ASTHMA

CASEPatient and Setting:RP, 51 year old female; urgent clinic visitChief Complaint:Severe wheezing, shortness of breath, coughing, and painful sinusesHistory 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 weekPast 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 symptomsplaced on ERT 2 yrs ago both for menopausal sx and osteoporosis mgtSurgical History:None

Family and Social History: Father died at age 59 of kidney failure 2 to hypertension; Mother died at age 62 of from a strokeNonsmoker, no alcohol intake, caffeine use; 4 cups of coffee and 4 diet colas per day

Medication History:Prednisone, 10 mg PO QD (since she was 4 5 years old)SereventDiskus inhaler 500/ 50 (fluticasone propionate 500 ug and salmeterol 50 ug per inhalation), 1 inhalation BIDAlbuterol inhaler, PRNAlendronat, 5 mg QDHydrochlorothiazide tablets, 25 mg PO BIDEnalapril tablets, 5 mg PO BIDConjugated estrogens (Premarin), 0. 62 5 mg PO QDMedroxyprogesterone acetate, 2.5 mg PO QDAllergiesNKDAPhysical Examination:GEN: pale, well-developed, anxious-appearing womanVS: BP 150/92, HR 92 RR 24 T 38.5C, Wt 61 kg H 161 cmHEENT: PERRLA, oral cavity without lesions, TM without signs of inflammation; sinuses tender to palpationCOR: RRR, normal s1 and s2CHEST: Bilateral inspiratory and expiratory wheezesABD: nontender, nondistended, no massesGU: UnremarkableRECT: Guaiac negativeEXT: UnremarkableNEURO: Oriented to time, place and person; CN intact

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 secHCT 0.37 (37)Mg 0.65 (1.3)INR 1.0Hgb 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 ASTHMABasis of DiagnosisUrgent clinic visitSevere wheezing, SOB, coughing, painful sinusesSteroid dependent asthmaBilateral inspiratory and expiratory wheezes upon PEPale, anxious-appearing womanPulmonary function test:Prebronchodilator:FEV1/FVC: 59%Post 2.5 mg albuterol:FEV1/FVC: 57.6%

DEFINITION OF ASTHMAAccording 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 FACTORENVIRONMENTAL FACTORGenetic, e.g., Genes pre-disposing to atopy Genes pre-disposing to airway hyperresponsivenessObesitySexAllergens Indoor:Domestic mites, furred animals (dogs, cats, mice), cockroach allergen, fungi, molds, yeasts Outdoor: Pollens, fungi, molds, yeastsInfections (predominantly viral)Occupational sensitiizersTobacco smokePassive smokingActive smokingOutdoor/Indoor Air PollutionDiet

SIGNS AND SYMPTOMSAsthma 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 attacksCONTROLLERS = 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 EXACERBATIONSCHRONIC ASTHMAShort-Acting B2 Agonist (SABA) Albuterol Terbutaline Metaproterenol Pirbuterol

Anticholinergics Ipatropium Bromide Tiotropium

Systemic Corticosteroids Prednisone (Oral) Prednisolone (IV)Inhaled Corticosteroid BudesonideFluticasone

Long-Acting B2 Agonist Salmeterol Formoterol

Leukotriene Modifiers Montelukast Zafirlukast Zileuton

IgE Monoclonal Antibody Ozalizumab

EFFICACYSAFETYSUITABILITYCOSTSABA++++++++

++++++AC+++++++++++ SystemicCS+++++++++++++

EFFICACYSAFETYSUITABILITYCOSTSABA++++ (DOC)++++

++++++AC+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.++++++++ SystemicCS++++ (used only if combination and/or initial therapy failed)++ +++++++

EFFICACYSAFETYSUITABILITYCOSTSABA++++ (DOC)++++ minimal a/e; all other brocnhodilators have the s/e mentioned)++++++AC+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.+++ (dry mouth, CNS a/e, poorly tolerated by elderly)+++ (patient is elderly)+SystemicCS++++ (used only if combination and/or initial therapy failed)++ (osteoporosis!! And TMTM a/e)+++ (osteoporosis!!)+++

EFFICACYSAFETYSUITABILITYCOSTSABA++++ (DOC)++++ minimal a/e; all other brocnhodilators have the s/e mentioned)++++++ (P992)AC+++ (SABA>AC in terms of bronchodilation); adjunct only to SABA.+++ (dry mouth, CNS a/e, poorly tolerated by elderly)+++ (patient is elderly)+ (P1498)SystemicCS++++ (used only if combination and/or initial therapy failed)++ (osteoporosis!! And TMTM a/e)+++ (osteoporosis!!)+++ (P500)

DRUG OF CHOICEConsidering the four parameters above, the drug class that will best benefit the patient is short acting2-agonist.

Short-Acting B2 AgonistThe 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 AGONISTSAlbuterol, Terbutaline, Metaproterenol, PirbuterolAll 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.

EFFICACYSAFETYSUITABILITYCOSTAlbuterol/Salbutamol++++++++++

+++Terbutaline+++++++++

++Metaproterenol++++++N/AN/APirbuterol++++++N/AN/A

EFFICACYSAFETYSUITABILITYCOSTAlbuterol/Salbutamol+++++++ (s/e rare to occur)+++

+++Terbutaline++++++ (many s/e)++

++

Metaproterenol++++++ (harmful metabolite;Less b2 selective )N/AN/APirbuterol++++++ allergic rxnN/AN/A

EFFICACYSAFETYSUITABILITYCOSTAlbuterol/Salbutamol+++++++ (s/e rare to occur)+++ (more preparations available)+++

Terbutaline++++++ (many s/e)++++

Metaproterenol++++++ (harmful metabolite;Less b2 selective )N/AN/APirbuterol++++++ allergic rxnN/AN/A

EFFICACYSAFETYSUITABILITYCOSTAlbuterol/Salbutamol+++++++ (s/e rare to occur)+++ (more preparations available)+++ P992/nebulizer 30x1s

Nebule:P35Terbutaline++++++ (many s/e)++++ P700/nebulizer 20x1s

Nebule: P39Metaproterenol++++++ (harmful metabolite;Less b2 selective )N/AN/APirbuterol++++++ allergic rxnN/AN/A

DRUG OF CHOICESince the patient is already on Albuterol and still exacerbated, we will need to add an adjunct. The most used adjuncts are anti-cholinergic 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 TREATMENTlow-flow oxygen therapyRoutine monitoring of oxygenation by pulse oximetry is warranted in all patients who do not respond to initial bronchodilator therapyPatients should be adequately hydrated but not overhydrated.

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

ICSLABALT modifiersAnti-IgE monoclonal Ab

EFFICACYSAFETYSUITABILITYCOSTICS++++++++++++LABA++++++ +++ ++++LT modif.++++++Anti-IgE++++++

EFFICACYSAFETYSUITABILITYCOSTICS++++ (most effective)++++++++LABA+++ (not for monotherapy)++++++ ++++LT modif.++ (add-on)++++Anti-IgE+++ (add-on)+++

EFFICACYSAFETYSUITABILITYCOSTICS++++ (most effective)+++ (dose-dependent a/e)++ (osteoporosis)+++LABA+++ (not for monotherapy)+++ (tolerance to A/E may be produced)+++ ++++LT modif.++ (add-on)++ (with DI)++Anti-IgE+++ (add-on)+++

EFFICACYSAFETYSUITABILITYCOSTICS++++ (most effective)+++ (dose-dependent 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 LABAICSBudesonideFluticasone

LABAFormeterolSalmeterol

ICS

EFFICACYSAFETYSUITABILITYCOSTBudesonide++++ ++++++Fluticasone++++++++ +++

ICS

EFFICACYSAFETYSUITABILITYCOSTBudesonide++ (PB 90% and low absorption)++ (GCArS)+++ (DI; weak mineralocorticoid activity)++++(P800)Fluticasone+++ (PB 91% and high absorption)++ (GCArS)++ (DI;)+++(P1148.70)

LABA

EFFICACYSAFETYSUITABILITYCOSTFormoterol++++ (onset:4mins 12hrs)+++++++++(P853)Salmeterol+++ (onset1-4hrs)++++++ ++(always in combination)

COMBINATION OF ICS+LABA

DRUGEFFICACYSAFETYSUITABILITYCOSTFormoterol / Budesonide(Symbicort)+++++++ (500/5mcg) (390/9mcg)++++++ (P839 x 1 canister x 60 doses) (P1635)Salmeterol / Fluticasone(Seretide)++++++ (more a/e; higher dosage to attain desired results compared to symbicort 160/4.5mcg) +++++ (P1728 x 1 canister x 60doses)

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!

Storage, Availability, Route, Drug Interaction *Glaucoma, cataract, Allergic rhinitis, SinusitisBeclometasone dipropionate and Flunisolide are less potent compared to Budesonide and Fluticasone AND ARE NOT AVAILABLE IN THE PHIL*