SlideShare a Scribd company logo

Beta-adrenergici: scelta motivata?

G
GLUP2010

E. Finazzi Agrò

1 of 52
Download to read offline
Beta-Adrenergici: una
scelta motivata?
Prof. Enrico Finazzi Agrò
Dept. of Experimental Medicine and Surgery
Tor Vergata University
Unit of Functional Urology
Tor Vergata University Hospital
S. Lucia Rehabilitation Hospital
Rome, ITALY
Beta3 Adrenergico:
una scelta motivata?
Beta3gonista
• Perché il Beta3 Agonista?
Other drug classes to treat OAB?
• “Despite intensive research, few new therapeutic principles have
emerged and been demonstrated to have sufficient efficacy and
adverse effect profiles to be accepted for approval and clinical
use”1
• Research indicated that stimulation of β3-receptors leads to
bladder relaxation
• Discovery of β3-adrenoceptors, predominately present on the
bladder wall development of β3-adrenoceptor agonist
1. Andersson KE. Curr Urol Rep 2013;doi:10.1007/s11934-013-0335-8; 2. Kennelly MJ Rev Urol 2010;12:12-9;
3. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202611s000lbl.pdf
First FDA-approved antimuscarinic agent2
1975
FDA-approval β3-agonist3
2012
M2 M33
AC PLC
Ca2+
Ca2+
cAMP IP3
–
Membr. Cell.
contraction
+
contractionrelaxation
+
Chapple CR. Urology. 2000;55:33-46
- -
Effects of NE e Ach on Bladder activity
Characterisation of bladder structures expressing β3
adrenoreceptors (β3AR)
• 15 human bladders from cadaveric organ donors (16-82 yr)
• Immunohistochemistry with β3AR C- and N-terminal antibodies on 20 µm
cryostat longitudinal sections of the bladder dome and trigone
• β3AR expression levels in mucosa and muscular layer:
• Co-expression analysis revealed:
– Highest expression in cholinergic vesicular acetylcholine transporter+ nerve fibres
– Less abundant expression in tyrosine hydroxylase+ nerve fibres
– Occasional expression in calcitonin gene-related peptide+ fibres
β3AR expression seems to be most abundant in cholinergic nerve fibres
of the human bladder, suggesting a therapeutic effect of β3AR
agonists through modulation of the bladder neural circuits
Coelho A. Eur Urol Suppl 2016;15(3):e308
Mucosa
• Nerve fibres intermingled on the
connective tissue: ++
• Urothelial or sub-urothelial IC-like cells: -
Muscular layer
• Nerve fibres coursing along smooth muscle
bundles: ++
• Smooth muscle cells: -

Recommended

Bladder sedatives mirabegron vs antimuscarinics in overactive bladder
Bladder sedatives mirabegron vs antimuscarinics in overactive bladderBladder sedatives mirabegron vs antimuscarinics in overactive bladder
Bladder sedatives mirabegron vs antimuscarinics in overactive bladderDr Mayank Mohan Agarwal
 
Baker lisbon peg
Baker  lisbon pegBaker  lisbon peg
Baker lisbon pegBartsMSBlog
 
Kanamycin Injection Taj Pharma SmPC
Kanamycin Injection Taj Pharma SmPCKanamycin Injection Taj Pharma SmPC
Kanamycin Injection Taj Pharma SmPCTajPharmaQC
 
Pegs m abs in rx ms
Pegs m abs in rx msPegs m abs in rx ms
Pegs m abs in rx msBartsMSBlog
 
Effectiveness of TNF-α blockers and IL-12/IL-23 blockers in the treatment of ...
Effectiveness of TNF-α blockers and IL-12/IL-23 blockers in the treatment of ...Effectiveness of TNF-α blockers and IL-12/IL-23 blockers in the treatment of ...
Effectiveness of TNF-α blockers and IL-12/IL-23 blockers in the treatment of ...wolass
 
Progress Toward Topical Therapy of AMD
Progress Toward Topical Therapy of AMDProgress Toward Topical Therapy of AMD
Progress Toward Topical Therapy of AMDRick Trevino
 

More Related Content

What's hot

Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...
Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...
Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...wolass
 
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease European School of Oncology
 
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANI
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIMy preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANI
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIAjayDudani1
 
Slides supportive final-1
 Slides supportive final-1 Slides supportive final-1
Slides supportive final-1spa718
 
30342 7 zactran overall sell sheet-fa-18947
30342 7 zactran overall sell sheet-fa-1894730342 7 zactran overall sell sheet-fa-18947
30342 7 zactran overall sell sheet-fa-18947Sullivan Higdon & Sink
 
P and T c\Competition 2014 monograph
P and T c\Competition 2014 monographP and T c\Competition 2014 monograph
P and T c\Competition 2014 monographKemper May
 
Reproduction after kidney transplant.
Reproduction after kidney transplant.  Reproduction after kidney transplant.
Reproduction after kidney transplant. ReggieL1
 
Yervoy monograph for P&T
Yervoy monograph for P&TYervoy monograph for P&T
Yervoy monograph for P&TKemper May
 
Oxaliplatin induced hypersensitivity reaction
Oxaliplatin induced hypersensitivity reactionOxaliplatin induced hypersensitivity reaction
Oxaliplatin induced hypersensitivity reactionChoying Chen
 
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...Effects and outcome of a policy of intermittent Imatinib treatment in elderly...
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...Mohsin Maqbool
 
Presentation at the CRS Mtg 2002
Presentation at the CRS Mtg 2002Presentation at the CRS Mtg 2002
Presentation at the CRS Mtg 2002gbalwani
 
Age Related Macular Degeneration- Update with Case Studies
Age Related Macular Degeneration- Update with Case StudiesAge Related Macular Degeneration- Update with Case Studies
Age Related Macular Degeneration- Update with Case Studiespresmedaustralia
 
Dabigatran Monograph
Dabigatran MonographDabigatran Monograph
Dabigatran MonographTerri Newman
 
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchangeStructural basis of omalizumab therapy and omalizumab-mediated IgE exchange
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchangeGul Muneer
 
Antibiotics 2015 in icu
Antibiotics 2015 in icuAntibiotics 2015 in icu
Antibiotics 2015 in icusamirelansary
 
Antibiotic therapy in the intensive care unit [autosaved]
Antibiotic therapy in the intensive care unit [autosaved]Antibiotic therapy in the intensive care unit [autosaved]
Antibiotic therapy in the intensive care unit [autosaved]Amrita Bhattacharyya
 

What's hot (18)

Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...
Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...
Ustekinumab therapy efficacy in psoriasis patients previously treated with bi...
 
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
 
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANI
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIMy preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANI
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANI
 
Wet armd treatment
Wet armd treatmentWet armd treatment
Wet armd treatment
 
Slides supportive final-1
 Slides supportive final-1 Slides supportive final-1
Slides supportive final-1
 
30342 7 zactran overall sell sheet-fa-18947
30342 7 zactran overall sell sheet-fa-1894730342 7 zactran overall sell sheet-fa-18947
30342 7 zactran overall sell sheet-fa-18947
 
P and T c\Competition 2014 monograph
P and T c\Competition 2014 monographP and T c\Competition 2014 monograph
P and T c\Competition 2014 monograph
 
Reproduction after kidney transplant.
Reproduction after kidney transplant.  Reproduction after kidney transplant.
Reproduction after kidney transplant.
 
Yervoy monograph for P&T
Yervoy monograph for P&TYervoy monograph for P&T
Yervoy monograph for P&T
 
Oxaliplatin induced hypersensitivity reaction
Oxaliplatin induced hypersensitivity reactionOxaliplatin induced hypersensitivity reaction
Oxaliplatin induced hypersensitivity reaction
 
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...Effects and outcome of a policy of intermittent Imatinib treatment in elderly...
Effects and outcome of a policy of intermittent Imatinib treatment in elderly...
 
Presentation at the CRS Mtg 2002
Presentation at the CRS Mtg 2002Presentation at the CRS Mtg 2002
Presentation at the CRS Mtg 2002
 
Age Related Macular Degeneration- Update with Case Studies
Age Related Macular Degeneration- Update with Case StudiesAge Related Macular Degeneration- Update with Case Studies
Age Related Macular Degeneration- Update with Case Studies
 
Dabigatran Monograph
Dabigatran MonographDabigatran Monograph
Dabigatran Monograph
 
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchangeStructural basis of omalizumab therapy and omalizumab-mediated IgE exchange
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange
 
Role of anti vegf in armd
Role of anti vegf in armdRole of anti vegf in armd
Role of anti vegf in armd
 
Antibiotics 2015 in icu
Antibiotics 2015 in icuAntibiotics 2015 in icu
Antibiotics 2015 in icu
 
Antibiotic therapy in the intensive care unit [autosaved]
Antibiotic therapy in the intensive care unit [autosaved]Antibiotic therapy in the intensive care unit [autosaved]
Antibiotic therapy in the intensive care unit [autosaved]
 

Similar to Beta-adrenergici: scelta motivata?

Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...
Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...
Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...Giuseppe Quintaliani
 
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone healthMCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone healthEuropean School of Oncology
 
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone health
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone healthMON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone health
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone healthEuropean School of Oncology
 
Asco 2006 Update Genitourinary Cancer Selected Abstracts
Asco 2006 Update Genitourinary Cancer Selected AbstractsAsco 2006 Update Genitourinary Cancer Selected Abstracts
Asco 2006 Update Genitourinary Cancer Selected Abstractsfondas vakalis
 
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Fight Colorectal Cancer
 
Stroke prevention in patients with atrial fibrillation
Stroke prevention in patients with atrial fibrillationStroke prevention in patients with atrial fibrillation
Stroke prevention in patients with atrial fibrillationMgfamiliar Net
 
Endocrine Treatment for Early Breast Cancer
Endocrine Treatment for Early Breast CancerEndocrine Treatment for Early Breast Cancer
Endocrine Treatment for Early Breast Cancermeducationdotnet
 
Pathways and targets how might these affect my treatment decisions gail eckh...
Pathways and targets  how might these affect my treatment decisions gail eckh...Pathways and targets  how might these affect my treatment decisions gail eckh...
Pathways and targets how might these affect my treatment decisions gail eckh...Fight Colorectal Cancer
 
The success of neurohormonal blockade: looking back – looking forward: Beta-b...
The success of neurohormonal blockade: looking back – looking forward: Beta-b...The success of neurohormonal blockade: looking back – looking forward: Beta-b...
The success of neurohormonal blockade: looking back – looking forward: Beta-b...drucsamal
 
Chronic paint r.gunadi pain update 22june2013 malang
Chronic paint r.gunadi pain update 22june2013 malang Chronic paint r.gunadi pain update 22june2013 malang
Chronic paint r.gunadi pain update 22june2013 malang dhoan Evridho
 
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma ProstateLocally Advanced Carcinoma Prostate
Locally Advanced Carcinoma ProstateSasikumar Sambasivam
 
New Treatments in HFrEF
New Treatments in HFrEFNew Treatments in HFrEF
New Treatments in HFrEFDuke Heart
 
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...European School of Oncology
 
Estado actual de terapia sistémica en cáncer renal metastásico
Estado actual de terapia sistémica en cáncer renal metastásicoEstado actual de terapia sistémica en cáncer renal metastásico
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
 
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásico
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoActualización en el abordaje terapéutico ante un cáncer colorrectal metastásico
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
 

Similar to Beta-adrenergici: scelta motivata? (20)

Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...
Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...
Giornate Nefrologiche Pisane 2009 - Ruggenenti la remissione della malattia r...
 
NSAIDs and ICON-G
NSAIDs and ICON-GNSAIDs and ICON-G
NSAIDs and ICON-G
 
targeted therapy
targeted therapytargeted therapy
targeted therapy
 
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone healthMCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health
MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health
 
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone health
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone healthMON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone health
MON 2011 - Slide 9 - M. Aapro - Antiemetics, growth factors, bone health
 
Asco 2006 Update Genitourinary Cancer Selected Abstracts
Asco 2006 Update Genitourinary Cancer Selected AbstractsAsco 2006 Update Genitourinary Cancer Selected Abstracts
Asco 2006 Update Genitourinary Cancer Selected Abstracts
 
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
 
Stroke prevention in patients with atrial fibrillation
Stroke prevention in patients with atrial fibrillationStroke prevention in patients with atrial fibrillation
Stroke prevention in patients with atrial fibrillation
 
Endocrine Treatment for Early Breast Cancer
Endocrine Treatment for Early Breast CancerEndocrine Treatment for Early Breast Cancer
Endocrine Treatment for Early Breast Cancer
 
Pathways and targets how might these affect my treatment decisions gail eckh...
Pathways and targets  how might these affect my treatment decisions gail eckh...Pathways and targets  how might these affect my treatment decisions gail eckh...
Pathways and targets how might these affect my treatment decisions gail eckh...
 
The success of neurohormonal blockade: looking back – looking forward: Beta-b...
The success of neurohormonal blockade: looking back – looking forward: Beta-b...The success of neurohormonal blockade: looking back – looking forward: Beta-b...
The success of neurohormonal blockade: looking back – looking forward: Beta-b...
 
Prostate cancer
Prostate cancer   Prostate cancer
Prostate cancer
 
7 capdevila
7 capdevila7 capdevila
7 capdevila
 
Chronic paint r.gunadi pain update 22june2013 malang
Chronic paint r.gunadi pain update 22june2013 malang Chronic paint r.gunadi pain update 22june2013 malang
Chronic paint r.gunadi pain update 22june2013 malang
 
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma ProstateLocally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
 
Rheumatic pain management
Rheumatic pain management Rheumatic pain management
Rheumatic pain management
 
New Treatments in HFrEF
New Treatments in HFrEFNew Treatments in HFrEF
New Treatments in HFrEF
 
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...
ECCLU 2011 - J.J. Battermann - Prostate cancer: All the truth about local tre...
 
Estado actual de terapia sistémica en cáncer renal metastásico
Estado actual de terapia sistémica en cáncer renal metastásicoEstado actual de terapia sistémica en cáncer renal metastásico
Estado actual de terapia sistémica en cáncer renal metastásico
 
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásico
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoActualización en el abordaje terapéutico ante un cáncer colorrectal metastásico
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásico
 

More from GLUP2010

Posterior defect surgery (principles and techniques) - R. Milani/ M. Frigerio
Posterior defect surgery (principles and techniques) - R. Milani/ M. FrigerioPosterior defect surgery (principles and techniques) - R. Milani/ M. Frigerio
Posterior defect surgery (principles and techniques) - R. Milani/ M. FrigerioGLUP2010
 
Relazione tra difetto anatomico e disfunzione - G. Dodi
Relazione tra difetto anatomico e disfunzione - G. DodiRelazione tra difetto anatomico e disfunzione - G. Dodi
Relazione tra difetto anatomico e disfunzione - G. DodiGLUP2010
 
Il buono e il cattivo della chirurgia - M. Soligo
Il buono e il cattivo della chirurgia - M. SoligoIl buono e il cattivo della chirurgia - M. Soligo
Il buono e il cattivo della chirurgia - M. SoligoGLUP2010
 
Anatomia del segmento posteriore - G. Minini
Anatomia del segmento posteriore - G. MininiAnatomia del segmento posteriore - G. Minini
Anatomia del segmento posteriore - G. MininiGLUP2010
 
Il ruolo dell’urodinamica
Il ruolo dell’urodinamica Il ruolo dell’urodinamica
Il ruolo dell’urodinamica GLUP2010
 
Epidemiologia e costi
Epidemiologia e costi Epidemiologia e costi
Epidemiologia e costi GLUP2010
 
Tossina botulinica: indicazioni, risultati e limiti
Tossina botulinica: indicazioni, risultati e limiti Tossina botulinica: indicazioni, risultati e limiti
Tossina botulinica: indicazioni, risultati e limiti GLUP2010
 
La farmacoterapia: dagli anticolinergici ai beta-adrenergici
La farmacoterapia: dagli anticolinergici ai beta-adrenergici La farmacoterapia: dagli anticolinergici ai beta-adrenergici
La farmacoterapia: dagli anticolinergici ai beta-adrenergici GLUP2010
 
Neuromodulazione tibiale: indicazioni, risultati e limiti
Neuromodulazione tibiale: indicazioni, risultati e limitiNeuromodulazione tibiale: indicazioni, risultati e limiti
Neuromodulazione tibiale: indicazioni, risultati e limitiGLUP2010
 
Prolasso e IUS: Chirurgia associata
Prolasso e IUS: Chirurgia associataProlasso e IUS: Chirurgia associata
Prolasso e IUS: Chirurgia associataGLUP2010
 
Strategie di prevenzione del danno perineale
Strategie di prevenzione del danno perinealeStrategie di prevenzione del danno perineale
Strategie di prevenzione del danno perinealeGLUP2010
 
Sessione dolore pelvico cronico: prevenzione e diagnosi
Sessione dolore pelvico cronico: prevenzione e diagnosiSessione dolore pelvico cronico: prevenzione e diagnosi
Sessione dolore pelvico cronico: prevenzione e diagnosiGLUP2010
 
Vescica Iperattiva : Strategie Farmacologiche
Vescica Iperattiva : Strategie FarmacologicheVescica Iperattiva : Strategie Farmacologiche
Vescica Iperattiva : Strategie FarmacologicheGLUP2010
 
Disfunzioni uretro-vescicali dopo sling: quale approccio?
Disfunzioni uretro-vescicali dopo sling: quale approccio?Disfunzioni uretro-vescicali dopo sling: quale approccio?
Disfunzioni uretro-vescicali dopo sling: quale approccio?GLUP2010
 
Dolore pelvico cronico: epidemiologia ed eziopatogenesi
Dolore pelvico cronico: epidemiologia ed eziopatogenesiDolore pelvico cronico: epidemiologia ed eziopatogenesi
Dolore pelvico cronico: epidemiologia ed eziopatogenesiGLUP2010
 
Nove anni di SIS: Quali evidenze?
Nove anni di SIS: Quali evidenze?Nove anni di SIS: Quali evidenze?
Nove anni di SIS: Quali evidenze?GLUP2010
 
PROLASSO E CHIRURGIA FASCIALE - Compartimento posteriore
PROLASSO E CHIRURGIA FASCIALE - Compartimento posteriorePROLASSO E CHIRURGIA FASCIALE - Compartimento posteriore
PROLASSO E CHIRURGIA FASCIALE - Compartimento posterioreGLUP2010
 
Limiti e biases delle evidenze scientifiche
Limiti e biases delle evidenze scientificheLimiti e biases delle evidenze scientifiche
Limiti e biases delle evidenze scientificheGLUP2010
 
Chirurgia protesica e compartimento posteriore: un connubio possibile?
Chirurgia protesica e compartimento posteriore: un connubio possibile?Chirurgia protesica e compartimento posteriore: un connubio possibile?
Chirurgia protesica e compartimento posteriore: un connubio possibile?GLUP2010
 
Vescica iperattiva: epidemiologia, costi ed impatto
Vescica iperattiva: epidemiologia, costi ed impattoVescica iperattiva: epidemiologia, costi ed impatto
Vescica iperattiva: epidemiologia, costi ed impattoGLUP2010
 

More from GLUP2010 (20)

Posterior defect surgery (principles and techniques) - R. Milani/ M. Frigerio
Posterior defect surgery (principles and techniques) - R. Milani/ M. FrigerioPosterior defect surgery (principles and techniques) - R. Milani/ M. Frigerio
Posterior defect surgery (principles and techniques) - R. Milani/ M. Frigerio
 
Relazione tra difetto anatomico e disfunzione - G. Dodi
Relazione tra difetto anatomico e disfunzione - G. DodiRelazione tra difetto anatomico e disfunzione - G. Dodi
Relazione tra difetto anatomico e disfunzione - G. Dodi
 
Il buono e il cattivo della chirurgia - M. Soligo
Il buono e il cattivo della chirurgia - M. SoligoIl buono e il cattivo della chirurgia - M. Soligo
Il buono e il cattivo della chirurgia - M. Soligo
 
Anatomia del segmento posteriore - G. Minini
Anatomia del segmento posteriore - G. MininiAnatomia del segmento posteriore - G. Minini
Anatomia del segmento posteriore - G. Minini
 
Il ruolo dell’urodinamica
Il ruolo dell’urodinamica Il ruolo dell’urodinamica
Il ruolo dell’urodinamica
 
Epidemiologia e costi
Epidemiologia e costi Epidemiologia e costi
Epidemiologia e costi
 
Tossina botulinica: indicazioni, risultati e limiti
Tossina botulinica: indicazioni, risultati e limiti Tossina botulinica: indicazioni, risultati e limiti
Tossina botulinica: indicazioni, risultati e limiti
 
La farmacoterapia: dagli anticolinergici ai beta-adrenergici
La farmacoterapia: dagli anticolinergici ai beta-adrenergici La farmacoterapia: dagli anticolinergici ai beta-adrenergici
La farmacoterapia: dagli anticolinergici ai beta-adrenergici
 
Neuromodulazione tibiale: indicazioni, risultati e limiti
Neuromodulazione tibiale: indicazioni, risultati e limitiNeuromodulazione tibiale: indicazioni, risultati e limiti
Neuromodulazione tibiale: indicazioni, risultati e limiti
 
Prolasso e IUS: Chirurgia associata
Prolasso e IUS: Chirurgia associataProlasso e IUS: Chirurgia associata
Prolasso e IUS: Chirurgia associata
 
Strategie di prevenzione del danno perineale
Strategie di prevenzione del danno perinealeStrategie di prevenzione del danno perineale
Strategie di prevenzione del danno perineale
 
Sessione dolore pelvico cronico: prevenzione e diagnosi
Sessione dolore pelvico cronico: prevenzione e diagnosiSessione dolore pelvico cronico: prevenzione e diagnosi
Sessione dolore pelvico cronico: prevenzione e diagnosi
 
Vescica Iperattiva : Strategie Farmacologiche
Vescica Iperattiva : Strategie FarmacologicheVescica Iperattiva : Strategie Farmacologiche
Vescica Iperattiva : Strategie Farmacologiche
 
Disfunzioni uretro-vescicali dopo sling: quale approccio?
Disfunzioni uretro-vescicali dopo sling: quale approccio?Disfunzioni uretro-vescicali dopo sling: quale approccio?
Disfunzioni uretro-vescicali dopo sling: quale approccio?
 
Dolore pelvico cronico: epidemiologia ed eziopatogenesi
Dolore pelvico cronico: epidemiologia ed eziopatogenesiDolore pelvico cronico: epidemiologia ed eziopatogenesi
Dolore pelvico cronico: epidemiologia ed eziopatogenesi
 
Nove anni di SIS: Quali evidenze?
Nove anni di SIS: Quali evidenze?Nove anni di SIS: Quali evidenze?
Nove anni di SIS: Quali evidenze?
 
PROLASSO E CHIRURGIA FASCIALE - Compartimento posteriore
PROLASSO E CHIRURGIA FASCIALE - Compartimento posteriorePROLASSO E CHIRURGIA FASCIALE - Compartimento posteriore
PROLASSO E CHIRURGIA FASCIALE - Compartimento posteriore
 
Limiti e biases delle evidenze scientifiche
Limiti e biases delle evidenze scientificheLimiti e biases delle evidenze scientifiche
Limiti e biases delle evidenze scientifiche
 
Chirurgia protesica e compartimento posteriore: un connubio possibile?
Chirurgia protesica e compartimento posteriore: un connubio possibile?Chirurgia protesica e compartimento posteriore: un connubio possibile?
Chirurgia protesica e compartimento posteriore: un connubio possibile?
 
Vescica iperattiva: epidemiologia, costi ed impatto
Vescica iperattiva: epidemiologia, costi ed impattoVescica iperattiva: epidemiologia, costi ed impatto
Vescica iperattiva: epidemiologia, costi ed impatto
 

Recently uploaded

KOSHTA CONCEPT IN AYURVEDA BY VIJAY R K
KOSHTA CONCEPT IN AYURVEDA  BY  VIJAY R KKOSHTA CONCEPT IN AYURVEDA  BY  VIJAY R K
KOSHTA CONCEPT IN AYURVEDA BY VIJAY R Kvinaykumarrkumabar
 
Cell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfCell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfMedicoseAcademics
 
Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.JULIANA BENAVIDES GUERRERO
 
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...Rajshri
 
Presentation on Cerebral Palsy and its orthotic management
Presentation on Cerebral Palsy and its orthotic managementPresentation on Cerebral Palsy and its orthotic management
Presentation on Cerebral Palsy and its orthotic managementeshasmalik27
 
Anesthesia Implications in cannabis Users.pptx
Anesthesia Implications in cannabis Users.pptxAnesthesia Implications in cannabis Users.pptx
Anesthesia Implications in cannabis Users.pptxhrowshan
 
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]Brian Peacock
 
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...KavyasriPuttamreddy
 
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxGLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxWINCY THIRUMURUGAN
 
Health powerpoint for catch -up fridays.
Health powerpoint for catch -up fridays.Health powerpoint for catch -up fridays.
Health powerpoint for catch -up fridays.JohnMarckySeoTeriomp
 
Staphylococcus.ppt.........ali.rasool.badr
Staphylococcus.ppt.........ali.rasool.badrStaphylococcus.ppt.........ali.rasool.badr
Staphylococcus.ppt.........ali.rasool.badrssuser06f49d
 
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Golden Helix
 
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...Dr. Madduru Muni Haritha
 
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.vrchk912
 
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...bkling
 
Macquarie Neurosurgery Journal Club 2022 PPT
Macquarie Neurosurgery Journal Club 2022 PPTMacquarie Neurosurgery Journal Club 2022 PPT
Macquarie Neurosurgery Journal Club 2022 PPTMQ_Library
 
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptx
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptxBiochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptx
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptxRajendra Dev Bhatt
 
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studies
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studiesHEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studies
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studiesRichard Clement
 
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...Abhinav S
 
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.Divya Kanojiya
 

Recently uploaded (20)

KOSHTA CONCEPT IN AYURVEDA BY VIJAY R K
KOSHTA CONCEPT IN AYURVEDA  BY  VIJAY R KKOSHTA CONCEPT IN AYURVEDA  BY  VIJAY R K
KOSHTA CONCEPT IN AYURVEDA BY VIJAY R K
 
Cell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfCell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdf
 
Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.
 
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
 
Presentation on Cerebral Palsy and its orthotic management
Presentation on Cerebral Palsy and its orthotic managementPresentation on Cerebral Palsy and its orthotic management
Presentation on Cerebral Palsy and its orthotic management
 
Anesthesia Implications in cannabis Users.pptx
Anesthesia Implications in cannabis Users.pptxAnesthesia Implications in cannabis Users.pptx
Anesthesia Implications in cannabis Users.pptx
 
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]
Psychedelic Interventions for Neurological Conditions [NAN 2022 Poster]
 
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...
SUNSCREEN, definition, classification, SPF value, history, mechanism, develop...
 
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxGLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
 
Health powerpoint for catch -up fridays.
Health powerpoint for catch -up fridays.Health powerpoint for catch -up fridays.
Health powerpoint for catch -up fridays.
 
Staphylococcus.ppt.........ali.rasool.badr
Staphylococcus.ppt.........ali.rasool.badrStaphylococcus.ppt.........ali.rasool.badr
Staphylococcus.ppt.........ali.rasool.badr
 
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
 
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
 
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
 
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...
Report Back from San Antonio Breast Cancer Symposium (SABCS) 2023: Spotlight ...
 
Macquarie Neurosurgery Journal Club 2022 PPT
Macquarie Neurosurgery Journal Club 2022 PPTMacquarie Neurosurgery Journal Club 2022 PPT
Macquarie Neurosurgery Journal Club 2022 PPT
 
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptx
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptxBiochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptx
Biochemistry of Carbohydrates for MBBS, BDS, Lab Med 2024.pptx
 
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studies
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studiesHEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studies
HEPATIKA 6 Nutritional supplement, six ingredients supported by clinical studies
 
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...
Circulatory shock Cardiogenic Shock Hypovolemic Shock Sepsis, Septic Shock an...
 
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.
ANTI-HYPERTENSIVE DRUG - RAUWOLFIA ROOT.
 

Beta-adrenergici: scelta motivata?

  • 1. Beta-Adrenergici: una scelta motivata? Prof. Enrico Finazzi Agrò Dept. of Experimental Medicine and Surgery Tor Vergata University Unit of Functional Urology Tor Vergata University Hospital S. Lucia Rehabilitation Hospital Rome, ITALY
  • 3. Beta3gonista • Perché il Beta3 Agonista?
  • 4. Other drug classes to treat OAB? • “Despite intensive research, few new therapeutic principles have emerged and been demonstrated to have sufficient efficacy and adverse effect profiles to be accepted for approval and clinical use”1 • Research indicated that stimulation of β3-receptors leads to bladder relaxation • Discovery of β3-adrenoceptors, predominately present on the bladder wall development of β3-adrenoceptor agonist 1. Andersson KE. Curr Urol Rep 2013;doi:10.1007/s11934-013-0335-8; 2. Kennelly MJ Rev Urol 2010;12:12-9; 3. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202611s000lbl.pdf First FDA-approved antimuscarinic agent2 1975 FDA-approval β3-agonist3 2012
  • 5. M2 M33 AC PLC Ca2+ Ca2+ cAMP IP3 – Membr. Cell. contraction + contractionrelaxation + Chapple CR. Urology. 2000;55:33-46 - - Effects of NE e Ach on Bladder activity
  • 6. Characterisation of bladder structures expressing β3 adrenoreceptors (β3AR) • 15 human bladders from cadaveric organ donors (16-82 yr) • Immunohistochemistry with β3AR C- and N-terminal antibodies on 20 µm cryostat longitudinal sections of the bladder dome and trigone • β3AR expression levels in mucosa and muscular layer: • Co-expression analysis revealed: – Highest expression in cholinergic vesicular acetylcholine transporter+ nerve fibres – Less abundant expression in tyrosine hydroxylase+ nerve fibres – Occasional expression in calcitonin gene-related peptide+ fibres β3AR expression seems to be most abundant in cholinergic nerve fibres of the human bladder, suggesting a therapeutic effect of β3AR agonists through modulation of the bladder neural circuits Coelho A. Eur Urol Suppl 2016;15(3):e308 Mucosa • Nerve fibres intermingled on the connective tissue: ++ • Urothelial or sub-urothelial IC-like cells: - Muscular layer • Nerve fibres coursing along smooth muscle bundles: ++ • Smooth muscle cells: -
  • 7. Tissue expression of the three β-adrenoceptor subtypes Brain: β1 • β2 • β3 Blood vessels: β2 Lungs: β2 Kidney: β1 • β2 Pancreas: β2 GI tract: β2 • β3 Uterus: β2 • β3 Skeletal muscle: β2 Adipose: β1 • β3 Heart: β1 • β2 Liver: β2 Gall bladder: β3 Bladder: β3 predominantly All three β-ARs are expressed in human bladder tissue but β3-AR mRNA accounts for 97% of total β-AR mRNA8 Tissue-specific expression of human β-ARs8-20
  • 8. Binding affinity (Ki) of mirabegron for human ARs1 Receptor subtype Mirabegron Ki, nmol/L* β1-AR 4,200 + 900 β2-AR 1,300 + 300 β3-AR 40 + 20.2 Lower Ki values represent higher affinity * Determined in in vitro receptor binding studies using Chinese hamster ovary cells expressing human β-AR subtypes ; values are means of three replicates (+ standard error)
  • 10. End-point co-primario: numero medio di minzioni per 24 h All p values <0.05 for Mirabegron 50 and 100 mg vs placebo Khullar V et al. Eur Urol 2013; 63: 283 – 295
  • 15. Women presenting with UI EAU guidelines 2016
  • 16. Men presenting with UI AUA guidelines 2014
  • 17. You should be able to have mirabegron if drugs called ‘antimuscarinics’ do not work, if they are not suitable for you, or their side effects are unacceptable
  • 18. Beta3Agonista • Funziona meglio in pazienti non responder a antimuscarinici?
  • 19. Prima o seconda linea di terapia? Mean number of UI episodes/24 h Khullar V et al. BMC Urology 2013, 13:45
  • 20. Prima o seconda linea di terapia? Mean number of micturitions/24 h Khullar V et al. BMC Urology 2013, 13:45
  • 21. Beta3Agonista Funziona meglio in pazienti non responder a antimuscarinici? NO
  • 22. Seconda linea di trattamento?
  • 23. Beta3Agonista Funziona in pazienti non responder a antimuscarinici?
  • 27. Beta3Agonista Combination > Solifenacin 5 mg Combination <> Solifenacin 10 mg (with less side effects)
  • 28. Beta3Agonista Funziona in pazienti non responder a antimuscarinici? SÌ… E anche in combinazione!
  • 30. Beta3Agonista In quali pazienti è particolarmente indicato?
  • 31. You should be able to have mirabegron if drugs called ‘antimuscarinics’ do not work, if they are not suitable for you, or their side effects are unacceptable
  • 32. Nitti VW et al. J Urol 2013; 190: 1320-1327
  • 33. Mirabegron in pazienti con BOO Nitti VW et al. J Urol 2013; 190: 1320-1327 Bladder Contractility Index Bladder Voiding Efficiency
  • 34. Beta3Agonista E allora in quali pazienti è particolarmente indicato? Pazienti con (rischio di) disturbo dello svuotamento…
  • 35. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (2012) Antihistamines Antiparkinson agents Skeletal muscle relaxants Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dimenhydrinate Diphenhydramine Hydroxyzine Loratadine Meclizine Benztropine Trihexyphenidyl Carisoprodol Cyclobenzaprine Orphenadrine Tizanidine Antidepressants Antipsychotics Amitriptyline Amoxapine Clomipramine Desipramine Doxepin Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine Chlorpromazine Clozapine Fluphenazine Loxapine Olanzapine Perphenazine Pimozide Prochlorperazine Promethazine Thioridazine Thiothixene Trifluoperazine Antimuscarinics (urinary incontinence) Antispasmodics Darifenacin Fesoterodine Flavoxate Oxybutynin Solifenacin Tolterodine Trospium Atropine products Belladonna alkaloids Dicyclomine Homatropine Hyoscyamine products Propantheline Scopolamine Drugs with strong anticholinergic properties
  • 37. Mirabegron is efficacious in the treatment of symptoms of OAB in older adults. These data appear to show that there is no loss of efficacy with age
  • 38. Mirabegron was well tolerated in older OAB patients with no difference in tolerability with age over a 1-year period. UTI and hypertension were the most frequent AE found in the population. However, in elderly subjects, these AE were more frequent in people treated with tolterodine than those under mirabegron over 12 months
  • 39. Beta3Agonista E allora in quali pazienti è particolarmente indicato? In pazienti anziani a rischio di sovraccarico anticolinergico…
  • 41. Nota Informativa Importante su mirabegron: nuove raccomandazioni relative al rischio di aumento della pressione arteriosa Pillole dal Mondo n. 842 15/09/2015 L’uso di mirabegron è ora controindicato nei pazienti affetti da ipertensione grave non controllata, intesa come Pressione Arteriosa Sistolica ≥180 mmHg e/o Pressione Arteriosa Diastolica ≥110 mmHg. È, quindi, necessario misurare la pressione arteriosa prima di intraprendere il trattamento e monitorarla regolarmente durante lo stesso, specialmente nei pazienti affetti da ipertensione.
  • 43. Pooled 12-week Phase III Studies (046, 047 and 074) CV Events Placebo (n=1380) Mirabegron Tolterodine ER 4mg (n=495) 25mg (n=432) 50mg (n=1375) 100mg (n=929) Incidence, n(%) of APTC/MACE 4 (0.3) 0 0 0 1 (0.2) Relative risk of APTC/MACE (95% CI) - NE NE NE - 1-year Phase III Study (049) CV Events Mirabegron Tolterodine ER 4mg (n=812) 50mg (n=812) 100mg (n=820) Incidence, n(%) of APTC/MACE 6 (0.7) * 0 4 (0.5) ** Relative risk of APTC/MACE (95% CI) 1.50 (0.35, 7.27) NE - NE = not evaluated due to insufficient data * nonfatal stroke (3 patients), nonfatal myocardial infarction (2 patients) and CV death (1 patient) ** CV death (2 patients), nonfatal myocardial infarction (1 patient) and nonfatal stroke (1 patient) Mirabegron Tollerabilità cardiovascolare Rosa et al., Eur Urol Eur Urol. 2016 Feb;69(2):311-23
  • 44. Ipertensione  E’ stato l’evento avverso più comune registrato nell’ambito degli studi di fase III  Nell’analisi aggregata degli studi è stata rilevata rispettivamente nel :  8.7% dei pazienti in trattamento con mirabegron 50 mg  8.5% dei pazienti in trattamento con placebo  L’aumento massimo SBP/DBP associato a mirabegron 50 mg è stato ≤1 mmHg reversibile dopo interruzione della terapia Rosa et al., Eur Urol Eur Urol. 2016 Feb;69(2):311-23 Pooled 12-week Phase III Studies (046, 047 and 074) CV Events Placebo (n=1380) Mirabegron Tolterodine ER 4mg (n=495) 25mg (n=432) 50mg (n=1375) 100mg (n=929) Incidence, n(%) of: Hypertension TEAEs 117 (8.5) 52 (12.0) 120 (8.7) 58 (6.2) 48 (9.7) Hypertension SAEs 0 0 1 (0.1) 0 1 (0.2) Discontinuations due to hypertension TEAEs 3 (0.2) 2 (0.5) 5 (0.4) 4 (0.4) 1 (0.2) Relative risk of hypertension TEAEs (95% CI) - 1.25 (0.86, 1.80) 1.02 (0.79, 1.32) 0.78 (0.56, 1.08) -
  • 45. Beta3Agonista E la safety? The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB.
  • 47. Persistence with antimuscarinic agents is poor • 12-month UK study on prescription data Wagg A et al. BJU Int 2012;110:1767-74 % of patients remaining on AM therapy over a period of 12 months 0 1 20 30 40 50 60 70 80 90 100 10 Patients(%) Months 9 108765432 11 12 Solifenacin (N=1,381) Tolterodine ER (N=1,758) Tolterodine IR (N=482) Oxybutynin ER (N=590) Oxybutynin IR (N=1371) Propiverine (N=97) Trospium (N=352) Darifenacin (N=23) Flavoxate (N=89) ER: extended release; IR: immediate release
  • 49. Persistence with anti-muscarinic and mirabegron treatment for OAB in daily clinical practice • Single-centre, retrospective study in N=701 pts with OAB treated with anti- muscarinic agent (N=356) or mirabegron (N=345) according to physician’s preference In daily clinical practice OAB pts seem to stay longer on mirabegron treatment than on anti-muscarinic treatment Ito N. Eur Urol Suppl 2016;15(3):e999 27% 21% 14% 63% 56% 52% 0% 20% 40% 60% 80% 1 yr 2 yr 3 yr %ofptson therapy Anti-muscarinic Mirabegron % pts Anti-muscarinic (N=356) Mirabegron (N=345) Symptom improvement 41.2% 68.5% No response to treatment 24.3% 25.2% Discontinuation due to AEs 9.4% 6.4% P<0.001 Data from poster
  • 50. Beta3Agonista E l’aderenza alla terapia? Potrebbe migliorare l’aderenza ad una terapia cronica
  • 52. Beta3Agonista: Conclusioni Altra categoria farmacologica rispetto ad AM Efficace Efficace in non responders ad AM Anche in combinazione con AM Vantaggi in alcuni soggetti Disturbo di svuotamento Anziano Safety simile Migliore aderenza rispetto ad AM

Editor's Notes

  1. 28/04/2016
  2. Clinical impact category: increases insights in mechanisms β3AR: β3 adrenoreceptors IC: interstitial
  3. The idea that there were two classes of adrenergic receptors (ARs), α and β, in the sympathetic autonomic nervous system was first established in 19481,2 In the late 1960s, β-ARs were further divided into two subtypes based on differences in the physiological effects of β-adrenergic stimulation with different ligands in the heart, adipose, and lung tissues3 As early as the 1970s, a third type of β-AR (non-β1 or -β2), had been proposed as the primary β-AR in the human bladder4 It had been known since the end of the 19th century that the bladder was innervated by both parasympathetic and sympathetic branches of the autonomic nervous system5 In the late 1980s, the β3-AR was identified and first confirmed in adipose tissue, where, in animal models, it was shown to play a role in lipolysis and thermoregulation6 The functional role of β3-AR in the human bladder was confirmed 20 years later7,8 References Tanaka Y et al. Clin Exp Pharmacol Physiol 2005; 32(7): 503–14 Ahlquist RP. Am J Physiol 1948; 153: 586–600; Lands AM et al. Nature 1967; 214: 597–8 Nergårdh A et al. Acta Pharmacol Toxicol (Copenh) 1977; 40: 14–21 De Groat WC, Saum WR. J Physiol 1972; 220: 297–314 Emorine LJ et al. Science 1989; 245: 1118–21 Fujimura T et al. J Urol 1999; 161: 680–5 Yamaguchi O. Urology 2002; 59(5 Suppl 1): 25–9 Westfall TC, Westfall DP. In: Brunton LL et al (Eds). Goodman’s and Gilman’s The Pharmacological Basis of Therapeutics (11th ed). New York, NY: Hill-McGraw, 2006 Berkowitz DE et al. Eur J Pharmacol 1995; 289: 223–8 Hertz L et al. Neurochem Int 2010; 57: 411–20 Rodriguez M et al. Brain Res Mol Brain Res 1995; 29: 369–75 Roberts SJ et al. Br J Pharmacol 1997; 120: 1527–35 Stiles GL et al. J Biol Chem 1983; 258: 8443–9 Wuest M et al. J Pharmacol Exp Ther 2009; 328: 213–22 Anthony A et al. Aliment Pharmacol Ther 1998; 12: 519–25 Igawa Y et al. Br J Pharmacol 1999; 126: 819–25 Gauthier C et al. J Clin Invest 1996; 98: 556–62 Krief S et al. J Clin Invest 1993; 91: 344–9 Dennedy MC et al. Am J Obstet Gynecol 2002; 187: 641–7
  4. Mirabegron is highly selective for the β3-AR subtype over the β1- and β2-ARs1 105-fold greater affinity for β3- vs β1-AR 33-fold greater affinity for β3- vs β2-AR References Food and Drug Administration. Advisory Committee Briefing Document: Mirabegron (YM178) for the Treatment of Overactive Bladder, April 2012
  5. E 1/3 di questa popolazione è stata rimossa dall lista di attesa per infiltrazione di tossina botulinica
  6. Abbiamo comunque già a disposizione dati specifici sull’anziano fragile. Questo sutudio di Wagg pubblicato lo scorso anno ha valutao efficacia e tollerabilità del mirabegron nei pazienti anziani. Quindi è stata arruolata una popolazione di pazienti ultrasessantiacinquenni, e l’analisi dei risultati è stata poi condotta mediante una stratificazione in due fasce, individui tra 65 e 75, e quelli con oltre 75 anni.
  7. Lo studio, come vedete dalle parole del testo che ho riportato in modo originale, dimostra che l’efficacia di mirabegron rispetto agli studi sulla popolazione generale non diminuisce con l’aumentare dell’età
  8. Mentre in relazione alla tollerabilità, non aumentano significativamente le percentuali degli eventi avversi, e soprattutto non aumentano le percentuali degli eventi avversi seri, fino ad 1 anno di folow-up. Ancor di più, l’ipertensione arteriosa e le infezioni urinarie risultano essere maggiormente rappresentate, nell’arco dei 12 mesi, nel bracio di trattamento con antimuscarinici, in questo caso rappresentati da tolterodina.
  9. In the 1-yr study, APTC/MACE events occurred in 0.7% of patients in the mirabegron 50 mg group (n = 812): nonfatal stroke (3 patients), nonfatal myocardial infarction (2 patients) and CV death (1 patient).
  10. Reporter comments: (1) Interesting real-life results on the persistence rate of patients treated with anticholinergics vs mirabegron. CI category: confimative data AE: adverse event OAB: overactive bladder