module 1 - basic concepts & principles.pdf

7/23/2019 Module 1 - Basic Concepts & Principles.pdf

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Basic Concepts& Principles

Module 1

Training of Inhalation Therapy

& Pediatric Asthma Management

Departemen IKA FKUI-RSCMUKK Respirologi PP IDAI


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Prof. Dr. Mardjanis Said, Sp.A(K)Prof. Dr. Mardjanis Said, Sp.A(K)

Born:Born: Payakumbuh, 1 September 1945Payakumbuh, 1 September 1945

Education:Education:

1.1. Faculty medicine, University Indonesia, 1970Faculty medicine, University Indonesia, 19702.2. Medical Post Graduate (Pediatrics), Faculty ofMedical Post Graduate (Pediatrics), Faculty of

Medicine Universitas Indonesia, 1976Medicine Universitas Indonesia, 1976

3. Pediatric Pulmonology Subspecialty, Faculty ofIndonesia 19871987

Recent position :Recent position :

Staff member of Division of Respirology

Lecturer on Pediatric Pulmonology andRespirology,Dept of Child Health, Faculty ofMedicine University of Indonesia


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Introduction - 1 In general, less use of Inhalation Therapy

(IT) in the treatment of respiratory cases Increasing trend of IT use among medical

practitioner and community

Lack of correct knowledge & skill in using it

Many misperception of IT among doctors

and patients It is the duty of doctors to overcome /

reduce the problems


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Introduction - 2 Inhalation therapy is a method of drugs

delivery into respiratory track byinhalation

Other name: Aerosol therapy

widely used in Respirology (Respiratoymedicine)

many respiratory drugs can be deliveredby this method

many advantages, with some limitations


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History

4000 BC: vapours and smoke

India, Egypt, Greece & Rome

1829 : Schneider & Waltz 1st aerosol

device

20th century developments 1930 : Large-sized nebuliser ; jet nebuliser

1955 : pMDI (1956 : Medihaler) 1970s : DPI 1980s : breath-actuated MDI

(Turbuhaler, Easyhaler)


6/466Muers, Thorax, 1997

Old days nebulizer


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Glass nebulizer

Muers, Thorax, 1997


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Semi modern nebulizer

Muers, Thorax, 1997


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Modern nebulizer

Muers, Thorax, 1997


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Drug delivery scheme systemic

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

topical

skin : cream, lotion

eye : drop, ointment

ear : drop,

nose : drop, spray

lung : inhalation


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Respiratory drug delivery scheme

systemic parenteral (injection): IV, IM, IC, SC

enteral (oral): tablet, capsule, syrup, etc

inhalation

Nebulizer

Dry powder inhaler (DPI)

Metered dose inhaler (MDI)


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Respiratory defense mechanism

non immunologic : the nose : aerodynamic filtering

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

particle entrapment hair, concha turbulence,

mucous layer muco-ciliary system

respiratory reflexes: sneeze, cough reflex

respiratory epithelium

immunologic : immune system


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Inhalation therapy challenge -1

Respiratory defense mechanism

nasal hair - entrapment

nasal turbinate - turbulence

expiratory reflex

mucociliary clearance cough reflex

tend to prevent and expelled outforeign material !!!


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Inhalation therapy challenge -2Respiratory defense mechanism is designed

to prevent all kinds of foreign bodies tocome or lodge into respiratory tract

Must find a way to overcome thechallenge of respiratory defense

mechanism

The key: particle size & deposition


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Principles of inhalation therapy -1to produce optimal size aerosol to bedeposited in the airways (respirableaerosol:


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Principles of inhalation therapy -2

target: along the respiratory tractnose,

sinus,trachea,bronchus,

bronchiolus, evenAlveolus

the size of aerosol determine the target

pre-requirement: the size of the particleshould be very small enough to reach each

part of respiratory tract


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Dispersion of fine particle

Rain : tiny drops of water ...

Dew : tiny drops of moisture condensed on cool

surface

Fog : vapour suspended in the air, thicker than

mist Mist : vapour suspended ... , less thick than fog

Haze : vapour suspende ... , thinner than mist

Smoke : ...

Smog : misture of smoke and fog


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RAIN in the field


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19FOG

on the mountain


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20MIST in the morning


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SMOKE in the forest


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SMOG in Montreal


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C

A

B

Mechanisms of deposition within the respiratory tract.

A. Impaction B. Sedimentation C. DiffusionEverard ML, et al. Pediatr Respir Med 1999; 286

Fate of particle


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DIFFUSION SEDIMENTATION INERTIAL IMPACTION

SMOG FOG

AUTOMOBILE EXHAUST PARTICULATES

TOBACCO SMOKE

VIRUSBACTERIA

DUSTS

POLLEN &FUNGAL SPORES

TRACHEOBRONC

HIAL

50.020.010.02.0 5.00.2 0.50.1 1.00.05

0.20

0

0.40

0.60

0.80

1.00

DEPO

SITIONFRA

CTION

TOTA

L

PULM

ONARY

AERODYNAMIC DIAMETER m (Microns)

FUMES


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Particles penetrate the respiratory tract to different degrees according to their size.This diagram also depicts the mechanisms that operate to clear particles from

the Respiratory tract according to size

AlveolarDucts & Sacs

Respiratorybronchiole

Terminal bronchus

Secondary bronchus

Primary bronchus

Trachea

Nasal cavity

7-10

> 10

2-5

< 2

< 2Alveoli

SEDIMENTATION+

DIFFUSION

DIFFUSION

SEDIMENTATION

IMPACTION

PARTICLE SIZE


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Aerosol particle size & location

aerosol

sizeupper resp lower resp parenchy

>10m + - -

7 - 10m + - -4 - 6m + + -

2 - 3m - + +1m - - +


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How to produce fine particle ? -1a

dispersion of liquid by high speed air flowjet nebulizer


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How to produce fine particle ? -1b

dispersion of liquid by ultrasound vibration ultrasonic nebulizer


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How to produce fine particle ? -2

dry powder in very

small size particle,generated bypatients breath

dry powderinhaler

(DPI)


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How to produce fine particle ? -3

liquid + propellant in

a high pressuredcontainer (canister)

metered doseinhaler

(MDI)


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Comparison

Thedevice drugform actuationneed for

coordination

Nebuliser liquid high flow /

vibration

-

DPI dry

powder

breath +

MDI liquid +propelan

highpressure

++


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Advantages of inhalation therapy

topical low dose

high

th/. ratio

directly toresp system

minimalside effects

safety oflongterm use

fast onset

reliever controllerDBS 2004


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Aerosols, resumeAerosols, resume Suspension of fine liquid or solid particle in air

Key to aerosol therapy is aerosol particle

Aerosol emerge at a velocity of 100km/h

80% drugs deposited in oropharynx 10% in the walls of the inhaler

10% in the lungs

Particle size important : determine themechanism; undergo impaction, sedimentation, ordeposition in respiratory tract or go in and out for

submicronic particles


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Indications

Deposition of broncho-active aerosols

Prevent or relieve bronchospasm or upperairway inflammation

Enhancement of secretion clearance

Sputum induction

Humidification of inspired gases

Prevent dehydration


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Pharmacokinetics of inhaled drugs

Pedersen & OPedersen & OPedersen & OPedersen & OByrne, 1997Byrne, 1997Byrne, 1997Byrne, 1997

Metereddose Delivered doseto patient Respiratoryavailability

SystemicavailabilityMetabolism

Liver

Gut

Portalvein

Systemicavailability is

the sum of therespiratory & theoral component


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Factors affecting inhaled drug delivery

Patient variables Aerosol characteristics

Particle size

Particle velocity Device type

Nebulizers

pressurized Metered-dose inhalers (pMDIs) Dry-powder inhalers (DPIs)

Interface / attachment Mouthpieces

Facemasks Spacers

Extension device Holding chambers

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

Dekker 2001;162:389-420.


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Patient Variables

Capability and cooperation

Physical coordination

Cognitive development

Adherence

Physical features

Inspiratory flow rate

Upper airway anatomy

Degree of lower airway obstruction

Barry et al.Adv Drug Deliv Rev. 2003;55:879-923; Everard ML.Adv Drug Deliv Rev. 2003;55:869-878;

Everard ML. Paediatr Respir Rev. 2003;4:135-142


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Aerosol Characteristics

Optimal particle size range for lungdeposition

Mass median aerodynamic diameter

(MMAD) of aerosol particles should be


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Particle Velocity and Patient Breathing

NebulizerNebulizer

MDIMDI

DPIDPI

ParticleParticlevelocityvelocity

SlowSlow FastFast(slower with(slower withspacer)spacer)

Depends onDepends oninspiratoryinspiratoryflowflow

BreathingBreathing Slow tidal,Slow tidal,withwith

occasionaloccasionaldeep breathsdeep breaths

SlowSlow(30 L/min or(30 L/min or

33--5 sec) deep5 sec) deepinhalationinhalation

RapidRapid(60 L/min or(60 L/min or

11--2 sec) deep2 sec) deepinhalationinhalation

NAEPP. Publication no. 97-4051; Kamin et al.J Aerosol Med. 2002;15:65-73; Agertoft et al.J Aerosol Med.

1999;12:161-169. Tandon et al. Chest. 1997;111:1361-1365. Bisgaard et al. Chapter 12. Drug Delivery to the

Lung. Marcel Dekker 2001;162:389-420.


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Inhalation velocity affects lung deposition

with nebulizer

Gamma-camera images of anterior lungs and trachea of 1 patient with asthma following slow

or rapid inspiration of radioaerosol

Slow Rapid

Reprinted fromJ Allergy Clin Immunol, v. 89, Laube BL, Norman PS, Addams III GK. The effect of aerosol

distribution on airway responsiveness to inhaled methacholine in patients with asthma. pp.510-18, 1992, with

permission from The American Academy of Allergy, Asthma & Immunology.


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Obstacles

Doctors perspective :

Time consuming Self medication by patient

Reduce patient visit

Higher cost

inhalation drug

devices & equipments


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Obstacles

Patients perspective :

Addicted

Disease in severe stage

Expensive

Danger


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Obstacles

Drugs & devices :

Not widely distributed

Relative expensive

Complex manouver (MDI, spacer)

Not all drug available in inhalation form


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Positive impact

Quality of tx Quality of life

Quality of tx Quality of life

INHALATION

ORAL

Patient get consultation

Financia

labilityoffamily

To other doctor Go abroad

Controlled asthma

Patient gets patient

-


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Thanks for

your attention

module 1 - basic concepts & principles.pdf

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