Terapia Inalatoria per casi particolari

1. Terapia Inalatoria per casi particolari Giancarlo Ottonello giancarloottonello@gmail.com

2. CPR drugs for endotracheal route

3. If the endotracheal route is to be used for administration of epinephrine, the limited available evidence suggests that the currently recommended dose of 0.01 mg/kg is likely to be too low to be effective. Given the paucity of high-quality clinical data regarding endotracheal epinephrine, the intravenous route should be used as soon as venous access is established. Given the complete lack of clinical data in newborns, endotracheal administration of naloxone is not recommended

4. Part 13: Neonatal ResuscitationWeb-based Integrated 2010 & 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Epinephrine • This topic was last reviewed in 2010. Dosing recommendations remain unchanged from 2010. • Intravenous administration of epinephrine may be considered at a dose of 0.01 to 0.03 mg/kg of 1:10 000 epinephrine. • If endotracheal administration is attempted while intravenous access is being established, higher dosing at 0.05 to 0.1 mg/kg may be reasonable. • Given the lack of supportive data for endotracheal epinephrine, it is reasonable to provide drugs by the intravenous route as soon as venous access is established.

5. Surfattante

6. Quali sono i pazienti più particolari? • Quelli che usano acqua ossigenata in aerosol per prevenire e trattare lo stress ossidativo nei polmoni e nell’organismo

7. Terapie inalatorie antiche ma ancora in voga

8. L’efficacia farmacologica dei cannabinoidi (non inalatorie ma terapeutiche come tisane o preparati galenici) • nausea e del vomito in pazienti affetti da neoplasie e Aids • attività antidepressiva, anticonvulsivante, antispasmodica, antitumorale e stimolante l’appetito. • effetto analgesico in sinergia con gli oppioidi (ridurre i dosaggi degli analgesici oppiacei necessari a trattare il dolore cronico) • effetti collaterali minimi, e comunque, così come per gli oppioidi, non è riportata alcuna tossicità d’organo

9. Respirare un aerosol della sostanza spruzzato in una stanza • Impregnare un calzino o straccio • spruzzare in un sacchetto di plastica e inalare • Spruzzare un inalante direttamente in bocca o il naso • Inalazione direttamente dall’apertra di un • contenitore

10. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

11. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

12. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Aerosolized Gene Therapies to Treat Lung Diseases Interfering RNA molecules have shown promise in suppressing gene expression, which could be useful in treating cancer For the most part, treatment of lung diseases with inhalation gene therapy is in preclinical development (using cell cultures and animal models) or in phase-1/2 human trials. Aerosolized gene therapies to treat lung cancer, M. tuberculosis, alpha-1 antitrypsin deficiency, and CF are under development.

13. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Therapies for M. tuberculosis The latest candidate for inhalation therapy for tuberculosis is siRNA. Researchers could Obtain suppression of lymphotactin in mice infected with M. tuberculosis. Lymphotactin is one of the chemokines known to participate in the formation of tuberculoid granuloma

14. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

15. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Therapies for Alpha-1 Antitrypsin Deficiency Twenty subjects (6 healthy, 7 with alpha-1 antitrypsin deficiency, and 7 with CF) inhaled 70 mg of radiolabeled alpha-1 antitrypsin in 2m L of solution. The mass median aerodynamic diameter of the aerosol was 4.0 m. The total lung deposition of alpha-1 antitrypsin was 70% of the nominal dose in the nebulizer, was similar in all study groups, and was unaffected by disease severity

16. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Therapies for Alpha-1 Antitrypsin Deficiency I-Neb: vibrating mesh technology

17. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 inhaled vasoactive intestinal peptide potential therapeutic role in treating asthma, pulmonary hypertension, and sarcoidosis.

18. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Granulocyte-Macrophage Colony-Stimulating Factor For treating Pulmonary alveolar proteinosis Treatment of pulmonary alveolar proteinosis with aerosolized GM-CSF is feasible, safe, and effective.

19. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

20. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Insulin microparticles (Technospheres) MannKind’s delivery system is called Afrezza. It is a pocket-size drug-device combination product . Insulin microparticles (Technospheres) are introduced into the device in an aspirin-like tablet, which is crushed when the device is closed, releasing drug as a dry powder

21. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

23. Aerosol con Heliox Scintigraphy scans from children with severe peripheral airway obstruction in the heliox group showed significantly higher cumulative lung irradiation (p 0.045) and significantly higher slope of the curve (p 0.017) than did the other 3 subgroups. Piva JP, Menna Barreto SS, Zelmanovitz F, Amantea S, Cox P. Heliox versus oxygen for nebulized aerosol therapy in children with lower airway obstruction. Pediatr Crit Care 2002;3(1):6–10

24. Casco - Helmet

25. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

26. Antibiotici: • Colistimetato sodico • Aztreonam • Ciprofloxacina liposomiale • Levofloxacina • Anfotericina B liposomiale

27. tobi podhaler novartis https://vimeo.com/34632746 Orbital multi breath high dose dry powder inhaler

28. Mucolitici: Dornase alfa

29. Mucolitici

30. Mucolitici Denufosol tetrasodio: attiva canali del cloro Lancovutide: incrementa il trasporto del cloro e la fluidità delle secrezioni

31. Antiinfiammatori Steroidi inalatori: scarsa evidenza di efficacia Alfa 1 antitripsina: non ancora evidenza di efficacia ma studi di durata sinora troppo breve: < 4 sett

32. Terapie biologiche nasal epithelial clone 1 (SPLUNC1)-derived peptides that treat Na+ hyperabsorption and rebalance CF airway surface liquid homeostasis. Inhaled protein/peptide-based therapies for respiratory disease Fellner et al. Molecular and Cellular Pediatrics (2016) 3:16

33. Casco - Helmet

34. Mesh nebulizer The Vibrating Mesh Technology Nebulizer is one of the latest innovations in the market and it uses a laser-drilled mesh membrane which vibrates to refine the droplet size and force the liquid through, thereby creating a very fine mist. This technology allows for faster processing and thus decreases treatment times significantly. Some of the advantages of the VMT Nebulizer is that is decreases the amount of liquid waste as well as the undesired heating of the medical liquid. It is however far more expensive than any of the other types of Nebulizers which is one of its greatest drawbacks.

35. Respiratory Care • September 2015 Vol 60 No 9 Current knowledge What this paper contributes to our knowledge In a group of normal subjects without lung disease using a crossover study design, a vibrating mesh nebulizer delivered a 2-fold greater dose of radiolabeled drug to the respiratory tract than a conventional jet nebulizer. The study used a full face mask without humidification. Clinical studies to confirm these findings in subjects with lung disease are warranted • Noninvasive ventilation (NIV) is a standard of care for exacerbations of chronic lung disease. These patients often require aerosolized medications during NIV. Many factors influence the efficacy of aerosol delivery during NIV, including the type of ventilator, mode of ventilation, circuit configuration (fixed leak or exhalation valve), humidity, interface, type of aerosol generator, position of the aerosol generator, and respiratory pattern.

36. Combinazioni di sostanze dentro ai nebulizzatori

37. Caratteristiche dei devices per nebulizzazione

39. Di cosa parleremo: • Terapia inalatorie di tipo genico • Terapia peptidica • Terapia inalatoria per diabete • Uso dell’elio come vettore per migliore efficacia • Farmaci e altre terapie inalatorie nella fibrosi cistica • Antibiotici • Mucolitici • Antiinfiammatori • Terapie biologiche • Farmaci nell’ipertensione polmonare

40. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Epoprostenolo Although epoprostenol was approved for continuous intravenous infusion, the intravenous formulation can be aerosolized and used therapeutically off-label. One of the limitations of epoprostenol (intravenous and nebulized) is its very short half-life (3–5 min).

41. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Iloprost Iloprost is an alternative prostacyclin that was first used clinically in Europe, where it is available in some countries by inhalation as well as intravenously. It was cleared in the United States for inhalation in 2004. It has a longer half-life than epoprostenol (7–8 min) and a half-life of pharmacodynamic activity of 0.5 h. Although this necessitates frequent treatments (at least 6 times/d), iloprost is approved for long-term use in out-patients Inhaled iloprost is administered using the I-neb aerosolized adaptive delivery system (Philips Respironics, Murrysville, Pennsylvania), which adapts to patient breathing patterns to optimize drug delivery

43. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 Treprostinil Treprostinil aerosol is administered via the Opti-Neb (TeleflexMedical,Reading,Pennsylvania),which,likethe I-neb, requires assembly, cleaning, and maintenance. However, treprostinil is administered 4 times/d, with up to 12 puffs each time, but less time is needed compared with I-neb treatments, which require many more steady breaths until the treatment is finished

44. RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6 iNO inhaled nitric oxyde

45. Conclusioni • Terapia inalatoria: strumento indispensabile in vari ambiti (già attuale o del futuro prossimo) • Terapia intensiva neonatale e pediatrica • Terapia cardiologica • Terapia medica per patologie varie • Terapia oncologica • Facilità di somministrazione, efficacia, risultati • Aspetti delicati legati alle modalità di somministrazione ed ai devices da utilizzare

46. Un aerosol che ci piace molto !!!