Download Utilizzazione degli AEROSOL: Giancarlo Ottonello

Terapia Inalatoria
per casi
particolari
Giancarlo Ottonello
[email protected]
CPR drugs for endotracheal route
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 highquality 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
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.
Part 13: Neonatal Resuscitation
Web-based Integrated 2010 & 2015 American Heart Association Guidelines for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care
Surfattante
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
Terapie inalatorie antiche ma ancora in voga
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
• 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
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
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
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.
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
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
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 alpha1 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
RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6
Therapies for Alpha-1 Antitrypsin Deficiency
I-Neb: vibrating mesh technology
RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6
inhaled vasoactive intestinal peptide
potential therapeutic role in treating asthma, pulmonary
hypertension, and sarcoidosis.
RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6
GranulocyteMacrophage ColonyStimulating Factor
For treating Pulmonary
alveolar proteinosis
Treatment of pulmonary alveolar
proteinosis with aerosolized GMCSF is feasible, safe, and effective.
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
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 aspirinlike tablet, which is crushed when the device is closed,
releasing drug as a dry powder
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
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
Casco - Helmet
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
Antibiotici:
•
•
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•
•
Colistimetato sodico
Aztreonam
Ciprofloxacina liposomiale
Levofloxacina
Anfotericina B liposomiale
tobi podhaler novartis
https://vimeo.com/34632746
Orbital multi breath high
dose dry powder inhaler
Mucolitici:
Dornase alfa
Mucolitici
Mucolitici
Denufosol tetrasodio: attiva canali del cloro
Lancovutide: incrementa il trasporto del cloro e la fluidità delle secrezioni
Antiinfiammatori
Steroidi inalatori: scarsa evidenza di efficacia
Alfa 1 antitripsina: non ancora evidenza di efficacia ma studi di durata sinora troppo breve: < 4 sett
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
Casco - Helmet
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.
Respiratory Care • September 2015 Vol 60 No 9
Current knowledge
What this paper contributes to our
knowledge
•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.
• 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
Combinazioni di sostanze dentro ai nebulizzatori
Caratteristiche dei devices per nebulizzazione
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
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).
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
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
RESPIRATORY CARE • JUNE 2015 VOL 60 NO 6
iNO inhaled nitric oxyde
Conclusioni
• Terapia inalatoria: strumento indispensabile in vari ambiti (già attuale
o del futuro prossimo)
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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
Un
aerosol
che ci
piace
molto !!!