computed tomography (CT) contrast
CLINICAL VIGNETTES
A 62-year-old man with a 40 pack-year smoking history presents to your office complaining of progressive shortness of breath. He has been using his niece’s albuterol inhaler with minimal relief of his symptoms. Visual inspection of the patient shows an increased anterior-posterior diameter of the chest. Auscultation of the lungs reveals a prolonged expiratory phase and pulmonary function tests reveal a decreased FEV1/FVC ratio. The patient shows mildly increased work of breathing after walking to the examination room, and exhales through pursed lips. Why has the albuterol therapy failed to relieve his shortness of breath?
This patient is suffering from COPD, a diagnosis supported by his long smoking history and physical findings. He appears to have a large emphysemic component to his disease. Emphysema is a pathologic diagnosis characterized by the destruction of alveolar tissue. Because of the destruction of the pulmonary parenchyma, oxygen exchange, and not oxygen delivery is the main issue for the patient. Therefore, a bronchodilator such as albuterol is minimally effective. COPD is characteristically an obstructive respiratory process that is nonresponsive to bronchodilators. This is in contrast to asthma, an obstructive pulmonary disease that is bronchodilator responsive.
A 12-year-old girl with a past medical history of asthma and allergic rhinitis presents with worsening asthma symptoms. She is now using her rescue inhaler every day for asthma exacerbations. She also awakens two to three times per week at night with shortness of breath and chest tightness. In the office, her peak flow volume measures 80% of the volume on her previous visit, when she had been feeling well. What is the most appropriate recommendation at this time?
This patient meets the criteria for moderate persistent asthma. Her symptoms are no longer being controlled on her albuterol rescue inhaler alone. Her history of allergic rhinitis suggests an allergic component to her asthma, so fastidious allergen avoidance is necessary. However, it is also appropriate at this time to add additional pharmacologic therapy to control her symptoms. An inhaled corticosteroid should be added to reduce airway inflammation and to prevent airway remodeling. Inhaled corticosteroids do not treat acute exacerbations, but decrease the frequency of attacks when taken regularly. The addition of a long-acting β2-adrenergic agonist such as salmeterol or formoterol could also be considered.
A mother brings in her 8-year-old boy who has been suffering from minor cold symptoms for 1 day with a cough that kept the child from sleeping well last night. After assuring the mother that the child has a minor viral illness that will not respond to antibiotics, you suggest over-the-counter Robitussin to control the coughing. The mother asks you about the active ingredient in the medication. You respond that the active ingredient is dextromethorphan, an opioid medication that is effective for cough suppression. The mother becomes quite agitated that you would suggest an addictive substance for her young child. What is the most appropriate counseling in this situation?
Dextromethorphan is the most widely used antitussive agent and has been available in various over-the-counter (OTC) preparations since the 1950s. It has the advantage over codeine of having less addictive potential and causing less constipation. It is FDA approved for OTC cough and cold formulations for children over the age of 6. Therefore, the mother can be counseled that this is a very safe medication with little to no addictive potential and will be effective in relieving her child’s symptoms. However, she must feel comfortable with her child’s therapy, and if this information does not assuage her fears, alternative therapies should be discussed. It is also true that while physiologic dependence does not occur in this agent to the level of other narcotic drugs, cough medications containing dextromethorphan are nevertheless used as a drug of abuse, especially in adolescent populations.