chronic lung disease that results from inflammation and bronchoconstriction of the lower airways, characterized by difficulty breathing.
constriction of the smooth muscle surrounding the airways in the lungs, resulting in a narrowing of the airways, wheezing, and shortness of breath.
Chronic obstructive pulmonary disease (COPD)
chronic lung disease that results in irreversible damage to the lung tissue.
medications that are taken on a regular schedule to control a disease or prevent its effects, even when symptoms are absent.
Cystic fibrosis (CF)
an inherited condition that causes the production of thickened mucus, resulting in damage primarily to the lungs and pancreas.
an environmental factor such as pollen, animal dander, pollution, or tobacco that stimulates a reaction.
acute worsening of disease symptoms.
an undesirable effect of the body’s immune system to an antigen.
medications that relax the muscles surrounding the airways within minutes when administered during an episode of bronchoconstriction.
a continuous whistling sound made by constricted airways.
After completing this chapter, you should be able to
Define asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Recall the pathophysiology of asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
List nonpharmacologic therapy options for asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
List pharmacotherapy options for asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Recognize differences in pharmacotherapy for asthma and chronic obstructive pulmonary disease.
State generic and brand names of medications used to treat asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Recognize the doses and common side effects of pharmacologic therapies for disorders of the respiratory system.
Chronic respiratory illness is a growing problem in the United States and the world. The most frequently diagnosed chronic respiratory disease states are asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF).1 Asthma affects roughly 300 million individuals worldwide, with an estimated 25 million of those individuals in the United States.1,2 Although prevalence rates of asthma increased significantly from 2001 to 2010, the rates remained relatively stable from 2010 to 2017.1 COPD is currently the fourth leading cause of death worldwide, but as the death rate continues to grow, it is projected to become the third leading cause of death in years to come.3,4 Due to continued exposure to COPD risk factors and the aging population, the disease burden is likely to increase in the coming years.4Cystic fibrosis is a life-threatening condition that affects approximately 70,000 individuals worldwide, with about half of those residing in the United States. In the 1970s, patients were not expected to live past their mid-teens; however, advances in the treatment of CF have extended their life expectancy exponentially.5,6 These chronic conditions require both nonpharmacologic and pharmacologic approaches to optimize management. Although these diseases are treated with many of the same drugs, it is important to note that they are used in different ways for each disease. The majority of medications are given via inhalation to limit the systemic side effects of the drugs. It is imperative that patients know how to properly administer inhaled medications–for more information on this see Chapter 18. Patients’ quality of life and longevity can be improved by using medications appropriately.2 This chapter discusses the pathophysiology and management of each condition.
Many community pharmacies provide health-related literature about respiratory disease and smoking cessation. Pharmacy technicians can contribute to the distribution of this valuable information.
Robert Juner is a 20-year-old college student who runs into the pharmacy wearing jogging clothes and having difficulty breathing. You have not seen him in the pharmacy before. He asks where your asthma medications are with single words. He finds Primatene Mist on the shelf before you can help him, opens the box, and inhales three puffs of medication very quickly. Then he comes to the counter to pay for it. He is breathing a little easier now, but his hands are shaking as he pays for the medication. You hear some whistling sounds in his chest, and he still seems to be in some distress.
Asthma is a chronic lung disease that results from persistent inflammation of the lower lung airways. The result of chronic lower lung airway inflammation is bronchoconstriction and decreased airflow, which in turn causes difficulty breathing. The lung inflammation and airway bronchoconstriction are normally reversible with the use of medications, or occasionally the symptoms will resolve spontaneously (Figure 19-1).7
Symptoms of reduced airflow include nighttime and early morning cough, wheezing (a whistling breath sound), shortness of breath, and chest tightness. These symptoms are commonly associated with exercise, but may occur spontaneously or in relation to a known allergen. Although these symptoms are the most common, each symptom does not have to be present for a diagnosis of asthma to be made. For example, a chronic cough may be the only symptom of asthma. The frequency at which these symptoms occur vary significantly, from daily (persistent asthma) to periodic (intermittent asthma). In addition to variable frequency, severity also differs among patients. Appropriate treatment should be individually tailored to fit each patient’s needs based their symptoms, frequency, and severity.8
Asthma is a complex condition that is not completely understood, but studies strongly support inherited genetic predisposition in combination with environmental triggers. Common environmental triggers of asthma include airborne allergens (dust mites, animals, molds, and pollen), viral infections (eg, respiratory syncytial virus [RSV] and rhinovirus), environmental pollution, tobacco, and some foods and additives (eg, wheat, eggs, preservatives). For an individual who has a genetic predisposition for asthma, exposure to an environmental trigger may activate what is known as a hypersensitivity reaction. A hypersensitivity reaction can be thought of as an allergic reaction that causes an influx of immune system defensive cells to flood the lungs and their airways. The influx of these defensive cells causes an increase in mucus production, narrowing of the airways, and overall lung airway inflammation, resulting in bronchoconstriction. The typical asthma symptoms of coughing, wheezing, shortness of breath, and chest tightness are a direct result of the inflammation caused by the hypersensitivity reaction. Collectively, the acute worsening of typical asthma symptoms, in combination with difficulty breathing, is referred to as an asthma exacerbation. The typical course for asthma is periods of exacerbation followed by periods of remission, during which asthma symptoms are not evident.7
The consequence of untreated chronic inflammation of the lung airways is an increased frequency of asthma exacerbations, possibly causing irreversible lung structural changes (airway remodeling). These structural changes can lead to a reduction in the ability of the lung to fully exchange air and completely oxygenate the body, resulting in an increased severity of asthma symptoms. Once airway remodeling is present, the ability to reverse inflammation and bronchoconstriction with medications is reduced (see Figure 19-1). However, with proper asthma therapy and good symptom control these structural changes can be prevented.2
Asthma is a condition that most often arises during childhood, with the majority of patients being diagnosed by the age of 5 years.2 A common theory, the hygiene hypothesis, suggests that susceptible individuals develop asthma and allergies because the allergic immunologic system develops instead of the system to fight infections.7 Simply put, individuals exposed to more bacteria, common allergens, and less antibiotic therapy have demonstrated a lower risk of asthma.7 Of those patients with childhood asthma, 30%–40% will have symptoms persist into adulthood.1 This chapter focuses on the management of adult asthma.
Types of Asthma
Acute—severe asthma symptoms that can progress quickly to an emergent, potentially fatal situation. Patients often experience cough, wheezing, and severe shortness of breath and chest tightness. Patients also often have difficulty talking.
Chronic—asthma symptoms progress from severe exacerbation to remission, where normal asthma symptoms (cough, wheezing, shortness of breath, and chest tightness) may fluctuate between remission and acute exacerbation. The time between exacerbation and remission is variable and generally depends on asthma control. An exacerbation may be brought on by an environmental trigger such as an allergen, virus, pollution, or tobacco smoke.
Cough-variant—a chronic cough is the most bothersome asthma symptom and may be the only asthma symptom experienced. The cough generally occurs during the night in this type of asthma.
Drug-induced—an asthma attack that is triggered after ingestion of a drug. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have both been associated with drug-induced asthma. Beta blockers have also been known to cause drug-induced asthma.
Exercise-induced—asthma symptoms are triggered by exercise. Exercise-induced asthma typically occurs after exercise has ended. The exact cause of exercise-induced asthma is not fully understood, but it is thought to be related to hyperventilation that induces constriction of the airway. Exercise-induced asthma will affect most asthma sufferers at some point during their disease course. It is also important to note that for some asthma sufferers, exercise may be the only time that asthma symptoms are experienced, and they have otherwise normal lung function at all other times. Exercise-induced asthma occurs more frequently in regions where the air is cold and dry and seems to be improved in regions where the air is warm and humid. Exercise should not be avoided by patients with exercise-induced asthma but, rather, preventative measures undertaken to ensure adequate exercise capacity.
Nocturnal—asthma that occurs during the night while the patient is sleeping. Lung function decreases during the night, falling to its lowest point at approximately 3:00 to 4:00 in the morning. The possible causes of nocturnal asthma include normal nocturnal hormonal functions, exposure to allergens or pollutants, gastroesophageal reflux, obstructive sleep apnea, or sinusitis.
From what type of asthma does Robert appear to be suffering?
The overall goal of asthma therapy is aimed at increasing asthma control. The Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention, states that long-term goals are risk reduction and symptom control.8 The US Department of Health and Human Services defines asthma control in two separate parts:2
Prevention of chronic asthma symptoms
Fast-acting asthma relief with a short-acting beta2-agonist when needed ≤ 2 days a week
Maintain (near) normal pulmonary function
Maintain normal activities of daily living (including exercise, other physical activity, and attendance at work or school)
Meet patient and family expectations of and satisfaction with asthma care
Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits or hospitalizations
Prevent progressive loss of lung function; for children, prevent reduced lung growth
Provide optimal pharmacologic therapy with minimal to no adverse effects
Nonpharmacologic therapy is an essential component to achieving good asthma control. This may include anything, other than medication therapy, that results in a reduction of asthma symptoms. For example, identifying and avoiding asthma triggers, close management of coexisting disease states, in-depth patient education, and the development of an asthma action plan.
Triggers are factors or conditions that are associated with a worsening in asthma symptoms. See Table 19-1 for examples. The identification of asthma triggers is the first step toward gaining good asthma control. Patient awareness of the environmental triggers that worsen asthma symptoms is crucial in controlling their symptoms. Once they are identified, patients can work to modify exposure to potential triggers in an attempt to reduce or even eliminate particular symptoms and achieve better asthma control. When other health conditions are not well managed, good asthma control is more difficult to achieve. It is important for patients to achieve control of those conditions to optimize their asthma management.
Patient education is an important component of managing any condition but is especially important for managing asthma. The patient should be educated in identifying asthma triggers, recognizing early signs and symptoms of an exacerbation, and how to properly use the inhaler device. Additional information regarding proper inhaler and nebulizer use can be found in Chapter 18. Providing patients with detailed knowledge empowers them to take an active role in their health and managing their condition. Proper education gives each patient the opportunity to achieve greater asthma control through avoidance of triggers, early treatment, and proper inhaler technique.
A written asthma action plan is critical to achieving good asthma control. An asthma action plan is a written set of instructions created by a patient with the healthcare provider. These instructions provide guidance for the patient based on lung function. The plan contains information on daily controller medications, reliever medications, trigger avoidance, and explicit directions on when to seek medical attention for an exacerbation. The action plan should be routinely updated to reflect changes in the patient’s medications.2,7,8
Asthma pharmacotherapy has two objectives:
Quick relief of acute bronchoconstriction and other asthma symptoms
Long-term prevention of bronchoconstriction and other asthma symptoms
Reliever/rescue medications are fast-acting medications taken on an as-needed basis for immediate relief of an asthma exacerbation. These medications directly target the bronchoconstriction and provide relief of asthma symptoms within minutes. The reliever medications have a short duration of action (approximately 4–6 hours), which allows them to be safe with multiple uses (up to three times at 20-minute intervals) until adequate relief of asthma symptoms has been obtained. All patients diagnosed with asthma should have a reliever medication available to provide fast relief of bronchoconstriction during acute asthma exacerbations. As-needed reliever medication may provide sufficient asthma control for those patients with intermittent mild asthma or exercise-induced bronchoconstriction when used prior to exercise. Frequency of reliever inhaler use is commonly monitored as a means of evaluating overall asthma control. The need for a quick-relief medication more than twice a week is an indication of poor asthma control and indicates the need for a controller or preventative asthma medication to gain better control.
Controller/prevention medications provide long-term control and prevention of asthma symptoms by decreasing the inflammation that leads to bronchoconstriction and the other asthma symptoms. This class of medications is used to treat persistent asthma that cannot be controlled with the use of a reliever medication alone. Preventative medications are taken on a routine basis, generally once or twice a day at specified times. They should be taken routinely, whether or not the patient is currently experiencing asthma symptoms, as the goal of these medications is long-term reduction of asthma symptoms. Controller medications should not be used on an as-needed basis due to their delayed onset and longer duration of action. Use of controller medications when immediate relief is desired could result in lack of immediate efficacy or toxic side effects. Standard pharmacologic management of asthma is based on recommendations from the National Asthma Education and Prevention Program and Global Initiative for Asthma, each providing a stepwise approach for asthma therapy management.2,8
The goal of asthma pharmacotherapy is to achieve and maintain good asthma control with the least amount of medication possible. The first step is to employ nonpharmacologic measures and only consider pharmacologic therapy if asthma is still not adequately controlled. The first pharmacotherapy given to all patients is a reliever medication, which may be the only medication needed for some patients. If good asthma control is not achieved with the use of a reliever medication alone, the next step is the addition of a controller medication. All steps (step = addition/subtraction of medication or the increase/decrease of medication dose) of therapy are trialed for a sufficient amount of time, and then asthma control is reevaluated before any adjustments in treatment are made. Medication doses are increased and/or the additional medications are added to the therapy regimen until adequate asthma control is achieved. Once a patient has maintained good asthma control for at least three months, decreasing doses and/or removing medications may be considered. This continuous cycle, personalized asthma management, consists of assessing, adjusting, and reviewing the patient’s response.8
Patient medication regimens should be reviewed on a routine basis to identify changes in therapy, including the addition of new medications and the discontinuation of any that are no longer used. This process may be referred to as a complete medication review (CMR).
Bronchodilators provide rapid relief of bronchoconstriction in the lower lung airways. Many have a quick onset of action and provide rapid relief of asthma symptoms. Bronchodilators have minimal effects on the inflammatory process that is the cause of bronchoconstriction; therefore, their main role in asthma treatment is control of acute symptoms and exacerbations.
Recall (from Chapter 4) that the autonomic nervous system (ANS) regulates many vital body activities, including heart rate, secretions, and breathing. The sympathetic system (SANS) is generally described as the fight or flight system as it increases heart rate and dilates the bronchi, while the parasympathetic system (PANS) decreases the heart rate, increases secretions, and constricts the bronchi. A stable internal environment is maintained through the activation and deactivation of these two systems. Sympathetic agonists stimulate receptors in the SANS. Beta agonists are more specific in that they stimulate mainly the beta receptors of the sympathetic system. β1 (beta1) receptors are located mainly in the heart and kidneys, while β2 (beta2) receptors are found primarily in the bronchi.
Epinephrine: Quick-Relief Medication
Epinephrine is a hormone that occurs naturally in the body and is released from the adrenal gland in emergency situations. It acts at all types of SANS receptors, including those in the lungs. When administered exogenously (as a medication), epinephrine is a very potent bronchodilator that can be given either as a systemic injection or inhaled directly into the lungs. Epinephrine administration results in profound bronchodilation very quickly, but the duration of action is short, only lasting approximately 60–90 minutes. Epinephrine also has a significant excitatory effect on the heart that limits its usefulness in the treatment of asthma. The excitatory effect of epinephrine on the heart includes symptoms such as fast heart rate and abnormal heartbeat and/or chest pain—all of which are amplified at increased doses.
There are currently two inhaled epinephrine dosage forms available over the counter, a nebulizer solution and a metered-dose inhaler (MDI). The nebulizer products are Asthmanefrin Refill and S2 (Racepinephrine), both containing 2.25% epinephrine. Primatene Mist, the MDI, like the other inhaled bronchodilators, only treats the symptoms, with no effect on the underlying cause of asthma. The use of these products is not recommended for the routine management of asthma. The involvement of a healthcare professional in the diagnosis and management of asthma is important not only to avoid the possibility of drug-induced side effects, but also to ensure good asthma control to avoid long-term irreversible lung structural changes.
It is important to note there are currently two Primatene products available over the counter. In addition to Primatene Mist, there are Primatene tablets. Though the products have the same brand name, the active ingredients are different. Primatene asthma tablets contain ephedrine and guaifenesin, while Primatene Mist contains epinephrine.
When Robert comes to the counter to pay for the Primatene Mist, how might a pharmacy technician be able to help him?
The main action of beta2 agonists is relaxation of the smooth muscles of the lung airways, resulting in dilation of the airways and relief of bronchoconstriction. Beta2 agonists have no effect on the inflammatory process that leads to bronchoconstriction and therefore provides only symptomatic asthma relief, with little direct effect on the heart. They can be separated into two groups based on duration of action: short-acting beta2 agonists (SABAs) and long-acting beta2 agonists (LABAs).
SABAs used in the treatment of asthma include albuterol (Ventolin, Proventil, and ProAir) and levalbuterol (Xopenex). These may be used as reliever medications during acute asthma attacks. SABAs can produce rapid relief of acute asthma symptoms during an acute exacerbation. The National Asthma Education and Prevention Program 2020 Focused Updates to the Asthma Management Guidelines report has updated recommendations regarding the use of SABAs.2 The report states that SABAs administered as needed remain the preferred management for intermittent asthma. However, the updated guidelines now recommend the use of combination low-dose inhaled corticosteroid (ICS)-formoterol as needed over SABAs in select individuals with persistent asthma. These changes in recommendations better align with the current Global Initiative for Asthma guideline.8 For adults and adolescents 12 years and older, the 2022 GINA guidelines recommend as needed low-dose ICS-formoterol therapy as the preferred reliever. However, the 2020 NAEPP report only recommends low-dose ICS-formoterol as reliever therapy for patients on Step 3 or 4. As discussed earlier, bronchodilators (SABAs) do not have any effect on the underlying cause of asthma and provide only rapid symptomatic asthma relief. Consequently, regular use of SABAs is associated with increased airway inflammation, while over-use shows an increased risk of asthma exacerbations. The use of SABAs in mild intermittent asthma must be monitored closely to assure adequate asthma control. Asthma is considered to be under good control if reliever therapies are used on two or fewer days per week. Exercise-induced bronchospasm may be prevented with the use of SABAs prior to exercise. SABAs are available in two inhalation preparations: inhaler and nebulizer solution. Inhalation reduces the incidence of side effects and is associated with a faster onset of action.
The duration of action of SABAs also varies, with the inhalation preparation having a shorter duration of action. The typical SABA inhaler dose is one to two puffs every 4–6 hours (depending on medication) as needed or three times at 20-minute intervals. SABAs are generally well tolerated, with side effects most notable at high doses. Side effects include angina (chest pain), atrial fibrillation (rapid heartbeat), arrhythmia (problems with heartbeat), cough, and tremor. SABAs should be used cautiously in patients with a history of cardiac problems.
What treatment for Robert’s asthma is suggested by the guidelines described?
Long-acting beta2 agonists (LABAs) are similar to SABAs in that they also provide symptomatic relief of bronchoconstriction. LABAs vary in their onset of action, but can provide bronchodilation for a much longer time than SABAs. The duration of action is at least 12 hours, which limits administration to once or twice daily. The majority of LABAs have a slower onset of action when compared with a SABA, so they must not be used as a reliever medication. Formoterol, a LABA, has a similar onset of action to those of SABAs. Formoterol, in combination with an ICS, is the only LABA that may be used as a reliever therapy for acute asthma symptoms. The role of LABAs in asthma therapy is prevention of chronic bronchoconstriction, as they do not treat the underlying disease process causing the bronchoconstriction. Currently, LABAs (except formoterol) are only indicated for use as part of combination therapy with ICSs for persistent asthma patients unable to achieve adequate asthma control with an ICS alone.
LABA monotherapy is not recommended due to a lack of data suggesting an improvement in asthma control, and a small but significant increase in risk of asthma-related death. LABAs should be taken routinely on a daily basis, regardless of asthma symptoms and should be continued even when the patient is not experiencing any asthma symptoms. When LABAs are taken routinely in combination with an ICS, they can help to prevent irreversible airway changes that can occur with uncontrolled asthma. Due to their longer duration of action, LABAs are conveniently taken once or twice daily. These are generally well-tolerated medications, with the most common side effects reported being headache, hypertension, dizziness, and chest pain.
The primary action of muscarinic antagonists is blocking the effects of acetylcholine at the muscarinic receptors, blocking the action of acetylcholine at these receptors preventing bronchoconstriction and reducing mucus secretion. These agents can be separated into two groups based on duration of action: short-acting muscarinic antagonist (SAMA) and long-acting muscarinic antagonist (LAMA). The use of muscarinic antagonists for asthma management is limited, as they are predominantly used for COPD. A SAMA/SABA (e.g. ipratropium/albuterol) combination may be used for the treatment of an acute asthma exacerbation, either via a nebulizer or MDI. One LAMA, tiotropium, is approved as maintenance therapy for moderate to severe asthma for those 12 years and older. It is more commonly prescribed in the following situations: 1) in addition to an ICS and LABA or 2) in addition to an ICS for patients intolerant of LABA therapy. For additional information on muscarinic antagonist therapy, see the COPD section.
Might long-acting beta2 agonists (LABAs) be dangerous for Robert?
Theophylline provides mild to moderate bronchodilation and, as a result, relief of asthma symptoms. Theophylline also possesses a mild anti-inflammatory effect, which reduces some of the inflammation that is causing the bronchodilation and asthma symptoms. Although theophylline therapy can address both the cause and symptoms of asthma, it is not a potent bronchodilator or anti-inflammatory agent. In addition to limited efficacy in asthma, side effects are common and can be life threatening. Therefore, sustained-release theophylline is not recommended for routine use in the management of asthma.
Theophylline use for the treatment of asthma is limited because of the availability of better medications. Theophylline has a very small range between where it is therapeutic (helpful) and toxic (harmful). Thus, theophylline blood concentrations must be monitored very closely via blood draws to assure good therapeutic outcome without serious toxic side effects. It is also highly reactive with other medications and has a serious side effect profile that increases with increased doses. The most common side effects associated with theophylline are tachycardia, nausea, vomiting, headache, dizziness, jitteriness, and insomnia. Persistent vomiting is a sign of theophylline toxicity (poisoning). The theophylline dose should never be doubled, even if the previous dose was missed, due to dose-related increased side effects and drug interactions, as well as the possibility of death.
Theophylline is available as a liquid, sustained-released capsules, and extended-release tablets.9 The dose is individualized for each patient based on weight and then adjusted based on blood theophylline concentrations. This is intended to assure that each patient receives just enough theophylline to achieve good asthma control, but not so much that dose-related side effects would be likely. Oral extended- or sustained-release theophylline is typically dosed once daily.
Glucocorticoid Therapy: Prevention Medication
As discussed in Chapter 9, hormonal steroids are produced naturally by the adrenal glands. While mineralocorticoids function to regulate the retention of salt and water, and the adrenal androgens regulate the reproductive system, glucocorticoids act on metabolism and the immune system. The effects of glucocorticoid steroids on the immune system make them a useful option for the treatment of asthma, and they will be the focus of this discussion.
Glucocorticoid steroids act on glucocorticoid receptors to elicit a specific function, which is based on the location of the target receptor. Glucocorticoid receptors are found throughout the body, making glucocorticoid steroids capable of causing systemic (body-wide) effects on the immune system and metabolism, including both desirable and undesirable effects. The challenge with using glucocorticoid therapy for treatment of asthma has been specifically targeting the respiratory system while minimizing effects on the rest of the body. The development of inhaled glucocorticoid therapy has helped enhance the desired anti-inflammatory effects of the steroid while reducing the undesired side effects by localizing therapy to the lungs through inhalation.
It should be noted that, while glucocorticoid is the technical name for this class of hormonal steroids that have an effect on the immune system, they are also commonly referred to as corticosteroids. The terms glucocorticoids and corticosteroids are used interchangeably when discussing this class of hormonal steroids. Glucocorticoid hormonal steroid therapy that is administered through inhalation is often referred to as inhaled corticosteroids (ICSs).
ICSs relieve inflammation through a reduction in the body’s normal immune response. Thus, they directly treat the underlying cause of bronchoconstriction and asthma symptoms, chronic inflammation. In asthma, the immune system is activated by an environmental trigger that induces a hypersensitivity reaction, which stimulates defensive cells to flood into the lungs and cause inflammation and bronchoconstriction. ICSs are able to block the immune system response to the environmental trigger so that defensive cells are never stimulated into action.
ICSs do not have a direct effect on bronchoconstriction and should not be used as a reliever medication, unless in combination with formoterol. ICSs primarily function as controller therapy that, when taken daily, significantly reduce the risk of asthma exacerbations and hospitalizations. When ICSs are used regularly these medications typically result in an overall decrease in bronchoconstriction, a direct result of controlling the underlying inflammation, and this can reduce reliever inhaler usage. It is important that all asthmatic patients have a reliever inhaler (SABA or ICS-formoterol combination) for rapid asthma relief, even if they are on daily controller therapy with an ICS.
ICSs are the most effective class of medications for achieving and sustaining good long-term asthma control and are the first-line medication therapy for any type of persistent asthma. ICS-formoterol as needed may be used for the management of mild intermittent symptoms.2 ICSs are typically administered as one to two puffs once to twice daily, but the exact dosing regimen is dependent on the particular medication. The dose of ICSs is highly variable because it depends on patient-specific factors and asthma severity. The exact dose must be determined through medication trials and individual patient response. Due to the side effects associated with corticosteroid therapy, the lowest effective dose should be used, to minimize the likelihood of systemic side effects associated with ICSs. Doses can be divided among three broad ranges: low, medium, or high daily dose. Leukotriene modifiers are considered alternative controller therapy or add-on therapy to ICS therapy.1,2 Alternative therapies are reserved for when patients are unable to tolerate ICS therapy at all or unable to tolerate dose increases necessary to achieve good asthma control. Leukotriene modifier therapy has been proven less effective than ICS for the treatment of asthma, especially in the reduction of exacerbations. Consequently, leukotriene modifiers are not recommended as first-line agents for the management of asthma, but may be used for the prevention of exercise-induced bronchoconstriction.
Leukotriene modifiers available include montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo). NAEPP 2020 and GINA 2022 consider oral leukotriene-modifying agents as alternative first-line controller therapy for adults and adolescents 12 years and older. Montelukast is approved for use in patients 12 months to adult and may be preferred for younger patients based on once daily dosing and variety of available preparations. The different oral preparations available include tablet, chewable tablet, and granule packet. The typical once daily dose for montelukast is 4–5 mg for children and 10 mg for patients aged 15 years or older. Montelukast has been associated with behavioral and mood changes, although the most common side effects for leukotriene modifiers are less severe, and include abdominal pain, cough, dizziness, and nasal congestion. Liver enzymes must be closely monitored as zafirlukast has been associated with liver impairment.
Mast Cell Stabilizer: Prevention Medication
Cromolyn sodium primarily functions as an asthma preventative agent aimed at increasing long-term asthma control. It targets the underlying inflammation that is caused when mast cells are stimulated by an environmental trigger. These mast cells release histamine and stimulate other cells to flood the airways, resulting in an increase in mucus production and bronchoconstriction. This medication has no direct effect on the symptoms of asthma, so is not generally used as a reliever medication for an acute exacerbation. Cromolyn sodium is not recommended for routine use due to the availability of more effective therapies, but may be considered an alternative to ICS therapy for control of mild persistent asthma, prevention of exercise-induced bronchoconstriction, and allergy-induced asthma when administered prior to a known exposure. Overall, cromolyn sodium has limited use in chronic asthma management due to its minimal efficacy compared to ICSs.
Cromolyn sodium is available as a nebulizer solution. It takes approximately 4–6 weeks of treatment to achieve the full effect, although some improvement is often seen in 1–2 weeks. Cromolyn sodium is dosed four times a day until the maximum effectiveness is reached, indicated by increased asthma control, at which time the dosing can be tapered to the lowest effective dose. It is very well tolerated, with the most common complaints being transient coughing and mild wheezing.
If Robert continues to have asthma symptoms, but ICSs are not indicated or tolerable, what other treatment might his healthcare provider prescribe?
Immunomodulator Therapy: Prevention Medication
Immunomodulator medications are sometimes referred to as monoclonal antibodies. They are a class of medications that have been designed using a combination of human and mouse protein to target a specific immune system cell, with the intention of either activating or deactivating the cell. By targeting specific cells within the inflammatory pathway, inflammation is directly prevented along with indirectly preventing the symptoms associated with inflammation. This therapy can result in a reduction of unwanted side effects because the medication has an effect only on the particular cell that induces the asthma symptoms. Targets for these drugs include immunoglobulin E (IgE) for allergic asthma and interleukin (IL)5/5R and IL4R for eosinophilic asthma. In recent years there has been an increase in the types of available immunomodulators for the management of asthma. Current immunomodulators available for the treatment of asthma include omalizumab (Xolair; anti-IgE), dupilumab (Dupixent; anti-IL4R), mepolizumab (Nucala; anti-IL5), reslizumab (Cinqair; anti-IL5), benralizumab (Fasenra; anti-IL5R), and tezepelumab (Tezspire; anti-TSLP). In many cases, these medications are effective only in specific types of asthma. For example, omalizumab targets the immune system cell, IgE, that is released when activated by an allergen; therefore it is only useful for patients with allergic asthma. Immunomodulator therapy is currently recommended for difficult-to-treat patients with an allergic or eosinophilic asthma diagnosis uncontrolled on high-dose ICS/LABA therapy. The addition of immunomodulator therapy may allow a dose reduction of ICS therapy.
Omalizumab administration can result in a severe allergic reaction known as an anaphylaxis. This reaction is triggered when the immune system recognizes the mouse protein portion of omalizumab as foreign and rallies to fight off the foreign substance that has entered the body. The result is a severe life-threatening reaction that must be treated immediately. To minimize the risk, patients initially receive therapy while being observed by a clinician for up to 2 hours following injection. Select patients may be approved for self-administration based on a risk assessment.
These immunomodulator therapies are not available orally due to inactivation of the drug in the gastrointestinal tract. Consequently, they must be administered subcutaneously (SUBQ) or intravenously (IV) at regular intervals. The doses of these medications may vary from weight-based (mg/kg) to fixed dosing based on immune cell levels. The most common side effects of these medications include injection site reactions (pain and bruising) and headache.
Omalizumab vials must be reconstituted with sterile water prior to administration. Using a 3-mL syringe and 18-gauge needle, a total of 1.4 mL of sterile water is added to the vial. After the addition of the sterile water, the medication vial must be kept upright and gently swirled for 1 minute to ensure that the entire product is evenly wet. The medication must be gently swirled for 5–10 seconds every 5 minutes until the medication is completely dissolved. The reconstitution process takes approximately 20 minutes but no more than 40 minutes. If the medication has not dissolved within 40 minutes, it should be discarded. The reconstituted medication should be inverted for 15 seconds prior to withdrawal. Using a 3-mL syringe and 18-gauge needle, all medication should be removed from the inverted vial. After all medication has been removed, the needle plunger should be pulled back to the end of the barrel to ensure that all medication is removed from the vial. The needle should be changed to a 25-gauge for subcutaneous injection. All air, large bubbles, and excess solution should be discarded from the syringe at this time, preserving the 1.2-mL (150 mg) dose. A thin layer of small bubbles may be present.
Combination Therapy: Prevention Medication
Combination therapy can consist of two or more medications within a single inhaler. As discussed earlier, the most effective medications for achieving long-term asthma control are ICSs, and as such, they are the first-line medication for intermittent and persistent uncontrolled asthma. When ICS medications fail to adequately control asthma symptoms, the next option is to consider either an increase in the ICS dose or the addition of another medication. An increased dose of the ICS may not be a viable option due to the increased side effects associated with higher doses. The addition of another asthma medication from a different class may significantly improve management of asthma symptoms as the two medications are both targeting the condition but at different points in the pathway. The addition of two medications from different classes can result in a greater reduction of asthma symptoms as both medications work together compared to either medication alone. The most common asthma medications to be used in combination are ICSs and LABAs. The ICS targets the inflammation and the LABA relieves the bronchoconstriction that is caused by the inflammation. This medication should be taken once or twice a day regardless of asthma symptoms. The side effects associated with combination therapy are consistent with the side effects experienced for each individual medication as discussed above.
Why might Robert eventually need more than one kind of inhaler or medication for his asthma? What is the difference between a reliever inhaler and a controller medication?
Chronic Obstructive Pulmonary Disease
COPD is similar to asthma in that it is also a chronic lung disease associated with chronic inflammation of the lung airways and decreased lung airflow. The main difference between asthma and COPD is that the decreased airflow in asthma is reversible, whereas in COPD it is only partially reversible and progresses over time. The immune system defensive cells that trigger the inflammation also differ between asthma and COPD. Asthma is typically diagnosed early in life whereas COPD is diagnosed in mid- to late life.
Joe Button is a 56-year-old man who is a regular patient in your pharmacy. He is classified as GOLD Grade 2/Group C and was started on salmeterol (Serevent Diskus) one puff twice daily about 4 weeks ago in addition to his tiotropium (Spiriva Respimat) two puffs once daily. Joe states that he experiences shortness of breath when going up or down a flight of stairs. He smoked two packs of cigarettes per day for 35 years but quit smoking about 2 years ago. He comes into the pharmacy to have his monthly tiotropium refilled but does not ask to have his salmeterol refilled.
The lung inflammation and damage associated with COPD is due primarily to toxic gas exposure. Toxic gas exposure causes a significant amount of inflammation in the lung airways extending into the lung vasculature. This inflammation, over time, leads to destruction of the lung tissue. As the body attempts to repair the damaged lung tissue, the tissue becomes scarred, making it incapable of fully exchanging air, and the end result is reduced lung function. The most common cause of COPD is smoking tobacco, but occupational pollutant exposure and environmental pollution can also be sources of toxic gas exposure. There also appears to be a genetic predisposition to COPD as not all patients who are exposed to toxic gas develop COPD, although the exact mechanism isn’t clearly understood at this time. The risk of COPD is additive, meaning that the risk increases with prolonged exposure times and multiple toxin exposures.
The inflammatory process in COPD differs from asthma, with different cells activating the inflammatory process. The inflammation pathway in COPD activates hypersecretion (excess secretion) of mucus. The cilia cells are also damaged from the toxic gas exposure; consequently, they are unable to protect the lungs from foreign particles as they do when they are functioning normally. The increased mucus production combined with the decreased ability of the cilia to protect the lungs lead to a persistent cough and increased sputum production that are the characteristic symptoms of COPD. The most frequent symptoms associated with COPD include shortness of breath, cough, and increased mucus and sputum production.
The inflammatory damage and resultant decreased lung function associated with COPD are mainly irreversible, and lung function will continue to worsen over time. There are currently no treatment options available to repair and restore damaged lung tissue. The major challenge with COPD is that many patients have already suffered significant irreversible lung tissue damage before a diagnosis of COPD has been established. Typically, COPD is diagnosed later in life and often after many years of repeated toxic gas exposure. Although the lung damage is not able to be fully reversed, further damage can be prevented and the progression of COPD possibly slowed with removal of toxic gas exposure, including smoking cessation.
The disease process of COPD is classified using two different systems. First, the degree of airflow limitation is divided into four grades based on lung function determined by spirometry, discussed in Chapter 18. The four grades are Gold 1, 2, 3, and 4, with the higher numbers correlating with more limited airflow (Table 19-2). Second, the degree of symptom burden is divided among four different groups based on the severity of symptoms and risk of exacerbations. The four groups are A, B, C, and D (Table 19-3). The initial and follow-up treatment recommendations are based on the appropriate COPD group.
The goals of COPD therapy include the following:10
Improve exercise tolerance
Improve health status
Prevent disease progression
Prevent and treat exacerbations
Smoking cessation therapy reduces the risk of developing COPD and slows the progression of COPD. Smoking cessation should be strongly encouraged as this can slow the decline in lung function and may also improve the typical COPD symptoms of persistent cough and increased sputum production. Although smoking cessation clearly improves overall COPD outcomes, it is difficult for many patients to achieve sustained smoking cessation and it often takes numerous attempts until the patient is successful. By the time of COPD diagnosis, many patients have smoked most of their lives, increasing the difficulty of smoking cessation. (For additional information about smoking cessation therapies, refer to Chapter 7.)
Pulmonary rehabilitation programs can decrease COPD symptoms, enabling patients to resume general activities of daily living (showering, dressing, and walking), resulting in marked improvement in their quality of life. These programs are centered on patient education and involve healthcare providers from several different specialties, including dietary, physical therapy, occupational therapy, and respiratory. Pulmonary rehabilitation programs involve close patient follow up with the healthcare team as they work toward improving their overall health status through guided exercise programs, special breathing techniques, and nutritional education.
Chronic oxygen therapy is recommended to increase the survival of COPD patients suffering from severe hypoxemia (low oxygen level) at rest, and as a quality-of-life improvement mechanism. A reduction in mortality (death) has been proven with continuous oxygen therapy for at least 15 hours per day compared to those not receiving oxygen therapy. It is important that all patients receiving oxygen therapy are instructed on the dangers associated with smoking and concurrent oxygen use.
There are no medications currently available that have been shown to decrease the progressive lung function decline associated with COPD. Instead, the goal of COPD pharmacotherapy is to reduce symptoms and exacerbations in an effort to improve overall health and thereby improve quality of life.; The Global Initiative for Chronic Obstructive Lung Disease provides guidelines for management based on the severity of disease, with medication therapy added in a step-wise approach based on patient response to therapy.10 This step-wise approach to therapy is similar to that for asthma. Proper inhaler technique may be difficult for some patients with COPD, considering many are elderly and this may have an impact on medication choice. See Medication Table 19-2.
Bronchodilator therapy is the primary treatment for COPD patients. As discussed earlier in the section on pharmacotherapy for asthma, bronchodilator therapy relieves bronchoconstriction by relaxation of the smooth muscles of the lung airways and provides symptomatic COPD relief. The three bronchodilator therapies that may be utilized in COPD are anticholinergics, beta2 agonists, and theophylline. No bronchodilator has been proven to be better than the others in the treatment of COPD.11 The choice of specific bronchodilator therapy is made based on airflow limitation, symptom burden, exacerbation risk, individual patient response to treatment, and patient-specific factors. Bronchodilator medications are available in short-acting and long-acting preparations and may be administered on an as-needed basis for immediate relief of symptoms or prescribed as routine therapy to prevent and reduce symptoms. Short-acting bronchodilators are preferred for as-needed therapy and are not recommended for use on a routine basis. Long-acting bronchodilators are recommended for use on a routine basis for the prevention and reduction of symptoms. Again, the exact medication regimen should be based on COPD severity and patient-specific factors.
The parasympathetic part of the autonomic nervous system (PANS) has many actions, including bronchoconstriction and increased secretions. Agents that interfere with acetylcholine, the primary neurotransmitter of the PANS, are referred to as anticholinergics, and they oppose PANS actions. Because of these effects (opposing bronchoconstriction and secretions), anticholinergics, especially of the antimuscarinic category (see Chapter 4) are indicated in the treatment of COPD symptoms. Anticholinergic medication is available in short-acting (SAMA—short-acting antimuscarinic) and long-acting (LAMA) preparations. Anticholinergic medications are generally well tolerated, with the most common side effects reported associated with upper respiratory tract infections, palpitations, dry mouth, metallic taste, and throat irritation.
Ipratropium is available as an inhaler and nebulizer solution in two preparations: ipratropium alone and as a combination with the beta2 agonist albuterol. Ipratropium is a short-acting bronchodilator with a duration of about 4–6 hours and an onset of effect of approximately 15–20 minutes. Ipratropium may be used for symptomatic relief on an as-needed basis, but SABAs may be preferred due to a faster onset (approximately 5 minutes). The combination of ipratropium and albuterol has been shown to increase bronchodilation more than either medication given alone.11 Ipratropium inhalation therapy is typically dosed as one to two inhalations four times a day, with a maximum of 12 inhalations in 24 hours. Nebulizer therapy may be given as one vial three to four times a day, with doses 6–8 hours apart.
There are several different LAMAs available, including tiotropium, umeclidinium, aclidinium, and glycopyrronium bromide. These medications are available in various formulations; either as singular agents or in combination with a LABA and/or ICS. LAMAs have been proven to reduce COPD exacerbations and improve patient response to pulmonary rehabilitation.11 LAMAs have a greater impact on reducing exacerbations compared to LABAs. Combination therapy with a LABA and a LAMA is a common regimen due to the reduction in exacerbations compared to either given alone. Such combinations are administered once or twice daily due to their long duration of action. Due to the prolonged duration of action and delayed onset of effect compared to SAMAs, these medications are not used as needed for immediate relief of COPD symptoms. LAMAs are indicated for daily administration to prevent and reduce symptoms.
The effects of beta2 agonists are the same as were discussed previously in the section on asthma pharmacotherapy. SABAs are an appropriate treatment for as-needed relief of acute exacerbations due to the fast onset of their bronchodilator effects (approximately 5 minutes). They can be used on a routine basis, but the short duration of action of SABAs and frequent dosing inhibits their usefulness as a daily therapy to decrease symptoms. As discussed earlier, the combination of ipratropium and albuterol has been found to result in better bronchodilation. The inhalation preparation of SABA is preferred over oral and parenteral forms—although all preparations have equivalent efficacy, the specificity of inhalation preparation to the lungs results in decreased side effects.
The available LABA preparations include salmeterol, formoterol, arformoterol, olodaterol, indacaterol, and vilanterol. These medications are available in various formulations, either as singular agents or in combination with a LAMA and/or ICS. The onset of action for LABAs is approximately 15–20 minutes, except for formoterol, which has an onset of 5 minutes. LABAs are appropriate for the prevention and reduction of COPD symptoms and are conveniently administered once or twice daily due to their long duration of action.
How would the medications prescribed for Joe be expected to improve his COPD?
Theophylline has shown modest bronchodilator effects for stable COPD patients.10 The effect on exacerbation rates is not well known at this time due to limited data. Theophylline therapy is associated with a wide variety of side effects and possible toxicity, including arrhythmias (irregular heartbeat) and seizures. Due to the limited effectiveness and side effects associated with therapy, theophylline is not routinely recommended for the management of COPD.
Phosphodiesterase-4 Enzyme Inhibitor
Roflumilast belongs to a class of drugs, the phosphodiesterase-4 enzyme inhibitors, which regulate inflammatory mediators in a variety of conditions. Roflumilast is the only one in this group used to treat COPD (as of this writing), and can reduce the risk of exacerbations in a small population of patients with COPD. It is reserved for patients with severe to very severe COPD, who have chronic bronchitis with a history of exacerbations requiring oral glucocorticoid therapy (discussed in the next section). It increases lung tissue levels of cyclic adenosine monophosphate (cAMP), a chemical that acts as a messenger in many cellular processes and reduces the numbers of some cells in the lung fluids. It is administered as an oral tablet on a routine (preventive) basis and is not useful as an as-needed bronchodilator for sudden breathing problems. The most common adverse reactions are diarrhea, decreased appetite, nausea, weight loss, headache, and insomnia. The adverse effects generally lessen over time. Though rarely, roflumilast can cause neuropsychiatric events and should be used with caution in patients experiencing depression or suicidal thoughts.
The routine use of inhaled corticosteroids (ICS) is not recommended for the management of COPD, except under certain circumstances. ICS monotherapy has not been shown to have long-term effects on the decline of lung function or mortality of patients with COPD. However, in combination with long-acting bronchodilators, they are more effective at improving lung function and reducing exacerbations compared to either medication alone. Patients with COPD who have an extensive exacerbation history may exhibit a greater benefit from ICS compared to patients who do not have frequent or severe exacerbations. A reduction in acute exacerbations can lead to an improved overall health status.10
Treatment with oral glucocorticoids is reserved for the management of acute exacerbations. As discussed in the section on asthma, glucocorticoids act on specific receptors throughout the body to reduce inflammation. There is an extensive list of long-term side effects of glucocorticoids, including bone weakening, easy bruising, increased risk of infections, and increased blood sugar. When used short term for the treatment of an exacerbation, systemic glucocorticoids have been shown to lessen the rate of treatment failure and rate of relapse, and to improve lung function and breathlessness. Prednisone is commonly used, and the recommended dose is 40 mg once daily for 5 days. Ultimately, when used for acute exacerbation, systemic glucocorticoids shorten recovery time and improve lung function in patients with COPD.
Preventive Immunization Therapy
Common and normally mild respiratory infections, such as the flu or pneumonia, can have serious and sometimes deadly consequences in patients with COPD. These patients already have reduced lung function and any infection that further reduces it could have deadly consequences. Preventive measures should be undertaken to ensure that the risk of infection is as low as possible. Patients with COPD should be advised to get the inactivated influenza vaccine (flu shot) every year. The pneumococcal vaccination (pneumonia vaccine) is normally one dose, but a second dose of the vaccination may be given 5 years after the first vaccination in some patient populations.11
Should the pharmacy technician inquire about the lack of refill of the salmeterol? Why might Joe not have his salmeterol prescription refilled?
Peter Jacobs is the father of a 10-year-old boy with cystic fibrosis. He has come into the pharmacy to get some cough syrup for his son’s terrible hacking cough.
Cystic fibrosis (CF) is an inherited chronic disease caused by a gene mutation. This gene mutation causes an alteration in the normal secretion and absorption of chloride and sodium in the mucus-secreting exocrine glands. The result of the altered sodium and chloride levels is a change in the consistency of the normal mucus secretion. The mucus secretions are abnormally thickened and sticky, making them difficult to clear, allowing the mucus to cover and clog several organ systems. The most notable effects of the thickened mucus are on the lungs and pancreas.
Pulmonary disease is considered the hallmark of CF; all patients with CF have concurrent pulmonary disease. The lungs normally have a thin layer of mucus that protects the lungs from foreign particles, but in CF this layer is thick and sticky. The thick mucus not only clogs the lungs, making it difficult to fully exchange oxygen, it also traps bacteria and foreign particles in the lungs, leading to chronic respiratory infections and continual inflammation. The result of the mucus on the lungs is damage and progressive decrease in lung function followed by respiratory failure.
Pancreatic enzyme deficiency is also a common difficulty in patients with CF. The thick mucus plugs the pancreatic ducts and blocks the release of pancreatic enzymes into the intestine. The pancreatic enzymes are needed for the digestion of fat and protein and the absorption of vitamins A, D, E, and K (fat-soluble vitamins). Without these pancreatic enzymes, malnutrition will occur. The signs and symptoms of decreased pancreatic enzymes are abdominal distension; foul-smelling, loose bowel movement; flatulence; and malnourishment. CF patients must replace the pancreatic enzymes to ensure proper nutrition and normal growth.
CF can also adversely affect other organs and organ systems in the body, causing problems with the intestines, liver, reproduction, and anemia to name a few. The effects on these systems are patient specific, whereas the issues with the lungs and pancreas are more global CF issues although the extent differs by patient. CF is a serious chronic disease that must include continual lifelong management to prevent and quickly control serious life-threatening exacerbations of the disease. The life expectancy of CF patients has steadily increased with the development of better management techniques and increased education on the importance of these techniques to reduce symptoms and improve quality of life and life expectancy.
Ensuring adequate nutrition for optimal growth and development through pancreatic enzyme replacement
Preventing lung damage and lung function decline by decreasing inflammation and aggressive infection prevention strategies, including airway clearance techniques and pharmacotherapy
Maintaining normal activities and quality of life
Patients with CF require increased caloric intake to maintain normal growth and development due to reduced nutrient absorption and increased calorie expenditures from difficulty breathing.5 The increased caloric intake recommendation may be anywhere between 110% and 200% of persons who do not have CF. All patients with CF should receive close nutritional guidance from a dietitian experienced with CF as dietary needs vary at different stages of life. For patients who are consistently underweight, nutritional supplements or enteral tube feedings may be required to maintain adequate nutrition. Adequate nutrition is essential to fight infections and maintain normal growth and development. A daily CF-specific multivitamin containing optimized doses of fat-soluble vitamins (A, D, E, and K) can ensure an adequate supply of vital nutrients.
There are specially-formulated vitamin combinations for patients with CF, including AquaADEKS, DEKAs, and others. These preparations contain primarily the fat-soluble vitamins A, D, E, and K that must be replaced to prevent malnutrition due to poor absorption. The normal dose is one tablet daily for children and two tablets daily for teenagers and adults.
Pancreatic enzyme replacement therapy (PERT) ensures proper absorption and utilization of protein, carbohydrates, and fats by the body. Pancreatic enzyme capsules contain microbeads that are covered with a protective coating. This protective coating ensures that the microbeads will reach the small intestine where they are needed for effective absorption. Consequently, the capsules must be swallowed whole or they may be opened and the microbeads swallowed, but they must not be chewed. The pancreatic enzymes must be given right before a meal or snack. The enzymes should not be mixed with hot foods as the heat will inactivate the enzymes. Pancreatic enzyme products differ in their enzyme ratios, and it is generally recommended that patients do not change products, as dosages may vary between products. Generic products are not recommended. The dose of pancreatic enzymes is highly individualized and tailored to individual patient needs. Pancreatic enzymes are generally well tolerated and are available in several formulations. All except Viokase have a protective coating but have differing amounts of lipase (for fat absorption), protease (protein absorption), and amylase (carbohydrate absorption). Examples of various pancreatic enzyme products are listed in Medication Table 19-3.
Pancreatic enzyme preparations are combinations of the enzymes lipase, protease, and amylase. Enzymes doses are expressed in USP units but differ in each formulation. Many brand names have multiple strengths, and the prescribed strength must be correctly chosen and dispensed. Dosing is commonly specified in “lipase units”—a prescription for Zenpep 25000 is for the product with lipase 25,000 USP units (but also includes protease 79,000 USP units and amylase 105,000 USP units) and cannot be interchanged with Zenpep 15000 or any of the other available pancreatic enzyme preparations.
While in the pharmacy Mr. Jacobs presents his son’s pancreatic enzymes prescription. His prescription reads Creon 24000, take three capsules with meals and two capsules with snacks. Dispense #500. You calculate that he should only need 330 (three meals, one snack per day) capsules for a 1-month supply. You change the quantity to reflect this and only dispense 330 for the month because the physician overprescribed. Is this okay?
Mechanical Clearance Techniques
Mechanical clearance techniques loosen lung mucus, allowing it to be expelled from the lungs. Removing the mucus from the lungs helps increase lung function and decreases the likelihood of infection by preventing bacteria from getting trapped within the lungs. The techniques are normally performed twice a day but may be performed up to 6 times a day during an exacerbation. The cough is an important way that a patient with CF clears the lungs; therefore, cough suppressants should never be recommended for a patient with CF.
Postural drainage and percussion is an external vibration technique used to loosen mucus to enhance its removal from the lungs. This technique involves the patient’s chest, sides, and back being rapidly vibrated manually with rapidly alternating cupped hands. This method requires the help of another person. The vibrations loosen the mucus, allowing it to be expelled through a forced cough. A similar technique involves the use of an inflatable vest that provides external mechanical vibration to the chest and back to help free the mucus for removal through a cough. The advantage of the inflatable mechanical vest is that therapy can be performed by the patient without the aid of another individual. A flutter valve device is a handheld device that causes an internal airway vibration when air is blown through it. The internal vibration, similar to the external vibrations, helps to free and mobilize the mucus, allowing it to be coughed up and expelled.
What advice might the pharmacist give Mr. Jacobs about the cough syrup he wants to buy?
The goal of pharmacologic therapy is to preserve lung function through aggressive prevention techniques, with mucus removal as well as anti-inflammatory and anti-infective medications while maintaining normal growth and development.5 Exacerbations must be treated quickly and aggressively to prevent life-threatening complications. Inhalation with the use of a metered dose inhaler or a nebulizer is the preferred route of administration as the medications are delivered directly to the lungs.
A primary part of treatment for patients with CF is airway clearance therapy, and it should be started within the first few months of life. The typical medications included in airway clearance therapy are albuterol (inhaled bronchodilator), hypertonic saline (short-acting inhaled mucolytic), mannitol (short-acting inhaled mucolytic), acetylcysteine (short-acting inhaled mucolytic), and dornase alfa (inhaled mucolytic). If the patient is using a bronchodilator regularly, the bronchodilator should be inhaled first, followed by the short-acting mucolytic therapy, and lastly dornase alfa. Inhaled antibiotics and other inhaled medications such as asthma inhalers should be administered after airway clearance therapy.
Mucolytic medications help to dissolve and thin the mucus to enhance the mucus removal techniques discussed earlier. Mucolytic products are administered via inhalation to ensure the mucolytic medication reaches the lungs. Dornase alfa is targeted to break up the accumulated deoxyribonucleic acid (DNA), resulting in thinned mucus and improved airflow to the lungs. The dose of dornase alfa is 2.5 mg one or two times a day to thin mucus secretions and help increase mucus clearance from the lungs. Side effects may include a sore throat and hoarse voice.
Hypertonic saline is a 7% sodium chloride solution. When administered by a nebulizer, this concentrated salt solution “pulls” more water into the lung fluid, resulting in thinner, less viscous bronchial secretions. It is typically given two to four times a day. Side effects of this medication may include cough, chest tightness, sore throat, and sneezing. If a patient is unable to tolerate the 7% solution, a 3 or 3.5% inhaled solution may be used.
Sodium chloride is available in a 7% solution for inhalation only.
It is vital that a 7% sodium chloride solution is used for inhalation only. If it were mistakenly administered intravenously, the patient would be subject to a potentially lethal medication error. This product should be labeled clearly for inhalation only and not kept near the room where injectable dosage forms are compounded or stored.
The use of anti-inflammatory medication can result in a reduction of lung inflammation and has been found to decrease the rate of decline in lung function over time. Ibuprofen anti-inflammatory treatment involves high doses of ibuprofen that require close monitoring, including obtaining regular blood ibuprofen levels. The effects of ibuprofen therapy are seen with long-term use and as a result a patient may not notice any change in overall health status. There are few patients in the United States currently on this therapy possibly due to the required routine blood draws. The most common side effect of ibuprofen therapy is stomach upset, with possible gastrointestinal bleeding. Azithromycin has been found to have anti-inflammatory effects. It is commonly given in lower anti-infective doses (three times weekly) to reduce inflammation in the patient with CF and not for its antibiotic effects.
With time, patients with CF develop chronic lung infection that is due to the thick mucus trapping pathogens in the lungs and causing infection. The chronic lung infection proliferates and causes an acute exacerbation of symptoms. The goal of anti-infective therapy is to improve lung function and prevent respiratory failure. Antibiotics used in patients with CF are available in a variety of formulations—oral, intravenous, and inhaled—depending on the indication. Choosing the appropriate antibiotic regimen is based on sputum cultures and the antibiotic sensitivity of pathogens. Commonly, patients with CF require higher doses and longer durations of antibiotic therapy than patients without CF to adequately recover from an infection. Unfortunately, the pathogens are not entirely cleared from the airways of patients with CF, which commonly leads to resistance. The development of resistant pathogens limits the antibiotic options available to treat infections and ultimately contributes to the decline in lung function. Antibiotics used for anti-infective therapy of cystic fibrosis are discussed in detail in Chapter 27.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a new class of medications that focus on the central defect of CF, gene mutations. These medications work to keep channels open longer, causing fluid to move into the airways, thinning secretions for easier clearance. There are over 2,000 different mutations requiring different medications for different mutations. Some of the medications are effective for multiple types of mutations. Specific tests must be performed prior to patients receiving CFTR modulator therapy to identify which gene mutations they have. Currently, there are four agents available for the treatment of CF, including elexacaftor/tezacaftor/ivacaftor (Trikafta), ivacaftor (Kalydeco), lumacaftor/ivacaftor (Orkambi), and tezacaftor/ivacaftor (Symdeko). These medications should be taken with a food high in fat and pancreatic enzymes if pancreatic insufficient. Side effects may include liver dysfunction, stomach pains, diarrhea, headache, and rash. Representative pharmacologic agents used in the treatment of cystic fibrosis are included in Medication Table 19-4.
Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are all chronic lung diseases that can severely affect a patient’s life and life expectancy. Beta agonists, anticholinergics, and glucocorticoids, as well as other medication classes, are commonly used to treat these diseases. Many of these drugs are administered via inhalation with a spacer or nebulizer. Ensuring that the patient has received adequate education on the proper use and cleaning techniques of this equipment is important to assure maximum patient health benefit. Patients should be encouraged to stop smoking and keep their immunizations up to date. Proper use of both nonpharmacologic and pharmacologic interventions can significantly improve their health status and quality of life. Pharmacists and pharmacy technicians can play an important role by ensuring that patients understand and use their medications properly.
The author wishes to acknowledge and thank Christina Bell, PharmD, and Sandra B. Earle, PharmD, BCPS, authors of this chapter in the first edition of this book.
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