Inhaled Route Flashcards
What is the inhaled route for?
Local action
What diseases can the inhaled route treat?
Asthma + COPD
Why do you administer a drug at site of action?
Rapid onset of action
What is the benefit of using smaller doses?
Reduces side effects + cost
Why is the inhaled route easy?
Large SA for absorption
Highly vascularised surface
Air-blood barrier thinner compared to other barriers
Why is it good to have highly vascularised surface?
Rapid absorption + onset of action
Why is it good that the air-blood barrier is thin?
Better drug permeability
What are the advantages?
Smaller doses can be used
Rapid absorption
Avoids GI environment
Avoids hepatic 1st-pass metabolism
Why is it good that it avoids the GI environment?
Minimises chemical + enzymatic drug degradation
What are the disadvantages?
Requires complex delivery devices = high cost
Can be difficult to use
Reproducibility of dose delivery = low
Dug absorption may be limited by mucus layer
What is a pharmaceutical aerosol?
2-phase system of solid particles or liquid droplets dispersed in air
Why is it good that an pharmaceutical aerosol is small?
Considerable stability as suspension
What happens in drug route?
Deposition —> dissolution —> absorption
What patient factors affect particle deposition?
Lung physiology
Breathing patterns
Coordination of aerosol with inspiration
Breath holding
What happens if a larger vol is inhaled?
Great peripheral distribution of particles + increased inhalation flow
Why do you ask patients to hold their breath?
Enhances deposition
What physiochemical factors affect particle deposition?
Aerodynamic size of drug particle
Shape + physical stability
What are the three particle deposition mechanisms?
Inertial impaction
Gravitational sedimentation
Brownian diffusion
Describe inertial impaction
Particles within air stream, having high momentum, impacts on airway’s walls rather than following changing air flow
Where is inertial impaction dominant?
Upper airways
> 5 micro m tho
What is gravitational sedimentation dependent on?
Particle size, density + residence time in airways
What size particles is gravitational sedimentation important for?
1-5 micro m
Where does gravitational sedimentation occur?
Small airways + alveoli = lower velocity
What size particles are important for Brownian diffusion?
0.5-1 micro m
Describe what happens in Brownian diffusion
Bombarded by random gas molecules + produce Brownian motion
= particles collide with airway walls
What happens to Brownian diffusion as particle size decreases?
Increases
What must the aerosolised powder do first?
Dissolve in mucus layer before absorption
What can dissolution be for poorly soluble drugs?
Rate limiting step
What happens once the drug is in solution?
Diffuse across mucus layer + enter aq environment of epithelial lining
What is mucociliary clearance?
Mucus layer constantly propelled along airways by rhythmic beating of cilia on epithelial cells
What happens to particles deposited in ciliated conducting airways?
Cleared by mucociliary clearance
What happens to particles deposited in alveolar region?
Cleared by macrophages
When can drug absorption only take place?
If dissolution is faster than clearance
What is hydrophobic material absorption dependent on?
Their O/W coefficient
Which compounds are poorly absorbed?
Hydrophilic
Which form is better absorbed?
Unionised form
What can the rate of absorption be influenced by?
Formulation
What are the different inhalation devices?
Pressurised metered dose inhaler (pMDIs)
Dry powder inhalers (DPIs)
Nebulisers
