Pharmaceutical Care IIIManagement of Asthma

Angela Singh, PharmDAssistant Professor of Pharmacy Practice

Florida A&M University College of Pharmacy

Overview of Asthma

• Inflammatory disease characterized by hyperresponsiveness of the airways.

• Inflammatory mediators include prostaglandins, histamine and leukotrienes.

• Inflammation results in bronchial smooth muscle spasms, vascular congestion, increased vascular permeability, mucous production and impaired ciliary function.

Case

• Chief Complaint– I have become increasingly short of breath

over the past few weeks.• HPI

– B.W is a 20 year-old woman who attends the university, majoring in business. She comes to the clinic today because she has noticed that she has been using her albuterol inhaler more frequently (3 to 4 times a week) and has also been experiencing symptoms at night more frequently (3 times/month).

Case

• SH– Denies any use of tobacco, consumes 10-12 drinks per week,

usually on the weekends, drinks one Coke daily and denies any use of illicit drugs.

• PE– Occasional expiratory wheezes bilaterally

• Diagnostic Tests– Peak expiratory flow variability is 25% and her FEV1 is 85%.

Current Medications

• Albuterol inhaler 2 puffs q 4 hours as needed for shortness of breath and/or wheezing.

• Ortho Novum as directed monthly.• Propranolol 40 mg twice daily• St. John’s Wort 300 mg three times daily.

Categories of Asthma

• Extrinsic/Allergic • Intrinsic

Etiology

• Innate Immunity

• Genetics

• Environmental Factors

Pathophysiology

• Acute Inflammation– Early response– Delayed Response

• Chronic Inflammation

• Bronchoconstriction

• Airway Hyperresponsiveness

• Airway Edema

Key Symptoms of Asthma

• Wheezing• History of any of the

following– Cough– Recurrent wheeze– Recurrent difficulty in

breathing– Recurrent chest

tightness• Symptoms occur or worsen

at night, awakening the patient

• Symptoms occur or worsen in the presence of– Exercise– Viral infection– Inhalant allergens– Irritants– Changes in weather– Strong emotional

expression– Menstrual Cycles

Co-Morbid Conditions that may Worsen Asthma

• GERD• Obesity• Obstructive Sleep Apnea (OSA)• Rhinitis• Stess/Depression

Diagnosis

• Medical History• Physical Examination• Spirometry

– Forced Vital Capacity (FVC)– Forced Expiratory Volume in one second (FEV1)

– FEV1 / FVC ratio

Diagnostic Tests

• FEV1/FVC ratio • Peak Flow Meters• Bronchoprovocation Test

Peak Flow Meters

Complications

• Acute

• Chronic

Classification Mild Intermittent

Mild

Persistent

Moderate Persistent

Severe Persistent

Frequency of Symptoms

< 2 days/week > 2 days/week Daily Continual

Night Time Symptoms

< 2 nights/month

> 2 nights/month

> 1 night/week Frequent

Peak Expiratory Flow Variability

< 20% 20-30% > 30% > 30%

Forced Expiratory

Volume in 1 second

> 80 % > 80% 60% to

80%

< 60%

Asthma Severity Classification

Case

• Based on her presentation how would you classify her asthma?

Treatment Goals

• Prevent chronic and troublesome symptoms

• Require infrequent use of inhaled SABA (< 2 times per week) for quick relief of symptoms (not including prevention of exercise-induced bronchospasm (EIB))

Non-Pharmacological Approaches

• Immunizations– Influenza vaccine – Doesn’t prevent asthma exacerbations during flu

season

• Allergen avoidance• Tobacco smoke, dust mites, animal dander, cockroach,

pollen, mold, exercise

• Education of the parents and the child.

Education

• Basic facts about asthma• Role of Medications• Patient Skills

– Taking medications correctly– Identifying and avoid environmental exposures– Self Monitoring – Asthma Action Plan

How to administer an inhaler…

• Take off the cap and shake the inhaler

• Breath out all the way • Hold your inhaler one of the

following ways– Hold inhaler 1 to 2 inches in

front of your mouth (about the width of two fingers)

– Use a spacer/ holding chamber. These come in many shapes and can be useful to any patient.

– Put the inhaler in your mouth.

• Breathe in slowly • As you start breathing in slowly

through your mouth, press down on the inhaler one time (If you use a holding chamber, first press down on the inhaler. Within 5 seconds, begin to breathe in slowly.

• Keep breathing in slowly, as deeply as you can.

• Hold your breath • Hold your breath as you count to

10 slowly, if you can. • Wait about 1 minute between

puffs.

Tips for Using an Inhaler

• Rinse mouth with water or mouth wash after using corticosteroid medication to prevent hoarseness and fungal infections in the mouth and throat.

• If you are taking more than one inhaled medication, it is important to take them in the correct order. Bronchodilating medications are usually taken first to open the airways and allow other types of medications to be more effectively inhaled into the lungs. Corticosteroids and cromolyn are inhaled after bronchodilating drugs.

• Avoid the use of over-the-counter inhalers. Most of these contain epinephrine, which is effective for only a short time and may cause rebound bronchospasm (making it more difficult to breathe).

• Take only the recommended number of puffs prescribed by your provider; over-use or incorrect use can be dangerous.

• Notify your doctor if any of the following occur: – You do not get relief from your metered dose inhaler – You have increasing shortness of breath despite use of inhalers – You are experiencing weakness, increased heart rate, shakiness,

insomnia, nervousness, headaches, nausea or vomiting

CFC vs HFA Inhalers

• Due to the Clean Air Act Chlorofluorocarbon (CFC) inhalers are being phased out of the market and replaced with hydrofluroalkane (HFA) inhalers.

• These inhalers require different instructions for priming, storage and use.

Pharmacologial Approaches

• Beta Agonists• Corticosteroids• Leukotriene Modifiers• Mast Cell Stabilizers• Theophylline• Monoclonal Antibodies

Short Acting Beta Agonists (SABA)Used for the Prevention and TREATMENT of Bronchospasms

Brand Name Generic Name Formulations Comments

Xopenex®

Xopenex HFA®

Pregnancy Category C

Levalbuterol Nebulizing Solution

Oral Aerosol

Store at room temperature. Protect from light. Contains 200 actuations. Vials should be used within two weeks after opening protective pouch.

Proventil HFA ®, Proair HFA ®, AccuNeb®

Ventolin HFA®

Combivent® (combination product), VoSpire ER®

Pregnancy Category C

Albuterol Oral Aerosol

Nebulizer Solution

Tablet

Extended Release Tablet

Syrup

Store at room temperature, each inhaler contains 200 actuations, Use nebulizing solution within one week of opening foil pouch.

Maxair ®

Pregnancy Category C

Pirbuterol Oral Aerosol

Autohaler

Contains 400 inhalations, Store at room temperature

Alupent®

Pregnancy Category C

Metaproterenol Oral Aerosol

Nebulizer

Syrup

Tablet

Store in a tight, light resistant container. Contains 200 actuations. Do not use if solution is brown or contains a precipitate.

Long Acting Beta Agonists (LABA)Used for the PREVENTION of bronchospasms

Brand Name Generic Name Dosage Forms Comments

Foradil®

Perforomist ®

Symbicort ® (combination product)

Pregnancy Category C

Formoterol Aerosol Powder

Nebulizing Solution

Store Foradil®

in refrigerator prior to dispensing, after dispensing store at room temperature. Remove capsules from blister pack immediately before using. Use within 4 months of purchase.

Serevent Diskus®

Advair HFA ® (combination product)

Pregnancy Category C

Salmeterol Aerosol Powder Store at room temperature away from direct light or heat. Stable for 6 weeks after removal from foil pouch. Not for the use of acute control of bronchospasms. Major substrate 3A4.

Beta Agonists

• Side Effects– Tachycardia– Insomnia– Nervousness– Hypokalemia– Hyperglycemia– Diarrhea– Dry Mouth– Tremors

• Drug Interactions– MAOIs– Sympathomimetic Agents– Beta Blockers– P450 3A4 Inhibitors &

Inducers• Salmeterol

– Caffeine– Yohimbine

Spacing Devices

CorticosteroidsGeneric Name Brand Name Formulations

Beclomethasone

Pregnancy Category C

QVAR ® Oral Aerosol

100 Actuations

Traimcinolone

Pregnancy Category C

Azmacort ®, Oral Aerosol

240 actuations

Flunisolide

Pregnancy Category C

Aerobid ® Aerospan HFA Oral Aerosol

100 actuations

Fluticasone

Pregnancy Category C

Flovent HFA ®

Flovent Diskus ®

Advair ®

Oral Aerosol

120 actuations

Mometasone

Pregnancy Category C

Asmanex ® Aerosol Powder

200 Actuations

Budesonide

Pregnancy Category B

Pulmicort Flexhaler ®

Pulmicort Respules ®

Symbicort ®

Aerosol Powder

120 Actuations

Nebulizer

Corticosteroids

• Oral Agents– Prednisone– Methylprednisilone– Prednisilone

• Adverse Effects– Oral candidiasis– Hoarseness– May slow bone growth in

children.– Cushing’s Effects– Osteoporosis– Hypertension– Cataracts– Glucose Intolerance– Skin Thinning– Depression

• Comments– Use SPACERS to minimize

local and systemic adverse effects.

– RINSE MOUTH with water after inhalations to prevent thrush infections.

– Use steroid inhalers as scheduled not as needed.

– Consider calcium and Vitamin D supplementation.

– Pulmicort Respules is the only nebulized approved steroid.

Corticosteroids: Drug Interactions

• Anti-diabetic agents

• 3A4 Inhibitors & Inducers– Flunisolide, Fluticasone, Mometasone,

Budesonide

Brand Name Generic Name Formulations

Intal Cromolyn Sodium

Oral Aerosol

200 actuations

Nebulizing Solution

Mast Cell Stabilizer

Mast Cell Stabilizers

• Adverse Effects– Unpleasant taste– Cough

• Drug Interactions– No significant drug

interactions

• Comments– Slow onset: may take 4-8

weeks for expected effect.– Alternative to steroids in

children.– Not for rapid relief.

Theophyilline ( Theodur, Uniphyl, Theo-24)

• Dose 10 mg/kg/day given BID-TID with a maximum dose of 900 mg daily.

• Therapeutic Levels– 5-15 mcg/mL

• Formulations– Controlled Release Tablet (Uniphyl)– Extended Release Capsule (Theo-24)– Elixir (Elixophyllin)

• Side Effects– Nausea– Vomiting– Nervousness– Tremors– Insomnia– Headache– Arrhythmia– Seizures

Theophylline cont.

• Drug Interactions– 3A4 and 1A2 Inhibitors &

Inducers– Caffeine

• Comments– Beneficial for night

symptoms.– Not for acute relief.

Leukotriene Modifiers

Generic Name Brand Name Formulation

Montelukast Singulair Tablets

Chewable Tablets

Granules

Zafirlukast Accolate Tablets

Leukotriene Modifiers

• Drug Interactions– Montelukast

• Inhibitors & Inducers of 2C9 & 3A4.

– Zafirlukast• Inhibits 2C9, 3A4• Inhibitors & Inducers of

2C9 (it is a major substrate).

• Adverse effects– Hepatotoxicity

• Liver function tests at baseline, every month x 3 months for one year

– Headache– GI Upset

Zileuton (Zyflo®)

• Inhibits the production of leukotrienes.

• Available as an extended release tablet

• Useful in mild persistent asthma and in combination with corticosteroids in moderate persistent asthma.

• Used in pateints > 12 years of age.

• Adverse Effects– Elevated liver enzymes.– Monitor hepatic enzymes

• Drug Interactions– Zileuton is a 1A2 and 3A4

inhibitor.

Omalizumab ( Xolair)

• Monoclonal antibody that acts by inhibiting IgE binding to mast cells and basophils.

• Administered subcutaneously every 2-4 weeks

• Must be refrigerated.

• Helpful in moderate to severe persistent allergy-related asthma.

• Use in > 12 years old• Second line therapy• Very expensive

Omalizumab (Xolair)

• Drug Interactions– No significant drug

interactions

• Adverse Effects– Injection site reaction– Urticaria– Thrombocytopenia– Anaphylaxis

Case

• Based on her medication profile are there any medications that may be interfering with the efficacy of albuterol? Are there any drug interactions within her profile?

Stepwise Approach to Asthma

• Intermittent = Step 1

• Mild = Step 2

• Moderate = Step 3 or Step 4

• Severe = Step 5 or Step 6

Stepwise Approach of Management of Asthma

Management of Exacerbations

• Assess Severity• Initial treatment

– Short acting beta agonist

• Good Response • Incomplete Response• Poor Response

Questions

• Angela Singh• angela.singh@famu.edu• 599-3359• Office # 345