RESP - D. AEROSOLS-COVERED Flashcards
1
Q
why are the lungs good at adsorbing drugs into systemic circulation
A
- massive SA but
- air velocity decreases as air goes deeper into lung
2
Q
why drug delivery via the lungs
A
- rapid onset of action
- smaller doses than oral formulations as avoid first-pass metabolism (10-40% reaches lungs and hence sys circulation)
- less systemic and GI adverse effects
- relatively comfortable
3
Q
advantages for local action in upper resp tract
A
- direct access
- rapid onset of action
- avoid GIT and first-pass hepatic metabolism
- lower doses
- fewer side effects
4
Q
advantages for systemic action
A
- avoids GIT (acidic pH, enzymes)
- avoids first-pass hepatic metabolism
- non-invasive
- high bioavailability
- rapid absorption, rapid onset of action (insulin - not degraded by proteases in stomach)
5
Q
what is the purpose of the airways
A
- heat and humidify inhaled air ‘conditioning’
- remove particles from inhaled air by deposition (filter) - KEY FUNCTION
- clear away deposited particles efficiently into GIT (via mucociliary escalator)
- particles shouldn’t reach alveoli where gas exchange takes place
- particles >10microns don’t reach alveoli
- 0.5-5microns deposit by impaction and sedimentation in lower regions
- <3microns can reach alveoli
6
Q
clearance of deposited particles
A
- upper airway regions (trachea, top of lung)
- epithelium covered with mucus which traps particles
- mucociliary escalator: cilia move mucus with particles towards pharynx, swallowed into GIT
- clearance in hours - alveolar region
- no mucus or cilia
- insoluble particles cleared very slowly (months/years)
- clearance of soluble: dissolve, enter blood stream
- clearance of insoluble by macrophages (phagocytosis) or surface tension effects (up to mucociliary escalator)
7
Q
how do we deliver pulmonary drugs
A
- aerosol: suspension of liquid/solid particles or droplets in a gas, sufficiently small to remain airborne for a considerable time
8
Q
properties to be an effective resp medicine
A
- deposit drug in appropriate lung position
- right dose
- overcome physiological barrier and resp defence mechanism
9
Q
Powder flow
A
10microns = stick together due to LSA and won’t flow so we granulate (form balls of particles which flow)
particle 70-100 microns = good flow
<70 microns = poor flow
10
Q
Inertial impaction
A
- most important in large airways
- air flows easily around bends
- particles in air leave flow due to inertia
- may impact on airway walls
- heavier the particle = more inertia (straight line)
*proportional to diameter^2 - bigger particles deposit quickly in upper airways ie - back of throat and swallowed
11
Q
Sedimentation (settling)
A
- most important in smaller airways and alveoli and horizontally orientated airways
- particles settle by gravitation on airway walls
- settling velocity proportional to diameter^2 - Stoke’s law
12
Q
what is the aerodynamic diameter
A
- diameter related to how particles behave in air
‘diameter of a ‘pretend’ sphere with a density of 1g/cm^3 that has the same settling velocity in air as particle of interest’ - governs deposition by sedimentation and inertial impaction
- different sized particles can have same aerodynamic diameter as can have different overall densities
13
Q
Brownian diffusion
A
- most important is smaller airways and mechanism for particles <0.5microns
- small particles leave original flow lines by diffusion and deposit onto airway walls
- displacement from flow line proportional to 1/diameter
- smaller particles therefore show more diffusion
14
Q
Interception
A
- not for spherical particles
- for fibre-like particles
- particles contact airway surface due to their physical size/shape
- long fibres easily intercepted
- not due to aerodynamic diameter
- not used for medicines
15
Q
electrostatic deposition
A
- charged particles attracted towards airway walls by electrostatic charges
- aerosols with high charge and conc can repel each other and drive particles towards airway walls
- only for freshly generated (and charged) aerosols ie: from nebulisers
