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AEROSOLS

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DEFINITION:

An aerosol comprises of solid or liquid particles

suspended in a gas

GOALS :High efficiency of drug deliveryReproducible dosingTargeted delivery to site of actionEase of device operation

Short duration of treatmentMinimized risk to the patient and clinicianCost - effectiveness

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CLASSIFICATION OF AEROSOLS

BLAND:

include heated or cooled sterile water/ saline

MEDICATED:

bronchodilators, steroids, mucokinetic agents , antallergic agents, local anesthesia, antimicrobials,surfactant, insulin , vosopressin

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AEROSOL PHYSICS

The depth of aerosol delivery is a function of manyvariables--

-size and physical characteristics of the aerosol

- amount of aerosol

- anatomy and geometry of the airway

- ventilatory pattern

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DEPOSITION OF AEROSOLS

Deposited by 3mechanisms:diffusion, inertialimpaction and

sedimentation

Filtered byURT

>100 u

Mouth, nose &

upper airway

5-100 u

Bronchi &bronchioles

2-5 U

Alveoli0.5-2 U

Stable (nodeposition)

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INDICATIONS OF AEROSALS

DIAGNOSTIC :

- Ventilation scans

- Airway responsiveness & bronchodilator reversibility

- Dosimetry

THERAPEUTIC:

- Treatment of airway and lung parenchymal diseases

- Systemic diseases ( D.M , D.I )

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INHALED THERAPIES

Bronchodilators, anti-inf.Asthma

VasodilatorsPulm. HTN

Bronchodilators, anti-inflammatories

COPD exacerbation

Antibiotics, surfactantPneumonia / sepsis

Surfactant, anti-inflammatories

ARDS

THERAPYDIAGNOSIS

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METHODS OF AEROSOLGENERATION

NEBULIZERS:

Pneumatic : - small volume, large volume small particlegenerator

Ultrasonic

METERED DOSE INHALERS:- (+ accessory device:spacer / chamber / spring loaded actuator)

DRY POWDER INHALERS : Rotahaler/ spinhaler/turbohaler/ diskhaler

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NEBULIZERS

Pneumatic/ Jet nebulizers :- work on Bernoullisprinciple

Small volume nebulizer (SVN): Hand-holdnebulizers / ventilator circuits

-gas flow rates : 6-8 l / m-optimal volume : 4-5ml

-particle size : 1-5 u

-10% of aerosol reaches its site of action-not ideal mode of aerosol delivery

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Pneumatic/ Jet nebulisers

ADVANTAGES

Patient coordination notrequired

Effective with tidalbreathing

High dose possible

Dose modification

Can be used with

supplemental oxygen Can deliver combination

therapies if compatible

DISADVANTAGES

Lack of portability

Pressurized gas sourcerequired

Lengthy treatment time Doesnt aerosolize

suspension well

Device preparation

required Performance variability

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ULTRASONIC NEBULISERS

Electric charge is applied to a piezo electriccrystal (transducer)- ultrasonic vibrations aregenerated

Size of aerosol particles depend on frequency ofthe transducer while the volume is related to theamplitude of the sound waves

Suitable for long duration aerosol delivery for

relief of bronchospasm, upper airway edema & forhumidification in tracheostomised patients

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ULTRASONIC NEBULISERS

ADVANTAGES

Patient coordination notrequired

High dose possible

No CFC release

Quiet, faster deliverythan jet nebuliszers

Newer designs areportable and small

DISADVANTAGES

Expensive

Need forelectricity/batteries

Possible drugdegradation

Contamination possible

Drug preparationrequired

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DRY POWDER INHALERS

COMPONENTS:

DEVICE: (Rotahaler /Spinhaler /

Turbuhaler/ Diskhaler)

DRUG RESERVIOR:- discrete gelatin capsules,

multidose strips

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DRY POWDER INHALERS

ADVANTAGES

Breath- actuated

Less patientco-ordination required

Propellant not required

Small & portable

Short treatment time

Dose counters innewer designs

DISADVANTAGES

Requires moderate tohigh inspiratory flow

Some units are single

dose Can result in high

pharyngeal deposition

Not all medicationsavailable

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METERED DOSE INHALERS

ADVANTAGES

Portable &compact

Rx time is short

No drug preparationrequired

Dose-dose reproducibilityhigh

No contamination of

contents

DISADVANTAGES

Coordination of breathingand actuation needed

High pharyngealdeposition

Upper limit to unit dosecontent

Remaining doses difficultto determine

Potential for abuse

Many use CFC

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Holding chamber, Reverse flowspacer, or spacer

ADVANTAGES

Reduces need forpatient co-ordination

Reduces pharyngeal

deposition

DISADVANTAGES

More expensive

Less portable

Can reduce doseavailable if not usedproperly

Inhalation can be

more complex forsome patients

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ACCP / ACAAIRECOMMENDATIONS

DPI

MDI with outspacer/holdingchambers/

Breathactuated MDI

Nebulizers

MDI withspacer/holdingchambers

SHORT

ACTINGBETA 2AGONISTS

LIMITED DATARECOMMENDEMERGENCYDEPT

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DPI

MDI with out

spacer/holdingchambers/

Breath

actuated MDI

Nebulizers

MDI with

spacer/holdingchambers

BETA2AGONISTS

LIMITED DATARECOMMENDINPATIENT

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MDI with or withoutspacer/ holdingchambers

DPI

CORTICOSTEROIDS

MDI with or withoutspacer/ holdingchambers

DPI

SHORT ACTINGBETA 2 AGONISTS

RECOMMENDASTHMAOUT PATIENT

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MDI with or without

spacer/ holdingchambers

DPI

Nebulizers

BETA2 AGONISTS

ANTICHOLINERGICS

RECOMMENDCOPDOUT PATIENT

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Frequent intermittent nebulization andcontinuous nebulizations are appropriatealternatives in severely dyspneic patients in ED

/ ICU

MECHANICAL VENTILATION: Bothnebulization and MDIs can be used but carefulattention to the technique is necessary

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AEROSOLS IN MECHANICAL

VENTILATION

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AEROSOLS IN M.V

Tidal volume >500ml

Slow inspiratory flow

Long inspiratory time

In simulated

spontaneous breaththan controlled m.v

Connection to the

circuit at app 15 cmfrom ETT

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HUMIDITY:

40% reduction increased impaction inventilatory circuits

Dry gas for longer

times harm themucosa

Disconnection VAP

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GAS DENSITY

High inspiratory flow-

turbulence-drugparticle impactionlosses

MDI- Drug deliverywas inverselycorrelated with density

NEBULIZER-Drug

output correlatedpositively with density

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AEROSOLS IN M.V

MDI:

Easy to administer

Less personnel time

Reliable dose No risk of bacterial

contamination

NEBULIZER:

Aerosol production isvariable

Particle size isvariable

Bacterialcontamination

Ventilatory settings

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NEW FRONTIERS

NEW DEVICES

Vibrating platetechnology

Intratracheal catheter

NEW DRUG

FORMULATIONS

Liposomalformulations

Surfactant therapy

GM-CSF

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VIBRATING PLATES

Aerosols with fine particle

fraction Portable, quiet, battery

operated

Higher efficiency of drugdelivery

Minimal residual drug left

Short nebulization time

Doesnt denature proteins/peptides

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INTRATRACHEAL CATHETER

Can be passed into

trachea via anendotracheal tube/bronchoscope

Ideal for targetedaerosol therapy withinlung

Surfactants,antibiotics,

DNA,suspensions canbe aerosolized

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LIPOSOME FORMULATIONS

Closed concentric

bilayer, nanometer insize

Extended therapeutic

response (slowrelease depot effect)

Delivers hydrophilic,hydrophobic drugs

Nucleic acids for genetherapy

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SURFACTANT THERAPY

Deficiency of endogenous surfactant inneonates

Adults with ALI

Appears promising as a treatment forvarious other disorders in critically ill

asthma, bronchiolitis, pneumonia, sepsis

and interstitial lung disease

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GM-CSF

PULMONARY ALVEOLAR PROTEINOSIS:

Patients pulmonary functions improved over 6months of intermittent therapy(250 mic.g bd)

METASTATIC CANCER:Low toxicity and promising antitumor effectagainst lung metastases

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HAZARDS OF AEROSOLTHERAPY

PATIENT:

Bronchospasm

Infection

Airway obstruction( sputum induction in patients

with poor cough reflex) Over hydration ( infants)

Thermal injury (heated aerosols)

Device malfunction Cardio toxicity (CFC)

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CARE GIVER:

Asthma in subjects with hyper-reactive airways

Infection

Rash Bronchospasm

Conjunctivitis

ENVIRONMENT: Ozone layer depletion by CFCs

aerosal

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