Respiratory System Flashcards
Routes of delivery for inhaled drugs
Nasal or pulmonary
Advantages of RDD
BOTH SYSTEMIC AND LOCAL EFFECTS Rapid onset Needle free Reduced total amount of drug Reduce side effects Avoids first-pass
Disadvantages of RDD
Not suitable for long term Dose inaccuracy Do not absorb Local side effects Mucociliary clearance Not for prolong release effects
Formulations of PDD
Particle deposition
Paricle size
Aerosols
Dry powder based
Devices of PDD
Nebulizers
Metered dose inhalers
Dry powder inhalers
Factors concerning PDD
Physiological and pathological condition of the lungs
Drug absorption and kinetics
A&P of PDD
Starts at the nose and ends at the alveolar sac in the lung
- Nasopharyngeal region
- Tracheo-bronchial region
- Alveolar region
Nasopharyngeal region
Includes airways from the nose to larynx
Tracheo-bronchial region
Central or conducting airway
Larynx to the terminal bronchioles (includes tranchea, and bronchi)
Alveolar region
Respiratory/peripheral/pulmonary airway
Comprised of respiratory, bronchioles, alveolar ducts, and alveoli
Branching of the airways
Single daughter branch is smaller than its mother
Sum of two daughter branches is larger than their mother
Increases with each order, further from the mouth –> larger the area
Surface areas of airways
Increase with increase in the generation
Increase with increasing distance of the airway from the glottis
Diameter of airways
Decrease with the increasing generation of airways
Inhaled drugs are delivered as
Droplets or particles
- Must be deposited in an appropriate lung region in sufficient quantity to be effective
Deposition by inertial impaction
Greater than 5 micrometers
Large or fast particles cannot travel in the same direction as the air stream
Increased with particle velocity, diameter, and density
- Based on SPEED/INERTIA
Deposition by sedimentation
Depends on GRAVITY
Varies with time and density
Low velocity
- Max residence time, small airways and lung periphery
Deposition by diffusion
Increased with TIME
Decreases with particle diameter
Independent of density
- Small airways and lung periphery
Physiological factors that affect particle deposition?
Lung anatomy Oral vs nasal inhalation Inspiratory flow rate Coordination of generation and inspiration Tidal volume Diseases
Routes of inhalation
Oral: lungs
Nasal: not oral
Inspiratory flow
Deposition in the first few generation of the respiratory tract increase with the increase inspiratory flow rate
Increasing IFR
Increased particle momentum and turbulence –> increase impaction in the proximal tracheobronchial region
- Decrease particle size
Slow IFR
advantageous for penetration of drug to the target receptor site in the small peripheral airways
Breath holding
- Deposition drugs
Hold breath for period of 5-10 seconds post inspiration - Particles will settle during this time
Pressurized meter dosing requires
hand-mouth coordinaiotn
Aerosol velocity
Droplet velocity is greater than IFR, droplet deposit in the oropharyngel region
- No hand eye coordination
Particle density
Micronized particles for inhalation have particles densities around 1 g
Large pourous particles physical diameters of 20 um and 0.4 densities = deposited
Aerodynamic diameter
Diameter of a sphere of unit density that has the same settling velocity in air as the aerosol particles in question
MMAD
Mass median aerodynamic diameter
- Attach inhaler with the throat, align plates, apply vacuum, collect powder and weigh, plot and determine the size from 50% at weight scale
Physical diameter increased with an what in particle density?
Decrease
Aerodynamic diameter decreases with an what in density?
Decrease
Size of droplets from MDIs
may decrease due to solvent evaporation
Broad respirable particle size range?
10-1 uM
Respirable fraction
Less than 5 um
Fine particle fraction
1-5 um
Particles 5-10 um
Impact in the upper airways but removed by coughing, swallowing and mucociliary processes
Particles between 0.5 - 5 um
Deposit in the alveolar levels by impaction and sedimentation
> 0.5 um particles
50% deposit in the alveoli by diffusion
Rest are exhaled
Effective penetration into the lungs?
1-5 um
Mucus barrier
Dry drugs dissolve in the mucus containing 90-95% water
Poorly soluble drugs, dissolution is the rate limiting step for absorption
- Highly soluble drugs dissolve in highly humid airways
Rate of diffusion depends on?
Mucus thickness
Drug weight
Drug mucus interaction
Mucociliary clearance
Respiratory system eliminates fluid, bacteria, and particulates
Accomplished by the close coordination of ciliary function, airway surface fluid secretion and mucin secretion
Alverolar clearance
Engulfed by macrophages
Eliminated via lumphatic system or into the pulmonary circulation
Hugh surface area?
Slightly larger than the small intestine
- Rapidly delivered to this area
Thin absorption barrier
Thickness is less
Rich vasculature
Receive 100% of cardiac output
Directly to the heart bypassing first pass
Nominal dose
Written on the package label
Metered dose
Amount contained in the metering unit
Delivered dose
Amount leaving the device
Fine particle dose
Amount contained in particles
Recovered amount
Amount recovered from wiping the face and hands with a tissue
Dose to subject
Inhaled dose minues the amount of drug leaving the subject through exhalation and mouth rinsing
