ASTHMA

CASE
Patient and Setting: RP, 51 year old female; urgent clinic visit Chief Complaint: Severe wheezing, shortness of breath, coughing, and painful sinuses History of Present Illness: Frequent asthma attacks for the past 2 months (April and May); Frequent sinus headaches over the last weeks, worse in the last week Past Medical History: History of periodic asthma attacks since childhood; Placed on ICS in her 30s and Prednisone when she was 45 yrs. old; Severe osteoporosis diagnosed 2 yrs ago; wrist fracture 2 yrs ago; placed on ALENDROLATE; Severe menopausal symptoms placed on ERT 2 yrs ago both for menopausal sx and osteoporosis mgt Surgical History: None

Allergies Family and Social History: NKDA Father died at age 59 of kidney failure 2 to hypertension; Mother died at age 62 of from Physical Examination: GEN: pale, well-developed, a stroke anxious-appearing woman Nonsmoker, no alcohol intake, VS: BP 150/92, HR 92 RR 24 T caffeine use; 4 cups of coffee 38.5C, Wt 61 kg H 161 cm and 4 diet colas per day HEENT: PERRLA, oral cavity without lesions, TM without signs of inflammation; sinuses tender Medication History: to palpation Prednisone, 10 mg PO QD COR: RRR, normal s1 and s2 (since she was 4 5 years old) CHEST: Bilateral inspiratory and SereventDiskus inhaler 500/ 50 expiratory wheezes (fluticasone propionate 500 ug ABD: nontender, nondistended, and salmeterol 50 ug per no masses inhalation), 1 inhalation BID GU: Unremarkable Albuterol inhaler, PRN RECT: Guaiac negative Alendronat, 5 mg QD EXT: Unremarkable NEURO: Oriented to time, place Hydrochlorothiazide tablets, 25 and person; CN intact mg PO BID Enalapril tablets, 5 mg PO BID Conjugated estrogens (Premarin), 0. 62 5 mg PO QD Medroxyprogesterone acetate,

LABORATORY RESULTS

Na 134 (134) Cr 106.1 (1.2) LDH 2.5 (150) K 4.9 (4.9) Glu 6.1 (110) WBC 5.2 X 109 (5.2 X 103) HCO3 30 (30) PT 12 sec HCT 0.37 (37) Mg 0.65 (1.3) INR 1.0

Hgb 8.1 (13) PO4 0.872 (2.7) AST 0.45 (27) Plts 201 x 109 (201 x 103) Ca 2.23 (8.9) ALT 0.4 (24) AlkPhos 1.32 (79) Cl 100 (100) ALB 38 (3.8) BUN 7.5 (21) T. Bili 3.4 (0.2)

PROBLEM #1: ACUTE EXACERBATION OF ASTHMA

Basis of Diagnosis
Urgent

clinic visit Severe wheezing, SOB, coughing, painful sinuses Steroid dependent asthma Bilateral inspiratory and expiratory wheezes upon PE Pale, anxious-appearing woman Pulmonary function test:
Prebronchodilator: FEV1/FVC: 59% Post 2.5 mg albuterol: FEV1/FVC: 57.6%

DEFINITION OF ASTHMA

According to the National Asthma Education and Prevention Program (NAEPP) of the Heart, Lung, and Blood Institute and the Global Initiative for Asthma (GINA), asthma is defined largely as a chronic inflammatory disorder of the airways, which emphasizes that asthma is not simply a disease of smooth muscle bronchoconstriction, as was once thought. The complex interrelationship between the presence and absence of genetic susceptibility and environmental factors influences the expression of the disease. The difficulty in defining asthma relates to the multiple factors that trigger bronchospasm and these factors are tabulated below:

FACTORS INFLUENCING DEVELOPMENT AND EXPRESSION OF ASTHMA

HOST FACTOR Genetic, e.g.,
Genes pre-disposing to atopy Genes pre-disposing to airway hyperresponsiveness

ENVIRONMENTAL FACTOR Allergens

Indoor:Domestic mites, furred animals (dogs, cats, mice), cockroach allergen, fungi,

Obesity Sex

molds,

yeasts Outdoor: Pollens, fungi, molds, yeasts Infections (predominantly viral)

Occupational sensitiizers Tobacco smoke Passive smoking Active smoking Outdoor/Indoor Air Pollution Diet

SIGNS AND SYMPTOMS

Asthma of sudden onset may be referred to as acute asthma, asthma exacerbation, or status asthmaticus. Symptoms of acute asthma are similar to those of chronic asthma and are characterized by shortness of breath, wheezing, cough, and chest tightness. Other symptoms such as tachypnea, tachycardia, retractions, cyanosis, and hypoxemia may also be present. S/Sx of asthma is d/t airway narrowing attributed to bronchoconstriction or bronchospasm and to inflammation of the airway.

TREATMENT OBJECTIVES
To reverse the bronchospasm (relievers) and inflammation (controllers) To minimize the need for ED visits or hospitalizations

RELIEVERS = acute attacks CONTROLLERS = for chronic treatment

AS PATIENT ENTERS YOUR CLINIC:

Give low-flow Oxygen (to prevent hypoxemia) Give relievers (for quick relief of DOB) Give controllers (depending on classification of the asthma) to reduce exacerbation attacks or ED visits.

ACUTE EXACERBATIONS Short-Acting B2 Agonist (SABA) Albuterol Terbutaline Metaproterenol Pirbuterol Anticholinergics Ipatropium Bromide Tiotropium Systemic Corticosteroids Prednisone (Oral) Prednisolone (IV)

CHRONIC ASTHMA Inhaled Corticosteroid Budesonide Fluticasone Long-Acting B2 Agonist Salmeterol Formoterol Leukotriene Modifiers Montelukast Zafirlukast Zileuton IgE Monoclonal Antibody Ozalizumab

EFFICACY SABA ++++

SAFETY ++++

SUITABILITY ++++

COST ++

AC

+++

+++

++++

Systemic CS

++++

++

++++

+++

EFFICACY SABA ++++ (DOC)

SAFETY ++++

SUITABILITY ++++

COST ++

AC

+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.

+++

++++

Systemic CS

++++ (used only if combination and/or initial therapy failed)

++

++++

+++

EFFICACY SABA ++++ (DOC)

SAFETY

SUITABILITY

COST ++

++++ ++++ minimal a/e; all other brocnhodilat ors have the s/e mentioned) +++ (dry mouth, CNS a/e, poorly tolerated by elderly) +++ (patient is elderly)

AC

+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.

Systemic CS

++++ (used only if combination and/or initial therapy failed)

++ +++ (osteoporosis! (osteoporosis!!) ! And TMTM a/e)

+++

EFFICACY SABA ++++ (DOC)

SAFETY

SUITABILITY

COST ++ (P992)

++++ ++++ minimal a/e; all other brocnhodilat ors have the s/e mentioned) +++ (dry mouth, CNS a/e, poorly tolerated by elderly) +++ (patient is elderly)

AC

+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.

+ (P1498)

Systemic CS

++++ (used only if combination and/or initial therapy failed)

++ +++ (osteoporosis! (osteoporosis!!) ! And TMTM a/e)

+++ (P500)

DRUG OF CHOICE

Considering the four parameters above, the drug class that will best benefit the patient is short acting2-agonist. Short-Acting B2 Agonist
The

most effective drugs in relaxing airway smooth muscle and reversing bronchoconstriction are short-acting 2 adrenergic receptor agonists. They are the preferred treatment for rapid symptomatic relief of dyspnea associated with asthmatic bronchoconstriction

SHORT-ACTING B2 AGONISTS
Albuterol, Terbutaline, Metaproterenol, Pirbuterol All four drugs have the same mechanisms of action and all produce relaxation of airway smooth muscle and inhibition of mediator release that causes bronchoconstriction. They may also inhibit microvascular leakage and increase mucociliary transport by increasing ciliary activity.

EFFICACY

SAFETY

SUITABILITY

COST

Albuterol/ ++++ Salbutamo l

+++

+++

+++

Terbutalin e

++++

++

+++

++

Metaproterenol

++++

++

N/A

N/A

Pirbuterol

++++

++

N/A

N/A

EFFICACY

SAFETY

SUITABILITY

COST

Albuterol/ ++++ Salbutamo l

+++ (s/e rare to occur)

+++

+++

Terbutalin e

++++

++ (many s/e)

++

++

Metaproterenol

++++

++ (harmful metabolite; Less b2 selective ) ++ allergic rxn

N/A

N/A

Pirbuterol

++++

N/A

N/A

EFFICACY

SAFETY

SUITABILITY

COST

Albuterol/ ++++ Salbutamo l

+++ (s/e rare to occur)

+++ (more preparations available)

+++

Terbutalin e

++++

++ (many s/e)

++

++

Metaproterenol

++++

++ (harmful metabolite; Less b2 selective ) ++ allergic rxn

N/A

N/A

Pirbuterol

++++

N/A

N/A

EFFICACY Albuterol/ ++++ Salbutamo l

SAFETY +++ (s/e rare to occur)

SUITABILITY +++ (more preparations available)

COST +++ P992/neb ulizer 30x1s Nebule:P3 5

Terbutalin e

++++

++ (many s/e)

++

++ P700/neb ulizer 20x1s Nebule: P39

Metaproterenol

++++

++ (harmful metabolite; Less b2 selective )

N/A

N/A

DRUG OF CHOICE

Since the patient is already on Albuterol and still exacerbated, we will need to add an adjunct. The most used adjuncts are anticholinergic agents. Thus, we will prescribe the patient with combination therapy of Ipratropium bromide plus Salbumatol (Combivent) available in inhaler form.
Albuterol/Salbutamol + Ipatropium Bromide = Combivent

(SABA)

(AntiCholinergic)

NON-PHARMACOLOGICAL TREATMENT
low-flow oxygen therapy Routine monitoring of oxygenation by pulse oximetry is warranted in all patients who do not respond to initial bronchodilator therapy Patients should be adequately hydrated but not overhydrated.

CHRONIC ASTHMA

Basis of Diagnosis: History of periodic asthma attacks since childhood and worsening during adolescence and early adulthood, accompanied by frequent asthma attacks for the past 2 months; chronic use of inhaled corticosteroids for 21 years and oral systemic corticosteroids for six years. Treatment Goal: To improve the quality of care by improving treatment outcomes Treatment Objectives: Maintain normal activity levels of the patient; Maintain near-normal pulmonary function by preventing irreversible narrowing or airway lumen; Provide optimal pharmacotherapy with minimal or no adverse effects; Minimal use of short-acting inhaled Beta-2-agonist;

Meet patients familys expectations of satisfaction with asthma care.

TREATMENT OF CHRONIC ASTHMA

Depends on the category/classification of asthma whether patient diagnosed as mild intermittentm mild persistent, moderate persistent, or sever persistent.

ICS LABA LT modifiers Anti-IgE monoclonal Ab

EFFICACY

SAFETY

SUITABILITY

COST

ICS

++++

+++

++

+++

LABA

+++

+++

+++

++++

LT modif.

++

++

Anti-IgE

+++

EFFICACY

SAFETY

SUITABILITY

COST

ICS

++++ (most effective)

+++

++

+++

LABA

+++ (not for monotherapy)

+++

+++

++++

LT modif.

++ (add-on)

++

Anti-IgE

+++ (add-on)

EFFICACY

SAFETY

SUITABILITY

COST

ICS

++++ (most effective)

+++ (dosedependent a/e)

++ +++ (osteoporosis )

LABA

+++ (not for monotherapy)

+++ (tolerance to A/E may be produced) +

+++

++++

LT modif.

++ (add-on)

+ (with DI)

++

Anti-IgE

+++ (add-on)

EFFICACY

SAFETY

SUITABILITY

COST

ICS

++++ (most effective)

+++ (dosedependent a/e)

++++

+++ (P1148)

LABA

+++ (not for monotherapy)

+++ (tolerance to A/E may be produced) ++

++++

++++ (P858)

LT modif.

++ (add-on)

+++ (with DI) ++ (P1296)

Anti-IgE

+++ (add-on)

++ (Ozalizumab n/a in Phil)

+ (P24,667)

COMBINATION OF ICS AND LABA

ICS
Budesonide Fluticasone

LABA
Formeterol Salmeterol

ICS
EFFICACY SAFETY SUITABILITY COST

Budesonid e

++

++

++

++++

Fluticason e

+++

++

+++

+++

ICS
EFFICACY SAFETY SUITABILITY COST

Budesonid e

++ (PB 90% and low absorption)

++ (GCArS)

+++ (DI; weak mineralocortic oid activity)

++++ (P800)

Fluticason e

+++ (PB 91% and high absorption)

++ (GCArS)

++ (DI;)

+++ (P1148.70)

LABA
EFFICACY SAFETY SUITABILITY COST

Formoterol ++++ (onset:4mins 12hrs)

+++

+++

+++ (P853)

Salmeterol +++ (onset14hrs)

+++

+++

++ (always in combination )

COMBINATION OF ICS+LABA
DRUG EFFICACY SAFETY SUITABILITY COST

Formoterol / Budesonide (Symbicort) Salmeterol / Fluticasone (Seretide)

++++

+++ (500/5mcg) (390/9mcg)

+++

+++ (P839 x 1 canister x 60 doses) (P1635) ++ (P1728 x1 canister x 60doses)

++++

++ (more a/e; higher dosage to attain desired results compared to symbicort 160/4.5mcg)

+++

The patient is taking medications: high-dose ICS + LABA [Fluticasone+Salmeterol 500/50g 1 inhalation BID] and oral corticosteroid [oral prednisone 10 mg PO QD

Before an oral systemic corticosteroid is introduced, a trial of high-dose ICS + LABA and a leukotriene receptor antagonist (Montelukast) may be considered. As an adjunct treatment, an anti-IgE medication such as Omalizumab may be added for patients who still suffer from frequent exacerbations despite the combination therapy. Treatment is then reviewed every 1 to 6 months by the patients physician in order to determine whether the patient needs to step up or down from the therapeutic regimen she is currently on. If the treatment is maintained, a gradual stepwise reduction can be done; however, if the control is not maintained then the treatment is stepped up.

KTHANKSBYE!