Aerosols - Physical Properties Of The Lung 1 Flashcards
Which parts of the lung are in transitional and respiratory zones?
Respiratory bronchioles
Alveolar ducts
Alveolar sacs
What happens to air velocity as you move down airway tree?
Decreases
What happens to diameter and length of lung generations as you move down the lung tree
Decreases
What happens to total cross sectional area (cm2) as you move down the airway tree?
Increases
Why delivery to the lungs? (Examples
- local effect e.g. bronchodilator / corticosteroid / antibiotics / mucolytics
- systemic effect e.g volatile anaesthetics (halothane), ergotamine tartarate (migraine), peptide drugs (insulin) TO AVOID FIRST PASS METABOLISM
- rapid onset of action
- smaller doses than oral formulations
- less systemic and GI adverse effects
- relatively comfortable
What is air velocity? What is its role? Problems it poses?
Pushes drug into lungs - rapidly decreases to alveoli so hard to target depths of lungs
What advantages are there to local action?
Direct access to site of action Rapid onset Avoids GI Tract Avoids 1st pass metabolism Lower doses Fewer side effects (systemic)
What are the advantages of systemic action?
- avoids GI Tract (avoids acidic pH, enzymes)
- avoids first pass hepatic metabolism
- non invasive, needle free
- high bioavailability as compared to other invasive routes
- rapid absorption and onset of action - insulin and opioids
From a physical perspective what is the purpose of the airways?
- heat and humidity air (conditioning)
- remove particles from the inhaled air by deposition (i.e act as a filter)
- clear away the deposited particles efficiently into the GI tract (clearance via mucociliary clearance)
Where should particles be able to reach in the airway tree?
Particles should not reach alveoli where the gas exchange takes place
What size particles reach alveoli?
Particle diameter >10 micro metres will not normally reach - smaller particles may
How are deposited particles cleared from the upper airway regions?
-covered with mucus
-mucociliary escalator : ciliary action moves mucus (with trapped particles) towards the pharynx, where it is swallowed into the GI Tract
Clearance within hours
How are deposited particles cleared from the alveolar region of the lungs?
- no mucus layer, no cilia
- insoluble particles cleared very slowly - months / up to a year
- clearance of soluble particles : dissolve and enter the blood stream
- clearance of insoluble particles by macrophages (phagocytosis) or surface tension effects (up to the mucociliary escalator)
What is an aerosol?
A suspension of liquid or solid particles in a gas, sufficiently small to remain airborne for a considerable time)
Criteria for an effective pulmonary drug aerosol?
- deposit in the appropriate lung region
- right quantity
- overcome physiological barriers and respiratory defence mechanisms
What are the five main mechanisms by which particles may deposit in the respiratory tract?
- inertial impact ion
- sedimentation
- diffusion
- interception
- electrostatic precipitation
What happens to particles that contact the airway walls?
Trapped and are not reentrained (brought back into the airflow)
Describe inertial impaction
Air flows easily around bends
Particles in the air leaves this flow due to their inertia and may impact on the airway walls
How does the size of a particle influence inertial impaction ? What does this mean for upper airways and why?
The heavier the particle the more inertia (proportional to diameter squared)
Most important in large airways as large velocities
More massive particles deposit quickly in the upper airways
What happens to particles that hit the airway walls ?
Reentrained
What is sedimentation ?
Particles settle by gravitation onto the airway walls
Where is sedimentation most likely to have greater effect?
Smaller airways and the alveoli where there is low flow velocities and small airway dimensions - horizontally orientated airways
What is settling velocity proportional to?
Diameter squared
What is aerodynamic diameter?
Parameter that governs deposits by sedimentation and inertial impaction
Determines the site of particle deposition in the lungs
Particles with a very different size can have the same aerodynamic diameter, because they have different overall densities
What is Brownian Diffusion?
What size particles / part of the lung is this mechanism particularly useful for?
Small particles leave their original flow lines by diffusion and can deposit onto the airway walls
- most important deposition mechanism for particles less than 0.5 micrometers
- most important in smaller airways (short distances, long residence time)
What is displacement from flow line proportional to in Brownian Diffusion?
1/diameter
Therefore smaller particles show much more diffusion
What is Interception?
Give particle examples
Without deviating from their original flow line, particles contact the airway walls as a result of their physical shape / size
Long fibres are easily intercepted
What is Electrostatic Deposition?
Charged particles are attracted towards the airway walls by electrostatic charges
- aerosols with high charge and concentration can repeal one another and drive particles towards the airway walls
What is Respirable Friction?
Percentage of drug present in aerosol particles less than 5 micro meters in size hence likely to be deposited
How can Respirable Fraction be determined? Examples
Sizing techniques
Use of devices which stimulate the inhalation process
E.g. Anderson Cascade Impacter
Next Generation Impinge
How can we imagine the lungs as a series of filters -which mechanisms are responsible for each stage of filtering?
- 5 micrometers impaction in pharynx
- 1-5 micrometers sedimentation in trachea, primary bronchi, secondary bronchi and terminal bronchi
- 1 micrometers diffusion in the alveoli
How can we particle size inhaled products?
1 microscopy (optical and electron) 2 laser diffraction (amount of diffraction through laser beam related to size) 3 aerosizer (time of flight between two laser beams--> measurement of aerodynamic diameter)
What are the advantages of electron microscopy?
Gives shape and texture data as well as size
What is different equivalent diameters?
In electron microscopy, shape of particles can be measured - need to be clear which image is used as particle looks different from different angles
Method of light diffraction
What is a limitation of this measurement ?
Small particles diffract light through large angle
Large particles diffract light through small angle
Detector measures light diffraction pattern produced
Computer calculates particle size distribution
-assumes spherical particle
How does an aerosizer work?
Measures particles that are blown through the instrument and are accelerated by a constant (known force due to this airflow).
Smaller particles are accelerate at a greater rate than large particles
Two laser beams measure time of flight through region by detecting the light scattering particles
Impaction methods of particle sizing
Use of artificial lungs
Measurement of the aerodynamic diameter of particles
Prediction of site of deposition
Operate on principle of inertial impaction
Impaction measuring apparatus
Stages connected by vacuum pump
Particles blown down the tunnel
Large particles unable to follow airstream and impact on upper stages
Smaller particles remain in the airstream and progress to next stage
Can be separated according to aerodynamic diameter
4 apparatus for impaction methods
Twin liquid impinger
Anderson cascade impactor
Multistage liquid impinger
Next generation impactor
Which parts of lung are in conducting zone?
Trachea
Bronchi
Bronchioles
Terminal bronchioles
