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Patologie e Farmaci dell’apparato
respiratorio
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Fisiologia dell’apparato respiratorio
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Asma bronchiale
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Confronto tra i bronchi di un individuo normale e di un
individuo asmatico
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Cambiamenti del bronchiolo nell’asma cronico
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Meccanismi dell’asma
InfiammazioneLinfociti Th
Leucotrieni
Farmaci
Broncodilatatori
Antisecretivi
Antinfiammatori
Antileucotrieni
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Farmaci dell’apparato respiratorio
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Fasi dell’asma e
trattamento
farmacologico
EMBP = eosinophil major
basic protein
ECP = eosinophil cationic
protein
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Recettore Beta2
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Desensitizzazione
In associazione con glucocorticoidi
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Glucocorticoidi
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Ruolo dei linfociti T nell’asma
APC = antigen presenting cell
P = plasmacellule
IgE = Immunoglobuline
P = plasmacellule
T cell T helper
IgE R
RIL-4
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Fasi dell’asma e
trattamento
farmacologico
EMBP = eosinophil major
basic protein
ECP = eosinophil cationic
protein
C4, D4
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Effetti dei glucocorticoidi sulla espressione genica
GRE- glucocorticoidi response element; SLPI –inib.leucoproteasi secretoria;MKP1-fosfatasi kinasi att. da mitogenp
CBP-proteina legante CREB; IkB-inibitore NF-kB; GILZ-leucine zipper indotta da Glu;
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Meccanismo dell’inibizione dell’espressione di geni infiammatori (deacetilazione) da parte di glucocorticoidi e teofillina
pCAF –fattore attivante; HAT- acetilazione degli istoni; HDAC2 = deacetilasi 2 degli istoni
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Farmacocinetica dei glucocorticoidi inalatori
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Effetto del distanziatore sull’erogazione di un aerosol inalabile
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Classificazione della gravità dell’asma e Trattamento
(Beta agonisti)
* Salbutanolo, pirbuterolo, terbutalina (15-30 min fino a 4-6 ore)
§ Salmeterolo, formoterolo (fino a 12 ore)
*
*
*
*
§
§
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Teofillina
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Broncodilatazione
Basso indice terapeutico (cuore, intestino)
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Dipendente dalla dose
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Cromoglicato e nedocromile
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Le reazioni di ipersensibilità
mediate dalle
immunoglobuline
• Inibisce macrofagi, eosinofili e
neutrofili, monociti
• Inibisce canale del cloro e riduce
iperpolarizzazione in cellule
infiammate che attiva aumento Ca
responsabile di degranulazione
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Farmaci antiasmatici broncodilatatori
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Antagonisti muscarinici (M1-M3)
• Ipratropio• Ossitropio• Tiotropio bromuro
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Modificatori e anti leucotrieni
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Biosintesi dei leucotrieni (LT), recettori per i leucotrieni e meccanismo dell’azione dei farmaci antileucotrienici
LO- lipossigenasi; LT- leucotriene; FLAP = helper protein 5-LO activating protein
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Siti d’azione dei
farmaci modificatori
dei leucotrieni
Zafirlukast
Montelukast
Zileuton
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Le reazioni di ipersensibilità mediate dalle
immunoglobuline
Omalizumab
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- Long-Acting Beta-adrenergic Agonist (LABA) +
glucocorticoidi (GC) antinfiammatori per via inalatoria
- LABA+GC per via inalatoria + teofillina a lento rilascio o
gli inibitori dei leucotrieni o tiotropio bromuro
- aggiunta di un trattamento orale con GC.
Strategie terapeutiche
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Broncopneumopatia cronica ostruttiva stabile
(BPCO)
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Trattamento della broncopneumopatia cronica
ostruttiva stabile (BPCO)
FEV = volume espirato forzato 1sec
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Farmaci per la terapia cronica dell’asma: aspetti farmacocinetici
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Farmaci antiasmatici: effetti collaterali e posologia
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