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Dr Muhammed Aslam Junior Resident MD Respiratory Medicine Academy Of Medical Science Pariyaram , Kannur

Inhalation delivery systems

Bronchodilator aerosol for asthma -1935 Conventional pressurized MDI - 1956

Pressurized metered dose inhaler (pMDI) MDI with spacers or holding chambers Breath actuated MDI Dry powder inhaler (DPI) Nebulizers

Pressurized MDI

Provides the force to generate the aerosol cloud and is also the medium in which the active component must be suspended or dissolved. Propellants in MDIs typically make up more than 99% of the delivered dose

Chlorofluorocarbons (CFCs)
most commonly used propellants were the chlorofluorocarbons CFC-11, CFC-12 and CFC-114. Banned due to adverse effect on ozone layer

hydrofluoroalkanes (HFA)
HFA 134a (1,1,1,2,-tetrafluoroethane) These new devices are more effective. The HFA propellant produces an aerosol with smaller particle size, resulting in improved deposition in the small airways and greater efficacy at equivalent doses compared with CFC MDIs.

When the valve is actuated propellant and drug leave the inhaler at high velocity Majority of drug impacts in oropharynx Less than 25% reaches the lung

Most efficient way of using MDI- steps

Shake the canister Place the mouthpiece of actuator between the lips Breathe out steadily Release the dose while taking a slow deep breath in Hold the breath in while counting to 10

Advantages of MDIs
Compact, portable ,convenient Multidose delivery capability Lower risk of bacterial contamination Suitable for emergency situation

Disadvantages of MDIs
Needs correct actuation and inhalation coordination- difficult for children and elderly patients Cold freon effect High pharyngeal drug deposition Flammability possibility of new HFA propellants Remaining dose difficult to determine

MDI with Spacer

Steps for Using a Spacer with an MDI Insert the inhaler/canister into spacer and shake. Breathe out. Put the spacer mouthpiece into your mouth. Press down on the inhaler once. Breathe in slowly (for 3-5 seconds). Hold breath for 10 seconds.

Advantages of MDI with spacer

Compensate for poor technique/coordination with MDI Spacers slow down the speed of the aerosol coming from the inhaler, meaning that less of drug impacts on the back of the mouth and somewhat more may get into the lungs. Because of this, less medication is needed for an effective dose to reach the lungs, and there are fewer side effects from corticosteroid residue in the mouth.

Large size and volume of device Bacterial contamination is possible; device needs to be cleaned periodically Electrostatic charges may reduce drug delivery to the lungs

Breath actuated MDI


Dry powder inhaler (DPI)

Single dose Devices

Had to be reloaded with capsule containing micronized drug in a large particle carrier powder ,usually lactose

Multiple DoseDevices

Breath-actuated Less patient coordination required Spacer not necessary Compact Portable No propellant Usually higher lung deposition than a pMDI

Disadvantages of DPI
Work poorly if inhalation is not forceful enough Many patients cannot use them correctly (e.g. capsule handling problems for elderly Most types are moisture sensitive Humidity potentially causes powder clumping and reduced dispersal of fine particle mass Need to reload capsule each time

Jet nebulizer Ultrasonic nebulizer

Pneumatic Jet Nebulizer

Delivers compressed gas through a jet, causing an area of negative pressure and drawing the liquid up the tube by the Bernoulli effect. The solution is entrained into the gas stream and then sheared into a liquid film that is unstable and is broken into droplets by surface tension forces. The fundamental concept of nebulizer performance is the conversion of the medication solution into droplets in the respirable range of 1-5 micrometers

Ultrasonic Nebulizer
Generates high-frequency ultrasonic waves (1.63 MHz) from electrical energy via a piezoelectric element in the transducer. These ultrasonic waves are transmitted to the surface of the solution to create an aerosol. Aerosol delivery is by a fan or the patients inspiratory flow; particle sizes may be larger with this device. A limitation of ultrasonic nebulizers is that they do not nebulize suspensions efficiently

Advantages Of Nebulizers
Provide therapy for patients who cannot use other inhalation modalities (eg, MDI, DPI) Allow administration of large doses of medicine Patient coordination not required Effective with tidal breathing Dose modification possible Can be used with supplemental oxygen

Disadvantages Of Nebulizers
Decreased portability Longer set-up and administration time Higher cost Electrical power source required Contamination possible

Drugs used in inhaler therapy

For Asthma
Taken from The Global Initiative for Asthma (GINA) 2011 guidelines

Inhaler Therapy
Inhaled glucocorticoids ,Long acting inhaled beta 2 agonists,Cromones,

Short acting beta 2 agonists, Anticholinergics

Inhaled Glucocorticosteroids
Most effective anti inflammatory medication for the treatment of persistent asthma Reduces asthma symptoms Improves quality of life Decrease Airway hyper responsiveness Improve lung function Control airway inflammation Decrease frequency and severity of exacerbations Decrease mortality

Inhaled Glucocorticosteroids
Beclomethasone dipropionate Budesonide Ciclesonide Flunisolide Fluticasone propionate Mometasone furoate Triamsinalone acetonide

Most of the benefit dose equivalent of 400 microgram budesonide per day Increasing dose Little benefit & more side effect Add-on therapy with another class controller is preferred over increasing dose of steroids Tobacco smoking decreases responsiveness to inhaled glucocorticoids

Local Side effects

Oropharyngeal candidiasis Dysphonia Cough (upper airway irritation) s/e reduced by spacer,mouth washing, prodrug(ciclesonide,beclomethasone)

Systemic side effect

Depends on dose , potency, delivery system, systemic bio availability ,half life, first pass metabolism, treatment duration Easy bruising, adrenal suppression, decreased bone mineral density ,cataract, glaucoma

Long acting inhaled beta2 agonists Salmeterol and formoterol Not as monotherapy Most effective when combined with inhaled glucocorticoids

Advantages of combination therapy

Improve symptoms scores Decreases nocturnal asthma symptoms Improve lung functions Decreases use of rapid acting inhaled b2 agonists Reduces no: of exacerbation Rapid control Reduces dose of inhaled glucocorticoids

Salmeterol and Formoterol has similar duration of action , but formoterol has more rapid onset Formoterol Budesonide combination can be given for both rescue and maintenance

Side effects
Less than oral treatment Cvs stimulation , skeletal muscle tremor Hypokalemia Refractoriness to beta 2 agonists

Sodium cromo Glycate , Nedocromil sodium Limited role Mild persistent asthma and exercise induced bronchospasm Less effective than low dose inhaled glucocorticoids s/e cough, sore throat , unpleasant taste

Reliever medications
Short acting beta 2 agonists Anti cholinergic

Rapid acting inhaled beta 2 agonist

Salbutamol , terbutaline, fenoterol, levalbuterol,reproterol,pirbuterol Medication of choice for relief of bronchospasm during acute exacerbation of asthma and pre treatment of exercise induced broncho constriction Should be used only on an as needed basis at lowest dose and frequency

s/e tremor, tachycardia

Anti cholinergic broncho dilators

Ipratropium bromide, oxitropium bromide Less effective than beta 2 agonists Combination with b2 agonistsignificant improvement

S/e dryness, bitter taste

In children

In children

Inhaler Therapy For COPD

Taken from Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2011

Beta2 Agonists
Effect of short acting b2 agonist- 4to 6 hrs Improves FEV1 and symptoms

Long acting beta2 agonist -12 hr or more Formoterol and salmeterol improves FEV1 ,lung volumes,dyspnoea,health related quality of life,exacerbation rates Indacaterol duration of action 24hrs

Anti cholinergic
Ipratopium bromide , oxitropium bromide, tiotropium bromide Broncho dilator action last longer than SABA- upto 8 hrs Tiotropium >24 hrs

Inhaled corticosteroids
Long term treatment with inhaled CS improves symptom , lung function ,quality of life, and reduces frequency of exacerbations in COPD patients with FEV1 < 60% Does not decline the long term decline of FEV1 nor mortality

Combination Therapy
Inhaled Coticosteroid with Long Acting B2 Agonist is more effective A triple therapy by adding tiotropium may furthur improves

Oxygen therapy

A number of inhalation devices are available for the treatment of pulmonary diseases, each with its own advantages and disadvantages. None has proven to be superior to the others in any of the clinical situations tested. Whichever device is chosen, the key to successful treatment lies at a proper inhaler technique

Thank you !!