Physical properties of the lung/Physics of particle inhalation Flashcards
Which part of the lung is drug deposition to be avoided and why?
- The upper respiratory tract (trachea/oropharynx)
- Deposition here results in drug just being swallowed into the GIT
Why do we deliver drugs to the lung/via the respiratory tract?
- Local effect; bronchodilators/corticosteroids/antibiotics/mucolytics
- Systemic effect; volatile anaesthetics (halothane), ergotamine tartarate (migraine), peptide drugs (insulin avoiding first pass effect normally broken down in stomach)
- Rapid onset of action (huge SA w/strong blood supply)
- Smaller doses than oral formulations
- Less systemic and GI adverse effects
- Relatively comfortable
What are the advantages of local action?
- Direct access to the site of disease
- Rapid onset of action
- Avoids GI tract and first-pass hepatic metabolism
- Lower doses
- Fewer side-effects
What are the advantages for systemic action?
- Avoids GI tract (acidic ph/enzymes)
- Avoids first-pass hepatic metabolism
- Non-invasive, needle-free
- High bioavailability as compared to other non-invasive routes
- Rapid absorption, rapid onset of action (insulin, opioids)
What is the purpose of the airways via a physical perspective?
- Heat and humidify the inhaled air (conditioning)
- Remove particles from inhaled air via deposition (like a filter)
- Clear away deposited particles efficiently into GI tract (clearance via mucociliary escalator)
- Particles should NOT reach the alveoli where gas exchange occurs
- Particles of diameter > 10µm do not reach the alveoli.
How are deposited particles cleared from the upper airway?
- Upper airways covered with mucus (salts/lactate/glycoproteins)
- Via mucociliary escalator; ciliary action moves mucus (w/particles) towards pharynx where it is swallowed to GIT
- Clearance within hours
How are deposited particles cleared from the alveolar region?
- Do not possess mucus layer or cilia
- Thus deposited insoluble particles cleared v. slowly (up to months or years)
- Soluble particles; cleared by dissolving and entry to blood stream
- Insoluble particles; cleared by macrophages via phagocytosis or via surface tension effects pushing them up to the mucociliary escalator
How must pulmonary drugs be delivered?
- Aerosol form; suspension of liquid or solid particles in a gas, sufficiently small to remain airborne for a considerable time
What are the 5 main mechanisms of particle deposition in the lung?
- Inertial impaction
- Sedimentation (settling)
- Diffusion
- Interception
- Electrostatic precipitation
What is inertial impaction?
Where is it most prevalent and why?
- Air flows easily round bends of bronchiole
- Particles in air leave this flow due to their inertia and may thus impact on airway walls
- Heavier the particle, the more the inertia (proportional to diameter)
- Most important in large airways (large velocities, bifurcations (when branches split off)
- Inertial trapping good for impact at desired site; small particle follows air flow, larger particle is trapped.
What is sedimentation?
Where is it most prevalent and why?
- Particles settle by gravitation onto airway wall
- Most important in smaller airways and the alveoli (low flow velocities, small airway dimensions) and horizontally orientated airways
- Settling velocity proportional to diameter
What parameter governs deposition by sedimentation and inertial impaction?
- Aerodynamic diameter; via Stoke’s law taking into account a particle’s density and size; aerodynamically a particle with greater density/small size is less favourable than a less dense/greater size particle
What is Brownian diffusion?
Where is it most prevalent and why?
- Small particles leave original air flow lines by diffusion and deposit onto airway walls
- Most important deposition mechanism for particles
What is interception?
Where is it most prevalent?
- Without deviating from OG flow lines, particles contact airway surface because of their physical size/shape (get stuck on bifurcations etc even tho following flow)
- Long fibres easily intercepted; small aerodynamic particle diameter, large in one dimension.
- Not important for inhaled drugs although drug particles are not usually perfectly spherical
What is electrostatic deposition?
Where is it most prevalent?
- Charged particles attracted towards airway walls by electrostatic charges
- Aerosols with high charge and concentration can repel each other and drive particles toward airway walls
- Not important other than for freshly generated (and charged) aerosols like in nebulisers
