Antiasthmatic drugs

DRUGS ACTING ON THE RESPIRATORY SYSTEM

DRUGS USED IN ASTHMA

DR Usama Asad Khatri

LEARNING OBJECTIVESLEARNING OBJECTIVES

At the end of the lecture students should be At the end of the lecture students should be able to:able to: ID signs and symptoms of asthma ID signs and symptoms of asthma Differentiate the various severities of asthmaDifferentiate the various severities of asthma Summarize an appropriate treatment regimen for Summarize an appropriate treatment regimen for

asthma of various severities.asthma of various severities.

INTRODUCTION

ASTHMAASTHMA

Chronic inflammatory disorder of the airways in Chronic inflammatory disorder of the airways in which many cells and cellular elements play a which many cells and cellular elements play a role. role.

In susceptible individuals, this inflammation In susceptible individuals, this inflammation causes recurrent episodes of wheezing, causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. particularly at night or in the early morning. These episodes are associated with widespread These episodes are associated with widespread but variable airflow obstruction that is reversible but variable airflow obstruction that is reversible either spontaneously, or with treatment.either spontaneously, or with treatment.

ASTHMAASTHMA

Most common chronic condition in childrenMost common chronic condition in children #1 cause of school absenteeism#1 cause of school absenteeism Morbidity and mortality highly correlated with Morbidity and mortality highly correlated with

poverty, urban air quality, indoor allergens, poverty, urban air quality, indoor allergens, lack of patient education, and inadequate lack of patient education, and inadequate medical caremedical care

About 5000 deaths annually.About 5000 deaths annually.

SIGNS & SYMPTOMS OF ASTHMASIGNS & SYMPTOMS OF ASTHMA

Usually associated with airflow obstruction of Usually associated with airflow obstruction of variable severity.variable severity.

Airflow obstruction is usually reversible, Airflow obstruction is usually reversible, either spontaneously, or with treatment.either spontaneously, or with treatment.

The inflammation associated with asthma The inflammation associated with asthma causes an increase in the baseline bronchial causes an increase in the baseline bronchial hyper responsiveness to a variety of stimuli.hyper responsiveness to a variety of stimuli.

PATHOGENESIS OF ASTHMA

The early reaction is immediate bronchoconstriction produced by histamine, tryptase, and other neutral proteases, leukotrines C4 and D4 and prostaglandins

These agents diffuse throughout the airway wall and cause vascular leakage

PATHOGENESIS OF ASTHMA

Late bronchoconstriction occurs after 2-8 hours by TH2 lymphocytes and interleukins 4, 5, 9 and 13, attracting and activating eosinophils and stimulating IgE production by B lymphocytes

ASTHMA TRIGGERSASTHMA TRIGGERS

AllergensAllergens Dust mites, mold spores, animal dander, Dust mites, mold spores, animal dander,

cockroaches, pollen, indoor and outdoor pollutants, cockroaches, pollen, indoor and outdoor pollutants, irritants (smoke, perfumes, cleaning agents).irritants (smoke, perfumes, cleaning agents).

Pharmacologic agents; ASA, beta-blockers.Pharmacologic agents; ASA, beta-blockers. Physical triggers (exercise, cold air, Physical triggers (exercise, cold air, distilled water,

and sulfur dioxide).sulfur dioxide). Diseases; GERD, viral and bacterial URI, rhinitis.Diseases; GERD, viral and bacterial URI, rhinitis. Physiologic factorsPhysiologic factors

Stress.Stress.

DIAGNOSTIC TESTINGDIAGNOSTIC TESTING

SpirometrySpirometry Recommended to do spirometry pre- and post- use Recommended to do spirometry pre- and post- use

of an albuterol MDI to establish reversibility of of an albuterol MDI to establish reversibility of airflow obstructionairflow obstruction

>> 12% reversibility or an increase in FEV1 of 12% reversibility or an increase in FEV1 of 200cc is considered significant200cc is considered significant

Obstructive pattern: reduced FEV1/FVC ratioObstructive pattern: reduced FEV1/FVC ratio Restrictive pattern: reduced FVC with a normal Restrictive pattern: reduced FVC with a normal

FEV1/FVC ratioFEV1/FVC ratio


SpirometrySpirometry Can be used to identify reversible airway Can be used to identify reversible airway

obstruction due to triggersobstruction due to triggers Can diagnose Exercise-induced asthma (EIA) or Can diagnose Exercise-induced asthma (EIA) or

Exercise-induced bronchospasm (EIB) by Exercise-induced bronchospasm (EIB) by measuring FEV1/FVC before exercise and measuring FEV1/FVC before exercise and immediately following exercise, then for 5-10 immediately following exercise, then for 5-10 minute intervals over the next 20-30 minutes minute intervals over the next 20-30 minutes looking for post-exercise bronchoconstrictionlooking for post-exercise bronchoconstriction


SpirometrySpirometry National Asthma Education and Prevention National Asthma Education and Prevention

Program (NAEPP) recommends spirometry:Program (NAEPP) recommends spirometry: For initial assessmentFor initial assessment Evaluation of response to treatmentEvaluation of response to treatment Assessment of airway function at least every 1-2 yearsAssessment of airway function at least every 1-2 years


Methacholine challengeMethacholine challenge Most common bronchoprovocative test in USMost common bronchoprovocative test in US Patients breathe in increasing amounts of Patients breathe in increasing amounts of

methacholine and perform spirometry after each methacholine and perform spirometry after each dosedose

Increased airway hyperresponsiveness is Increased airway hyperresponsiveness is established with a 20% or more decrease in FEV1 established with a 20% or more decrease in FEV1 from baseline at a concentration < 8mg/dlfrom baseline at a concentration < 8mg/dl

May miss some cases of exercise-induced asthmaMay miss some cases of exercise-induced asthma


Diagnostic trial of anti-inflammatory Diagnostic trial of anti-inflammatory medication (preferably corticosteroids) or an medication (preferably corticosteroids) or an inhaled bronchodilatorinhaled bronchodilator Especially helpful in very young children unable to Especially helpful in very young children unable to

cooperate with other diagnostic testing.cooperate with other diagnostic testing. There is no one single test or measure that can There is no one single test or measure that can

definitively be used to diagnose asthma in every definitively be used to diagnose asthma in every patient.patient.

GOALS OF ASTHMA TREATMENTGOALS OF ASTHMA TREATMENT

Control chronic and nocturnal symptomsControl chronic and nocturnal symptoms Maintain normal activity, including exerciseMaintain normal activity, including exercise Prevent acute episodes of asthmaPrevent acute episodes of asthma Minimize ER visits and hospitalizationsMinimize ER visits and hospitalizations Minimize need for reliever medicationsMinimize need for reliever medications Maintain near-normal pulmonary functionMaintain near-normal pulmonary function Avoid adverse effects of asthma medicationsAvoid adverse effects of asthma medications

TREATMENT OF ASTHMATREATMENT OF ASTHMA

Global Initiative for Asthma (6-point plan)Global Initiative for Asthma (6-point plan) Educate patients to develop a partnership in asthma Educate patients to develop a partnership in asthma

managementmanagement Assess and monitor asthma severity with symptom Assess and monitor asthma severity with symptom

reports and measures of lung function as much as reports and measures of lung function as much as possiblepossible

Avoid exposure to risk factorsAvoid exposure to risk factors Establish medication plans for chronic management in Establish medication plans for chronic management in

children and adultschildren and adults Establish individual plans for managing exacerbationsEstablish individual plans for managing exacerbations Provide regular follow-up careProvide regular follow-up care

CLASSIFICTION OF DRUGS CLASSIFICTION OF DRUGS USED IN ASTHMAUSED IN ASTHMA

A) Short term relievers used for relief of acute A) Short term relievers used for relief of acute bronchoconstriction:bronchoconstriction:

1.1. Beta Adrenergic agonistsBeta Adrenergic agonists

2.2. MethylxanthinesMethylxanthines

3,3, Anrimuscrinic agentsAnrimuscrinic agents


1.1. Beta Adrenergic agonists: Beta Adrenergic agonists:(i) Drugs acting on both β1 and β2receptors: Epinephrine Ephedrine Isoproterenol

(ii) Beta2 selective drugs: Albuterol Terbutaline Metaproterenol Pirbuterol Bitolterol Salmoterol Formoterol


2. Methylxanthines: Theophylline Theobromine Caffeine

3. Antimuscarinic agents: Ipratropium


B) Long term controllers for reduction of B) Long term controllers for reduction of symptoms and prevention of attacks:symptoms and prevention of attacks:

1. Corticosteroids1. Corticosteroids

2.2. Leukotriene pathway antagonists Leukotriene pathway antagonists

3. Inhibitors of mast cell degranulation3. Inhibitors of mast cell degranulation


1. Corticosteroids: Prednisolone Hydrocortisone Beclomethasone Triamcinolone Fluticasone Budesonide Mometasone


2.2. Leukotriene pathway antagonists: Leukotriene pathway antagonists: Zileuton Zafirlukast Montelukast

3. Inhibitors of mast cell degranulation:3. Inhibitors of mast cell degranulation: Cromolyn sodium Nedocromil

PHARMACODYNAMICS OF PHARMACODYNAMICS OF ΒΒ-ADRENERGIC RECEPTORS-ADRENERGIC RECEPTORS

Beta-2 receptors are the predominant receptors in Beta-2 receptors are the predominant receptors in bronchial smooth musclebronchial smooth muscle

Stimulate adenylyl cyclase, which increases Stimulate adenylyl cyclase, which increases synthesis of cAMP which leads to relaxation of synthesis of cAMP which leads to relaxation of bronchial smooth muscle and inhibition of release bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivityof mediators of immediate hypersensitivity

Inhibits release of mast cell mediators such as Inhibits release of mast cell mediators such as histamine, leukotrienes, and prostaglandin-D2.histamine, leukotrienes, and prostaglandin-D2.

Beta1-receptors are predominant receptors in heart, Beta1-receptors are predominant receptors in heart, but up to 10-50% can be beta2-receptors.but up to 10-50% can be beta2-receptors.

BETA ADRENERGIC AGONISTSBETA ADRENERGIC AGONISTS

a) Non selective beta adrenergic agonists:a) Non selective beta adrenergic agonists:Epinephrine:Epinephrine: It stimulates alpha and beta1as well as beta2 It stimulates alpha and beta1as well as beta2

receptors. receptors. It is an effective rapid acting bronchodilator when It is an effective rapid acting bronchodilator when

injected S/C (0.4 mL of 1:1000 solution) or inhaled injected S/C (0.4 mL of 1:1000 solution) or inhaled as a microaerosol from a pressurised canister (320 as a microaerosol from a pressurised canister (320 mcg/ puff).mcg/ puff).

Adverse effects tachycardia, arrythmias and Adverse effects tachycardia, arrythmias and worsening of angina pectoris. worsening of angina pectoris.

BETA ADRENERGIC AGONISTSBETA ADRENERGIC AGONISTS

Ephedrine:Ephedrine: Used in asthma for longest time. Longer duration and lower potency than epinephrine. Not much used nowadays due to development of β2-

selective agents.

Isoproterenol: A potent bronchodilator , producing effect in 5

minutes. Duration of action 60-90 minutes. High doses associated with cardiac arrhythmias

leading to death.

BETA-2 ADRENERGIC AGONISTS:BETA-2 ADRENERGIC AGONISTS:

Short acting Short acting ββ-2 selective adrenergic agonists:-2 selective adrenergic agonists: Short acting drugs eg albuterol, terbutaline, Short acting drugs eg albuterol, terbutaline,

and perbuterol are available as metered-dose and perbuterol are available as metered-dose inhalers. They are potent bronchodilators.inhalers. They are potent bronchodilators.

Bronchodilation is maximal within 15-30 Bronchodilation is maximal within 15-30 minutes and persists for 3-4 hours. minutes and persists for 3-4 hours.

Toxic effects are minimized when these drugs Toxic effects are minimized when these drugs are delivered by inhalation.are delivered by inhalation.

BETA-2 ADRENERGIC AGONISTSBETA-2 ADRENERGIC AGONISTS

Albuterol and terbutaline are available in tablet Albuterol and terbutaline are available in tablet form, one tablet 2or 3 times daily is the usual form, one tablet 2or 3 times daily is the usual regimen but thisroute is rarely prescribed.regimen but thisroute is rarely prescribed.

Terbutaline is available for S/C injection (0.25 Terbutaline is available for S/C injection (0.25 mg) The indication for this route are severe mg) The indication for this route are severe asthma requiring emergency T/M when asthma requiring emergency T/M when aersolized therapy is not available or has been aersolized therapy is not available or has been ineffective. ineffective.

BETA-2 ADRENERGIC AGONISTSBETA-2 ADRENERGIC AGONISTS

Long acting beta-2 selective agonists:Long acting beta-2 selective agonists: Salmeterol, a potent selective beta-2 agonist, Salmeterol, a potent selective beta-2 agonist,

that achieves its long duration of action as a that achieves its long duration of action as a result of high lipid solubility. This increaes the result of high lipid solubility. This increaes the affinity of the drug for the beta adrenoceptors. affinity of the drug for the beta adrenoceptors.

The drug appears to interact with inhaled The drug appears to interact with inhaled corticosteroids to improve asthma control. corticosteroids to improve asthma control.

Long acting drugs should not be used in acute Long acting drugs should not be used in acute bronchospasm.bronchospasm.

METHYLXANTHINESMETHYLXANTHINESTheophylline:Theophylline:

Narrow therapeutic index/Maintain 5-20 mcg/mLNarrow therapeutic index/Maintain 5-20 mcg/mL Variability in clearance leads to a range of doses that Variability in clearance leads to a range of doses that

vary 4-fold in order to reach a therapeutic dose.vary 4-fold in order to reach a therapeutic dose.

Mechanism of action:Mechanism of action: Smooth muscle relaxation (bronchodilation).Smooth muscle relaxation (bronchodilation). Suppression of the response of the airways to stimuli.Suppression of the response of the airways to stimuli. Increases force of contraction of diaphragmatic Increases force of contraction of diaphragmatic

muscles.muscles. Interacts with many other drugs.Interacts with many other drugs.

METHYLXANTHINESMETHYLXANTHINES

Previously used to be main-stay of asthma Previously used to be main-stay of asthma therapy. therapy.

The bronchodilation produced by theophylline The bronchodilation produced by theophylline is the major therapeutic action in asthma. is the major therapeutic action in asthma.

Most preparations of theophylline are well Most preparations of theophylline are well absorbed from GIT. absorbed from GIT.

For oral therapy with prompt- release For oral therapy with prompt- release formulation the typical dose is 3-4 mg/kg every formulation the typical dose is 3-4 mg/kg every 6hours. 6hours.

METHYLXANTHINESMETHYLXANTHINES

Adverse effects of theophylline:Adverse effects of theophylline: Anorexia, nausea, vomiting, abdominal Anorexia, nausea, vomiting, abdominal

discomfort, headache and anxiety may occur. discomfort, headache and anxiety may occur. Higher levels may cause seizures or Higher levels may cause seizures or

arrythmias.arrythmias. Toxic levels may occur in patients with liver Toxic levels may occur in patients with liver

disease.disease.

METHYLXANTHINES - EFFECTSMETHYLXANTHINES - EFFECTS

(A) CNS effects: Mild cortical arousal with increased alertness and

deferral of fatigue Caffeine containing beverages cause nervousness

and insomnia in unusually sensitive patients and bronchodilation in patients with asthma.

Medullary stimulation and convulsions . Nervousness and tremors are toxic effects of larger

doses.

METHYLXANTHINES - EFFECTSMETHYLXANTHINES - EFFECTS(B) Cardiovascular effects: Direct positive chronotropic and inotropic effects on

the heart. In unusually sensitive patients few cups of coffee can

cause arryhthmias but in normal persons high doses administered parenterally produce only sinus tachycardia and increased cardiac output.

Relaxation of vascular smooth on larger doses except cerebral vessels where they cause contraction.

Ordinary consumption raise peripheral vascular resistance and BP slightly, probably by releasing catecholamines.

Increases viscosity of blood in some cases.

METHYLXANTHINES - EFFECTSMETHYLXANTHINES - EFFECTS(C) Effects on GIT: Stimulation of gastric acid and digestive enzymes

secretion.

(D) Effects on kidney: Weak diuresis (especially theophylline).

(E) Effects on smooth muscles: Bronchodilation. Also inhibits antigen-induced histamine release.

(F) Effects on skeletal muscles: Strengthening of contraction.

ANTIMUSCRINIC AGENTSANTIMUSCRINIC AGENTSMOA:MOA: Muscarinic antagonists Muscarinic antagonists

competitively inhibit the competitively inhibit the effect of acetylcholine at effect of acetylcholine at muscarinic receptors ie muscarinic receptors ie block the contraction of block the contraction of airway smooth muscle airway smooth muscle and the increase in the and the increase in the secretion of mucus.secretion of mucus.

ANTIMUSCRINIC AGENTSANTIMUSCRINIC AGENTS

Ipratropium bromide a quaternary ammonium Ipratropium bromide a quaternary ammonium derivative of atropine is used .It is delivered in derivative of atropine is used .It is delivered in high doses by inhalation route. high doses by inhalation route.

Clinical uses:Clinical uses: Addition of Ipratropium enhances the Addition of Ipratropium enhances the

bronchodilation produced by nebulized bronchodilation produced by nebulized Albuterol in acute severe asthma. Albuterol in acute severe asthma.

In patients intolerant of inhaled beta agonist In patients intolerant of inhaled beta agonist agents. agents.

ANTIMUSCRINIC AGENTSANTIMUSCRINIC AGENTS

Atropine is effective intravenously as well asaerosol, effect lasting for 5 hours

Adverse effects of antimuscrinics include urinary retention, tachycardia, loss of visceral accommodation and agitation.

LONG TERM CONTROLLERSLONG TERM CONTROLLERS

CORTICOSTEROIDS:CORTICOSTEROIDS: They reduce bronchial reactivity, cause They reduce bronchial reactivity, cause

contraction of engorged vessels in bronchial contraction of engorged vessels in bronchial mucosa, and inhibition of the infiltration of mucosa, and inhibition of the infiltration of asthmatic airways by lymphocytes , asthmatic airways by lymphocytes , eosinophils and mast cells.eosinophils and mast cells.

Oral and parenteral corticosteroids are Oral and parenteral corticosteroids are reserved for patients who require urgent T/M. reserved for patients who require urgent T/M.

CORTICOSTEROIDSCORTICOSTEROIDS

Urgent T/M is often begun with an oral dose of Urgent T/M is often begun with an oral dose of 30-60 mg prednisone /day. Or an I/V dose of 30-60 mg prednisone /day. Or an I/V dose of 1mg/kg methylprednisolone every 6 hours. The 1mg/kg methylprednisolone every 6 hours. The daily dose is decreased after air way obstruction daily dose is decreased after air way obstruction is relieved and it is customary to administer is relieved and it is customary to administer corticosteroids early in the morning .corticosteroids early in the morning .

In most patients this systemic corticosteroid In most patients this systemic corticosteroid therapy can be discontinued in a week or 10 therapy can be discontinued in a week or 10 days. days.

CORTICOSTEROIDSCORTICOSTEROIDSINHALED INHALED

CORTICOSTEROIDS:CORTICOSTEROIDS: AerosolT/M is the most effective AerosolT/M is the most effective

way to avoid the systemic effects. way to avoid the systemic effects. An averge daily dose of 4 puffs An averge daily dose of 4 puffs twice daily of Beclomethasone twice daily of Beclomethasone (400mcg/day) is usually given. (400mcg/day) is usually given. In switching patients from oral to In switching patients from oral to inhaled corticosteroid therapy inhaled corticosteroid therapy oral therapy is slowly tapered off. oral therapy is slowly tapered off.


Adverse effects of inhaled coticosteroids:Adverse effects of inhaled coticosteroids: High doses of inhaled steroids may cause High doses of inhaled steroids may cause

adrenal suppression .adrenal suppression . Oropharyngeal candidiasis. Oropharyngeal candidiasis. HoarsenessHoarseness Risks of cataracts and osteoporosis in adults Risks of cataracts and osteoporosis in adults

over the long term use.over the long term use. Transient slowing of rate of growth in children.Transient slowing of rate of growth in children.


Clinical Uses: Used in emergency. Regular controller therapy is maintained with

aerosol corticosteroids. Urgent treatment started with prednisolone 30-60

mg orally or methylprednisolone 1 mg/kg I/V. In most patients discontinued in 10 days. Aerosol therapy decreases the systemic side

effects.

DRUGS OF ASTHMA-II

Clinical uses Clinical uses Chronic use of inhaled corticosteroids Chronic use of inhaled corticosteroids Reduces symptoms and improves pulmonary Reduces symptoms and improves pulmonary

function in mild asthma.function in mild asthma. Reduces or eliminates the use of oral Reduces or eliminates the use of oral

corticosteroids in severe asthma. corticosteroids in severe asthma. CautionCaution Inhaled corticosteroids are effective only so long Inhaled corticosteroids are effective only so long

as they are taken.as they are taken.

PharmacotherapyPharmacotherapy

Mast cell stabilizers (cromolyn/nedocromil)Mast cell stabilizers (cromolyn/nedocromil) Inhibits release of mediators from mast cells Inhibits release of mediators from mast cells

(degranulation) after exposure to specific antigens(degranulation) after exposure to specific antigens Blocks Ca2+ ions from entering the mast cellBlocks Ca2+ ions from entering the mast cell Safe for pediatrics (including infants)Safe for pediatrics (including infants) Should be started 2-4 weeks before allergy season Should be started 2-4 weeks before allergy season

when symptoms are expected to be effectivewhen symptoms are expected to be effective Can be used before exercise (not as good as ICS)Can be used before exercise (not as good as ICS) Alternate med for persistent asthmaAlternate med for persistent asthma

Mast cell stabilizersMast cell stabilizers Cromolyn and NedocromylCromolyn and Nedocromyl MOAMOA An alteration in the function of delayed chloride An alteration in the function of delayed chloride

channels in the cell membrane results in:channels in the cell membrane results in: Inhibition of the early response to an antigenic Inhibition of the early response to an antigenic

challenge of mast cells challenge of mast cells Inhibition of the inflammatory response of Inhibition of the inflammatory response of

eosinophils to inhalation of allergens.eosinophils to inhalation of allergens.

Clinical uses Clinical uses They are only of value when taken prophylactically. They are only of value when taken prophylactically. When used as aerosols (by nebulizer or MDI) they When used as aerosols (by nebulizer or MDI) they

effectively inhibit both antigen-and exercise- induced effectively inhibit both antigen-and exercise- induced asthma. Cromolyn is taken as a single T/M prior to asthma. Cromolyn is taken as a single T/M prior to exercise or unavoidable exposure to allergen.exercise or unavoidable exposure to allergen.

Cromolyn or Nedocromil when taken Cromolyn or Nedocromil when taken regularly 2-4 puffs 2-4 times daily by patients regularly 2-4 puffs 2-4 times daily by patients with nonseasonal asthma, reduces with nonseasonal asthma, reduces symptomatic severity and the need for symptomatic severity and the need for bronchodilator medication. bronchodilator medication.

Addition of nedocromil to a standard dose of Addition of nedocromil to a standard dose of an inhaled corticosteroid appears to improve an inhaled corticosteroid appears to improve asthma control. asthma control.

Adverse effects Adverse effects Minor throat irritation, cough, and mouth dryness and Minor throat irritation, cough, and mouth dryness and

rarely chest tightness and wheezing. rarely chest tightness and wheezing. Serious adverse effects dermatitis, myositis, or Serious adverse effects dermatitis, myositis, or

gastroenteritis occurs in less than 2% of patients. gastroenteritis occurs in less than 2% of patients. Very few cases of pulmonary infiltration and Very few cases of pulmonary infiltration and

anaphylaxis have been reported.anaphylaxis have been reported.

PharmacotherapyPharmacotherapy

Leukotriene receptor antagonistsLeukotriene receptor antagonists Leukotriene-mediated effects include:Leukotriene-mediated effects include:

Airway edemaAirway edema Smooth muscle contractionSmooth muscle contraction Altered cellular activity associated with the Altered cellular activity associated with the

inflammatory processinflammatory process Receptors have been found in airway smooth Receptors have been found in airway smooth

muscle cells and macrophages and on other pro-muscle cells and macrophages and on other pro-inflammatory cells (including eosinophils and inflammatory cells (including eosinophils and certain myeloid stem cells) and nasal mucosacertain myeloid stem cells) and nasal mucosa

Leukotriene pathway inhibitorsLeukotriene pathway inhibitors Zileuton a 5- lipoxygenase inhibitorZileuton a 5- lipoxygenase inhibitor Montelukast, Zafirlukast LTD4 – receptor Montelukast, Zafirlukast LTD4 – receptor

antagonists. antagonists. They improve asthma control. They improve asthma control. They are given orally can be given in patients who They are given orally can be given in patients who

comply poorly with inhaled therapies. comply poorly with inhaled therapies. Montelukast can be used in children as young as 6 Montelukast can be used in children as young as 6

years of age. It can be taken without regards to meals years of age. It can be taken without regards to meals and only once-daily convenient dosage. and only once-daily convenient dosage.

Various severities of asthmaVarious severities of asthma

Step-wise pharmacotherapy treatment program Step-wise pharmacotherapy treatment program for varying severities of asthmafor varying severities of asthma Mild Intermittent (Step 1)Mild Intermittent (Step 1) Mild Persistent (Step 2)Mild Persistent (Step 2) Moderate Persistent (Step 3)Moderate Persistent (Step 3) Severe Persistent (Step 4)Severe Persistent (Step 4)

Patient fits into the highest category that they Patient fits into the highest category that they meet one of the criteria formeet one of the criteria for

Mild Intermittent AsthmaMild Intermittent Asthma

Day time symptoms Day time symptoms << 2 times q week 2 times q week Night time symptoms Night time symptoms << 2 times q month 2 times q month PEF or FEV1 PEF or FEV1 >> 80% of predicted 80% of predicted PEF variability < 20%PEF variability < 20%

PEF and FEV1 values are only for adults and for PEF and FEV1 values are only for adults and for children over the age of 5children over the age of 5

Mild Persistent AsthmaMild Persistent Asthma

Day time symptoms > 2/week, but < 1/dayDay time symptoms > 2/week, but < 1/day Night time symptoms < 1 night q weekNight time symptoms < 1 night q week PEF or FEV1 PEF or FEV1 >> 80% of predicted 80% of predicted PEF variability 20%-30%PEF variability 20%-30%

Moderate Persistent AsthmaModerate Persistent Asthma

Day time symptoms q dayDay time symptoms q day Night time symptoms > 1 night q weekNight time symptoms > 1 night q week PEF or FEV1 60%-80% of predictedPEF or FEV1 60%-80% of predicted PEF variability >30%PEF variability >30%

Severe Persistent AsthmaSevere Persistent Asthma

Day time symptoms: continualDay time symptoms: continual Night time symptoms: frequentNight time symptoms: frequent PEF or FEV1 PEF or FEV1 << 60% of predicted 60% of predicted PEF variability > 30%PEF variability > 30%

Pharmacotherapy for Adults and Pharmacotherapy for Adults and Children Over the Age of 5 Years Children Over the Age of 5 Years

Step 1 (Mild intermittent asthma)Step 1 (Mild intermittent asthma) No daily medication neededNo daily medication needed PRN short-acting bronchodilator (albuterol) MDIPRN short-acting bronchodilator (albuterol) MDI Severe exacerbations may require systemic Severe exacerbations may require systemic

corticosteroidscorticosteroids Although the overall diagnosis is “mild Although the overall diagnosis is “mild

intermittent” the exacerbations themselves can still intermittent” the exacerbations themselves can still be severebe severe

Pharmacotherapy for Adults and Pharmacotherapy for Adults and Children Over the Age of 5 YearsChildren Over the Age of 5 Years

Step 2 (Mild persistent)Step 2 (Mild persistent) Preferred TreatmentPreferred Treatment

Low-dose inhaled corticosteroid dailyLow-dose inhaled corticosteroid daily Alternative Treatment (no particular order)Alternative Treatment (no particular order)

CromolynCromolyn Leukotriene receptor antagonistLeukotriene receptor antagonist NedocromilNedocromil Sustained release theophylline to maintain a blood level Sustained release theophylline to maintain a blood level

of 5-15 mcg/mLof 5-15 mcg/mL


Step 3 (Moderate persistent)Step 3 (Moderate persistent) Preferred TreatmentPreferred Treatment

Low-to-medium dose inhaled corticosteroidsLow-to-medium dose inhaled corticosteroids WITH long-acting inhaled beta2-agonistWITH long-acting inhaled beta2-agonist

Alternative TreatmentAlternative Treatment Increase inhaled corticosteroids within the medium dose Increase inhaled corticosteroids within the medium dose

rangerange Add leukotriene receptor antagonist or theophylline to Add leukotriene receptor antagonist or theophylline to

the inhaled corticosteroidthe inhaled corticosteroid


Step 4 (Severe persistent)Step 4 (Severe persistent) Preferred TreatmentPreferred Treatment

High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids AND long-acting inhaled beta2-agonistsAND long-acting inhaled beta2-agonists AND (if needed) oral corticosteroidsAND (if needed) oral corticosteroids

Pharmacotherapy for Infants and Pharmacotherapy for Infants and Young Children (<5 years)Young Children (<5 years)

Step 1(mild intermittent)Step 1(mild intermittent) No daily medication neededNo daily medication needed


Step 2 (mild persistent)Step 2 (mild persistent) Preferred treatmentPreferred treatment

Low-dose inhaled corticosteroidsLow-dose inhaled corticosteroids Alternative treatmentAlternative treatment

Cromolyn (nebulizer preferred)Cromolyn (nebulizer preferred) OR leukotriene receptor antagonistOR leukotriene receptor antagonist


Step 3 (moderate persistent)Step 3 (moderate persistent) Preferred treatmentPreferred treatment

Low-dose inhaled corticosteroids and long-acting beta2-Low-dose inhaled corticosteroids and long-acting beta2-agonistagonist

OR Medium-dose inhaled corticosteroidsOR Medium-dose inhaled corticosteroids Alternative treatmentAlternative treatment

Low-dose inhaled corticosteroids with either:Low-dose inhaled corticosteroids with either: Leukotriene receptor antagonistLeukotriene receptor antagonist OR theophyllineOR theophylline


Step 4 (severe persistent)Step 4 (severe persistent) Preferred treatmentPreferred treatment

High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids AND long-acting inhaled beta2-agonistAND long-acting inhaled beta2-agonist AND (if needed) Oral corticosteroidsAND (if needed) Oral corticosteroids

For young children, inhaled medications should be For young children, inhaled medications should be given by nebulizer, dry powder inhaler (DPI), or given by nebulizer, dry powder inhaler (DPI), or MDI with a chamber/spacerMDI with a chamber/spacer

Acute ExacerbationsAcute Exacerbations

Inhaled albuterol is the treatment of choice in Inhaled albuterol is the treatment of choice in absence of impending respiratory failureabsence of impending respiratory failure

MDI with spacer as effective as nebulizer with MDI with spacer as effective as nebulizer with equivalent dosesequivalent doses

Adding an antibiotic during an acute Adding an antibiotic during an acute exacerbation is not recommended in the exacerbation is not recommended in the absence of evidence of an acute bacterial absence of evidence of an acute bacterial infectioninfection

Acute ExacerbationsAcute Exacerbations

BeneficialBeneficial Inhaled atrovent added to beta2-agonistsInhaled atrovent added to beta2-agonists High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids MDI with spacer as effective as nebulizerMDI with spacer as effective as nebulizer OxygenOxygen Systemic steroidsSystemic steroids

Likely to be beneficialLikely to be beneficial IV theophyllineIV theophylline

Exercise-induced BronchospasmExercise-induced Bronchospasm

Evaluate for underlying asthma and treat Evaluate for underlying asthma and treat SABA are best pre-treatmentSABA are best pre-treatment Mast cell stabilizers less effective than SABAMast cell stabilizers less effective than SABA Anticholinergics less effective than mast cell Anticholinergics less effective than mast cell

stabilizersstabilizers SABA + mast cell stabilizer not better than SABA + mast cell stabilizer not better than

SABA aloneSABA alone

TREATMENT OF CHRONIC TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASEOBSTRUCTIVE PULMONARY DISEASE

Acute stage inhalation of a short acting beta Acute stage inhalation of a short acting beta agonist eg albuterol,or an anticholinergic drug agonist eg albuterol,or an anticholinergic drug eg ipratropium bromide or the two in eg ipratropium bromide or the two in combination is usually effective.combination is usually effective.

Persistent symptoms of exertional dyspnea and Persistent symptoms of exertional dyspnea and limitation of activities requires a long acting limitation of activities requires a long acting beta agonist or long acting anticholinergic.beta agonist or long acting anticholinergic.

Severe airflow obstruction or a H/O Severe airflow obstruction or a H/O exacerbations: regular use of an inhaled exacerbations: regular use of an inhaled corticosteroid reduces the incidence of future corticosteroid reduces the incidence of future exacerbations. exacerbations.

Theophylline may be used to increase Theophylline may be used to increase ventilatory capacity.ventilatory capacity.

Antibiotics are used in exacerbations of Antibiotics are used in exacerbations of COPD.COPD.

ANTI TUSSIVE AGENTS ANTI TUSSIVE AGENTS DEXTROMETHORPHAN Asynthetic DEXTROMETHORPHAN Asynthetic

derivative of morphine , suppresses the derivative of morphine , suppresses the response of the cough centre. response of the cough centre.

CODEINE decreases the sensitivity of cough CODEINE decreases the sensitivity of cough centres to peripheral stimuli and decreases centres to peripheral stimuli and decreases mucosal secretions.mucosal secretions.

QuestionQuestion

Which one of the following is true concerning Which one of the following is true concerning control of mild persistent asthma in the control of mild persistent asthma in the pediatric population?pediatric population? Cromolyn should not be used under age 5Cromolyn should not be used under age 5 Atrovent should be added if beta-agonists do not Atrovent should be added if beta-agonists do not

maintain control of asthmamaintain control of asthma LABA should be added if SABA is ineffectiveLABA should be added if SABA is ineffective SABA may be used q2h to maintain controlSABA may be used q2h to maintain control Initial treatment should be an inhaled anti-Initial treatment should be an inhaled anti-

inflammatory such as ICS or cromolyninflammatory such as ICS or cromolyn

Answer EAnswer E

Initial medications for chronic asthma should Initial medications for chronic asthma should include an anti-inflammatory such as ICS or include an anti-inflammatory such as ICS or cromolyn. Cromolyn is safe for all pediatric cromolyn. Cromolyn is safe for all pediatric age groups. Atrovent is useful in COPD, but age groups. Atrovent is useful in COPD, but very limited use in asthma. Albuterol should very limited use in asthma. Albuterol should be used up to every 4 hours prn. Overuse of be used up to every 4 hours prn. Overuse of inhaled beta-agonists has been associated with inhaled beta-agonists has been associated with an increased mortality rate. an increased mortality rate.

QuestionQuestion

It is estimated allergic rhinitis affects how may It is estimated allergic rhinitis affects how may people in the US?people in the US? 20 million20 million 40 million40 million 50 million50 million 100 million100 million

Answer: B 40 millionAnswer: B 40 million

QuestionQuestion

Which one of the following statements concerning Which one of the following statements concerning the association between allergic rhinitis and asthma is the association between allergic rhinitis and asthma is false?false? Almost all patients with allergic asthma also have Almost all patients with allergic asthma also have

symptoms of rhinitissymptoms of rhinitis About 1/3 of patients with allergic rhinitis also have About 1/3 of patients with allergic rhinitis also have

asthmaasthma Pharmacologic treatment for allergic rhinitis will not Pharmacologic treatment for allergic rhinitis will not

improve the symptoms of asthmaimprove the symptoms of asthma Patients with allergic rhinitis and patients with asthma Patients with allergic rhinitis and patients with asthma

exhibit peripheral eosinophilia and basophilia.exhibit peripheral eosinophilia and basophilia.

Answer: CAnswer: C

Patients with asthma should have their allergic Patients with asthma should have their allergic rhinitis treatedrhinitis treated

People with asthma and allergic rhinitis who People with asthma and allergic rhinitis who are treated for their allergic rhinitis have a are treated for their allergic rhinitis have a significantly lower risk of subsequent asthma-significantly lower risk of subsequent asthma-related events than those not treated for related events than those not treated for allergic rhinitis.allergic rhinitis.

QuestionQuestion

Which one of the following findings on a nasal Which one of the following findings on a nasal smear suggests a diagnosis of allergic rhinitis?smear suggests a diagnosis of allergic rhinitis? > 10% neutrophils> 10% neutrophils > 10% eosinophils> 10% eosinophils < 10% neutrophils< 10% neutrophils > 10% erythrocytes> 10% erythrocytes

Answer: B >10% eosinophilsAnswer: B >10% eosinophils

QuestionQuestion

Which of the following statements is true?Which of the following statements is true? An acceptable strategy for eliminating sedating An acceptable strategy for eliminating sedating

effects of 1effects of 1stst-generation antihistamines and -generation antihistamines and containing the cost of 2containing the cost of 2ndnd-generation is to use 2nd--generation is to use 2nd-generation in the AM and 1generation in the AM and 1stst-generation in the PM-generation in the PM

In most states, patients taking 1In most states, patients taking 1stst-generation are -generation are considered “under the influence of drugs.”considered “under the influence of drugs.”

Mast cell stabilizers are becoming an excellent Mast cell stabilizers are becoming an excellent choice for children because of their ability to treat choice for children because of their ability to treat symptoms after they have started and their safetysymptoms after they have started and their safety

Answer: BAnswer: B

Patients taking 1Patients taking 1stst-generation antihistamines -generation antihistamines are considered “under the influence of drugs.” are considered “under the influence of drugs.” The sedating effects have been shown to carry The sedating effects have been shown to carry over to the next day even when taken only at over to the next day even when taken only at night and this type of chronic use is not night and this type of chronic use is not recommended.recommended.

Mast cell stabilizers should be started before Mast cell stabilizers should be started before symptoms develop, not after.symptoms develop, not after.

Antiasthmatic drugs

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