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

ASTHMAASTHMA
 Chronic inflammatory disorder of the airways inChronic inflammatory disorder of the airways in
which many cells and cellular elements play awhich many cells and cellular elements play a
role.role.
 In susceptible individuals, this inflammationIn 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 widespreadThese episodes are associated with widespread
but variable airflow obstruction that is reversiblebut 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 withMorbidity and mortality highly correlated with
poverty, urban air quality, indoor allergens,poverty, urban air quality, indoor allergens,
lack of patient education, and inadequatelack 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 ofUsually 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 asthmaThe inflammation associated with asthma
causes an increase in the baseline bronchialcauses 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 outdoorcockroaches, pollen, indoor and outdoor
pollutants, irritants (smoke, perfumes, cleaningpollutants, irritants (smoke, perfumes, cleaning
agents).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,Diseases; GERD, viral and bacterial URI,
rhinitis.rhinitis.
 Physiologic factorsPhysiologic factors

DIAGNOSTIC TESTINGDIAGNOSTIC TESTING
 SpirometrySpirometry
 Recommended to do spirometry pre- and post- useRecommended to do spirometry pre- and post- use
of an albuterol MDI to establish reversibility ofof an albuterol MDI to establish reversibility of
airflow obstructionairflow obstruction
 >> 12% reversibility or an increase in FEV1 of12% 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 normalRestrictive pattern: reduced FVC with a normal
FEV1/FVC ratioFEV1/FVC ratio

 Can be used to identify reversible airwayCan be used to identify reversible airway
obstruction due to triggersobstruction due to triggers
 Can diagnose Exercise-induced asthma (EIA) orCan diagnose Exercise-induced asthma (EIA) or
Exercise-induced bronchospasm (EIB) byExercise-induced bronchospasm (EIB) by
measuring FEV1/FVC before exercise andmeasuring FEV1/FVC before exercise and
immediately following exercise, then for 5-10immediately following exercise, then for 5-10
minute intervals over the next 20-30 minutesminute intervals over the next 20-30 minutes
looking for post-exercise bronchoconstrictionlooking for post-exercise bronchoconstriction

 National Asthma Education and PreventionNational 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 ofPatients breathe in increasing amounts of
methacholine and perform spirometry after eachmethacholine and perform spirometry after each
dosedose
 Increased airway hyperresponsiveness isIncreased airway hyperresponsiveness is
established with a 20% or more decrease in FEV1established 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-inflammatoryDiagnostic trial of anti-inflammatory
medication (preferably corticosteroids) or anmedication (preferably corticosteroids) or an
inhaled bronchodilatorinhaled bronchodilator
 Especially helpful in very young children unable toEspecially 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 canThere is no one single test or measure that can
definitively be used to diagnose asthma in everydefinitively 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 asthmaEducate patients to develop a partnership in asthma
managementmanagement
 Assess and monitor asthma severity with symptomAssess and monitor asthma severity with symptom
reports and measures of lung function as much asreports and measures of lung function as much as
possiblepossible
 Avoid exposure to risk factorsAvoid exposure to risk factors
 Establish medication plans for chronic management inEstablish 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 DRUGSCLASSIFICTION OF DRUGS
USED IN ASTHMAUSED IN ASTHMA
A) Short term relievers used for relief ofA) Short term relievers used for relief of
acute bronchoconstriction:acute 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 ofB) Long term controllers for reduction of
symptoms and prevention of attacks:symptoms and prevention of attacks:
1. Corticosteroids1. Corticosteroids
2.2. Leukotriene pathway antagonistsLeukotriene 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 OFPHARMACODYNAMICS OF
ΒΒ-ADRENERGIC RECEPTORS-ADRENERGIC RECEPTORS
 Beta-2 receptors are the predominant receptors inBeta-2 receptors are the predominant receptors in
bronchial smooth musclebronchial smooth muscle
 Stimulate adenylyl cyclase, which increasesStimulate adenylyl cyclase, which increases
synthesis of cAMP which leads to relaxation ofsynthesis of cAMP which leads to relaxation of
bronchial smooth muscle and inhibition of releasebronchial smooth muscle and inhibition of release
of mediators of immediate hypersensitivityof mediators of immediate hypersensitivity
 Inhibits release of mast cell mediators such asInhibits 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 beta2It stimulates alpha and beta1as well as beta2
receptors.receptors.
 It is an effective rapid acting bronchodilator whenIt is an effective rapid acting bronchodilator when
injected S/C (0.4 mL of 1:1000 solution) or inhaledinjected S/C (0.4 mL of 1:1000 solution) or inhaled
as a microaerosol from a pressurised canister (320as a microaerosol from a pressurised canister (320
mcg/ puff).mcg/ puff).
 Adverse effects tachycardia, arrythmias andAdverse 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 actingShort 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-doseand perbuterol are available as metered-dose
inhalers. They are potent bronchodilators.inhalers. They are potent bronchodilators.
 Bronchodilation is maximal within 15-30Bronchodilation 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 drugsToxic 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 tabletAlbuterol and terbutaline are available in tablet
form, one tablet 2or 3 times daily is the usualform, 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 (0.25Terbutaline is available for S/C injection (0.25
mg) The indication for this route are severemg) The indication for this route are severe
asthma requiring emergency T/M whenasthma requiring emergency T/M when
aersolized therapy is not available or has beenaersolized 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 athat achieves its long duration of action as a
result of high lipid solubility. This increaes theresult 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 inhaledThe drug appears to interact with inhaled
corticosteroids to improve asthma control.corticosteroids to improve asthma control.
 Long acting drugs should not be used in acuteLong acting drugs should not be used in acute
bronchospasm.bronchospasm.

METHYLXANTHINESMETHYLXANTHINES
Theophylline:Theophylline:
 Narrow therapeutic index/Maintain 5-20 mcg/mLNarrow therapeutic index/Maintain 5-20 mcg/mL
 Variability in clearance leads to a range of dosesVariability in clearance leads to a range of doses
that vary 4-fold in order to reach a therapeuticthat vary 4-fold in order to reach a therapeutic
dose.dose.
Mechanism of action:Mechanism of action:
 Smooth muscle relaxation (bronchodilation).Smooth muscle relaxation (bronchodilation).
 Suppression of the response of the airways toSuppression of the response of the airways to
stimuli.stimuli.
 Increases force of contraction of diaphragmaticIncreases force of contraction of diaphragmatic
muscles.muscles.
 Interacts with many other drugs.Interacts with many other drugs.

 Previously used to be main-stay of asthmaPreviously used to be main-stay of asthma
therapy.therapy.
 The bronchodilation produced by theophyllineThe bronchodilation produced by theophylline
is the major therapeutic action in asthma.is the major therapeutic action in asthma.
 Most preparations of theophylline are wellMost preparations of theophylline are well
absorbed from GIT.absorbed from GIT.
 For oral therapy with prompt- releaseFor oral therapy with prompt- release
formulation the typical dose is 3-4 mg/kgformulation the typical dose is 3-4 mg/kg
every 6hours.every 6hours.

Adverse effects of theophylline:Adverse effects of theophylline:
 Anorexia, nausea, vomiting, abdominalAnorexia, nausea, vomiting, abdominal
discomfort, headache and anxiety may occur.discomfort, headache and anxiety may occur.
 Higher levels may cause seizures orHigher levels may cause seizures or
arrythmias.arrythmias.
 Toxic levels may occur in patients with liverToxic 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.

(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.

(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 AGENTS
MOA:MOA:
 Muscarinic antagonistsMuscarinic antagonists
competitively inhibit thecompetitively inhibit the
effect of acetylcholine ateffect of acetylcholine at
muscarinic receptors iemuscarinic receptors ie
block the contraction ofblock the contraction of
airway smooth muscleairway smooth muscle
and the increase in theand the increase in the
secretion of mucus.secretion of mucus.

 Ipratropium bromide a quaternary ammoniumIpratropium bromide a quaternary ammonium
derivative of atropine is used .It is deliveredderivative of atropine is used .It is delivered
in high doses by inhalation route.in high doses by inhalation route.
Clinical uses:Clinical uses:
 Addition of Ipratropium enhances theAddition of Ipratropium enhances the
bronchodilation produced by nebulizedbronchodilation produced by nebulized
Albuterol in acute severe asthma.Albuterol in acute severe asthma.
 In patients intolerant of inhaled beta agonistIn patients intolerant of inhaled beta agonist
agents.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, causeThey reduce bronchial reactivity, cause
contraction of engorged vessels in bronchialcontraction of engorged vessels in bronchial
mucosa, and inhibition of the infiltration ofmucosa, 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 areOral 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 doseUrgent T/M is often begun with an oral dose
of 30-60 mg prednisone /day. Or an I/V doseof 30-60 mg prednisone /day. Or an I/V dose
of 1mg/kg methylprednisolone every 6 hours.of 1mg/kg methylprednisolone every 6 hours.
The daily dose is decreased after air wayThe daily dose is decreased after air way
obstruction is relieved and it is customary toobstruction is relieved and it is customary to
administer corticosteroids early in theadminister corticosteroids early in the
morning .morning .
 In most patients this systemic corticosteroidIn most patients this systemic corticosteroid
therapy can be discontinued in a week or 10therapy can be discontinued in a week or 10
days.days.

INHALEDINHALED
CORTICOSTEROIDS:CORTICOSTEROIDS:
 AerosolT/M is the mostAerosolT/M is the most
effective way to avoid theeffective way to avoid the
systemic effects. An avergesystemic effects. An averge
daily dose of 4 puffs twicedaily dose of 4 puffs twice
daily of Beclomethasonedaily of Beclomethasone
(400mcg/day) is usually(400mcg/day) is usually
given. In switching patientsgiven. In switching patients
from oral to inhaledfrom oral to inhaled
corticosteroid therapy oralcorticosteroid therapy oral
therapy is slowly tapered off.therapy is slowly tapered off.

Adverse effects of inhaled coticosteroids:Adverse effects of inhaled coticosteroids:
 High doses of inhaled steroids may causeHigh doses of inhaled steroids may cause
adrenal suppression .adrenal suppression .
 Oropharyngeal candidiasis.Oropharyngeal candidiasis.
 HoarsenessHoarseness
 Risks of cataracts and osteoporosis in adultsRisks of cataracts and osteoporosis in adults
over the long term use.over the long term use.
 Transient slowing of rate of growth inTransient slowing of rate of growth in
children.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.

 Clinical usesClinical uses
 Chronic use of inhaled corticosteroidsChronic use of inhaled corticosteroids
 Reduces symptoms and improves pulmonaryReduces symptoms and improves pulmonary
function in mild asthma.function in mild asthma.
 Reduces or eliminates the use of oralReduces or eliminates the use of oral
corticosteroids in severe asthma.corticosteroids in severe asthma.
 CautionCaution
 Inhaled corticosteroids are effective only soInhaled corticosteroids are effective only so
long as they are taken.long as they are taken.

PharmacotherapyPharmacotherapy
 Mast cell stabilizers (cromolyn/nedocromil)Mast cell stabilizers (cromolyn/nedocromil)
 Inhibits release of mediators from mast cellsInhibits 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 seasonShould 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 chlorideAn 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 antigenicInhibition of the early response to an antigenic
challenge of mast cellschallenge of mast cells
 Inhibition of the inflammatory response ofInhibition of the inflammatory response of
eosinophils to inhalation of allergens.eosinophils to inhalation of allergens.

 Clinical usesClinical 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) theyWhen used as aerosols (by nebulizer or MDI) they
effectively inhibit both antigen-and exercise- inducedeffectively inhibit both antigen-and exercise- induced
asthma. Cromolyn is taken as a single T/M prior toasthma. 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 takenCromolyn or Nedocromil when taken
regularly 2-4 puffs 2-4 times daily by patientsregularly 2-4 puffs 2-4 times daily by patients
with nonseasonal asthma, reduceswith nonseasonal asthma, reduces
symptomatic severity and the need forsymptomatic severity and the need for
bronchodilator medication.bronchodilator medication.
 Addition of nedocromil to a standard dose ofAddition of nedocromil to a standard dose of
an inhaled corticosteroid appears to improvean inhaled corticosteroid appears to improve
asthma control.asthma control.

 Adverse effectsAdverse effects
 Minor throat irritation, cough, and mouth dryness andMinor throat irritation, cough, and mouth dryness and
rarely chest tightness and wheezing.rarely chest tightness and wheezing.
 Serious adverse effects dermatitis, myositis, orSerious 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 andVery 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 theAltered cellular activity associated with the
inflammatory processinflammatory process
 Receptors have been found in airway smoothReceptors 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 andinflammatory 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 – receptorMontelukast, Zafirlukast LTD4 – receptor
antagonists.antagonists.
 They improve asthma control.They improve asthma control.
 They are given orally can be given in patients whoThey 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 6Montelukast can be used in children as young as 6
years of age. It can be taken without regards to mealsyears 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 programStep-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 theyPatient 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 symptomsDay time symptoms << 2 times q week2 times q week
 Night time symptomsNight time symptoms << 2 times q month2 times q month
 PEF or FEV1PEF or FEV1 >> 80% of predicted80% of predicted
 PEF variability < 20%PEF variability < 20%
 PEF and FEV1 values are only for adults and forPEF 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 FEV1PEF or FEV1 >> 80% of predicted80% 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 FEV1PEF or FEV1 << 60% of predicted60% of predicted
 PEF variability > 30%PEF variability > 30%

Pharmacotherapy for Adults andPharmacotherapy for Adults and
Children Over the Age of 5 YearsChildren 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 systemicSevere exacerbations may require systemic
corticosteroidscorticosteroids
 Although the overall diagnosis is “mildAlthough the overall diagnosis is “mild
intermittent” the exacerbations themselves can stillintermittent” the exacerbations themselves can still
be severebe severe

 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 levelSustained release theophylline to maintain a blood level
of 5-15 mcg/mLof 5-15 mcg/mL

 Step 3 (Moderate persistent)Step 3 (Moderate persistent)
 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 doseIncrease inhaled corticosteroids within the medium dose
rangerange
 Add leukotriene receptor antagonist or theophylline toAdd leukotriene receptor antagonist or theophylline to
the inhaled corticosteroidthe inhaled corticosteroid

 Step 4 (Severe persistent)Step 4 (Severe persistent)
 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 andPharmacotherapy 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)
 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)
 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 beFor young children, inhaled medications should be
given by nebulizer, dry powder inhaler (DPI), orgiven 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 inInhaled albuterol is the treatment of choice in
absence of impending respiratory failureabsence of impending respiratory failure
 MDI with spacer as effective as nebulizer withMDI with spacer as effective as nebulizer with
equivalent dosesequivalent doses
 Adding an antibiotic during an acuteAdding an antibiotic during an acute
exacerbation is not recommended in theexacerbation is not recommended in the
absence of evidence of an acute bacterialabsence of evidence of an acute bacterial
infectioninfection

Acute ExacerbationsAcute Exacerbations
 BeneficialBeneficial
 Inhaled atrovent added to beta2-agonistsInhaled atrovent added to beta2-agonists
 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 treatEvaluate 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 cellAnticholinergics less effective than mast cell
stabilizersstabilizers
 SABA + mast cell stabilizer not better thanSABA + mast cell stabilizer not better than
SABA aloneSABA alone

 TREATMENT OF CHRONICTREATMENT OF CHRONIC
OBSTRUCTIVE PULMONARY DISEASEOBSTRUCTIVE PULMONARY DISEASE
 Acute stage inhalation of a short acting betaAcute stage inhalation of a short acting beta
agonist eg albuterol,or an anticholinergic drugagonist eg albuterol,or an anticholinergic drug
eg ipratropium bromide or the two ineg ipratropium bromide or the two in
combination is usually effective.combination is usually effective.
 Persistent symptoms of exertional dyspnea andPersistent symptoms of exertional dyspnea and
limitation of activities requires a long actinglimitation of activities requires a long acting
beta agonist or long acting anticholinergic.beta agonist or long acting anticholinergic.

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

 Theophylline may be used to increaseTheophylline may be used to increase
ventilatory capacity.ventilatory capacity.
 Antibiotics are used in exacerbations ofAntibiotics are used in exacerbations of
COPD.COPD.

 ANTI TUSSIVE AGENTSANTI TUSSIVE AGENTS
 DEXTROMETHORPHAN AsyntheticDEXTROMETHORPHAN Asynthetic
derivative of morphine , suppresses thederivative of morphine , suppresses the
response of the cough centre.response of the cough centre.
 CODEINE decreases the sensitivity of coughCODEINE decreases the sensitivity of cough
centres to peripheral stimuli and decreasescentres to peripheral stimuli and decreases
mucosal secretions.mucosal secretions.

QuestionQuestion
 Which one of the following is true concerningWhich one of the following is true concerning
control of mild persistent asthma in thecontrol 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 notAtrovent 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 shouldInitial medications for chronic asthma should
include an anti-inflammatory such as ICS orinclude an anti-inflammatory such as ICS or
cromolyn. Cromolyn is safe for all pediatriccromolyn. Cromolyn is safe for all pediatric
age groups. Atrovent is useful in COPD, butage groups. Atrovent is useful in COPD, but
very limited use in asthma. Albuterol shouldvery limited use in asthma. Albuterol should
be used up to every 4 hours prn. Overuse ofbe used up to every 4 hours prn. Overuse of
inhaled beta-agonists has been associated withinhaled beta-agonists has been associated with
an increased mortality rate.an increased mortality rate.

QuestionQuestion
 It is estimated allergic rhinitis affects how mayIt is estimated allergic rhinitis affects how may
people in the US?people in the US?
 20 million20 million
 Answer: B 40 millionAnswer: B 40 million

QuestionQuestion
 Which one of the following statements concerningWhich one of the following statements concerning
the association between allergic rhinitis and asthma isthe association between allergic rhinitis and asthma is
false?false?
 Almost all patients with allergic asthma also haveAlmost all patients with allergic asthma also have
symptoms of rhinitissymptoms of rhinitis
 About 1/3 of patients with allergic rhinitis also have asthmaAbout 1/3 of patients with allergic rhinitis also have asthma
 Pharmacologic treatment for allergic rhinitis will notPharmacologic treatment for allergic rhinitis will not
improve the symptoms of asthmaimprove the symptoms of asthma
 Patients with allergic rhinitis and patients with asthmaPatients 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 allergicPatients with asthma should have their allergic
rhinitis treatedrhinitis treated
 People with asthma and allergic rhinitis whoPeople with asthma and allergic rhinitis who
are treated for their allergic rhinitis have aare 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 forrelated events than those not treated for
allergic rhinitis.allergic rhinitis.

QuestionQuestion
 Which one of the following findings on a nasalWhich 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 sedatingAn 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 excellentMast cell stabilizers are becoming an excellent
choice for children because of their ability to treatchoice 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 carryThe sedating effects have been shown to carry
over to the next day even when taken only atover to the next day even when taken only at
night and this type of chronic use is notnight and this type of chronic use is not
recommended.recommended.
 Mast cell stabilizers should be started beforeMast cell stabilizers should be started before
symptoms develop, not after.symptoms develop, not after.

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