export_kompella respiratory drug delivery Flashcards
What are some agents administered by inhalation?
Localized Effects:
- Anti-asthma: bronchodilators and anti-inflammatory.
- Mucokinetics.
- Antimicrobials.
Systemic Effects:
- General Anesthetics
- Peptide/Protein Drugs
Why respiratory delivery for systemic effects?
- Huge surface area
- Thin alveolar epithelium
- High blood supply
- No hepatic first pass metabolism
- Rapid onset of action
What are other routes can present problems for systemic delivery?
- Oral route: high metabolism of some drugs.
- Parental route: expensive, painful, and poor acceptance
- Pulmonary route - even proteins are absorbed
How are drugs absorbed through the epithelium?
- Passive diffusion through membranes or aqueous pores (most common).
- Carrier mediated transport.
- Endocytosis
How do you use an aerosol?
Remove dust cap, shake, exhale, mouth piece into mouth and close, inhale slowly and deeply while pressing actuator, remove the aerosol and hold breath, allow 5 minutes between doses.
What are some factors that influence particle deposition in lungs?
- Physical properties of the aerosol (particle size, density, shape, size distribution, charge, and hygroscopicity).
- Device: design of metered dose inhalers - pMDIs, dry powder inhalers (DPIs), and nebulizers. Use of spacer device.
- Patient related factors: Lung geometry and breathing pattern.
What are some patient related factors influencing particle deposition in lungs?
- Lung geometry: adults vs. infants, healthy vs. disease states, angle of patient’s neck.
- Breathing pattern: oral vs nasal inhalation, respiratory flow rate, tidal volume, time for breath hold.
slow, large volume breathing and control of cough improves deposition.
What are the mechanisms of particle deposition in lungs?
Impaction, Sedimentation, Diffusion
Where does impaction occur in the lungs and what are some properties?
- Occurs in upper and large conducting airways.
- Favored by high flow velocities and rapid changes in flow directions.
- Significant for particles > 2um
- Increases with particle size.
Where does sedimentation occur in lungs and what are some of its properties?
- Occurs in the small conducting airways and in alveolar regions.
- Favored by deep slow breathing.
- Negligible for particles less than .5 um.
- Main mechanism of deposition of aerosols.
Where does diffusion occur in the lungs and what are its properties?
- Occurs in lung periphery with small lung dimensions.
- Favors breath holding.
Becomes effective for particles less than 0.5 um
- Increases with decreasing particle size
Where are some places that deposition occurs and what are the mechanisms?
- Extrathoracic (nasal/oral, pharynx, larynx).- inertial impaction
- Tracheobronchial deposition - primarily sedimentation, but also inertial impaction.
- Alveolar - sedimentation, diffusion for very small particles.
How are drugs removed from the respiratory tract?
- mucociliary clearance
- coughing
- alveolar permeation into systemic circulation
- metabolism in the lung
What are the different inhalation delivery devices?
- Aerosols: pressurized canister releases drug and patient breathes in.
- Inhaler : patient receives drug into lungs by inhaling.
- Nebulizer: produces a fine mist for patient to inhale through a mask for about 10-15 min.
Note*: Aerosols are very finely subdivide liquid or solid particles that are dispersed in and surrounded by air
What are the classification of aerosol products?
Space spray: highly pressurized, finely divided particles <50um, 85% propellant.
Surface Spray: larger particles, wet and coarse, 30-70% propellant. E.g. dermatologic sprays.
Foam sprays: emulsions of propellants with product concentrate, 6-10% propellant. E.g. vaginal foams, medicated foams, shaving cream.
What is a pressurized metered dose inhaler (pMDI)?
- pocket-sized, hand-held, multiple dose inhalation system that provides consistent, measured dose into lungs.
- Safe, effective, reliable, mainstay of asthma treatment.
What are the advantages of a pMDI?
- Dose can be delivered without contamination.
- Protects formulations that are sensitive to oxygen and moisture.
- Through valves, can deliver controlled and consistent dosages.
What are the components of aerosols?
- Canister (glass, metal, plastics)
- Actuator, valve
- Propellant, concentrate
What are the formulation components of aerosols?
- Propellant
- Liquified gases ((fluorinated hydrocarbons (HFA & CFCs) and hydrocarbons (butane, propane, isobutane))
- Compressed gases (nitrous oxide, carbon dioxide, nitrous). - minimal pharmaceutical use.
- Solvents (non-pharmaceutical use)
What are the two types of aerosols?
- Homogeneous (two phase)
* Heterogeneous (three phase)
How are aerosols filled?
- Cold filling: cool concentrate and propellant, add to chilled container, attach spray assembly.
- Disadvantages: aqueous solutions can’t be added as ice is formed. Some propellant is lost.
Pressure filling: Add product to container, attach valve, fill with propellant from pressurized container. - Advantages: less risk of moisture contamination, propellant is not lost.
What are aerosols tested for?
- Components
- Peformance (e.g. net contents, dosage)
- Flammability
- Biological Activity
What is contained in the product concentrate of aerosols?
- Active ingredient
- Anti-oxidants
- Surfactants
- Solvent
What are the label warnings of aerosols?
- Don’t inhale if not for respiratory therapy.
- Contents under pressure so don’t incinerate or puncture
- Don’t spray into eyes or nasal areas
- Keep away from children
What are the problems with pMDIs and what are the solutions?
- Problems: impaction from the rapid expansion of propellant and CFCs.
- Solutions: Spacer device (reduce velocity, particle size, droplet size, and impaction in patient) Use HFAs instead of CFCs.
What is a dry-powder inhaler?
- No compressed propellant, dry powders.
- Dry powder delivered by inhalation. Depend on patient’s ability to inhale.
- Some DPIs use pump or an electric motor.
- Powder entrainment is a function of ability of patient to inhale and the resistance of the device to passage of air.
What is the problem with dry powder inhalers?
- performance largely dependent on patient factors
- greater the resistance of the device, greater the patient discomfort
- particle aggregation due to static charge
What is the ideal DPI ?
One where it is able to consistently emit a complete dosage regardless of inhalation energy level at a comfortable level and where particles are deaggregated into smaller sizes.
What are the different types of dry powder inhalers?
Rotainhaler - insert capsules of medication powder each time.
Turbuhaler - does not require loading with capsules. Has window that shows dosages left.
Diskhaler - uses medication pack in blister packs.
Diskus or Accuhaler - medication is in foil pouches that is pierced to release medication.
What is a nebulizer?
- It is driven by a compressed air machine which provides medication in the form of a mist.
- Consists of a mask with a mouthpiece.
- Used by children
What effect do spacers on MDI have?
They are more efficient at delivering drugs at target site.
What is Exubera?
It is an inhalation device made for diabetes. Should not be used in people who smoke, start smoking, or quit smoking in last 6 months. May get cough, dry mouth, or chest discomfort.
