Inhalational techniques

Inhalational techniques

1. Inhalational Route of Drug Administration

2. Asthma/ COPD Disease Epidemiology – Indian Scenario Asthma COPD Prevalence 38 million 55 million Age Group All age groups > 40 years Salvi S. Lancet Glob Health 2018; 6: e1363–74

3. Role of Inhaled therapy: Asthma and COPD

4. Inhaled Drug Delivery Cornerstone Treatment for Asthma & COPD Inhalation- A cornerstone of treatment for patients with asthma & COPD Better Drug Delivery Safe & effective Rapid & assured results Rogliani P, Calzetta L, Coppola A, Cavalli F, Ora J, Puxeddu E, Matera MG, Cazzola M. Optimizing drug delivery in COPD: the role of inhaler devices. Respiratory medicine. 2017 Mar 1;124:6-14. Gregoriano C, Dieterle T, Breitenstein AL, Dürr S, Baum A, Maier S, Arnet I, Hersberger KE, Leuppi JD. Use and inhalation technique of inhaled medication in patients with asthma and COPD: data from a randomized controlled trial. Respiratory research. 2018 Dec;19(1):237.

5. Inhalational Route

6. Pulmonary Delivery of Drug Lung India. 2012 Jan-Mar; 29(1): 44–49

7. Pulmonary Delivery of Drug (contd..) The alveolar epithelium of the distal lung has been shown to be an absorption site for most of the therapeutics and various macromolecules. Advantages over peroral applications are the comparatively low enzymatic activity, rapid absorption of drug and the capacity for overcoming first-pass metabolism . It has been already reported that, the local respiratory disorders and some systemic diseases can be well treated by delivering the drugs through pulmonary route. This includes the topical treatment of asthma,COPD , local infectious diseases, pulmonary hypertension, the systemic use of insulin, human growth hormones, and oxytocin Lung India. 2012 Jan-Mar; 29(1): 44–49

8. History of Inhalation therapy

9. Origin of Inhalers The word ‘inhaler’ was first used by the English physician , John Mudge . In his 1778 book, A Radical and Expeditious Cure for a recent Catarrhous Cough, he discloses to us his invention of an inhaler. It was adapted from a pewter tankard and the use of opium vapour to treat cough. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

10. Inhalation Therapy In Ancient Times Long before Bennet , Stern and Mudge were describing inhalers and advocating inhalation therapy , inhalation was being practised in many parts of the world. The inhalation of the vapour of black henbane is recorded in the ancient Egyptian Ebers papyrus (1,554 BC) Egyptian physicians threw the weed onto hot bricks. It caused caused the alkaloid contents of the plant to vapourise so that the breathless patient could inhale. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

11. The First Pressurised Inhaler The first ‘powered’ or pressurised inhaler was invented in France by Sales- Girons in 1858. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

12. The Treatment Of Asthma

13. In 1860, Henry Hyde Salter published his famous text , On Asthma its Pathology and Treatment . He systematically reviewed the treatment options of the period, including inhaled therapies, and distinguished between: Depressants ( ipecacuanha , tobacco, tartar-emetic), stimulants (coffee, alcohol), and Sedatives (tobacco, chloroform, opium, stramonium , lobelia and indian hemp). Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

14. The First Dry Powder Inhaler In London in 1864, Newton patented an inhaling apparatus for the delivery of dry powder medications. He observed that the powder needed to be finely pulverised and that it had to be kept dry — principles that still apply to dry powder inhalers today. This device is probably the earliest recorded dry powder inhaler. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

15. The Nelson Inhaler In 1865, a new invention was reported in The Lancet . T he Improved Nelson Inhaler from the well-known pharmacy supplier S.Maw & Sons in London. The Nelson inhaler is still manufactured to this day, with very few modifications Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

16. The Formal Recognition Of Inhalation Therapy The 1867 edition of the British Pharmacopoeia was the first to formularise inhalation therapies. It listed five medications: Vapor acidi hydrocyanici Vapor chlori Vapor coniae Vapor creasoti Vapor iodi I nhalation therapy had won its spurs and had been formally accepted as a means of medical treatment. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

17. The First Nebulisation Devices Da Costa published a fine account of inhalation medications and devices in 1867. Among the devices described are the hand-ball spray and the Siegle’s steam spray inhaler — a German invention from the early 1860’s. Siegle’s steam spray used the Venturi principle to atomise liquid medication, and this was, in effect, the beginning of nebuliser therapy. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

18. Siegle's steam spray inhaler, early 1860 Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

19. Notable Inhalers And Inhaled Therapies From A Hundred Years Ago

20. Ceramic inhalers. Numerous versions of the Nelson inhaler and other ceramic inhalers appeared to deliver medicinal products . In Europe the enamel inhalers fulfilled a similar purpose Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

21. Pillow I nhaler This clever approach involved the use of a small shallow pot in a specially made pillow . Volatile inhalants were put into the pot. T hese were vapourised through the night, delivering medication to the sleeping patient. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

22. Combustible powders These were to be burnt and the arising vapour inhaled. Most contained stramonium plus other alkaloids such as belladonna and lobelia. Well known examples include Braters Powder, Kinsman Powder, Green Mountain Powder, Kellogg’s Powder, Schiffmann’s Powder , and Himrod’s . Many were also produced as asthma cigarettes and as a pipe mixture Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

23. Menthol Inhalers In 1774, Gaubius first extracted crystals from peppermint oil. Later to be known as menthol, inventors have been finding ways of delivering its cooling vapours to the respiratory tract. Menthol and eucalyptus oil are well known today as over-the-counter therapies for cough and cold relief. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

24. Maxim I nhaler Sir Hiram Maxim, an American living in London, was an inveterate inventor. Most famous for the Maxim machine gun, he also invented a steam driven flying machine. In August 1909 , plagued by the effects of the London atmosphere , he developed and patented his own inhaler . It resembled a glass retort and delivered a combination of menthol and pine essence and was known as the Pipe of Peace. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

25. Maxim Inhaler Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

26. Aerohalor Abbott launched the Aerohalor with a preparation of penicillin for inhalation. Additionally a further presentation of the bronchodilator Norethisderone was also made available . The Abbott Aerohalor , a DPI, used a lactose-based formulation to deliver penicillin from small capsules known as ‘sifters ’ Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

27. The Abbott Aerohaler , 1948 Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

28. Modern Times

29. pMDI Undoubtedly the most significant event of the 1950’s was the development in 1955 of the pressurised metered dose inhaler ( pMDI ). Nowadays, pMDIs have become a very important inhalation technology with annual sales currently in excess of 400 million units. The drugs , of course, have been updated and the propellant technology improved through the use of less environmentally-damaging HFAs. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

30. Spinhaler Dr. Roger Altounyan ,a former Spitfire pilot who was very familiar with aerodynamics , he invented the Spinhaler . It is a capsule inhaler that used a small propeller to create turbulence. It was necessary to find alternatives to the standard pMDI technology because the dose to be delivered exceeded the capability of pMDI metering valves. S odium cromoglycate was launched in 1967 as a Spinhaler device . Some years later a pMDI version was created , using a lower dose. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

31. Spinhaler

32. Salbutamol Inhaler Salbutamol was the first of the selective bronchodilators , relatively free from secondary effects on other systems. Salbutamol was formulated : In a pMDI, as a dry powder inhaler in the rotahaler and the diskhaler and Was also produced as nebulised , tablet and syrup formulations. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

33. Rotahaler It is a dry powder capsule inhaler simply required twisting for a loaded capsule to be pulled apart and the powder to be inhaled through a mesh. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

34. Diskhaler The Diskhaler represented an important step forward. I t did not require reloading for every dose, so it was the first multi-unit dose dry powder inhaler. This inhaler used a cartridge with foiled sealed pre-measured doses. These are perforated at the time of use to permit the drug to be inhaled Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

35. Beclomethasone In 1972 Allen & Hanbury’s marketed the first inhaled steroid, beclomethasone, in the same inhalers as salbutamol. Numerous steroids have subsequently been developed, and some have led to new inhaler developments. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

36. Budesonide In 1987, Astra Zeneca launched a novel steroid, budesonide , in a new multi-dose dry powder inhaler. It did not depend on each dose being isolated. R ather , the drug substance was kept in a reservoir from which individual doses were taken at administration. This device, the Turbuhaler , has also proved very popular. I n a similar way is now used to administer bronchodilators, inhaled steroid , and combinations of the two . Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

37. Turbohaler Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

38. Contd.. Subsequent development of dry powder inhalers has followed the three themes described above: Capsule inhalers The multiple-unit dose inhalers and The reservoir devices. Sanders M. Primary Care Respiratory Journal (2007) 16 (2): 71-81

39. Drugs Via Inhalational route

40. Small Airways Contribute Significantly To Total Lung Resistance Beam SD P T. 2010 Jul;35(7):377-416.

41. D eposition of Inhaled D rugs

42. Advantages and Disadvantages of Inhalational route

43. Advantages and Disadvantages of Inhalational route These can be reviewed under the following : Compliance with inhalers Pharmacokinetic Issues Efficacy and safety

44. Breath-actuated MDI Population : Aged ≥5 years May be particularly useful for patients unable to coordinate inhalation and actuation or for elderly patients

45. Breath-actuated MDI: Advantages Indicated for patients unable to coordinate inhalation and actuation May be particularly useful in the elderly Less variation in emitted dose due to reproducible actuation

46. Breath-actuated MDI: Disadvantages Patients may incorrectly stop inhalation at actuation Cannot be used with available spacer/ valved -holding chamber devices

47. Dry Powder Inhalers (DPI) Population: Aged ≥4 years Most children aged < 4 years may not generate sufficient inspiratory flow

48. DPI: Advantages Breath actuated Less patient coordination required compared with a pMDI device No need for propellant Portable and compact Can be used quickly No preparation of drug required Dose counters in newer designs

49. DPI: Disadvantages Some units are single dose Loss of dose if patient exhales through the device Can result in high pharyngeal deposition Upper limit to unit dose content

50. Spacer/holding chamber Aged ≥4 years (< 4 years old, valved holding chamber with face mask) Indicated for patients who have difficulty performing adequate MDI technique

51. Spacer/holding chamber: Advantages Reduced need for coordination Reduced pharyngeal deposition

52. Spacer/holding chamber: Disadvantages Complexity of inhalation may be increased for some patients Increases expense and decreases portability compared with MDI alone Development of static charge on the inner walls can attract aerosol particles to the walls and reduce lung delivery Integral actuator devices may alter aerosol properties compared with native actuator

53. Nebulizers Population: Patients of any age who cannot use a metered-dose inhaler with a valved holding chamber and a face mask

54. Nebulizers: Advantages Patient coordination not required Effective with tidal breathing May be able to administer multiple medications Dose modification is possible May be used at any age

55. Nebulizers: Disadvantages Lack of portability (jet nebulizers ) Lengthy treatment times Device cleaning required and contamination possible Lack of availability of some medications in a preparation that can be nebulized Suspensions not aerosolized well (ultrasonic nebulizers ) Variability of performance efficiency among different nebulizers

56. Nebulizers: Disadvantages (contd..) Less efficient than other devices (waste ) Expensive (ultrasonic nebulizers) More effective if triggering the device is coordinated with inspiration Face mask must fit appropriately

57. Advantages of Using MDIs American Thoracic Society

58. Compliance with Inhalers

59. Compliance with Inhalers Compliance with asthma therapy has the added dimension that treatment frequently includes the use of inhalers: Which are relatively complicated devices and Which many patients (especially children and the elderly) find difficult to use Indeed, it has been shown that the great majority of elderly patients cannot use inhalers properly, despite adequate instructions. Leonardo MF et al . Drugs. 1996;52 Suppl 6:20-8.

60. Despite of using MDI, outcomes are not as expected… As we face many challenges

61. Adherence R emains a Key Challenge.. Aggarwal D et al. Journal of Clinical and Diagnostic Research. 2017 Dec, Vol-11(12): OC14-OC18 Conclusion : Monitoring of medication adherence seems to be a better tool than self reported adherence for the evaluation of adherence to ICS in asthma

62. Non-adherence - A Troublemaker! Accidental and intentional non-adherence with therapy at least twice a week was reported by 27% and 24%, respectively. Lack of perceived symptoms was the main reason for non-adherence. Some of the patient’s belief which are the cause of non-adherence: Fear of adverse effects and addiction Complexity of therapy Psychological factors It is estimated that nearly 45% patients do not adhere to therapy (in terms of filling/refilling prescriptions or maintaining prescribed medication schedule), which adversely impacts clinical outcomes and patient quality of life.

63. In Inhalation therapy, non-adherence is very common 63 Complete adherence to Inhaled Therapy occurs only in 33.6% * * Humenberger, M., Horner, A., Labek, A. et al. Adherence to inhaled therapy and its impact on chronic obstructive pulmonary disease (COPD). BMC Pulm Med 18, 163 (2018) doi:10.1186/s12890-018-0724-3

64. GINA & GOLD- Recommends to Check the Adherence Non- Adherence to be assessed for gaining optimal clinical outcome GINA 2020 Guidelines GOLD 2020 Guidelines https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-POCKET-GUIDE-FINAL_WMS.pdf

65. Use of Digital Technology for Adherence-Making the Change to Data Driven Treatment Digital monitoring has been shown to have a positive impact on adherence in both asthma and COPD and is rising in popularity because of its precision and objectiveness. Dekhuijzen R, Lavorini F, Usmani OS, van Boven JF. Addressing the impact and unmet needs of nonadherence in asthma and chronic obstructive pulmonary disease: where do we go from here?. The Journal of Allergy and Clinical Immunology: In Practice. 2018 May 1;6(3):785-93.

66. For patients, clinicians and researchers, digital technologies such as those addressing adherence and inhaler technique offer the opportunity to advance personalized care for patients with respiratory diseases. Longitudinal, real-time data collected through digital platforms can provide Precise understanding of the interaction of a patient’s adherence Symptoms Disease course, which can be used to develop and support adherence management strategies Blakey JD, Bender BG, Dima AL, Weinman J, Safioti G, Costello RW. Digital technologies and adherence in respiratory diseases: the road ahead. European Respiratory Journal. 2018 Nov 1;52(5).

67. Conclusion T he inhaled route of administration features prominently in current treatment guidelines for the management of patients with asthma . Inhaled short-acting beta 2 agonists are effective, well tolerated and have a rapid onset of action, making them agents of choice as rescue therapy . However, some patients find it difficult to use inhalers, and a number of different types of errors in inhalation technique that can impair efficacy. Leonardo MF et al . Drugs. 1996;52 Suppl 6:20-8.

68. Thank You