AEROSOL DELIVERY DEVICES Ma. Henrietta O. de la Cruz, M.D.

Educational components of Asthma Treatment Strategies Teaching and monitoring the inhalation technique of drugs is important. Short courses of oral corticosteroids are occasionally needed. All persons with asthma should avoid exposure to high allergen concentrations (Gøtzsche et al., 2004) [B] and, for example, sensitizing chemicals at work. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should be used cautiously, as 10 to 20% of patients with asthma are allergic to these drugs. Smoking may wreck the results of asthma care. Develop an ACTION PLAN for self management The treatment should be tailored for each patient according to the severity of the disease and modified flexibly step-by-step. Self-management of drug dosing is encouraged (written instructions!). Allergen immunotherapy may help some patients (Abramson, Puy, & Weiner, 2003; Malling, 1998) [A].

Why inhalation therapy? Oral Slow onset of action Large dosage used Greater side effects Not useful in acute symptoms Inhaled route Rapid onset of action Less amount of drug used Better tolerated Treatment of choice in acute symptoms

Particle deposition

Uses of Aerosols Diagnostic use bronchial aerosol challenge THERAPEUTIC COPD and Asthma Beta2-Adrenergic agonists anticholinergic drugs steroids cromolyn sodium Alveolar diseases emphysema (recombinant alpha1- antitrypsin) interstitial lung diseases (steroids, questionable reports) Abnormalities of the Mucociliary Transport System reduce tenacious mucus widely applied in clinical practice but may have little scientific basis Diagnostic use bronchial aerosol challenge measurement of dimensions of airways and alveoli ventilation scintigraphy mucociliary clearance alveolar particulate clearance

Therapeutic Uses of Aerosols Immunization and Lung infections pseudomonas infection in cystic fibrosis pneumocystis infection in HIV infection Systemic drug delivery inhaled analgesia with fentanyl or morphine nasal sprays for calcitonin, oxytocin

Aerosol delivery equipment small volume nebulizers large volume nebulizers metered dose inhalers dry powder inhaler continuous therapy nebulizers auxiliary spacing devices *other specialized aerosol delivery equipment to reduce mass median aerodynamic diameter of 2- 5 um

MDI: metered dose inhaler Using your MDI correctly: Remove the cap from the mouthpiece and shake the MDI well. Exhale slowly though pursed lip. Hold the inhaler upright and place it in front of your mouth.  Keep your mouth slightly open.  Breathe in deeply (and at the same time) press the inhaler between your thumb and forefinger.  This forces the medication from the inhaler in a “puff” that you then inhale into your lungs. Remove the inhaler from your mouth, holding your breath counting to 10. Then exhale slowly through pursed lips.  Most inhaler instructions ask you to take two puffs. You need to wait about two minutes before taking the second puff, using the same technique as described in steps 1, 2, 3 and 4 above.

Laryngeal deposit with MDI 45-95% of the drug impacts in the oropharyngeal region only 5-25% reaches the lower airways regional deposition depends on: specific drug and MDI inhalation pattern and airway geometry hand-breath coordination deposition improves dramatically if a holding chamber is used inertia due to mass cause particles to continue their present trajectory rather than follow curvature of airways impaction is proportional to: velocity diameter of particle sharpness of airway turns inverse of airway radius impaction is dominant in the major and segmental bronchi for rapidly inhaled particles greater than 4 um

MDI vs Nebulizer 4-12 puffs by MDI with spacer achieves same degree of bronchodilation as one 2.5 mg nebulized treatment of albuterol MDI with spacer are cheaper & faster delivery

Spacers and Holding Chambers reduction of drug deposition in the oropharynx to 3-35% (from 45-95%) minimizes local side effects of steroids amount of systemic drug uptake via the stomach and intestine is reduced by 40-80% demands of coordination when using a spacer are minimal asthmatic infant elderly

Dry Powder Devices

Powder Devices Dry powder inhalers (DPI’s) are breath activated, multidose or single dose, portable devices containing a drug in general, they deliver a greater amount of drug as small respirable particles (<5-6um) if inhalation flow rate is high only few patients above 6y.o. are unable to create large enough flow rates

Aerosol Generation and Delivery: Powder Devices the usual deposition pattern is 50-70% in the oropharynx and 10-35% in the lungs (not very different from pMDI’s) deposition rates vary according to the types of DPI turbuhaler is among the most efficient, having a lung deposition of 25-35%

HOW TO USE TURBOHALERS Unscrew and lift off the cover. Hold the inhaler upright with the grip downwards.To load the inhaler with a dose, turn the grip as far as it will go in both directions, listening for a click. Do not hold the mouthpiece when you load the inhaler.  Breathe out. Do not breathe out through the mouthpiece. Place the mouthpiece gently between your teeth, close your lips and inhale forcefully and deeply through your mouth.  Remove the inhaler from your mouth before breathing out. If more than one dose has been prescribed, repeat steps 2-5. Replace the cover.  Rinse your mouth out with water. Do not swallow. 

Mechanisms: Sedimentation depends on the terminal velocity of a particle under the influence of gravity terminal velocity is proportional to: density of particle diameter of particle enhanced by breath- holding or slow steady breathing

Comparison between MDI & DPI High velocity aerosols Requires hand breath co- ordination Delivery of medicines independent of external factors Time consuming to teach Requires deep& slow breathing only Aerosol velocity depends on inspiratory flow rate No hand breath co- ordination needed Delivery of medication largely dependent on external factors Easy to teach Requires high inspiratory flow>28L/min

Deposition% Loss in air Apparatus GI Lung MDI DPI Nebulizer

SMALL VOLUME NEBULIZERS PORTABLE MODEL SVN

Aerosol Generation and Delivery: Nebulizers solutions or suspensions of drugs can be aerosolized via nebulizers nebulizers are driven ultrasonically or by compressed air most of the drug is retained in the nebulizer, and only about 2-10% reaches the lower airways Nebulizers require few instructions, less supervision & coordination & maybe preferred by the Patient new brands work only during inspiration, so loss from aerosolization during expiration is reduced

Mechanisms of Aerosol Deposition Inertial impaction Sedimentation Diffusion Electrostatic precipitation Interception

Mechanisms: Diffusion important mechanism for deposition of particles <0.5um in diameter extremely small particles are displaced by the random bombardment of gas molecules and collide with the airway walls does not account for much of the deposition of therapeutic aerosols

Choice of inhalation therapy Infants Nebulizer Children < 4 years Nebulizer 4 year DPI/MDI/Spacer 7 years DPI/MDI Adults MDI/DPI Acute episodes Nebulizer

Hazards of therapy Bronchospasm Over hydration Overheating of inspired gases Delivery of contaminated aerosol Tubing condensation draining into the airway Malfunction of device and/or improper technique may result in underdosing. improper technique (inappropriate patient use) overdosing. Complications of specific pharmacologic agent may occur. CFC: affect the environment by its effect on the ozone layer

INFECTION CONTROL: MEDICATIONS: Universal Precautions for body substance isolation. SVN and LVN are for single patient use or should be subjected to high-level disinfection between patients. Published data establishing a safe use-period for SVN and LVN are lacking; however they probably should be changed or subjected to high-level disinfection at approximately 24-hour intervals. MEDICATIONS: Medications should be handled aseptically. Tap water should not be used as the diluent. Medications from multidose sources in acute care facilities must be handled aseptically and discarded after 24 hours. MDI accessory devices are for single patient use only. Cleaning of accessory devices is based on aesthetic criteria. There are no documented concerns with contamination of medication in MDI canisters.

Patient Education in the Clinic Explain nature of the disease (i.e. inflammation) Explain action of prescribed drugs Stress need for regular, long-term therapy Allay fears and concerns Peak flow reading Treatment diary / booklet

Patient Education Consider issuing a peak flow meter & giving appropriate education on peak flow monitoring Review or develop a written plan for managing relapses Review the patient’s understanding of the causes of exacerbations, correct uses of medication & actions to be taken for worsening symptoms or peak flow measurement

Self Management Plan Keep it simple If your PEFR falls below 50-80% of your personal best start taking your oral steroids. Or if you start waking at night with symptoms or develop a cough on exertion.

Assessment of efficacy Proper technique applying device Patient response to or compliance with procedure Objectively measured improvement (eg, increased FEV1 or peak flow)

Demonstration