This document discusses inhaled medications used to treat bronchial asthma. It defines asthma and describes the main types of inhaled medications: beta-2 agonists, anticholinergics, and corticosteroids. It discusses the mechanisms of action and examples of drugs for each type. The document also covers various inhaler devices including metered dose inhalers, dry powder inhalers, and nebulizers. It describes advantages and disadvantages of inhaled medications and proper techniques for using different inhaler devices.

1. INHALED MEDICATION IN
BRONCHIAL ASTHMA
BY: DR RAJ KUMAR
SECOND YR PG

2.  Definition of bronchial asthma
 Inhaled medications used in asthma
 Various types of inhaler devices
 Advantages and disadvantages of inhaled medications

3. Definition of bronchial asthma
 Asthma is a heterogeneous disease ,usually characterized
by chronic airway inflammation . It is defined by the history
of respiratory symptoms such as wheeze , shortness of
breath, chest tightness and cough that vary over time and
in intensity , together with variable expiratory airflow
limitation.

4. Inhaled medications in asthma
 A wide variety of agents are used in management of asthma, of which
main inhaled medications include beta-2 adrenergic agonists,
anticholinergics, and corticosteroids.
 1) Beta-2 agonists: MOA:- These drugs activate B2-adrenegic receptors
resulting in an increase in intracellular cAMP, which lead to relaxation of
airway smooth muscle cells.
 B2 agonists act as functional antagonists; that is they prevent and reverse
the contraction of airway smooth muscle cells by bronchoconstrictors.

5.  1) Beta-2 agonists: This include saba and laba
 Saba’s- salbutamol, terbutaline, albutarol, bambuterol.
 Laba’s – salmeterol, formeterol.
 2)Anti-cholinergics:
 MOA:-They induce airway smooth muscle relaxation by blocking muscarinic
receptors on airway smooth muscle , inhibiting vagally mediated cholinergic tone.
 They include: ipratropium bromide, tiotropium bromide.

6.  3)Corticosteroids :They reduce the number and activation of
inflammatory cells in the airways.
 Reduction in eosinophils, activated T-lymphocytes, and surface mast
in the airways contribute to lessening of airway hyper-responsiveness.
 The main pathway is inhibition of transcription factors NF-kB and AP-1.
 Example : budesonide, beclamethasone, fluticasone, ciclesonide.

7. Low, medium and high daily doses of
inhaled corticosteroids

8. Advantages and disadvantages of
inhaled medication
Advantages:
 Less systemic toxicity
 More rapid onset of action of drug
 Delivery to target site
Disadvantages:
 Time and effort consuming
 Limitation of delivery device

9. Deposition of aerosol particles in
lungs:

11. Graphical representation of deposition of
particles based on size:

12. Drug receptors:
 Receptors for inhaled bronchodilators are distributed through
out the lungs, but they have their greatest effect on receptors
located in conducting airways. By targeting these receptors,
bronchodilators open up the large airways.
 Corticosteroid receptors are also present throughout the
airways and inflammation has been shown to exist in all
regions of lungs in asthma.
 For this reason uniform distribution of ICS throughout the
lungs is preferable .

13. Nasal versus oral inhalation:
 Nose is more effective filter than mouth. Thus, inhalation
through the mouth is preferred route for aerosol delivery
of the drug.
 This is a potential issue while treating infants and toddlers
as they tend to breath with noses using facemask.

14. INHALER DEVICES
Drug delivery to the lungs via the inhaled route remain
the corner- stone therapy for patients with asthma.
Inhaled therapy targets drug directly to the lung and allow
a distinct therapeutic advantage over systematic therapy
with the use of smaller drug doses, a more rapid onset of
therapeutic action, and decreased adverse effects.

15. Types of inhaler devices:
There are several type of inhaler devices and drug delivery
system used in clinical practice for management of asthma.
This include pressurized metered dose inhaler(pMDI),
spacers, dry powder inhaler (DPIs), and nebulizers

17. Metered dose inhaler
 Metered dose inhaler is an inhaler device with specified
doses that provides a certain dose of active agent in each
puff.
 Pressurized metered dose inhalers are a type of MDIs that
work based on the pressurized propellant in the aerosol
chamber.

18.  MDI consists of 3 main parts
 1)canister
 2)plastic actuator and
 3) metering valve

20. Pressurized MDI

21. Pressurized metered dose inhalers
 The pMDIs contain the drug as a liquid suspension or solution
with the propellant sealed in the canister and, other
formulation ingredients may be present such as ethanol ,
chemical preservatives , flavoring agents , and surfactants.
 Most inhaler therapies are now free of CFCs propellants having
being replaced by non-ozone–depleting propellants such as
HFCs and HFAs.

22. Mechanism of pMDI:
 Upon actuation of the pMDI canister , there is quick
vaporization of the propellant and this provides the force to
aerosolize and propel the liquid drug out of the canister at high
velocity.
 Vaporization of the propellants also causes cooling of the drug
aerosol which can some times give rise to the “cold freon
effect’’ which is the sensation experienced by some patients of
cold aerosol hitting the back of their oro-pharynx, which can
stop them from inhaling the drug and some times cause
paradoxical bronchospasm.

23.  Some of the formulation ingredients added to the pMDIs described above
have shown to cause bronchospasm, wheeze, and cough in asthma patients.
 This pMDIs are portable, compact and inexpensive.
 Optimal clinical efficacy with a pMDI is obtained when the device is
actuated at the start of a deep and slow inhalation lasting for 5 -10 seconds
followed, at the end of inspiration.
 Failure to inhale slowly and deeply with pMDI is a more common mistake
than the actual patient coordination between inhalation and actuation.

25. How to use MDI without spacer:

26. Steps of using MDI:
 1)Remove the cap and prime the inhaler to ensure proper
mixing of the drug and propellant.
 1)Hold the inhaler with mouth piece on bottom and canister on
the top.
 3)Breath out fully and place the mouth piece between the lips .
 4)As you begin to breath in, press down on the canister.
 5)Continue to breath in slowly and deeply and hold your breath
for 5-10 seconds.
 6)Breath out. If you are supposed to take 2nd puff, wait 15-30
seconds and repeat steps 1-5.

27. Breath actuated MDI
 Newly BA-pMDIs and BC-pMDI have been introduced.
BA-pMDI depend on patients inspiratory effort to trigger
and activate the inhaler device whereas BC-pMDI do not
depend on patients inspiratory flow for actuation.

28.  Metered dose inhalers are often preferred to other type of
inhalation devices in the treatment of asthma, since they
are compact and convenient.
 However, even with the best inhalation technique, only
10-15 percent of the drug reaches the lungs.
 Consequently, although MDIs seem easy to use, many
patients do not use them properly, and many physicians
are similarly misinformed with the advice they give.

29.  One of the major difficulties that patients have is the so
called “hand-lung” problem, with inability to coordinate
actuation of the aerosol with inhalation.
 The correct choice of inhaled flow rate and breath holding
pause are vital. A combination of two factor a slow deep
inhalation followed by 10 seconds of breath-holding –are
needed for maximal deposition of aerosol in the lung.

30. Spacers:
 Spacer devices are used with pMDIs and are designed to assist
in the delivery of the inhaled drug to lungs and reduce oro-
pharyngeal deposition by slowing the high velocity of the
emitted aerosol cloud.
 The plastic wall of the spacer traps large drug particles and this
decreases oro-pharyngeal impaction, which may lead to
decrease in local unwanted side effects, particularly with CSs,
and also reduce the systemic adverse effects by minimizing the
amount of drug absorbed by GIT.

31. Types of spacers:
 There are various types of spacers which include
 1)spacer with valve: there is a valve in mouth piece, only
allowing airflow through the chamber when the patient inhales.
 2)spacer without valve: it is simply an extension, that requires
reasonable good amount of coordination.
 3)reverse flow device.
 To reduce the electrostatic charge in spacers which can
significantly reduce the dose of the drug to be delivered to
lungs, spacer should be primed with pMDI prior to use.

32. With chamber

33. MDI with Spacer

34. Steps of using MDI with spacer:
1) Remove the cap and prime the inhaler to ensure proper
mixing of the drug and propellant.
2) Fix the mouth piece of the inhaler into open end of the spacer.
Breath out fully to empty the lungs.
3) Insert mouth piece of the spacer in mouth between teeth and
seal it tightly with lips.
4) Actuate one dose into the chamber of the spacer.
5) Instruct the patient to inhale and exhale using normal tidal
volume into the spacer atleast 5 times.

35. Advantages of MDI with spacer:
a) Compensation for patients poor technique/coordination
with MDI.
b) Spacers slow down the speed of the aerosol coming from
the inhaler, meaning that less drug impacts on the back of
the mouth and more may enter into the lungs. Because of
this, less medication is needed for an effective dose to
reach the lungs, and their will be fewer side effects from
inhaled corticosteroids with spacer.

36. Disadvantages:
a) Large size and volume of device
b) Bacterial contamination is possible; device needs
to be cleaned periodically
c) Electrostatic charges may reduce drug delivery to the lungs

37. Dry powder inhalers:

38. DRY POWDER INHALERS
 DPIs are propellant-free devices that contain finely milled
powdered drug particles bound into loose aggregates or,
drug particles associated with larger carrier molecules such
as lactose.
 DPI devices are breath – actuated in their operation, and
critically rely on the patient’s inspiratory effort to
deaggregate the drug from its carrier particle to achieve
optimal delivery and deposition within the lungs.

39. Types of DPIs :
 DPIs can be classified into single dose delivery systems that either
require drug to be individually loaded into inhaler prior to the use or
where individual doses are dispensed from the punctured gelatin
capsules. In contrast multi-dosing delivery avoid the inconvenience
with repeated drug loading and can be divided into “multi-dose’’ or
“multi-unit dose’’ systems.
 Multi-dose systems deliver the drug that is metered from a powder
reservoir, whereas multi-unit dose devices either contain drug sealed
in individual foil blisters, or drug sealed in pockets on a moving strip

40. Single dose DPIs:

41. Dry powder inhaler (DPI)

42. SINGLE DOSE DEVICE

43. Multiple Dose Devices

45. Steps of using DPI:

49. Steps of using DPI:
1) Remove the cap of the inhaler.
2) Flip up the mouth piece to open the inhaler. Place the
capsule in the inhaler and close it.
3) Press the buttons on the side of the DPI. You will hear a
click sound. Now the device is loaded with the dose.
4) Turn your head away from the device and breath out as
much as possible .

50. 4) Place the device in your mouth and breathe in as
forcefully and deeply as you can.
5) Hold your breath for 10 seconds.
6) Take the DPI away from your mouth and exhale slowly.
7) If more than one dose is prescribed, repeat steps 1 to 5
for each dose.
8) When your treatment is complete, open the inhaler
remove the empty capsule and replace the device

51. Nebulizers:

52. •The fundamental concept of nebulizer
performance is the conversion of the
medication solution into droplets in the
respirable range of 1-5 micrometers.

53. Nebulizers :
 The main type of nebulizers commonly used in clinical
practice can be divided into two categories:

54. Jet nebulizer:
 1) Jet nebulizers : this nebulizers uses either compressed
gas or an electrical compressor to generate aerosolized
particles from liquid suspension.

56.  2) Ultrasonic nebulizer : They utilize vibration from a
piezoelectric crystal at a high frequency to produce
aerosol clouds for inhalation from the liquid drug .
 This nebulizers are small and less noisy compared to jet
nebulizer.

60. References:
 Fishman’s text book of pulmonology.
 Crofton and douglas’s respiratory diseases.
 Ers article on inhalation therapies by B.L.Laube, H.M.Everard,
P. Diot.
 Delivery of inhaled medication in adults by Dean Hess, Rajiv
Dhand.

62. Next seminar is klebsiella pneumonia by
dr.sudheer reddy on 16-12-2020.