bronchodilators

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Bronchodilators and OtherBronchodilators and Other
Respiratory AgentsRespiratory Agents

Drugs AffectingDrugs Affecting
the Respiratory Systemthe Respiratory System
• BronchodilatorsBronchodilators
– Xanthine derivativesXanthine derivatives
– Beta-agonistsBeta-agonists
• AnticholinergicsAnticholinergics
• Antileukotriene agentsAntileukotriene agents
• CorticosteroidsCorticosteroids
• Mast cell stabilizersMast cell stabilizers

Instructors may want to useInstructors may want to use
EIC Image #94:EIC Image #94:
Airway Restrictive FactorsAirway Restrictive Factors

Bronchodilators: Xanthine DerivativesBronchodilators: Xanthine Derivatives
• Plant alkaloids: caffeine, theobromine, andPlant alkaloids: caffeine, theobromine, and
theophyllinetheophylline
• Only theophylline is used as a bronchodilatorOnly theophylline is used as a bronchodilator
Examples:Examples: aminophyllineaminophylline
dyphillinedyphilline
oxtriphyllineoxtriphylline
theophylline (Bronkodyl, Slo-bid,theophylline (Bronkodyl, Slo-bid,
Theo-Dur,Uniphyl)Theo-Dur,Uniphyl)

Mechanism of ActionMechanism of Action
• Increase levels of energy-producing cAMP*Increase levels of energy-producing cAMP*
• This is done competitively inhibitingThis is done competitively inhibiting
phosphodiesterase (PDE), the enzyme thatphosphodiesterase (PDE), the enzyme that
breaks down cAMPbreaks down cAMP
• Result: decreased cAMP levels, smoothResult: decreased cAMP levels, smooth
muscle relaxation, bronchodilation, andmuscle relaxation, bronchodilation, and
increased airflowincreased airflow
*cAMP = cyclic adenosine monophosphate*cAMP = cyclic adenosine monophosphate

Drug EffectsDrug Effects
• Cause bronchodilation by relaxing smooth musclesCause bronchodilation by relaxing smooth muscles
of the airways.of the airways.
• Result: relief of bronchospasm and greater airflowResult: relief of bronchospasm and greater airflow
into and out of the lungs.into and out of the lungs.
• Also causes CNS stimulation.Also causes CNS stimulation.
• Also causes cardiovascular stimulation: increasedAlso causes cardiovascular stimulation: increased
force of contraction and increased HR, resulting inforce of contraction and increased HR, resulting in
increased cardiac output and increased blood flowincreased cardiac output and increased blood flow
to the kidneys (diuretic effect).to the kidneys (diuretic effect).

Therapeutic UsesTherapeutic Uses
• Dilation of airways in asthmas, chronicDilation of airways in asthmas, chronic
bronchitis, and emphysemabronchitis, and emphysema
• Mild to moderate cases of asthmaMild to moderate cases of asthma
• Adjunct agent in the management of COPDAdjunct agent in the management of COPD
• Adjunct therapy for the relief of pulmonaryAdjunct therapy for the relief of pulmonary
edema and paroxysmal nocturnal edema inedema and paroxysmal nocturnal edema in
left-sided heart failureleft-sided heart failure

Side EffectsSide Effects
• Nausea, vomiting, anorexiaNausea, vomiting, anorexia
• Gastroesophageal reflux during sleepGastroesophageal reflux during sleep
• Sinus tachycardia, extrasystole, palpitations,Sinus tachycardia, extrasystole, palpitations,
ventricular dysrhythmiasventricular dysrhythmias
• Transient increased urinationTransient increased urination

Bronchodilators: Beta-AgonistsBronchodilators: Beta-Agonists
• Large group, sympathomimeticsLarge group, sympathomimetics
• Used during acute phase of asthmaticUsed during acute phase of asthmatic
attacksattacks
• Quickly reduce airway constriction andQuickly reduce airway constriction and
restore normal airflowrestore normal airflow
• Stimulate betaStimulate beta22 adrenergic receptorsadrenergic receptors
throughout the lungsthroughout the lungs

Three typesThree types
• Nonselective adrenergicsNonselective adrenergics
– Stimulate alphaStimulate alpha11, beta, beta11 (cardiac), and beta(cardiac), and beta22 (respiratory)(respiratory)
receptors.receptors.
Example: epinephrineExample: epinephrine
• Nonselective beta-adrenergicsNonselective beta-adrenergics
– Stimulate both betaStimulate both beta11 and betaand beta22 receptors.receptors.
Example: isoproterenol (Isuprel)Example: isoproterenol (Isuprel)
• Selective betaSelective beta22 drugsdrugs
– Stimulate only betaStimulate only beta22 receptors.receptors.
Example: albuterolExample: albuterol

• Begins at the specific receptor stimulatedBegins at the specific receptor stimulated
• Ends with the dilation of the airwaysEnds with the dilation of the airways
Activation of betaActivation of beta22 receptors activate cAMP, whichreceptors activate cAMP, which
relaxes smooth muscles of the airway and resultsrelaxes smooth muscles of the airway and results
in bronchial dilation and increased airflow.in bronchial dilation and increased airflow.

• Relief of bronchospasm, bronchial asthma,Relief of bronchospasm, bronchial asthma,
bronchitis, and other pulmonary disease.bronchitis, and other pulmonary disease.
• Useful in treatment of acute attacks as wellUseful in treatment of acute attacks as well
as prevention.as prevention.
• Used in hypotension and shock.Used in hypotension and shock.
• Used to produce uterine relaxation to preventUsed to produce uterine relaxation to prevent
premature labor.premature labor.
• Hyperkalemia—stimulates potassium to shiftHyperkalemia—stimulates potassium to shift
into the cell.into the cell.

Alpha-BetaAlpha-Beta BetaBeta11 and Betaand Beta22 BetaBeta22
(epinephrine)(epinephrine) (isoproterenol)(isoproterenol) (albuterol)(albuterol)
insomniainsomnia cardiac stimulationcardiac stimulation hypotensionhypotension
restlessnessrestlessness tremortremor vascularvascular
headacheheadache
anorexiaanorexia anginal painanginal pain tremortremor
cardiac stimulationcardiac stimulation vascular headachevascular headache tremortremor
vascular headachevascular headache

Respiratory Agents:Respiratory Agents:
General Nursing ImplicationsGeneral Nursing Implications
• Encourage patients to take measures thatEncourage patients to take measures that
promote a generally good state of health inpromote a generally good state of health in
order to prevent, relieve, or decreaseorder to prevent, relieve, or decrease
symptoms of COPD.symptoms of COPD.
– Avoid exposure to conditions that precipitateAvoid exposure to conditions that precipitate
bronchospasms (allergens, smoking, stress, air pollutants)bronchospasms (allergens, smoking, stress, air pollutants)
– Adequate fluid intakeAdequate fluid intake
– Compliance with medical treatmentCompliance with medical treatment
– Avoid excessive fatigue, heat, extremes in temperature,Avoid excessive fatigue, heat, extremes in temperature,
caffeinecaffeine

• Encourage patients to get prompt treatmentEncourage patients to get prompt treatment
for flu or other illnesses, and to getfor flu or other illnesses, and to get
vaccinated against pneumonia or flu.vaccinated against pneumonia or flu.
• Encourage patients to always check withEncourage patients to always check with
their physician before taking any othertheir physician before taking any other
medication, including OTC.medication, including OTC.

• Perform a thorough assessment beforePerform a thorough assessment before
beginning therapy, including:beginning therapy, including:
– Skin colorSkin color
– Baseline vital signsBaseline vital signs
– Respirations (should be <12 or >24 breaths/min)Respirations (should be <12 or >24 breaths/min)
– Respiratory assessment, including PORespiratory assessment, including PO22
– Sputum productionSputum production
– AllergiesAllergies
– History of respiratory problemsHistory of respiratory problems
– Other medicationsOther medications

• Teach patients to take bronchodilatorsTeach patients to take bronchodilators
exactly as prescribed.exactly as prescribed.
• Ensure that patients know how to useEnsure that patients know how to use
inhalers, MDIs, and have the patientsinhalers, MDIs, and have the patients
demonstrate use of devices.demonstrate use of devices.
• Monitor for side effects.Monitor for side effects.

Nursing ImplicationsNursing Implications
• Monitor for therapeutic effectsMonitor for therapeutic effects
– Decreased dyspneaDecreased dyspnea
– Decreased wheezing, restlessness, and anxietyDecreased wheezing, restlessness, and anxiety
– Improved respiratory patterns with return toImproved respiratory patterns with return to
normal rate and qualitynormal rate and quality
– Improved activity toleranceImproved activity tolerance
• Decreased symptoms and increasedDecreased symptoms and increased
ease of breathingease of breathing

Bronchodilators: Nursing ImplicationsBronchodilators: Nursing Implications
Xanthine DerivativesXanthine Derivatives
• Contraindications: history of PUD orContraindications: history of PUD or
GI disordersGI disorders
• Cautious use: cardiac diseaseCautious use: cardiac disease
• Timed-release preparations should not beTimed-release preparations should not be
crushed or chewed (causes gastric irritation)crushed or chewed (causes gastric irritation)

• Report to physician:Report to physician:
PalpitationsPalpitations NauseaNausea VomitingVomiting
WeaknessWeakness DizzinessDizziness Chest painChest pain
ConvulsionsConvulsions

• Be aware of drug interactions with:Be aware of drug interactions with:
cimetidine, oral contraceptives, allopurinolcimetidine, oral contraceptives, allopurinol
• Large amounts of caffeine can haveLarge amounts of caffeine can have
deleterious effects.deleterious effects.

Beta-Agonist DerivativesBeta-Agonist Derivatives
• Albuterol, if used too frequently, loses itsAlbuterol, if used too frequently, loses its
betabeta22-specific actions at larger doses.-specific actions at larger doses.
• As a result, betaAs a result, beta11 receptors are stimulated,receptors are stimulated,
causing nausea, increased anxiety,causing nausea, increased anxiety,
palpitations, tremors, and increasedpalpitations, tremors, and increased
heart rate.heart rate.

Beta-Agonist DerivativesBeta-Agonist Derivatives
• Patients should take medications exactlyPatients should take medications exactly
as prescribed, with no omissions or doubleas prescribed, with no omissions or double
doses.doses.
• Patients should report insomnia, jitteriness,Patients should report insomnia, jitteriness,
restlessness, palpitations, chest pain, orrestlessness, palpitations, chest pain, or
any change in symptoms.any change in symptoms.

Anticholinergics:Anticholinergics:
• Acetylcholine (ACh) causes bronchialAcetylcholine (ACh) causes bronchial
constriction and narrowing of the airways.constriction and narrowing of the airways.
• Anticholinergics bind to the ACh receptors,Anticholinergics bind to the ACh receptors,
preventing ACh from binding.preventing ACh from binding.
• Result: bronchoconstriction is prevented,Result: bronchoconstriction is prevented,
airways dilate.airways dilate.

AnticholinergicsAnticholinergics
• Ipratropium bromide (Atrovent) is the onlyIpratropium bromide (Atrovent) is the only
anticholinergic used for respiratory disease.anticholinergic used for respiratory disease.
• Slow and prolonged actionSlow and prolonged action
• Used toUsed to preventprevent bronchoconstrictionbronchoconstriction
• NOT used for acute asthma exacerbations!NOT used for acute asthma exacerbations!

Anticholinergics: Side EffectsAnticholinergics: Side Effects
Dry mouth or throatDry mouth or throat Gastrointestinal distressGastrointestinal distress
HeadacheHeadache CoughingCoughing
AnxietyAnxiety
No known drug interactionsNo known drug interactions

AntileukotrienesAntileukotrienes
• Also called leukotriene receptor antagonistsAlso called leukotriene receptor antagonists
(LRTAs)(LRTAs)
• New class of asthma medicationsNew class of asthma medications
• Three subcategories of agentsThree subcategories of agents

AntileukotrienesAntileukotrienes
Currently available agents:Currently available agents:
• montelukast (Singulair)montelukast (Singulair)
• zafirlukast (Accolate)zafirlukast (Accolate)
• zileuton (Zyflo)zileuton (Zyflo)

Antileukotrienes:Antileukotrienes:
• Leukotrienes are substances released whenLeukotrienes are substances released when
a trigger, such as cat hair or dust, starts aa trigger, such as cat hair or dust, starts a
series of chemical reactions in the body.series of chemical reactions in the body.
• Leukotrienes cause inflammation,Leukotrienes cause inflammation,
bronchoconstriction, and mucus production.bronchoconstriction, and mucus production.
• Result: coughing, wheezing, shortnessResult: coughing, wheezing, shortness
of breathof breath

• Antileukotriene agentsAntileukotriene agents preventprevent leukotrienesleukotrienes
from attaching to receptors on cells in thefrom attaching to receptors on cells in the
lungs and in circulation.lungs and in circulation.
• Inflammation in the lungs isInflammation in the lungs is blockedblocked, and, and
asthma symptoms are relieved.asthma symptoms are relieved.

Antileukotrienes: Drug EffectsAntileukotrienes: Drug Effects
By blocking leukotrienes:By blocking leukotrienes:
• Prevent smooth muscle contraction of thePrevent smooth muscle contraction of the
bronchial airwaysbronchial airways
• Decrease mucus secretionDecrease mucus secretion
• Prevent vascular permeabilityPrevent vascular permeability
• Decrease neutrophil and leukocyte infiltrationDecrease neutrophil and leukocyte infiltration
to the lungs, preventing inflammationto the lungs, preventing inflammation

Antileukotrienes: Therapeutic UsesAntileukotrienes: Therapeutic Uses
• Prophylaxis and chronic treatment of asthmaProphylaxis and chronic treatment of asthma
in adults and children over age 12in adults and children over age 12
• NOT meant for management of acuteNOT meant for management of acute
asthmatic attacksasthmatic attacks
• Montelukast is approved for use in childrenMontelukast is approved for use in children
age 2 and olderage 2 and older

Antileukotrienes: Side EffectsAntileukotrienes: Side Effects
zileutonzileuton zafirlukastzafirlukast
HeadacheHeadache HeadacheHeadache
DyspepsiaDyspepsia NauseaNausea
NauseaNausea DiarrheaDiarrhea
DizzinessDizziness Liver dysfunctionLiver dysfunction
InsomniaInsomnia
Liver dysfunctionLiver dysfunction
montelukast has fewer side effectsmontelukast has fewer side effects

• Ensure that the drug is being used forEnsure that the drug is being used for
chronic management of asthma, notchronic management of asthma, not
acute asthma.acute asthma.
• Teach the patient the purpose of the therapy.Teach the patient the purpose of the therapy.
• Improvement should be seen in aboutImprovement should be seen in about
1 week.1 week.

• Check with physician before taking anyCheck with physician before taking any
OTC or prescribed medications—manyOTC or prescribed medications—many
drug interactions.drug interactions.
• Assess liver function before beginningAssess liver function before beginning
therapy.therapy.
• Medications should be taken every night onMedications should be taken every night on
a continuous schedule, even if symptomsa continuous schedule, even if symptoms
improve.improve.

CorticosteroidsCorticosteroids
• Anti-inflammatoryAnti-inflammatory
• Used for CHRONIC asthmaUsed for CHRONIC asthma
• Do not relieve symptoms of acuteDo not relieve symptoms of acute
asthmatic attacksasthmatic attacks
• Oral or inhaled formsOral or inhaled forms
• Inhaled forms reduce systemic effectsInhaled forms reduce systemic effects
• May take several weeks before fullMay take several weeks before full
effects are seeneffects are seen

Corticosteroids:Corticosteroids:
• Stabilize membranes of cells that releaseStabilize membranes of cells that release
harmful bronchoconstricting substances.harmful bronchoconstricting substances.
• These cells are leukocytes, or whiteThese cells are leukocytes, or white
blood cells.blood cells.
• Also increase responsiveness of bronchialAlso increase responsiveness of bronchial
smooth muscle to beta-adrenergicsmooth muscle to beta-adrenergic
stimulation.stimulation.

Inhaled CorticosteroidsInhaled Corticosteroids
• beclomethasone dipropionatebeclomethasone dipropionate
(Beclovent, Vanceril)(Beclovent, Vanceril)
• triamcinolone acetonidetriamcinolone acetonide
(Azmacort)(Azmacort)
• dexamethasone sodium phosphatedexamethasone sodium phosphate
(Decadron Phosphate Respihaler)(Decadron Phosphate Respihaler)
• flunisolide (AeroBid)flunisolide (AeroBid)

Inhaled Corticosteroids:Inhaled Corticosteroids:
• Treatment of bronchospastic disordersTreatment of bronchospastic disorders
that are not controlled by conventionalthat are not controlled by conventional
bronchodilators.bronchodilators.
• NOT considered first-line agents forNOT considered first-line agents for
management of acute asthmatic attacksmanagement of acute asthmatic attacks
or status asthmaticus.or status asthmaticus.

• Pharyngeal irritationPharyngeal irritation
• CoughingCoughing
• Dry mouthDry mouth
• Oral fungal infectionsOral fungal infections
Systemic effects are rare because of the lowSystemic effects are rare because of the low
doses used for inhalation therapy.doses used for inhalation therapy.

• Contraindicated in patients with psychosis,Contraindicated in patients with psychosis,
fungal infections, AIDS, TB.fungal infections, AIDS, TB.
• Cautious use in patients with diabetes,Cautious use in patients with diabetes,
glaucoma, osteoporosis, PUD, renalglaucoma, osteoporosis, PUD, renal
disease, CHF, edema.disease, CHF, edema.
• Teach patients to gargle and rinse the mouthTeach patients to gargle and rinse the mouth
with water afterward to prevent thewith water afterward to prevent the
development of oral fungal infections.development of oral fungal infections.

• Abruptly discontinuing these medicationsAbruptly discontinuing these medications
can lead to serious problems.can lead to serious problems.
• If discontinuing, should be weaned for aIf discontinuing, should be weaned for a
period of 1 to 2 weeks, and only ifperiod of 1 to 2 weeks, and only if
recommended by physician.recommended by physician.
• REPORT any weight gain of more than 5REPORT any weight gain of more than 5
pounds a week or the occurrence of chestpounds a week or the occurrence of chest
pain.pain.

Mast Cell StabilizersMast Cell Stabilizers
• cromolyn (Nasalcrom, Intal)cromolyn (Nasalcrom, Intal)
• nedocromil (Tilade)nedocromil (Tilade)

Mast Cell StabilizersMast Cell Stabilizers
• Indirect-acting agents that prevent theIndirect-acting agents that prevent the
release of the various substances thatrelease of the various substances that
cause bronchospasmcause bronchospasm
• Stabilize the cell membranes ofStabilize the cell membranes of
inflammatory cells (mast cells, monocytes,inflammatory cells (mast cells, monocytes,
macrophages), thus preventing release ofmacrophages), thus preventing release of
harmful cellular contentsharmful cellular contents
• No direct bronchodilator activityNo direct bronchodilator activity
• Used prophylacticallyUsed prophylactically

Mast Cell Stabilizers:Mast Cell Stabilizers:
• Adjuncts to the overall managementAdjuncts to the overall management
of COPDof COPD
• Used solely for prophylaxis, NOT forUsed solely for prophylaxis, NOT for
acute asthma attacksacute asthma attacks
• Used to prevent exercise-inducedUsed to prevent exercise-induced
bronchospasmbronchospasm
• Used to prevent bronchospasm associatedUsed to prevent bronchospasm associated
with exposure to known precipitating factors,with exposure to known precipitating factors,
such as cold, dry air or allergenssuch as cold, dry air or allergens

Mast Cell Stabilizers: Side EffectsMast Cell Stabilizers: Side Effects
CoughingCoughing Taste changesTaste changes
Sore throatSore throat DizzinessDizziness
RhinitisRhinitis HeadacheHeadache
BronchospasmBronchospasm

Mast Cell Stabilizers:Mast Cell Stabilizers:
• For prophylactic use onlyFor prophylactic use only
• Contraindicated for acute exacerbationsContraindicated for acute exacerbations
• Not recommended for children under age 5Not recommended for children under age 5
• Therapeutic effects may not be seen for upTherapeutic effects may not be seen for up
to 4 weeksto 4 weeks
• Teach patients to gargle and rinse the mouthTeach patients to gargle and rinse the mouth
with water afterward to minimize irritation towith water afterward to minimize irritation to
the throat and oral mucosathe throat and oral mucosa

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