Inhalation TherapyInhalation TherapyBasic Concepts & PrinciplesBasic Concepts & Principles

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IntroductionIntroduction

IntroductionIntroduction

In general, In general, less useless use of Inhalation Therapy of Inhalation Therapy IncreasingIncreasing trend of IT use trend of IT use LackLack of correct knowledge & skill in using it of correct knowledge & skill in using itMany Many misperceptionmisperception of IT among doctors of IT among doctors and patientsand patientsIt is the duty of doctors to It is the duty of doctors to overcomeovercome (mengatasi - menanggulangi)/ (mengatasi - menanggulangi)/ reduce the reduce the problems problems

IntroductionIntroduction

Inhalation Therapy is a method of drugs Inhalation Therapy is a method of drugs delivery delivery into respiratory trackinto respiratory track Other name: Other name: Aerosol therapyAerosol therapy Many respiratory Many respiratory drugsdrugs can be delivered can be delivered Many Many advantagesadvantages, with some limitations, with some limitations

IndicationsIndications

Deposition of bronchoactive aerosolsDeposition of bronchoactive aerosolsEnhancement of secretion clearanceEnhancement of secretion clearanceSputum inductionSputum inductionHumidification of respired gasesHumidification of respired gasesPrevent dehydrationPrevent dehydrationPrevent or relieve bronchospasm or upper Prevent or relieve bronchospasm or upper airway inflammationairway inflammation

Old days nebulizer Old days nebulizer

Glass nebulizerGlass nebulizer

Semi modern nebulizerSemi modern nebulizer

Modern nebulizerModern nebulizer

Muers, Thorax, 1997Muers, Thorax, 1997

Drug delivery schemeDrug delivery scheme

systemicsystemic– parenteral (injection): IV, IM, IC, SCparenteral (injection): IV, IM, IC, SC– enteral (oral): tablet, capsule, syrup, etcenteral (oral): tablet, capsule, syrup, etctopicaltopical– skin : cream, lotionskin : cream, lotion– eye : drop, ointmenteye : drop, ointment– ear : drop,ear : drop,– nose : drop, spraynose : drop, spray– lung : lung : inhalationinhalation

Respiratory drug delivery schemeRespiratory drug delivery scheme

systemicsystemic– parenteral (injection): IV, IM, IC, SCparenteral (injection): IV, IM, IC, SC– enteral (oral): tablet, capsule, syrup, etcenteral (oral): tablet, capsule, syrup, etc

InhalationInhalation– NebulizerNebulizer– Dry powder inhaler (DPI)Dry powder inhaler (DPI)– Metered dose inhaler (MDI)Metered dose inhaler (MDI)

Respiratory defense mechanism

non immunologicnon immunologic : : – the nose : aerodynamic filteringthe nose : aerodynamic filtering

air conditioner (humidifier, temperature optimizer) air conditioner (humidifier, temperature optimizer) – plexus Hesselbach, conchaplexus Hesselbach, concha

particle entrapment  hair, concha turbulence, particle entrapment  hair, concha turbulence,

– mucous layermucous layer– muco-ciliary systemmuco-ciliary system– respiratory reflexes: sneeze, cough reflexrespiratory reflexes: sneeze, cough reflex– respiratory epitheliumrespiratory epithelium

immunologicimmunologic

Inhalation therapy challengeInhalation therapy challenge

Respiratory defense mechanism• nasal hair – entrapment • nasal turbinate - turbulence• expiratory reflex• mucociliary clearance• cough reflex

→ tend to prevent and expelled out foreign material !!!

Inhalation therapy challengeInhalation therapy challenge

Respiratory defense mechanism is Respiratory defense mechanism is designed designed to prevent all kinds of foreignto prevent all kinds of foreign bodies to come or lodge into respiratory bodies to come or lodge into respiratory tracttractMust Must find a wayfind a way to overcome the challenge to overcome the challenge of respiratory defense mechanismof respiratory defense mechanism

The key: The key: particle size & depositionparticle size & deposition

Principles of inhalation therapy

to produce optimal size aerosol to be deposited in the airways (respirable aerosol: <10µm)aerosol is dispersion of fine liquid or solid particle in mist form, produced by – high air flow, or – vibration, or – pressure, or – breath actuated

Principles of inhalation therapyPrinciples of inhalation therapy

target: target: along the respiratory tractalong the respiratory tract – nose, nose, – sinus, sinus, – trachea, trachea, – bronchus, bronchus, – bronchiolus, even bronchiolus, even – Alveolus Alveolus the size of aerosol – determine the targetthe size of aerosol – determine the targetpre-requirement : the size of the particle should pre-requirement : the size of the particle should be very small enough to reach each part of be very small enough to reach each part of respiratory tractrespiratory tract

Dispersion of fine particleDispersion of fine particle

RainRain : tiny drops of water ... : tiny drops of water ...DewDew : tiny drops of moisture condensed on cool : tiny drops of moisture condensed on cool surface (surface (embunembun))

FogFog : vapour suspended in the air, thicker than : vapour suspended in the air, thicker than mist (mist (kabutkabut))MistMist : vapour suspended ... , less thick than fog : vapour suspended ... , less thick than fogHazeHaze : vapour suspende ... , thinner than mist : vapour suspende ... , thinner than mist

SmokeSmoke : ... : ...SmogSmog : misture of smoke and fog ( : misture of smoke and fog (asapasap))

RAIN in the field

FOG on the mountain

MIST in the morning

MIST of Niagara

SMOKE in the forest

SMOG in Montreal

Comparison of systemic vs inhalation drug

A

Aerosol delivery systemsAerosol delivery systems

The 3 principle types of devices widely The 3 principle types of devices widely used are:used are:MDIMDI: Metered dose inhalers: Metered dose inhalersDPIDPI: Dry powder inhalers: Dry powder inhalersNebulizersNebulizers

When to try inhaled When to try inhaled medicationsmedications

Baby with a history of wheezingBaby with a history of wheezingStrong family history of asthmaStrong family history of asthmaModerate or severe distressModerate or severe distressSuction, evaluate, medication, evaluate !Suction, evaluate, medication, evaluate !Use a respiratory score to evaluateUse a respiratory score to evaluateMany studies show some short term Many studies show some short term improvement but very limited data improvement but very limited data showing earlier discharge, decreased showing earlier discharge, decreased hospitalization or shorter duration of hospitalization or shorter duration of symptomssymptoms

Aerosol particle size & location

AerosolSize

Upper resp Lower resp Parenchym

>10μm ++ -- --

7 - 10μm + - -4 - 6μm + + -2 - 3μm -- ++ ++

1μm -- -- ++

<1μm no deposition

How to produce fine particle ?

dispersion of liquid by high speed air flow → jet nebulizer

How to produce fine particle ?

dispersion of liquid by ultrasound vibration→ ultrasonic nebulizer

How to produce fine particle ?

Dry powder in Dry powder in very small sizevery small size particle, generated (dihasilkan) particle, generated (dihasilkan) by patient’s breathby patient’s breath→ → dry powder inhalerdry powder inhaler ( (DPIDPI))

How to produce fine particle ?

liquid + propellant in a high pressured

container (canister) → metered dose Inhaler

(MDI)

Comparison

Thedevice

drugform

Actuation/dihasilkan

need forcoordination

Nebuliser Liquid High flow / vibration

-

DPI DryPowder

Breath +

MDI liquid +propelan

Highpressure

++

Advantages of inhalation therapy

topical

directly to resp system

low dose

minimalside effects

High th/.ratio

fast onsetsafety of

longterm use

reliever controller

Aerosols, resumeAerosols, resumeSuspension of fine liquid or solid particle in air   Suspension of fine liquid or solid particle in air   KeyKey to aerosol therapy is particle size to aerosol therapy is particle sizeAerosol emerge (timbul) at a velocity of Aerosol emerge (timbul) at a velocity of 100km/h100km/h80% drugs deposited in oropharynx 80% drugs deposited in oropharynx 10% in the walls of the inhaler10% in the walls of the inhaler10% in the lungs10% in the lungsParticle size important : determine the Particle size important : determine the mechanism; 2-5µ undergo impaction, mechanism; 2-5µ undergo impaction, sedimentation, or deposition in respiratory tract sedimentation, or deposition in respiratory tract or go in and out for submicronic particlesor go in and out for submicronic particles

IndicationsIndications

Deposition of broncho-active aerosolsDeposition of broncho-active aerosolsPrevent or relieve Prevent or relieve bronchospasmbronchospasm (AB) or (AB) or upper airway inflammation (Croup Syndr)upper airway inflammation (Croup Syndr)Enhancement of secretion clearanceEnhancement of secretion clearanceSputum inductionSputum inductionHumidification of inspired gasesHumidification of inspired gasesPrevent dehydration Prevent dehydration

Factors affecting inhaled drug deliveryFactors affecting inhaled drug delivery

Patient variablesPatient variablesAerosol characteristicsAerosol characteristics– Particle size Particle size – Particle velocityParticle velocity

Device typeDevice type– Nebulizers Nebulizers – pressurized MDIpressurized MDI– DPIDPI

Interface / attachmentInterface / attachment– MouthpiecesMouthpieces– Facemasks Facemasks

SpacersSpacers– Extension deviceExtension device– Holding chambersHolding chambers

Barry et al. Barry et al. Adv Drug Deliv Rev. Adv Drug Deliv Rev. 2003;55:879-923; Bisgaard et al. 2003;55:879-923; Bisgaard et al. Chapter 12Chapter 12. Drug Delivery to the Lung. . Drug Delivery to the Lung. Marcel Marcel Dekker 2001;162:389-420.Dekker 2001;162:389-420.

Patient VariablesPatient Variables

Capability and cooperation Capability and cooperation – Physical coordinationPhysical coordination– Cognitive developmentCognitive development– AdherenceAdherence

Physical featuresPhysical features– Inspiratory flow rateInspiratory flow rate– Upper airway anatomyUpper airway anatomy– Degree of lower airway obstructionDegree of lower airway obstruction

Barry et al. Barry et al. Adv Drug Deliv Rev. Adv Drug Deliv Rev. 2003;55:879-923; Everard ML. 2003;55:879-923; Everard ML. Adv Drug Deliv Rev. Adv Drug Deliv Rev. 2003;55:869-878; 2003;55:869-878; Everard ML. Everard ML. Paediatr Respir Rev. Paediatr Respir Rev. 2003;4:135-1422003;4:135-142

Aerosol Characteristics Aerosol Characteristics Particle sizeParticle size

Optimal particle size range for lung Optimal particle size range for lung depositiondeposition– Mass median aerodynamic diameter (MMAD) Mass median aerodynamic diameter (MMAD)

of aerosol particles should be <5 µmof aerosol particles should be <5 µm– Respirable fraction, MMAD = 1 to 5 µmRespirable fraction, MMAD = 1 to 5 µm– Particles <1 µm may be too small for Particles <1 µm may be too small for efficient efficient

depositiondeposition

39 Barry et al. 39 Barry et al. Adv Drug Deliv Rev. Adv Drug Deliv Rev. 2003;55:879-923; Newhouse MT. 2003;55:879-923; Newhouse MT. Chest. Chest. 1982;82:39S-41S.1982;82:39S-41S.

Obstacles Doctors perspective :

Time consuming Time consuming Self medication by patientSelf medication by patient““Reduce” patient visitReduce” patient visitHigher cost Higher cost – inhalation druginhalation drug– devices & equipmentsdevices & equipments

ObstaclesPatient’s perspective :

Addicted Addicted Disease in severe stageDisease in severe stageExpensive Expensive Danger Danger

ObstaclesObstaclesDrugs & devices :Drugs & devices :

Not widely distributedNot widely distributedRelative expensive Relative expensive Complex manouver (MDI, spacer)Complex manouver (MDI, spacer)Not all drug available in inhalation form Not all drug available in inhalation form

Hazards of therapyHazards of therapy

BronchospasmBronchospasmOver hydrationOver hydrationOverheating of inspired gasesOverheating of inspired gasesDelivery of contaminated aerosolDelivery of contaminated aerosolTubing condensation draining into the Tubing condensation draining into the airwayairway

Comparison between MDI & DPIComparison between MDI & DPI

contains contains CFCCFCHigh velocity aerosolsHigh velocity aerosolsRequires Requires hand breathhand breath co co ordinationordinationDelivery of medicines Delivery of medicines independent of external independent of external factorsfactorsTimeTime consuming to teach consuming to teachRequires deep & slow Requires deep & slow breathing onlybreathing only

No CFCNo CFCAerosol velocity depends Aerosol velocity depends on on inspiratory flow rateinspiratory flow rateNo hand breath No hand breath coordination neededcoordination neededDelivery of medication Delivery of medication largely largely dependentdependent on on external factorsexternal factorsEasy to teachEasy to teachRequires high inspiratory Requires high inspiratory flow>28L/minflow>28L/min

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