Aerosol Drug Therapy — Vocabulary Flashcards

Aerosol Drug Therapy - Study Notes

Aerosol Output

• Output refers to the mass of fluid or drug contained in the aerosol.
• Output rate = mass of aerosol generated per unit time.
• Output varies depending on the nebulizer or inhaler used.
• Emitted dose = mass of drug leaving the mouthpiece as aerosol.
• Measured by collecting aerosol that leaves the nebulizer on filters.
• Gravimetric analysis measures aerosol weight.
• Assay measures quantity of drug.
• Practical relevance: understanding how much drug is available for inhalation and how device design affects dose delivery.

Particle Size (1 of 2)

• Particle size depends on three factors:
  • Substance being nebulized.
  • Method used to generate the aerosol.
  • Environmental conditions.
• Methods to measure medical aerosol particle distribution include:
  • Cascade impaction
  • MMAD — mass median aerodynamic diameter, ext{MMAD}
  • Laser diffraction
  • VMD — volume median diameter, ext{VMD}
• Measurement techniques help predict where particles will deposit in the respiratory tract.

Particle Size (2 of 2)

• Aerosols can be heterodisperse or monodisperse:
  • Heterodisperse: contains particles of many different sizes.
  • Monodisperse: particles of similar sizes.
• Geometric standard deviation (GSD) describes variability of particle sizes.
• Definitions:
  • Heterodisperse aerosols have a wide size range.
  • Monodisperse aerosols have similar sizes.
• Greater the GSD, wider the range of particle sizes and more heterodisperse the aerosol.

Deposition (1 of 6)

• Only a fraction of the emitted aerosol is inhaled (emitted dose).
• Only a fraction of the inhaled aerosol is deposited in the lungs (respirable dose).
• Amount of drug inhaled is called the inhaled mass.
• The portion of inhaled mass that can reach the lower airways is the respirable mass.

Deposition (2 of 6)

• Deposition is influenced by:
  • Inspiratory flow rate
  • Flow pattern
  • Respiratory rate
  • Inhaled volume
  • I:E ratio
  • Breath-holding
• Key deposition mechanisms:
  • Inertial impaction
  • Gravimetric sedimentation
  • Brownian diffusion

Deposition (3 of 6)

• Inertial impaction:
  • Aerosol in motion collides with and deposits on surfaces.
  • Primary deposition mechanism for larger particles (>
    5 μm).
  • Greater mass and velocity increase inertia and tendency to continue on the original path.

Deposition (4 of 6)

• Sedimentation:
  • Particles settle out of suspension due to gravity.
  • Primary mechanism for deposition of small particles (1–5 μm).
  • Breath-holding after inhalation increases sedimentation and distribution across lungs.
  • Greater particle mass leads to faster settling.

Deposition (5 of 6)

• Brownian diffusion:
  • Primary deposition mechanism for very small particles (< 3 μm).
  • Deep within the lung, particles between 1 and 0.5 μm have very low mass and remain in suspension, often exhaled.
  • Particles < 0.5 μm have greater retention rate in the lungs.

Deposition (6 of 6)

• Regional deposition targets and recommended MMADs:
  • Upper airway (nose, larynx, trachea): ext{MMAD} ext{ range } = 5 ext{ to } >50 \n \, ext{μm}
  • Lower airways: ext{MMAD range } = 2 ext{ to } 5 \, ext{μm}
  • Parenchyma / alveolar region: ext{MMAD range } = 1 ext{ to } 3 \, ext{μm}
  • Parenchyma: ext{MMAD} < 0.1 \, ext{μm}

Aging Process (1 of 2)

• Aging describes how an aerosol suspension changes over time.
• Factors influencing aging:
  • Composition of the aerosol
  • Initial particle size
  • Particle size changes due to evaporation or hygroscopic water absorption
  • Time in suspension
  • Ambient conditions

Quantifying Aerosol Delivery (1 of 2)

• Scintigraphy:
  • A drug is tagged with a radioactive substance, aerosolized, and inhaled.
  • A scanner measures distribution and intensity of radiation across the device, head, and thorax.
  • Used to calculate the percentage of drug retained by the device and delivered to various areas in the patient.
• Assay in blood or urine over time:
  • Does not estimate actual lung delivery but provides insight into systemic drug levels after aerosol administration.

Hazards of Aerosol Therapy

• Primary hazard: adverse reaction to the medication.
• Other hazards:
  • Infection risk
  • Airway reactivity
  • Pulmonary and systemic effects of bland aerosols
  • Drug concentration changes during nebulization
  • Eye irritation
  • Secondhand exposure to aerosol drugs

Pressurized Metered Dose Inhalers (pMDI) – Overview (1 of 9)

• Pressurized canister contains prescribed drug in volatile propellant with surfactant and dispersing agent.
• Most commonly prescribed method of aerosol therapy.
• Portable, compact, easy to use; provides multidose convenience.
• Major limitation: Lacks a counter to indicate the number of doses remaining in the canister.

Pressurized Metered Dose Inhalers (2 of 9)

• Most pMDIs are “press and breathe.”
• Variations:
  • Aerospan: built-in valveless spacer improves hand-breath coordination.
  • Breath-actuated pMDIs: trigger activated during inhalation, reducing need for coordination between actuation and inhalation.

Pressurized Metered Dose Inhalers (3 of 9)

• Variations (continued): Tempo inhaler.
• Temperature can affect performance; nozzle size and cleanliness affect output.
• Debris on nozzle or actuator orifice reduces emitted dose.

Pressurized Metered Dose Inhalers (4 of 9)

• Priming and handling:
  • Priming required for new or unused devices.
  • Shaking device and releasing one or more sprays into air ensures drug-propellant mixing.
  • Timing of actuation intervals is important.
  • Propellant release cools the device and changes aerosol output.

Pressurized Metered Dose Inhalers (5 of 9)

• Aerosol delivery characteristics:
  • pMDIs can produce particles in the respirable range: ext{MMAD} ext{ in } [2,6] \, ext{μm}
  • About 80 ext{%} of aerosol deposits in the oropharynx.
  • Pulmonary deposition ranges 10 ext{%} to 20 ext{%} in adults and larger children.

Pressurized Metered Dose Inhalers (6 of 9)

• Technique for use:
  • Actuate at the beginning of inspiration.
  • Mouthpiece held about 4\text{ cm} in front of an open mouth.

Pressurized Metered Dose Inhalers (7 of 9)

• Open-mouth technique concerns:
  • Ipratropium bromide with poor coordination can spray into eyes.
  • Anticholinergic agents linked to increased ocular pressure.
  • Steroid pMDIs may increase opportunistic oral yeast infection and dysphonia.

Pressurized Metered Dose Inhalers (8 of 9)

• Accessory devices for pMDIs:
  • Spacer concepts: small volume adapters, open tube designs, bag reservoirs, and valved holding chambers.
  • Spacers add distance between pMDI and mouth, reducing initial forward velocity and oropharyngeal deposition; they reduce the need for hand-breath coordination.
  • Spacers are simple valveless extension devices.

Pressurized Metered Dose Inhalers (9 of 9)

• Holding chambers:
  • Incorporate one or more valves to prevent aerosol in the chamber from being cleared on exhalation.
  • Provide less oropharyngeal deposition, higher respirable drug dosages, and better protection from poor hand-breath coordination than simple spacers.

Dry Powder Inhalers (1 of 4)

• DPI are breath-actuated dosing systems.
• Patient creates aerosol by drawing air through a dose of finely milled drug powder.
• Dispersion of powder depends on turbulent flow within the inhaler.
• Flow is a function of the patient’s ability to inhale powder with sufficiently high inspiratory flow rate.
• DPIs do not use propellants and do not require hand-breath coordination used for pMDIs.

Dry Powder Inhalers (2 of 4)

• DPI design categories:
  • Unit-dose DPI: Aerolizer and Handihaler dispense individual doses from punctured gelatin capsules.
  • Diskhaler: contains a case of four or eight blister packets on a disk inserted into the inhaler.
  • Multiple-dose Drug Reservoir DPI: Twisthaler, Flexhaler, Diskus—preloaded with quantity of drug sufficient for dispensing 120 doses.

Dry Powder Inhalers (3 of 4)

• Factors affecting DPI performance and delivery:
  • Intrinsic resistance and inspiratory flow rate
  • Humidity and moisture exposure
  • Patient’s inspiratory flow ability
  • Technique: patients must generate an inspiratory flow rate of at least 40-60\,\mathrm{L/min} to produce a respirable powder aerosol
  • DPIs should not be used by infants, small children, those unable to follow instructions, or patients with severe airway obstruction
  • Cleaning per product label.

Dry Powder Inhalers (4 of 4)

• New DPI technologies: Easyhaler, Ellipta, Podhaler, Tudorza, Pressair, Spiromax.

Pneumatic (Jet) Nebulizers (1 of 4)

• Most nebulizers are powered by high-pressure oxygen or air.
• Power sources include portable compressors, compressed gas cylinders, or 50-psi wall outlets.
• Factors affecting performance:
  • Nebulizer design, flow, gas source, density, humidity and temperature, and formulation characteristics.

Pneumatic (Jet) Nebulizers (2 of 4)

• Small-volume nebulizers (SVNs) categories and effects:
  • Continuous nebulizer with simple reservoir: may increase inhaled dose by 5\%-10\%, or from 10\% to 11\% with a 6\text{-inch} reservoir tube.
  • Continuous nebulizer with collection reservoir bag: bag reservoirs hold aerosol generated during exhalation, allowing small particles to remain in suspension for inhalation next breath; larger particles rain out; attributed to a 30\%-50\% increase in inhaled dose.
• Small-volume nebulizer improvements depend on reservoir design.

Pneumatic (Jet) Nebulizers (3 of 4)

• Other SVN variants:
  • Breath enhanced (BE): generate aerosol continuously using vents/one-way valves.
  • Breath actuated nebulizer (BAN): can increase inhaled aerosol mass by 3- to 4\text{-fold} over conventional continuous nebulization.

Pneumatic (Jet) Nebulizers (4 of 4)

• SVN technique and considerations:
  • Slow inspiratory flow optimizes SVN deposition.
  • Choice between mask or mouthpiece depends on patient ability, preference, and comfort.
  • Infection control: nebulizers should be cleaned and disinfected, or rinsed with sterile water, and air dried between uses.

Large Volume Jet Nebulizers (1 of 5)

• L/V jet nebulizers are used to deliver aerosolized drugs to the lung, especially when standard dosing is ineffective in severe bronchospasm.
• Referred to as HIGH-OUTPUT extended aerosol respiratory therapy nebulizers.

Large Volume Jet Nebulizers (2 of 5)

• Small Particle Aerosol Generator (SPAG):
  • Regulator connected to two flowmeters controlling flow to the nebulizer and through the drying chamber.
  • Nebulizer flow should be maintained at approximately 7\,\mathrm{L/min} with total flow from both meters not less than 15\,\mathrm{L/min}.
  • Problems include caregiver exposure to drug aerosol; exposure occurs mainly when delivering ribavirin via a mechanical ventilator circuit.

Large Volume Jet Nebulizers (3 of 5)

• Other delivery devices:
  • Hand-bulb atomizers and nasal spray pumps for upper airway delivery (sympathomimetic, anticholinergic, anti-inflammatory, anesthetic aerosols).
  • Large volume USNs.
  • Vibrating mesh nebulizers.

Large Volume Jet Nebulizers (4 of 5)

• Smart nebulizers:
  • I-neb (Phillips Respironics): breath-actuated passive vibrating mesh; adaptive aerosol delivery monitors pressure changes and inspiratory time for the first three breaths; drug aerosolized over 50\% of the inspiratory maneuver during the fourth and subsequent breaths.
  • Released for delivery of prostacyclin.

Large Volume Jet Nebulizers (5 of 5)

• Akita (Activaero) smart nebulizer:
  • Controls inspiratory flow to keep it slow (approx. 12-15\,\mathrm{L/min}) to reduce impaction loss in upper airways.
  • Patient pulmonary function stored on a smart card to program device when to generate aerosol during inhalation.

Special Medication Delivery Issues (1 of 2)

• Infants and children: smaller airway diameter, faster breathing, nose breathing filters out large particles, lower minute volumes, variable cooperation.
• Aerosols should never be administered to a crying child; crying reduces lower airway deposition of aerosol medication.

Special Medication Delivery Issues (2 of 2)

• Blow-by technique:
  • Used if patient cannot tolerate mask treatment.
  • Practitioner directs aerosol from nebulizer toward patient’s nose and mouth, at a distance of several inches from face.
• Selecting an aerosol drug delivery system:
  • Must be prescribed for appropriate patients and used properly.

Assessment-Based Bronchodilator Therapy Protocols (1 of 2)

• Role of RT:
  • Assess patient response.
  • Ongoing patient assessment is key to effective bronchodilator therapy.
  • Peak flow measurement can provide trends if the same device is used from one treatment to the next.

Assessment-Based Bronchodilator Therapy Protocols (2 of 2)

• Components of patient assessment:
  • Patient interviewing
  • Observation
  • Measurement of vital signs
  • Auscultation
  • Blood gas analysis (ABG)
  • Oximetry
• Conduct dose-response titration to determine best dosage for patients with moderate obstruction.
• Patient education.

Special Considerations (1 of 8)

• Aerosol therapy for pulmonary arterial hypertension (PAH):
  • Iloprost
  • Treprostinil
  • Administered with specific nebulizers in discrete doses repeated throughout the day; other formulations may exist.

Special Considerations (2 of 8)

• Acute care and off-label use:
  • Off-label use: clinicians may consider nonstandard doses, frequency, and devices for approved inhaled drugs in acute care.
  • Use of drugs not approved for inhalation (e.g., heparin or certain antibiotics) should be avoided when an approved alternative exists.
  • Off-label administration should be backed by departmental or institutional policies.

Special Considerations (3 of 8)

• Continuous nebulization for refractory bronchospasm:
  • Albuterol doses 5–20 mg/hour have been used safely in adults and children.
  • Patient reassessed every 30 minutes for first 2 hours; then hourly.
  • Monitor for adverse drug responses.
  • Positive response defined as an increase in peak expiratory flow rate (PEFR) of at least 10\% after the first hour; goal is at least 50\% of the predicted value.

Special Considerations (4 of 8)

• Trans-nasal pulmonary aerosol delivery:
  • Aerosol administration to mechanically ventilated patients.
  • Four primary forms of aerosol generator: SVN, USN, VM, pMDI with third-party adapter.

Special Considerations (5 of 8)

• Aerosol administration to mechanically ventilated patients — response assessment:
  • Measure changes in the difference between peak and plateau pressures.
  • A drop in peak pressure during mechanical ventilation suggests effective bronchodilation.
  • Automatic positive end-expiratory pressure (PEEP) levels may decrease in response to bronchodilators.
  • Monitor breath-to-breath variations.

Special Considerations (6 of 8)

• Placement of aerosol generators in the ventilator circuit:
  • Place in adult ventilation without bias flow: 18–24 inches from the patient in the inspiratory limb to increase inhaled dose for jet nebulizers.
  • pMDI, USN, and VM nebulizer devices are more efficient when placed close to the patient at the circuit wye.

Special Considerations (7 of 8)

• Noninvasive ventilation:
  • Administered with standard and bilevel (biPAP) ventilators.
  • Bilevel ventilators may use a flow turbine with a valve or leak that vents excess flow to the atmosphere.
  • A VM nebulizer delivers a greater inhaled dose than an SVN during noninvasive ventilation.
• High-flow nasal oxygen:
  • Type and location of nebulizer, cannula size, respiratory pattern, and oxygen flow affect inhaled dose.
  • Heliox (80:20) improves aerosol delivery at higher flow rates.

Special Considerations (8 of 8)

• Intrapulmonary percussive ventilation (IPV):
  • Provides high-frequency oscillation of the airway while administering aerosol particles.
  • Place the aerosol generator in the circuit as close to the patient’s airway as possible.
• High-frequency oscillatory ventilation (HFOV):
  • Administration of albuterol sulfate via VM placed between the ventilator circuit and patient airway delivers >10\% of the dose to infants and adults.

Controlling Environmental Contamination (1 of 2)

• Nebulized drugs may enter the room directly from the nebulizer or during patient exhalation.
• Pentamidine and ribavirin pose health risks to caregivers.
• Continuous pneumatic nebulizers produce the greatest amount of second-hand aerosol.

Controlling Environmental Contamination (2 of 2)

• Mitigation strategies:
  • Use one-way valves and filters where appropriate.
  • Negative-pressure rooms and treatment booths help contain aerosols.
  • Personal protective equipment (PPE) is recommended when caring for patients with diseases that can spread by the airborne route.