module 18 - pharmacotherapy for respiratory disorders

65
Geriatric Pharmacy Review Module 18: Pharmacotherapy for Respiratory Disorders

Upload: geekay79

Post on 18-Apr-2015

93 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Module 18 - Pharmacotherapy for Respiratory Disorders

Geriatric  Pharmacy  Review  

 Module  18:  Pharmacotherapy  for  Respiratory  Disorders    

Page 2: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Accreditation Information

ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This home study web activity has been assigned 1.5 credit hours.

ACPE UPN: 0203-0000-10-044-H01-P

Release Date: 12-10-2010

Expiration Date: 12-10-2013

To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the on-line assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.

Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.

Page 3: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Content Experts

Current Content Expert:

Nicole Brandt, PharmD, CGP, BCPP

Assistant Professor, Geriatric Pharmacotherapy University of Maryland School of Pharmacy &

Director Educational and Clinical Programs Lamy Center

Devra Dang, PharmD, BCPS, CDE Associate Clinical Professor University of Connecticut School of Pharmacy

Faculty Disclosure:

Nicole Brandt, PharmD, CGP, BCPP has no relevant financial relationships to disclose. Devra Dang, PharmD, BCPS, CDE has no relevant financial relationships to disclose. Tom Snader, PharmD, FASCP has no relevant financial relationships to disclose.

Legacy Content Expert:

Tom Snader, PharmD, FASCP

President TCS Pharmacy Consultants &

Clinical Associate Professor of Clinical Pharmacy USP - Philadelphia College of Pharmacy

Page 4: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Asthma in the Elderly

Learning Objectives:

By the end of this Review Concept you should be able to:

• Define asthma and its prevalence in the elderly.

• Describe the pathogenesis of asthma.

• Describe the phases of asthma attacks and their corresponding symptoms in elderly patients.

• Specify diagnostic parameters for asthma.

• List the types of drugs used to treat asthma.

• Describe the pharmacology of each drug class and the major drugs within each class.

• Recommend specific clinical guidelines and pharmacotherapy for asthma management.

• Recognize major adverse effects of asthma drug therapies in the elderly.

• Discuss important age related factors and interactions with coexisting disease therapies.

Page 5: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Introduction to Asthma

Defining Characteristics:

• Airway inflammation, leading to bronchospasms, narrowing of airways and reduced airflow • Recurrent episodes • Airflow obstruction is usually reversible • Increased airway responsiveness to a variety of stimuli

Epidemiology:

• Affects 3-6% of adults > age 70 • Asthma-related deaths are highest in elderly population • May be overlooked when other conditions are present (e.g., COPD) • Costs >$6 billion annually in the US

The aging of the respiratory system occurs at a constant rate and each individual has a unique threshold for experiencing pulmonary impairment. Once this threshold is reached, a variety of lung problems may appear. One of these problems is asthma. Asthma is a disease characterized by airway inflammation, leading to bronchospasms, narrowing of airways and reduced airflow. Episodes are recurrent, and airflow obstruction is usually reversible. Asthma may be overlooked in the elderly when other disorders such as chronic obstructive pulmonary disease are also present.

Page 6: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pathogenesis of Asthma

Pathogenesis of Asthma

• Airway inflammation is caused by the overreaction to such triggering stimuli as exercise, infections, cold, beta- blockers, chemicals, allergens and emotions

• Mechanisms of this overreaction include release of histamine by mast cells, actions of leukotrienes, platelet activating factors, and other spasmogenic and chemotactic agents

• Histamine is released from mast cells when an allergen or other antigen bridges molecules of IgE attaches to the cell surface

• Asthmatics are extremely sensitive to histamine acting on the H1 receptors

• Incomplete reversibility of obstruction occurs in the elderly due to chronic, severe asthma and aging factors such as smooth muscle hypertrophy and fibrosis

The airway inflammation characteristic of asthma is caused by an overreaction to such triggering stimuli as exercise, infections, cold, beta-blockers, chemicals, allergens and emotions. A common trigger for acute attacks in the elderly is respiratory infection by rhinovirus. While sensitivity to some inhaled allergens is less prevalent in seniors, age-related changes in the lung may help to increase the severity of attacks. Understanding this age-related difference can help avoid over-diagnosis and the premature treatment of asthma-like conditions with inappropriate medications.

Page 7: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Phases of Asthma

Graphic Diagram Of Early And Late Phases Of Asthma (Including Some Medication Classes)

Page 8: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Phases of Asthma

Many asthmatics display two phases during their attacks: an early or initial onset phase and a delayed or late onset phase. The early phase symptoms include coughing, tightness in the chest, dyspnea and wheezing due to bronchospasms.

Early phase symptoms can be reversed with beta agonists. The late phase symptoms include the early symptoms plus excessive mucous secretion, edema, fatigue and vasodilation effects. Late phase symptoms may be resolved with corticosteriods; however, bronchodilators do not work for late phase symptoms. Cromolyn sodium blocks both early and late phase symptoms.

Page 9: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Classification of Asthma

Step 1 – Mild Intermittent

Step 2 – Mild Persistent

Step 3 – Moderate Persistent

Step 4 – Severe Persistent

Pulmonary Function Tests Used to Classify Asthma:

• FEV1: Forced Expiratory Volume in 1 second (liters) • PEF: AM/PM variation in Peak Expiratory Flow (liters per minute) • FVC: Ratio of FEV1 to Forced Vital Capacity(FEV1: FVC)

While the signs and symptoms of asthma attacks may vary from one individual to the next, the four step classification scheme shown on your screen integrates pulmonary function tests to help match the severity of an attack to the suggested treatment guidelines. Parameters commonly used include the forced expiratory volume in one second or F-E-V-1, and the variation between late afternoon and early morning measurements of the peak expiratory flow or P-E-F. The ratio of FEV1 to forced vital capacity or F-V-C also indicates an asthmatic condition if less than seventy percent. For older patients, the limit for this ratio is lower than for younger patients.

While these pulmonary function tests are useful, the frailty of the elderly patient and limitations of the care setting may make such tests impractical to implement. The use of subjective and objective information on functional level, comfort level, exercise tolerance and Activities of Daily Living (ADLs) may provide the only guidance available.

Page 10: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Diagnostic Parameters for Asthma

Diagnostic Parameters for Asthma

Step 1 Parameters:

• Day Symptoms:< 2 x week • Night Symptoms:< 2 x month • Effects: brief - a few hours to few days, with normal lung function between attacks • FEV1:> 80% of predicted amount • PEF variability:< 20%

Step 2 Parameters:

• Day Symptoms:> 2 x week, 1 x day • Night Symptoms:> 2 x month • Effects: may change activities and sleep • FEV1:at least 80% of predicted amount • PEF variability:20 – 30%

Step 3 Parameters:

• Day Symptoms: daily • Night Symptoms:> 1 x week • Effects: will change activities and sleep • FEV1:60 – 80% • PEF variability:> 30%

Page 11: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Diagnostic Parameters for Asthma

Step 4 Parameters:

• Day Symptoms: continuous • Night Symptoms: continuous • Effects: limits all physical activities and sleep • FEV1:< 60% of predicted value • PEF variability:> 30%

Diagnostic parameters for each step are shown here. Many elderly asthmatics have reduced lung function and long histories of asthma. For those patients with other health problems, a correct diagnosis is important. Upon testing, if F-E-V-1 improves more than twelve percent after proper use of an inhaled bronchodilator, asthma is a likely diagnosis. Even intermittent attacks can be life threatening and require a visit to the emergency room. A simple and easy-to-follow treatment plan must be developed for each patient in order to avoid possible emergency situations.

Page 12: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differential Diagnosis of Asthma

Source: Adapted from NAEPD Working Group Report (Considerations for diagnosing and managing asthma in the elderly: NAEPD Working Group Report. Washington, DC: Nation Institutes of Health/National Heart, Lung, and Blood Institute; 1996. US Department of Health and Human Services publication NIH 95-3675).

CHARACTERISTIC ASTHMA COPD

History    

Episodic  wheeze   Common   Less  common;  may  occur  with  exacerba9ons  

Nocturnal  dyspnea  or  cough   Common   Not  common  

Cough  with  phlegm   Present  in  >40%  of  cases;  common  in  those  who  smoke  

Characteris9c  of  chronic  bronchi9s  

Other  allergic  symptoms  (rhini9s,  conjunc9vi9s)  

Frequent   Infrequent  

Smoking   Less  common   Almost  always  associated  

Past  history  of  asthma   Common   Uncommon  

Family  history  of  allergy   Frequent   Less  frequent  

Page 13: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differential Diagnosis of Asthma

Source: Adapted from NAEPD Working Group Report (Considerations for diagnosing and managing asthma in the elderly: NAEPD Working Group Report. Washington, DC: Nation Institutes of Health/National Heart, Lung, and Blood Institute; 1996. US Department of Health and Human Services publication NIH 95-3675).

CHARACTERISTIC   ASTHMA   COPD  

Physical  Examina;on    

Wheeze   Common   Common  aQer  forced  expira9on  or  cough  

Laboratory  Findings    

Pulmonary  func9on   Similar  to  COPD   Similar  to  asthma  

Chest  X-­‐ray   OQen  normal;  may  show  hyperinfla9on  

Vessels,  focal  hyperaera9on  (emphysema)  Markings  (chronic  bronchi9s)  

Eosinophilia   More  common   Less  common  

Posi9ve  skin  tests   More  common   Less  common  

Response  to  Therapy    

FEV1  response  to  beta2-­‐antagonist   FEV1  with  symptom  relief   LiZle/no  change  in  FEV1  with  poor  symptom  relief  

Page 14: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differential Diagnosis of Asthma

Once related symptoms of heart disease, cancer, pneumonia and other conditions have been ruled out, it is important to differentiate asthma from otherobstructive pulmonary diseases. This chart illustrates the key differences between asthma and underlying C-O-P-D.

Page 15: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Asthma Therapeutic Agents

Quick Relief Medications:

• Short-acting inhaled ß-2 agonists • Inhaled anticholinergics • Oral corticosteroids-“short course bursts”

Long-Term Controllers:

• Inhaled and oral corticosteroids • Cromolyn sodium, nedocromil • Methylxanthines • Long-acting ß-2 agonists • Leukotriene modifiers

Once a diagnosis of asthma has been confirmed, appropriatepharmacological treatment may be initiated. The main types of drugs used to treat asthma include bronchodilators, anti-inflammatory drugs, anti-allergy drugs and theleukotriene modifiers, the latter of which are also indicated as anti-allergy medications. These agents may be further differentiated based on whether they provide short-term or long-term therapeutic benefits. Because many older adults are being treated for concurrent health conditions, the risk of adverse drug interactions is increased for the elderly asthmatic. Close attention to drug dosing and control of symptoms is essential for the long-term management of asthma in the geriatric population. Because of their general frailty and health status, many elderly will require the use of a spacer with metered dose inhalants. The use of both M-D-Is and nebulizers by elderly patients should be closely monitored by health care personnel.

Page 16: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Quick Relief Medications: Short-Acting Inhaled b-Agonists, Non Selective

Quick Relief Medications:Short-Acting Inhaled b-Agonists, Non Selective

Epinephrine (Bronkaid Mist®, Primatene):

• Mechanism of Action:works non-selectively to produce bronchodilation by increasing cAMP production, leading to smooth muscle relaxation in airway • Duration:0.5 – 2 hours

Isoproterenol (Aerolone®):

• Mechanism of Action:works like epinephrine but with fewer cardiovascular effects • Duration:0.5 – 2 hours

For most patients, short-acting beta 2 agonists are most effective in providing quick relief from the symptoms of asthma. In general, inhaled beta 2 agonists are preferred over oral forms because they produce fewer systemic side effects.

Epinephrine works non-selectively to produce bronchodilation by increasing cyclic A-M-P production leading to smooth muscle relaxation in the airways. Epinephrine has a rapid onset and short duration of action after parenteral administration. It is not effective when given orally. Caution must be used since its non-selective actions include alpha and beta 1 effects. Like epinephrine, isoproterenol has the beta 1 effect of increasing heart rate, but with fewer adverse cardiovascular effects. It is still considered second line therapy.

Page 17: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Quick Relief Medications: Short-Acting Inhaled b-Agonists, Beta-2 Selective

Mechanism of Action (all):

• Increases cAMP but acts more selectively to produce bronchodilation effects

• Still has beta-1 activity, but not as much as non-selective agents

Albuterol (Proventil®):

• Inhaler:2 puffs (90 mcg/puff), q 15 minutes prior to exercise • Nebulizer:1.25 – 5 mg (0.5%) in 2 – 3cc of saline q4 – 8h • Syrup:2 mg/mL • Duration:4 – 8 hours

Bitolterol (Tornalate®):

• Inhaler:2 puffs (370 mcg/puff), tid – qid prn • Nebulizer:0.5 – 3.5 mg (0.2%) in 2 – 3cc of saline q4 – 8h • Duration:4 – 8 hours

Terbutaline (Brethaire®):

• Inhaler:2 puffs (200 mcg/puff) tid – qid prn • Duration:4 – 8 hours

Levalbuterol (Xopenex®):

• (R)-isomer of the racemic albuterol • Requires lower doses and has less

cardiovascular and CNS adverse effects when compared to albuterol

• Currently only available in a nebulizer solution • Nebulizer:0.63 mg tid, every 6 – 8 hours • Inhaler: not available

Page 18: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Quick Relief Medications: Short-Acting Inhaled b-Agonists, Beta-2 Selective

Albuterol, bitolterol, and terbutaline also increase cyclic A-M-P but act more selectively to produce bronchodilation effects. Terbutaline may be given orally and subcutaneously while albuterol may also be given orally. These selective agents may cause muscle tremor, tachycardia and palpitations. Although rarely used in adults, albuterol is available in a syrup dosage form, typically as 2 mg/mL. However, you must be aware that albuterol syrup typically contains sorbitol or saccharin and should be used cautiously in patients with Diabetes. Levalbuterol is the R-isomer of albuterol and is available in a nebulizer solution. It has the advantage of having less systemic side effects when compared to other beta-agonists. Beta 2 agonists can be less effective with continuous use, due to down regulation of beta 2 receptors. If patients are using their beta agonists on a frequent basis then other therapies, depending on their level of asthma, should be added to their regimen since short acting beta 2 agonists are not indicated for long term control.

Page 19: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Quick Relief Medications: Anticholinergics and Prednisone

Ipratropium (Atrovent®):

• Mechanism of Action: Derivative of atropine that blocks the release of acetylcholine from nerves in the airways, thereby preventing constriction of the bronchioles • Onset: slower action than the beta-agonists • Inhaler: 2 – 3 puffs (18 mcg/puff), q6h • Nebulizer: 0.25 – 0.5 mg(0.025%) mg q6h

Prednisone:

• Mechanism of Action: Lipid soluble corticosteroid that inhibits phospholipases responsible for mediating the release of factors causing inflammation in acute asthma exacerbations • Administration: oral • Dosing:short course “bursts” – 40 – 60 mg/d as a single, or 2 divided doses, for 3 – 10 days

The anticholinergics used in asthma treatment are muscarinic antagonists which are effective with emotionally-triggered attacks but have little effect against allergen-induced exacerbations. Ipratropium is a derivative of atropine and acts to block release of acetylcholine from nerves in the airways, thereby preventing constriction of the bronchioles. Its use in acute asthma is controversial, but it may be effective in severe acute asthma.

Ipratropium is most effective in patients with C-O-P-D. Tiotropium, a new long acting anticholinergic, to date has not been studied to assess the efficacy in asthma.

Page 20: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Long Term Control Medications: Inhaled Corticosteroids

Mechanism of Action (all):

Inhibit phospholipases responsible for mediating the release of factors causing inflammation in asthma exacerbations

• Beclomethasone (Beclovent®, Vanceril®):2 puffs tid – qid (42 mcg/puff) D.S. 2 puffs bid (84 mcg/puff)

• Triamcinolone (Azmacort®):2 puffs tid – qid (100 mcg/puff) Max 16 puffs/day

• Flunisolide (Aerobid®):2 puffs bid (250 mcg/puff) Max 8 puffs/day

• Budesonide (Pulmicort®):1 – 2puffs bid (200 mcg/puff) • Fluticasone (Flovent®):1 – 2 puffs bid (44 mcg/puff)

Max 20 puffs/day

Note: All patients in step 2 and higher should be maintained on an inhaled corticosteroid, unless contraindicated, with short-acting ß2-agonists available for acute attacks

Inhaled corticosteroids are the cornerstone of maintenance therapy in asthma patiens. They work similar to prednisone, but have less adverse effects due to decreased systemic absorption. Agents in this class include beclomethasone, triamcinolone, flunisolide, budesonide, and fluticasone. The choice of agent depends on systemic absorption, dosing frequency, and steroid potency. These agents must be used cautiously in elderly patients with infections and other diseases. Once patients are stablized, they should be tapered down to the lowest possible steroid dose to avoid side effects. Unlike inhaled beta-agonists, inhaled corticosteroids will not give immediate relief during an acute attack. Therefore, they should be used on a daily basis along with short acting beta-agonist as needed for acute attacks. Drugs such as the leukotriene modifiers and non-steroidal anti-inflammatory agents are useful as adjuvant therapy to decrease total steroid dose.

Page 21: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Long-Term Control Medications: Cromolyn and Nedocromil

Cromolyn sodium(Crolom®, Intal®):

• Mechanism of Action: Inhibits release of chemical mediators by mast cells when stimulated Can also be used prior to exposure to prevent an attack • Typical dose:2 – 4 puffs (1 mg/puff) TID – QID

Nedocromil (Tilade®):

• Mechanism of Action: Works in a similar way Inhibits more mediators and is effective against more types of asthma • Typical dose:2 – 4 puffs (1.75 mg/puff) TID – QID

Related Medications:

Azelastine (Astelin®) Nasal spray

• Antihistamine • Typical dose:2 sprays in each nostril twice daily (137mcg/spray)

Page 22: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Long-Term Control Medications: Cromolyn and Nedocromil

A majority of the cases of asthma in the elderly involve a chronic disease state and continuous treatment. An important treatment goal is to limit the adverse effects of asthma medications. Because the cromolyn and nedocromil class of drugs have very minor contraindications, they are frequently prescribed for children.

Cromolyn sodium inhibits the release of chemical mediators by mast cells when stimulated by exercise, cold air and allergens. Cromolyn can also be used prior to exposure to the above triggers in order to prevent an attack. It is the least toxic long term treatment for asthma.

Nedocromil works in a similar way, but inhibits more mediators and is effective against more types of asthma than cromolyn. Studies showed that cromolyn may be more effective for nighttime asthma and FEV1. Like the inhaled corticosteroids, these agents do not play a role in acute attacks and patients should still use their beta-agonists during acute attacks.

Page 23: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Other Long-Term Control Medications

Long-Acting ß-2 Agonists:

• Used prophylactically to control exacerbations • SR-Albuterol (Proventil Repetabs®): 1 tablet (4 mg/tablet) q 12 h • Salmeterol (Serevent®): 2 puffs (21 mcg/puff) q12h

Oral Corticosteroids:

• Due to ADEs, only used long term if other therapies fail

Methylxanthines:

• Help to elevate cAMP and regulate adenyl cyclase activity to maintain open airways • Theophylline (Theo-Dur®): starting dose 10 mg/kg/d up to 300 mg max Usual dose is 800 mg/d

Leukotriene Modifiers:

• Leukotrienes are important proinflammatory agents and induce bronchoconstriction and mucus production in the respiratory tract through blocking the effects of leukotrienes • Zafirlukast (Accolate®): 20 mgbid • Zileuton (Zyflo®): 2 tablets (300 mg/tablet) qid, with meals and at bedtime • Montelukast (Singulair®): 10mg hs

Page 24: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Other Long-Term Control Medications

Other medications sometimes used in the long-term treatment of asthma include long-acting beta 2 agonists, corticosteroids, methylxanthines, and leukotriene modifiers. Long-acting beta 2 agonists such as sustained-release albuterol, salmeterol, bitolterol and terbutaline are used prophylactically in order to treat and prevent exacerbations. Because of the adverse effects of corticosteroids such as prednisone, long-term therapy is contraindicated in the elderly unless other therapies fail. Methylxanthines, such as theophylline, help to elevate cyclic AMP and regulate adenyl cyclase activity to maintain open airways, but they have a narrow therapeutic index and are not recommended first line. However, they may have added benefit in treatment of nocturnal asthma.

Leukotriene modifiers include selective leukotriene D4 receptor antagonists such as zafirlukast and montelukast, as well as zilueton, a 5-lipoxygenase inhibitor, which inhibits leukotriene formation. These newer agents attempt to prevent the actions of chemical modifiers on tissues affecting the airways. Leukotriene modifiers have proven benefit in exercise-induced asthma and have also been proven to decrease asthma exacerbations, decrease the need for rescue therapy, and to allow decreased doses of inhaled corticosteroids.

Page 25: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Asthma Treatment Guidelines

Step 1 Treatment:

• Quick relief using short-acting, inhaled ß-2 agonists prn • If used more than 2x week, new diagnostic assessment, including long term control therapy, is recommended • Short acting inhaled beta 2 agonist or cromolyn before exercise or exposure to antigen

Step 2 Treatment:

• Quick relief using short-acting, inhaled b-2 agonists prn (not to exceed 3 – 4 times/day) • Long-term control using one of the following daily:

- Low dose inhaled corticosteroid, cromolyn or nedocromil - Leukotriene modifiers if compatible - SR theophylline if other agents are not tolerated

Step 3 Treatment:

• Quick relief using short-acting, inhaled b-2 agonists prn (not to exceed 3 – 4 times/day) • Long-term control to reduce number/severity of exacerbations, using daily doses of either:

- Medium dose inhaled corticosteroid - Low to medium dose corticosteroid and a choice of long-acting b-2 agonists (especially for nocturnal

symptoms) or SR theophylline

• Only if needed: Medium to high-dose inhaled corticosteroid and choice of long-acting b-2 agonists or SR theophylline

Page 26: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Asthma Treatment Guidelines

Step 4 Treatment:

• Quick relief using short-acting, inhaled b-2 agonists prn (up to 3 – 4 times a day) • Long term control to manage symptoms includes all of the following on a daily basis:

•  High dose inhaled corticosteroid and •  Long acting b-2 agonists (inhaled or as tablets) or sustained release theophylline and •  Oral corticosteroid as tablets or liquid

Guidelines for a stepwise approach to asthma treatment stress the use of anti-inflammatory agents as first line therapy and the development of an action plan. While the importance of avoiding asthma triggers cannot be overemphasized, the success of the treatment plan may ultimately depend upon patient education and the clinician-patient partnership. Once the basic facts about asthma, emergency procedures and medications are taught, specific inhaler techniques and self -management issues help elderly patients avoid major problems.

Page 27: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management Priorities for the Elderly Patient with Asthma

Management Priorities for the Elderly Patient with Asthma

Balance treatments with quality of life and the ability to live independently Obtain proper dosage to avoid under medicating and triggering acute exacerbations Watchpotential for adverse effects or for interactions with other drugs Consider preventive measures such as getting influenza and pneumococcal vaccines

Traditionally, there have been two approaches to gaining control of asthma. The first is to start with high doses and step down to amounts needed. The second is to gradually step up doses to find optimum treatment levels. In elderly patients, higher initial dosages may be contraindicated and even life threatening. The step up approach can provide a safer plan while the initial choice of alternative medications may be the most important decision for older asthmatics. Examples include using cromolyn and nedocromil for long-term control regimens.

Page 28: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Effects Associated with Asthma Medications

ADEs Associated with ß-2 Agonists:

• Muscle and nerve tremor • Myocardial ischemia • Complex ventricular arrhythmias • Hypo or hypertension • Hypokalemia related heart and muscle effects • Overuse leading to airway hyperresponsiveness

ADEs Associated with Theophylline: •  • Insomnia and nervousness • Cardiac arrhythmias • Seizures and organic brain syndromes • Nausea, vomiting and GERD effects • Toxicity with hepatic disease

ADEs Associated with Other Asthma Medications: •  • Inhaled corticosteroids such as triamcinolone may cause oropharyngeal candidiasis (thrush) • Systemic steroids can lead to depression, peptic ulcers, high blood pressure, cataracts, osteoporosis, and metabolic effects • Leukotriene modifiers can cause hepatotoxicity and Churg-Strauss syndrome • Ipratropium causes mucosal dryness

Page 29: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Effects Associated with Asthma Medications

One of the most important management priorities for the elderly asthma patient is the limitation of adverse effects of asthma medications. Some of these effects can be avoided with simple precautions. For example, patients on steroid inhalers should rinse their mouth and expectorate following use.

Other adverse effects can be a source of great concern, especially when used at higher and more frequent doses. Although rare, the leukotriene modifiers have been associated with Churg-Strauss syndrome. Some researchers believe it is caused by the reduction in inhaled steroid dose.

However, a case has been reported in a patient who wasn’t taking any steroids. While cromolyn and nedocromil have very minor adverse drug effects, many of the other long term treatments have unwanted and potentially dangerous effects.

Page 30: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Drug Interactions Associated with Asthma Medications

Drug Interactions Associated with Asthma Medications

• Cardiac drugs, particularly beta adrenergic blockers such as propranolol can cause acute bronchospasms and reduce effectiveness of other asthma medications • Aspirin may increase airway obstruction • ACE inhibitors can produce chronic coughs which reduce asthma medication effects • Cholinergic agents and nonsteroidal anti-inflammatory drugs can be a cause of bronchospasms

Many elderly asthmatics are also being treated for other health problems and risk a variety of adverse drug interactions. A good example is the use of eye drops containing beta blockers. In asthmatics, these eye drops could lead to fatal bronchoconstriction. A complete assessment of all medications should be part of the individualized treatment plan.

Page 31: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources For additional information, see:

Anderson C. J. & Bardana E.J. Jr. Asthma in the elderly: the importance of patient education. Comprehensive Ther 1996:22(6): 375-83.

Braman SS. Asthma in the Elderly.Clin Geriatr Med 2003: 19:57-75.

Connolly, M. J.Aging, late-onset asthma and the beta-adrenoceptor. Pharmacology & Therapeutics 1993; 60(3): 389-404.

Lackner, T. E. . Theophylline dose determinations in geriatric patients: pharmacokinetic considerations. Consult Pharm 1994; 9: 78-82.

O'Brien-Ladner, A.Asthma: new insights in the management of older adults. Geriatrics 1994.; 49(11): 20-5, 30-2.

Quadrelli SA, Roncoroni A. Features of Asthma in the Elderly. Journal of Asthma 2001;38(5):377-89.

Renwick DS, Conolly MJ. Improving Outcomes in Elderly Patients with Asthma. Drugs & Aging 1999;14(1):1-9.

Sherman, C. B. Late-onset asthma: making the diagnosis, choosing drug therapy. Geriatrics 1995; 50(12): 24-33.

Tockman, M. S.Aging of the respiratory system, in Principles of Geriatric Medicine and Gerontology, Hazzard, W.R. et al. eds. Third edition. 1994, chapter 48: 555-64. Serevent FDA Prescribing Letter: http://www.fda.gov/medwatch/SAFETY/2003/serevent.htm

Page 32: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Chronic Obstructive Pulmonary Disease

Learning Objectives:

By the end of this Review Concept you should be able to:

• State the definition and risk factors for diseases comprising COPD.

• Describe the clinical features of COPD.

• Outline current therapy options.

• Discuss the recommended pharmacotherapy and specific drug usage.

• Evaluate medication dosages for expected outcomes.

• Recognize changes in therapy as COPD symptoms become more severe.

• Discuss therapy implications for the elderly.

Page 33: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Introduction to COPD

Defining Characteristics:

• Chronic, progressive airway obstruction • Caused by chronic bronchitis, emphysema, or combination thereof • Chronic bronchitis (“blue bloater”): cough and increased sputum present for at least 3 months of the year for 2 consecutive years • Emphysema (“pink puffer”): permanent and abnormal enlargement of the airspace distal to terminal bronchioles and destructive changes of the alveolar walls without fibrosis

Epidemiology:

• Affects more than 5 million adults > age 55 • Accounts for 13% of hospitalizations • Health care costs >$5 billion • 4th leading cause of death in US • Over 95% of deaths are in adults > age 55

Chronic obstructive pulmonary disease (C-O-P-D) is defined as persistent limitation in expiratory airflow that is not significantly reversible with the use of bronchodilators. This family of chronic obstructive pulomnary diseases includes emphysema and chronic bronchitis. Most patients have a combination of both of these conditions. C-O-P-D has long been associated with the elderly and the effects of smoking. Chronic obstructive pulmonary disease is the fourth leading cause of death in the United States, and ninety-five percent of C-O-P-D related deaths are in individuals over the age of fifty-five. The progressive nature of the disease can force many lifestyle changes on older adults, and the frequency of exacerbations can have a devastating effect on their quality of life.

Page 34: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differentiating COPD and Asthma

“Adapted from NAEPD Working Group Report (Considerations for diagnosing and managing asthma in the elderly: NAEPD Working Group Report. Washington, DC: Nation Institutes of Health/National Heart, Lung, and Blood Institute; 1996. US Department of Health and Human Services publication NIH 95-3675).”

CHARACTERISTIC    ASTHMA   COPD  

History  

Episodic  wheeze   Common   Less  common;  may  occur  with  exacerba9ons  

Cough  with  phlegm   Present  in  >40%  of  cases;  common  in  those  who  smoke  

Characteris9c  of  chronic  bronchi9s  

Other  allergic  symptoms  (rhini9s,  conjunc9vi9s)  

Frequent   Infrequent  

Smoking   Less  common   Almost  always  associated  

Past  history  of  asthma     Common   Uncommon  

Family  history  of  allergy     Frequent   Less  Frequent  

Physical  Examina;on  

Wheeze   Common   Common  aQer  forced  expira9on  or  cough  

Page 35: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differentiating COPD and Asthma

“Adapted from NAEPD Working Group Report (Considerations for diagnosing and managing asthma in the elderly: NAEPD Working Group Report. Washington, DC: Nation Institutes of Health/National Heart, Lung, and Blood Institute; 1996. US Department of Health and Human Services publication NIH 95-3675).”

CHARACTERISTIC    ASTHMA   COPD  

Laboratory  Findings  

Pulmonary  func9on   Similar  to  COPD   Similar  to  asthma  

Chest  X-­‐ray   OQen  normal;  may  show  hyperinfla9on    

Vessels,  focal  hyperaera9on  (emphysema)  

Markings  (chronic  bronchi9s)  Eosinophilia   More  common   Less  common  

Posi9ve  skin  tests   More  common   Less  common  

Response  to  Therapy  

FEV1  response  to  beta2-­‐antagonist  

FEV1  with  symptom  relief     LiZle/no  change  in  FEV1  with  poor  symptom  relief  

Page 36: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Differentiating COPD and Asthma

The symptoms of chronic obstructive pulmonary disease are very similar to asthma. Like asthma, chronic obstructive pulmonary disease presents with bronchospasms and hyperresponsiveness of the airways. However, these reactions are mainly due to a cholinergic reflex by vagus stimulation of irritant receptors. Other differences between these two respiratory conditions are shown on your screen.

Emphysema is primarily a result of the abnormal and permanent enlargement of the air spaces distal to the terminal bronchioles with destructive changes in their walls. Chronic bronchitis is associated with airway fibrosis, mucous gland enlargement, excessive secretions, and mucosal inflammation with edema. It is important to remember that while asthma is a reversible condition, chronic obstructive pulomnary disease is irreversible.

There are some reversible components to COPD. According to reference below a 2004 article in Chronic Obstructive Pulmonary Disease Pharmacotherapy, these components may include reversing the accumulation of inflammatory cells, mucus, and plasma exudates in bronchi.

Page 37: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Major Risk Factors Associated with COPD

Major Risk Factors Associated with COPD

• Smoking directly linked to 80-90% of patients with COPD • Passive or second hand smoking • Ambient air pollution and local environmental and workplace factors • Hyperresponsive airways • Gender (males > females) • Race (Caucasians more susceptible) • Deficiency in alpha -1-antitrypsin ( < 1%, usually associated with emphysema)

Risk factors for chronic obstructive pulmonary disease focus on the long-term smoking habits of the elderly as well as exposure to environmental pollution and workplace irritants. A typical medical history reveals a smoking pattern of twenty cigarettes each day for twenty years.

Since 1968, there has been a progressive increase in the age-adjusted death rate for C-O-P-D, with the number of women being diagnosed with COPD increasing dramatically. While the disease itself has no cure, some respiratory parameters may be reversible to the extent of restoring a measure of lifestyle important to the patient. Many patients also relate their quality of life to the frequency of C-O-P-D episodes. It is in this area that the geriatric pharmacist can have the greatest impact.

Page 38: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Features of COPD

Progression:

• Presents as acute chest illness or untreatable cough in the 5th decade of life • Shortness of breath evident by the 6th or 7th decade of life

Common Signs & Symptoms:

• Weakness • Fatigue • Wheezing • Dyspnea, particularly on excertion

Lab Findings:

• Chest x-ray shows vessels, focal hyperaeration (emphysema) or markings (chronic bronchitis) • Eosinophilia (less common)

Stages:

Stage 0: At Risk: Chronic symptoms, Exposures to riskf actors, normal spirometry Stage 1 –Mild: FEV1/FVC<70%,FEV1>80%, With or withoutsymptoms Stage 2 – Moderate: FEV1/FVC<70%, 50%>FEV1<80%, With or without symptoms Stage 3 – Severe:FEV1/FVC<70%, 30%>FEV1<50% With or withoutsymptoms Stage 4 – Very Severe:FEV1/FVC<70%, FEV1<30% or presence ofchronic respiratory failure or right heart failure

Page 39: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Features of COPD

Clinically, chronic obstructive pulmonary disease is defned as chronic, productive cough for three months in two successive years when other causes for the cough are medically excluded. Progressive weakness and fatigue are also common. Many of the clinical signs and symptoms of chronic obstructive pulmonary disease can be associated with other disease states.

For example, wheezing and dyspnea are also symptomatic of asthma. It is important to rule out asthma, lung cancer, pneumonia and other infections, cardiac and blood pressure problems, and other conditions in order to focus on a treatment plan for C-O-P-D.

The recently updated stages of C-O-P-D are based on FEV-1 values, which indicate a much more severe disease when compared to asthma. FEV1 is the forced expiratory volume after 1 second. The stages of COPD were defined by the Global Initiative for Chronic Lung Disease or GOLD.

Page 40: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Therapeutic Options for COPD

• Eliminate smoking and/or reduce exposure to pollutants, irritants • Use preventive measures such as the pneumococcal and influenza vaccines • Administer:

• Beta-2agonists with careful dosing • Theophylline with careful dosing • Anticholinergics such as ipratropium, tiotropium • Corticosteroids in some cases • Oxygen (18 hrs/day, < 3 liters/min) • Antibiotics as needed

Treatment plans for chronic obstructive pulmonary disease are based upon the severity and frequency of symptoms, and must integrate oxygen use, physical therapies, and other adjunct therapy as necessary. Once the patient has stopped smoking and preventative measures are taken, individualized pharmacotherapy may be more effective. A stepwise approach to therapy is optimal. Although resting pulse oximetry may be over ninety percent, dramatic decreases may follow a minimal amount of exercise.

For this reason, at least eighteen hours a day of continuous oxygen therapy at less than three liters per minute is standard for chronic C-O-P-D patients. Only smoking cessation and long term oxygen therapy have been shown to improve survival while drug therapy will only improve symptoms.

Page 41: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild COPD and Variable Symptoms with Beta-2 agonists

• Albuterol (Proventil®): • 1 – 2 puffs every 2 – 6 h, up to 8 – 12 puffs in 24 h • Onset of action is 5 minutes

• Terbutaline (Brethaire®): • 1 – 2 puffs every 6 –8 h

• Bitolteral (Tornalate®): • 2 puffs every 8 h, max of 2 puffs every 4 hours

• Pirbuterol (Maxair®): • 1 – 2 puffs every 6-8 h, max of 12 puffs in 24 hours

For mild chronic obstructive pulmonary disease with variable symptoms, short acting selective beta-2 agonists such as albuterol may be used. The dosage is one to two puffs every two to six hours up to a maximum of eight to twelve puffs in twenty-four hours. Beta agonists have been associated with muscle and nerve tremors, myocardial ischemia, and arrhythmias.

Page 42: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD– Step 1

Ipratropium (Atrovent®):

• 3 – 6 puffs qid; max 16 puffs/day • Onset of action is 15 minutes • Duration is 4 – 6 hours

Tiotropium (Spiriva®):

• Mechanism of Action: Quarternary ammonium compound that strongly binds to the muscarnic receptors in airway smooth muscle cells and mucus glands.

• Onset: Begins to work in about 30 minutes after inhalation and persists for 24 hours Reaches maximum effect by day 8

• Inhaler:18mcg daily administered by Handihaler which is a breath activated, dry powder inhalation device

AND

If additional relief is needed after maximum doses are reached, an inhaled beta-2 agonist may be used for quick relief 1 – 4 puffs qid, but watch for ADEs

OR Consider combination inhalers such as ipratropium + albuterol (Combivent®)

Page 43: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD– Step 1

Although beta-2 agonists are useful in the p-r-n treatment of patients with acute episodes of chronic obstructive pulmonary disease, they are notrecommended as first line therapy for patients with more advanced disease. For most elderly patients with mild to moderate C-O-P-D and daily symptoms, anticholinergic therapy with agents such as ipratropium bromide may be more effective.

In fact, the American Thoracic Society now recommends ipratropium as first line therapy in C-O-P-D. Ipratropium is used as a metered dose inhalant aerosol two to six puffs every six to eight hours. Tiotropium is a new once daily maintenance treatment indicated for COPD Except for mucosal dryness, both drugs have few adverse effects. Once the maximum dosage of ipratropium has been reached, a beta 2 agonist M-D-I aerosol one to four puffs up to four times each day may be prescribed as needed for quick relief.

However, once beta-2 agonists have been added to the therapeutic regimen, the systemic side effects are often mistaken for benefits making them difficult to discontinue. Adverse reactions such as cardiac effects, tremors, and propensity for tachyphylaxis makes these drugs less than optimal choices. Therapeutic duration and costs may be reduced by using new combination inhalers, such as Combivent® or ipratropium/albuterol.

Page 44: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD – Step 2

Theophylline (Theo-Dur®):

• 200 – 400 mg bid or 400-800 mg qhs • Serum level of 8-12 mcg/mL is optimum

AND

SR Albuterol (Proventil Repetabs®, Volmax®):

• 4 – 8 mg/d or at night only

AND

If needed, a mucokinetic agent (e.g., guaifenesin, trypsin, acetylcysteine) to break up thick sputum

When anticholinergics and sympathomimetics fail to provide sufficient relief from the symptoms of chronic obstructive pulmonary disease, theophylline may be added to the therapeutic regimen. Theophylline may improve respiratory muscle function, cardiac output, heart performance, and stimulate the respiratory nerve center to work more efficiently. Taken at bedtime,theophylline can reduce nocturnal bronchospasms. While sustained release theophylline is useful for elderly patients unable to use M-D-I aerosols, toxicity can be a problem. Side effects of theophylline include insomnia, arrhythmias, and seizures. Careful dosing is needed to prevent adverse effects and keep serum levels at eight to twelve micrograms per milliliter. If a metered dose inhaler and spacer do not provide sufficient relief, nebulizer treatment should be considered before administering oral theophylline. When treating step three patients, you should also consider use of sustained release albuterol. Mucokinetic may be used to break up thick sputum, but the risk/benefit ratio of such drugs should be carefully considered.

Page 45: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD: Step 3

Treatment of Patients with Mild to Moderate COPD: Step 3

Corticosteroids: prednisone may be administered in dosages up to 40 mg/d x 10-14 days

CHECK FOR IMPROVEMENT

• If No: lower daily dose or alternate with lower daily doses such as 7.5 mg •  If still no improvement, stop abruptly

• If Yes: consider MDI aerosol dosing to reduce bronchial hyperreactivity

If additional control of symptoms is needed, the use of oral corticosteroids may be considered. These agents have had limited use in the treatment of chronic obstructive pulmonary disease because they provide therapeutic benefits to only about ten to fifteen percent of patients, and their adverse effects can be very debilitating. Prednisone is a typical example of such an agent. It may be titrated up to forty milligrams per day for ten to fourteen days.

If the patient shows no improvement, consider lowering the daily dose or alternating with lower daily doses. If the patient still does not improve, stop prednisone treatment immediately. Adverse drug effects to watch for include depression, peptic ulcers, and osteoporosis. It is important to remember that not all inhaled steroids are equally dosed or absorbed, and that systemic absorption can be significant with older agents.

Page 46: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD: Steps 3 & 4

Treatment of Patients with Mild to Moderate COPD:Steps 3 & 4

Increase beta-2 agonist dose such as MDI with spacer 6-8 puffs every 1/2 -2 hours or inhalant unit dose every 1/2 –2 hours

OR

Administer terbutaline or SC epinephrine 0.1-0.5 mg

AND/OR

Increase ipratropium dosage such as MDI with spacer 6 – 8 puffs every 3 – 4 hours or inhalant solution of ipratropium 0.5 mg every 4 – 8 hours

AND

Administer IV theophylline to serum level 10 – 12 mcg/mL

AND ADD:

IV methylprednisolone, 50 – 100 mg immediately, then every 6 – 8 hours o Taper off as soon as possible

Page 47: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Patients with Mild to Moderate COPD: Steps 3 & 4

AND

A mucokinetic agent if sputum is very viscous (e.g., N-acetylcysteine, Mucomyst®)

AND

An antibiotic if indicated Consider oxygen therapy if patient is hypoxemic

Treatment of elderly patients with severe and/or continuing symptoms of chronic obstructive pulmonary disease should receive either increased doses of beta agonists or subcutaneous injections of epinephrine. If the patient is taking ipratropium, the dosage may also be increased as shown. For patients with severe symptoms, consider administering intravenous theophylline or methylprednisolone. If the patient’s sputum is very viscous, a mucokinetic agent may be needed, such as N-acetylcysteine.

Page 48: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management Priorities for the Elderly Patient with COPD

• Balance treatments with quality of life and the ability to live independently • Obtain proper dosage through proper inhalation techniques to avoid undermedicating or overmedicating • Watch for potential for adverse effects or for interactions with other drugs

In elderly patients being treated for chronic obstructive pulmonary disease, high doses are usually contraindicated. Medication should be gradually increased until optimum therapeutic effects are reached. The “start low-go slow” approach can provide a safer plan while the proper medication or combination of medications is being determined.

Page 49: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Drug Effects Associate with COPD Medications

ADEs Associated with Beta-2 Agonists:

• Muscle and nerve tremor • Myocardial ischemia • Complex ventricular arrhythmias • Hypo or hypertension • Hypokalemia related heart and muscle effects • Overuse leading to airway hyperresponsiveness

ADEs Associated with Theophylline:

• Insomnia and nervousness • Cardiac arrhythmias • Seizures and organic brain syndromes • Nausea, vomiting, and GERD effects • Toxicity with hepatic disease

ADEs Associated with Corticosteroids: •  • Depression • PUD • HTN • Cataracts • Osteoporosis • Metabolic effects

One of the most important issues to consider when managing elderly patients with chronic obstructive pulmonary disease is the risk of adverse effects produced by the therapeutic agents discussed earlier. Adverse drug interactions should also be considered. For example, beta blockers and angiotensin-converting enzyme inhibitors can reduce the effectiveness of many of the medications discussed. Also, anticholinergic agents are not recommended for use in COPD patients with glaucoma, nor are beta agonists recommended for use in recent post-myocardial infarction patients.

Page 50: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Alberts, W. M. & Rolfe, M. W.A step care approach to managing COPD. Hosp Formul1994: 29: 756-66.

Chapman, K.M. & Winter, L. COPD: using nutrition to prevent respiratory function decline. Geriatrics1996: 57: 37-42.

Kuhl, D. A, Agiri, O. A., & Mauro, L. S. Beta-agonists in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Ann Pharmacother1998: 28(12): 1379-88.

Pawels R, Sonia Buist A, Calverley P, Jenkins C, Hurd S. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD). Workshop summary. Am J Respir Crit Care Med 2001; 163: 1256-1276.

Ramsdell, J. Use of theophylline in the treatment of COPD. Chest1995: 107(5 Suppl): 206S-209S.

Rossi A., Ganassini A., Tantucci C., Grassi V. Aging and the respiratory system. Aging1996:8(3): 143-61.

Page 51: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Seemungal, T.A.R., et al..Effect of Exacerbation on Quality of Life in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care. Med1998: 157(5): 1418-22.

Senior, R. M., Anthonisen, N. R.Chronic Obstructive Pulmonary Disease (COPD). Am.J. Respir. Crit. Care Med 1998:157: S139-S147.

Yohannes AM, Hardy CC. Treatment of Chronic Obstructive Pulmonary Disease in Older Patients. Drugs Aging 2003:20(3):209-228.

Web Sites:

American Thoracic Society at: http://www.thoracic.org

Page 52: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cough in the Elderly

Learning Objectives:

By the end of this Review Concept you should be able to:

• Define the types of coughs associated with respiratory disorders.

• Discuss the implications of chronic coughing in the elderly.

• Recognize medications that may produce or enhance coughing.

• Recommend alternative drugs and adjunct medications to reduce or eliminate coughing.

• Integrate cough management into a comprehensive treatment plan.

Page 53: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Introduction to Coughs

• Defined as a forceful and sometimes violent expiration preceded by a preliminary inspiration

• May be acute or chronic

• May be referred to as “wet” or “dry”

• Caused by chemical, infectious, mechanical and thermal stimuli

A cough can be defined as a forceful and sometimes violent expiration preceded by a preliminary inspiration. In healthy individuals, coughing serves those suffering from an arrhythmia by helping to restore a normal heartbeat. However, coughing may become counterproductive when it becomes a chronic symptom of other diseases. It can be particularly stressful in elderly patients already experiencing other health problems

Page 54: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

The Coughing Mechanism

Coughs are mainly caused by chemical, infectious, mechanical, and thermal stimuli, especially extremely cold temperatures. The cough begins with an irriration of the nerves in the respiratory tract. The irritation may come from a plug of mucus in the airway, from post-nasal drip, or from exposure to a chemical aerosol, such as hair spray. As the glottis closes, expiratory muscles in the ribcage and abdomen generate intrathoracic pressures that are fifty to one hundred percent greater than are generated through other types of forced expiration.

Page 55: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Etiology of Cough

Acute (< 3 weeks):

• Chemical irritation • Colds • Pneumonia • CHF

Chronic (> 3 weeks):

• Smoking • Asthma • GERD • Post-nasal drip syndrome

Coughs may be acute or chronic. An acute cough is one that lasts less than three weeks. Its most frequent cause is the common cold. Chronic cough lasts more than three weeks and is most often caused by smoking, asthma, and gastroesophageal reflux disease. A chronic persistent cough is one that is not associated with hemoptysis or prior history of chronic respiratory disease. Post-nasal drip syndrome can cause a chronic cough by a number of different factors, but is usually a symptom that indicates allergies or allergic rhinitis.

Page 56: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Respiratory Sources of Cough in the Elderly

Respiratory Sources of Cough in the Elderly

• Asthmatic:combined with dyspnea • Bronchial:source in airways • Dry:no moisture involved • Productive or effective:sputum, mucous, or other exudate is expectorated • Hacking:repeated quick efforts • Spasmodic or paroxysmal:deep airways • Harsh:seen in laryngitis • Pulmonary:severe due to major infection

While a cough in the elderly may be unrelated to any respiratory problems, it is often directly related to illnesses with a pulmonary component. Some types of coughs—such as productive, purulent coughs that the patient cannot clear well—can lead to more serious reinfection, painful episodes of dyspnea, and insomnia. The use of cough medications can be both beneficial or harmful depending on the condition of the patient and interactions with other medications.

Page 57: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Diagnosis of Chronic Cough

History: •  Day vs. evening cough • Pain • Hemoptysis • Sputum production • Medications (e.g., ACE inhibitors) • Trigger factors

Physical Examination: • Hoarseness • Dyspnea • Wheezing, especially post-exercise • Crepitations, rhonchi • Weight loss

Lab Studies: • Chest x-ray • Spirometry, lung volumes,diffusing capacity • Bronchial provocation challenge • Skin test for atopy • Home peak flow monitoring • ENT exam/microlaryngoscopy • Paranasal sinus x-rays and CT

Diagnosis of cough relies on a combination of patient history, physical examination, and pulmonary tests. A drug history is also important. For example, patients who are taking ACE inhibitors because of the bradykinin-induced dry, nagging, cough that has been associated with ACE inhibitors. Others may have cough secondary to congestive heart failure or pneumonia.

The history should document patient experiences with pain, hemoptysis, and sputum production. Day and evening coughing behavior and its relation to position, either sitting or standing, should also be noted. The physical exam should reveal any dyspnea, post-exercise wheezing, and hoarseness. Any changes in weight should be recorded. With respect to laboratory studies, chest x-ray, spirometry, and lung volumes are especially useful. Other diagnostic tools listed here may be used if the diagnosis is more elusive.

Page 58: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management of Chronic Cough in the Elderly

Management of Chronic Cough in the Elderly

• Management is based on underlying cause • Treatment may need to be aimed at more than one etiology • Asthma, post-nasal drip, and chronic bronchitis should be treated along conventional lines • Specific antitussive therapy is directed at the etiology or mechanism causing the cough (e.g., cigarette smoking, postnasal drip) • Nonspecific antitussive therapy is directed at the symptom rather than the etiology

Prevention and Prophylaxis

• Annual immunization against influenza is standard practice for older individuals • Pneumonia vaccine also should be given to older individuals who are at risk

Management of chronic cough in the elderly is based on treatment of the underlying causes. Conditions such as asthma, post-nasal drip, and chronic bronchitis should be treated along conventional lines. Although specific therapy is universally more successful than non-specific therapy, cough may be treated with non-specific medications such as dextromethorphan, codeine, and hydrocodone. Post-viral cough may be effectively treated with ipratropium.

Page 59: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Cough with Codeine

Dosing: • Initial dose:10 – 20 mg po qid • Maintenance dose:10 – 30 mg po qid

Adverse Drug Reactions: • Normal doses:urine retention, itching, vertigo, palpitations or bradycardia, sweating, mild CNS effects (e.g., sedation, mood changes) • Higher doses:constipation, dryness of the mouth, respiratory depression, nausea, & vomiting

Drug-Drug Interactions: • Effects are increased with alcohol and cimetidine • Analgesic effects are inhibited with neuroleptic and antidepressive agents

Contraindications: • Advanced respiratory insufficiency • Bronchial asthma • Raised intracranial pressure

Precautions: • Elderly with heart failure, bronchial asthma, or gastroesophageal reflux

Page 60: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Cough with Codeine

Codeine is an opioid with good antitussive properties. Codeine raises the stimulus threshold of the cough center and thus has a cough suppressing effect.

For years, it has been the gold standard to which all other antitussive drugs are compared. When tested against placebos, codeine reduced coughing by forty percent with a dose of fifteen milligrams and by sixty percent with a dose of sixty milligrams.

For dry, nonproductive cough, the initial loading dose is ten to twenty milligrams every six hours with a maintenance dose of ten to thirty milligrams every six hours. Codeine has side effects characteristic ofother opioids, but they are comparatively mild.

Retention of urine, itching, vertigo, palpitations or bradycardia, sweating, and mild central nervoussystem effects have been observed. Although respiratory depression with therapeutic doses is very rare, the use of codeine is contraindicated in patients with advanced respiratory insufficiency or bronchial asthma.

There is also a danger of addiction for subjects with previous or current opioid dependence. The effect of codeine is increased by other drugs with centrally suppressing effects and by the enzyme inhibitor cimetidine. Cimetidine is a cytochrome P-450 2D6 inhibitor, the same enzyme that codeine is a substrate of.

This inhibition by cimetidine can lead to increased levels of codeine which can lead to increased adverse drug effects, most notably of which is sedation. Neuroleptic and antidepressive agents can competitively inhibit the enzyme responsible for the analgesic effect of codeine.

Page 61: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Cough: Dextromethorphan

Dosing: •  20 – 30 mg po TID – QID

ADEs: • Euphoria, restlessness, misperception, hallucinations, and other mental status changes • GI symptoms • Skin reactions

Drug-Drug Interactions: •  In combination with MAO inhibitors, can cause a severe reaction with fever, hypertension, and arrhythmias • Can interact with memantine (Namenda®) to worsen confusion and potentially cause hallucinations

Contraindications: •  Advanced respiratory insufficiency • Hepatic disease

Dextromethorphan is a powerful antitussive agent that is a synthetic relative of codeine. It has central cough suppressant action, but it does not have the characteristic analgesic, sedating, or constipating side effects of opioids. A typical dose is twenty to thirty milligrams every six to eight hours. Comparative doses of dextromethorphan have been better tolerated than codeine, but its relative effectiveness has not yet been established. Dextromethorphan is indicated for patients with dry cough, rather than productive cough, and is contraindicated in case of advanced respiratory insufficiency or hepatic disease. High doses may cause neuropsychiatric symptoms such as euphoria, restlessness, misperception, hallucination, and other mental status changes as well as gastrointestinal symptoms and skin reactions. In combination with monoamine oxidase inhibitors, dextromethorphan can cause a severe reaction with fever, hypertension, and arrhythmias.

Page 62: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Cough with Hydrocodone

Dosing: • Typical dose:5 – 10 mg every 4 to 6 hours prn • Maximum dose:40 mg/d with 5 mg dose, 60 mg/d with 10 mg dose

ADEs: • Respiratory depression • Tolerance and dependence

Drug-Drug Interactions: • Concurrent therapy with other narcotic analgesics, antipsychotics, antianxiety agents, sedatives, hypnotics, TCAs may potentiate CNS depression

Contraindications: • Advanced respiratory insufficiency • Bronchial asthma

Hydrocodone bitartrate is an opioid antitussive and analgesic used for the relief of cough and moderate to moderately severe pain. It is stronger than codeine, andis associated with greater risks of respiratory depression and dependence. Hydrocodone bitartrate is available in the United States only in fixed combinations with non-opiate drugs such as acetaminophen or aspirin. The usual adult dose is five to ten milligrams every four to six hours as needed not to exceed forty milligrams per day. The smallest effective dose should be administered as infrequently as possible to minimize the development of tolerance and physical dependence. Concurrent therapy with other narcotic analgesics, antipsychotics, antianxiety agents, sedatives, hypnotics and other CNS drugs such as tricyclic antidepressants may result in potentiation of CNS depression.

Page 63: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Effects of Cough Medications

• Oversuppression of cough reflex • Analgesic and sedative effects • Addictive properties

Cough management in the elderly is controversial when inflammation of the respiratory tract is involved. As a protective mechanism, coughs help to clear fluid buildup and prevent reinfection from occurring. It would be inadvisable to completely suppress this action and its related benefits.

Conversely, a persistent or severe cough can disturb sleep, cause incontinence, rib fractures,general weakness, and reduce the effectiveness of certain medications. Once more serious and life-threatening causes for a cough has been ruled out, control of acute episodes and some chronic symptoms can proceed.

Page 64: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Medication Induced Coughs

Coughs may be induced by ACE Inhibitors: Lisinopril (Prinivil®, Zestril®) Benazepril (Lotensin®) Captopril (Capoten®) Enalapril (Vasotec®) Fosinopril (Monopril®)

• ACE-Inhibitors may be replaced with Angiotensin II Receptor Blockers, ARBs, (e.g. losartan, candesartan) if not contraindicated due to disease state • Medication induced coughs may be treated with cromolyn sodium (Intal®)

Medications themselves can be the source of coughing and interfere with other treatments for respiratory disorders. These include the angiotensin-converting enzyme inhibitors such as lisinopril. Fosinopril is supposed to have the least incidence of cough when compared to the other agents.

Adding medications may eliminate the cough or reduce symptoms. For example, cromolyn sodium may be prescribed to suppress coughs caused by ACE inhibitors such as lisinopril. Angiotensin receptor blockers such as losartan provide some of the same benefits as ACE inhibitors without the cough, and may be used instead of ACE inhibitors if not contraindicated due to the diagnosed disease state.

Once again, a review of all medications is an important step in treating the elderly.

Page 65: Module 18 - Pharmacotherapy for Respiratory Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Fillit, H. M., Picariello G. Practical geriatric Assessment. 2nd edition, St. Louis: Mosby; 1997.

Hargreaves M.(1993). On Cromolyn Sodium for ACE Inhibitor Cough Brit. J. Clin. Pract,47: 319-20

Bem J. L. & Peck, R. Dextromethorphan: an overview of safety issues. Drug Saff 1992: (7): 190-9

Hydrocodone Bitartrate Monograph. (1997). In: McEvoy, G. K., editor. AHFS Drug Information 1997. Bethesda: American Society of Health-System Pharmacists.

Widdicombe J, Kamath S. Acute Cough in the Elderly. Drugs Aging 2004:21(4)243-258.