Deja Review Pharmacology, 2nd Edition

CHAPTER 7. Pulmonary Agents

 

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:

 

  1. Epinephrine
  2. Albuterol

 

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:

 

  1. Loratadine
  2. Desloratadine
  3. Fexofenadine

 

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.