mecanismos vaso activos ii - wordpress.com · 2017-06-15 · •alpha-adrenoceptor antagonistas...
TRANSCRIPT
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Mecanismos Vaso activos IIProf. Dr. Mag. Rafael Porcile
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Í A
Universidad Abierta Interamericana
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VASODILATADORES
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Clasificaciones
clásicas
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•Alpha-adrenoceptor antagonistas (alpha-blockers)
•Angiotensina converting enzyme (ACE) inhibitors
•Angiotensin receptor blockers (ARBs)
•Beta2-adrenoceptor agonists (β2-agonists)
•Calcium-channel blockers (CCBs)
•Centrally acting sympatholytics
•Direct acting vasodilators
•Endothelin receptor antagonists
•Ganglionic blockers
•Nitrodilators
•Phosphodiesterase inhibitors
•Potassium-channel openers
•Renin inhibitors
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
Endotelina
E1
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Vasopresina
HistaminaAngiotensina II
IP3
RhoKinasa
Angiotensina II
Tromboxano A2
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
Endotelina
E1
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Vasopresina
HistaminaAngiotensina II
IP3
RhoKinasa
Angiotensina II
Tromboxano A2
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Cuatro tipos de
vasodilatadores • GMP c o AMP c dependientes
• Inhibidores ALFA
• Inhibidores directos del Ca
citoplasmático
• Inhibidores directos dela Fosforilacíon
cadena liviana de la miosina
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Histamina
![Page 12: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/12.jpg)
Fosforilación
Catalítica cadena
liviana miosinaPGE2
Epoprostenol
Selexipag
AMP c2
Histamina
Adenosina
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Fosforilación
Catalítica cadena
liviana miosinaPGE2
Epoprostenol
Selexipag
AMP c2
Histamina
Adenosina
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Epoprostenol (Flolan)
WHO Class III / IV
Intravenosa vía central venouscatheter
Half life approx 4
Minutes
DISPONIBILIDAD
EN ARGENTINA
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Meta-Analysis of Published Randomized Controlled
With Epoprostenol in Pulmonary Arterial Hypertension
by Mantel–Haenszel and Peto Methods
The analysis included 215 patients in 3 trials.
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Selexipag
Selexipag is a prostacyclin IP receptor
agonist. It is not prostacyclin or a
prostacyclin analog. It is orally available
and undergoes rapid hydrolysis to the
active metabolite, ACT-333679
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Selexipag
Selective prostacyclin IP receptor agonist
The GRIPHON study
Designed to demonstrate a
prolongation of time to the first
morbidity/mortality event for
selexipag compared to placebo and
to evaluate the safety of the
selexipag in PAH patients.
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Selexipag
Selective prostacyclin IP receptor agonist
The GRIPHON study
.
Selexipag decreased the risk of a
morbidity/mortality event versus placebo
by 39% (p<0.0001). Efficacy observed was
consistent across the key subgroups: age, gender, WHO
Functional Class, PAH etiology and background PAH therapy.
Patients were treated for up to 4.3 years. The overall tolerability
profile of selexipag in GRIPHON was consistent with
prostacyclin therapies
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Histamina
![Page 28: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/28.jpg)
Tres tipos de vasodilatadores
• GMP c o AMP c dependientes
• Inhibidores directos del Ca
citoplasmático
• Inhibidores directos dela Fosforilacíon
cadena liviana de la miosina
![Page 30: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/30.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
Endotelina
E1
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Vasopresina
HistaminaAngiotensina II
IP3
RhoKinasa
Angiotensina II
Tromboxano A2
![Page 31: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/31.jpg)
Calcio
GMPc
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
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Guamilato
ciclasa
fosforilada
En la membrana
Guamilato
ciclasa soluble
En el citoplasma
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GMPcEstimula
Guamilato
ciclasa
soluble
En el
citoplasma
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO
Donantes de
oxido nítrico
Relaxina
Vericiguat
Riociguat
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Calcio
GMPc
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 42: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/42.jpg)
Guamilato
ciclasa
Posforilada
Reduce la concentración de
Calcio citoplasmática
Guamilato
ciclasa soluble
En el citoplasma
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GMPcEstimula
Guamilato
ciclasa
soluble
En el
citoplasma
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO
Donantes de oxido
nítrico
Riociguat
Ulatitide
Relaxina
Vericiguat
![Page 47: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/47.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 48: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/48.jpg)
RIOCIGUAT
Dosificación.
Por vía oral 1mg, 3 veces por día
durante 2 semanas. Dosis diaria
máxima 7,5mg (25mg 3 veces por
día).
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Left Ventricular Systolic
Dysfunction Associated With
Pulmonary Hypertension
Riociguat Trial
201 pacientes con insuficiencia cardiaca
causada por HAP secundaria a disfunción
sistólica ventricular izquierda.
A Phase IIb Double-Blind, Randomized, Placebo-
Controlled, Dose-Ranging Hemodynamic Study
Bonderman D et al. Circulation. 2013;128:502-511
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Left Ventricular Systolic
Dysfunction Associated With
Pulmonary Hypertension
Riociguat Trial
Aumentaron el índice cardiaco (0.4 Lキmin−1キm−2; p= 0.0001) y el índice de volumen
de eyección (5.2 mlキm−2; p= 0.0018) sin que
se observaran cambios en la frecuencia
cardiaca ni la presión sistólica sistémica.
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Left Ventricular Systolic
Dysfunction Associated With
Pulmonary Hypertension
Riociguat Trial
Asimismo se registró una mejoría de la
calidad de vida asociada al tratamiento con
riociguat reflejada en una disminución de la
puntuación del Minnesota Living With Heart
Failure Score (p= 0.0002)
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Asimismo se registró una mejoría de la calidad de vida asociada al
tratamiento con riociguat reflejada en una disminución de la puntuación del
Minnesota Living With Heart Failure Score (p= 0.0002)
Bonderman D et al. Circulation. 2013;128:502-511 Copyright © American Heart Association, Inc. All rights reserved.
¿Mortalidad?
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Primary analysis:
NT-proBNPreduction in pooled 2.5/5/10 mg dose groups >
reduction in placebo (NS, [email protected]
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El análisis final en el grupo de
mayor dosis se asoció a menor
numero de eventos y mejoría de
la fracción de eyección a 12 meses
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Calcio
GMPc
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 64: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/64.jpg)
Calcio
GMPc
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 66: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/66.jpg)
• AUMENTO DEL 20 %
VM CARDÍACO A
PARTIR DEL PRIMER
TRIMESTRE
• Caida del 30 %
RESISTENCIAS
VASCULARES
SISTEMICAS
• AUMENTO DE LA
COMPLIANCE
VASCULAR ARTERIAL
30 %
• AUMENTO DEL FLUJO
PLASMATICO RELAN
45 %
Se producen en el cuerpo lúteo
del ovario, la mama y, durante
el embarazo, también en la
placenta, corion, y decidua.
![Page 74: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/74.jpg)
GMPcEstimula
Guamilato
ciclasa
soluble
En el
citoplasma
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO
Vericiguat
Relaxina
Ulatitide
![Page 75: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/75.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 76: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/76.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
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Ulatitide
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GMPcEstimular
Guamilato
ciclasa
fosforilada
En la
membrana
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO [email protected]
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 87: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/87.jpg)
Los péptidos natriuréticos son eliminados por el NPR-C y la
neprilisina
ANP: péptido natriurético auricular; Ang: angiotensina; AT1: angiotensina II tipo 1; BNP: péptido natriurético tipo B; cGMP: monofosfato de guanosina cíclico;
CNP: péptido natriurético tipo C; GTP: trifosfato de guanosina; IC: insuficiencia cardíaca; PN: péptido natriurético; RPN: receptor del péptido natriurético; SRAA: sistema renina-angiotensina-aldosterona
Levin et al. N Engl J Med 1998;339;321–8; Gardner et al. Hypertension 2007;49:419–26; Molkentin. J Clin Invest 2003;111:1275–77; Nishikimi et al. Cardiovasc Res 2006;69:318–28; Guo et al. Cell Res
2001;11:165–80; Von Lueder et al. Circ Heart Fail 2013;6:594–605; Yin et al. Int J Biochem Cell 2003;35:780–3; Mehta & Griendling. Am J Physiol Cell Physiol 2007;292:C82–97
GTPGTP
cGMPPéptidos inactivos
ANP/CNPANP BNP
NPR-A
Internalización
Neprilisina
Vasodilación
fibrosis/hipertrofia cardíacas
natriuresis/diuresis
Señalización y
efectos de los
PNDegradación y
depuración de los
PN
La neprilisinaes una
endopeptidasa
que degrada
múltiples
péptidos
endógenos vaso
activos, glucagon,
neurotensina,
oxitocina, y
bradikinina
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Original Article
Angiotensin–Neprilysin Inhibition versus Enalapril in
Heart Failure
John J.V. McMurray, M.D., Milton Packer, M.D., Akshay S. Desai, M.D., M.P.H., Jianjian Gong, Ph.D., Martin P. Lefkowitz, M.D., Adel R. Rizkala, Pharm.D., Jean L. Rouleau, M.D., Victor C. Shi, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., Michael R. Zile, M.D., for the PARADIGM-HF Investigators and Committees
N Engl J MedVolume 371(11):993-1004
September 11, 2014
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La inhibición conjunta del sistema
renina – angiotensina y neprilisina
ha sido superior que la inhibición
de sólo uno de ellos.
Sin embargo en ensayos clínicos la
inhibición conjunta de la enzima
convertidora de angiotensina y
neprilisina se asoció a angioedema.
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ANP: péptido natriurético auricular; Ang: angiotensina; AT1: angiotensina II tipo 1; BNP: péptido natriurético tipo B; cGMP: monofosfato de guanosina cíclico;
CNP: péptido natriurético tipo C; GTP: trifosfato de guanosina; PN: péptido natriurético; RPN: receptor del péptido natriurético; SRAA: sistema renina-angiotensina-aldosterona
Levin et al. N Engl J Med 1998;339;321–8; Gardner et al. Hypertension 2007;49:419–26; Molkentin. J Clin Invest 2003;111:1275–77; Nishikimi et al. Cardiovasc Res 2006;69:318–28; Guo et
al. Cell Res 2001;11:165–80; Von Lueder et al. Circ Heart Fail 2013;6:594–605; Yin et al. Int J Biochem Cell 2003;35:780–3; Mehta & Griendling. Am J Physiol Cell Physiol 2007;292:C82–97;
Langenickel & Dole. Drug Discovery Today: Ther Strateg 2012;9:e131–9
Cascadas
de señalización
GTP GTP
cGMP
Péptidos inactivos
ANP/CNPANP BNP
NPR-A
CNP
NPR-B
Fragmentos de
PN inactivosANP/CNP/BNP
NPR-C
Ang II
receptor AT1
Internalización
Reciclado
del receptor
Neprilisina
Vasodilación
fibrosis/hipertrofia cardíacas
natriuresis/diuresis
Vasoconstricción
fibrosis/hipertrofia cardíacas
retención de sodio/agua
Sacubitrilo/valsartan
Sacubitrilo
Potenciación del sistema de
péptidos natriuréticos Supresióndel SRAA
Valsartán
El Sacubitrilo/valsartán potencia simultáneamente los efectos beneficiosos del
sistema de PN al tiempo que bloquea los efectos perjudiciales del SRAA
Vasoconstricción
fibrosis/hipertrofia cardíacas
retención de sodio/agua
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Screening Criteria,.
McMurray JJ et al. N Engl J Med 2014;371:993-1004.
Se incluyeron 10513pacientes en clase funcional II,
III o IV, con fracción de eyección
igual o menor al 40%.
Se randomizaron 8442a dos
ramas:
*Enalapril (10 mg cada 12
horas) *LCZ696 (200 mg c/12
hs).
ADD ON
Antagonistas de aldosterona
(54%), beta bloqueantes (93%),
y digitales (29%).
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Según estos resultados, se necesitarán
tratar (NNT) a 35 personas para evitar
una muerte
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2016 ESC Guidelines for the
diagnosis and treatment of acute
and chronic heart failure
DOI: http://dx.doi.org/10.1093/eurheartj/ehw1282129-
2200 First published online: 20 May 2016
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Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction.
Piotr Ponikowski et al. Eur Heart J 2016;37:2129-2200
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
• Pacientes con tratamiento sub óptico
Antagonistas de aldosterona (54%),
EMPHASIS-HF6
(2014)2.737 pacientes Beneficios clave de la eplerenona
(ARM) vs. placebo:
•37% mortalidad por causa CV u
hospitalización por IC
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
• En el período de Run In Prueba 2071 pacientes
quedaron afuera por intolerancia El 20% .
Incluyeron solo a los tolerantes sin utilizar ITT
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
• ¿Los resultados son extrapolables a
pacientes con icc estadio A y B o C en
clase funcional I?
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
¿Como afecta la droga el uso del
pro bnp como medio diagnostico
y de monitoreo?
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
¿Aumenta el riesgo de
alzhéimer? El B amiloide es
lisado por la neprilisina
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
La insuficiencia cardíaca es un
trastorno que afecta a los ancianos,
pero en el PARADIGMA-HF la edad
promedio fue de 64 años de edad,
bastante menor que el típico
paciente con insuficiencia cardíaca.
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CUESTIONES PENDIENTE
LUEGO DEL ESTUDIO
La dosis de valsartán (del LCZ696) fue de
200 mg dos veces al día, es decir, la dosis
máxima del valsartán. Mientras que el
enalapril (del grupo control) se dosificó
con 10 mg dos veces al día, inferior a la
dosis máxima es de 40 mg al día
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GMPcEstimula
Guamilato
ciclasa soluble
En el citoplasma
Estimular
Guamilato
ciclasa
fosforilada
En la membrana
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO
Inhibir su degradación por la fosfodiesterasa
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GMPc
SOLO TRES LLAVES HACIA LA ESTIMULACÍON
DEL GMP CICLICO
Inhibir su degradación por la
fosfodiesterasa
![Page 106: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/106.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 107: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/107.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
GMPc
AMP c
Fosfodiesterasa
Oxido Nítrico
BNP
Sildenafil
Cilostazol
Sarcubitrilo
Nitroglicerina
Nitro prusiato de Sodio
Di nitrato de isosorbide
Riociguat
Serelaxina
Ularitide
![Page 110: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/110.jpg)
Sildenafil Improves Exercise Capacity and Quality of Life in
Patients With Systolic Heart Failure and Secondary Pulmonary
Hypertension
Gregory D. Lewis, Ravi Shah, Khurram Shahzad, Janice M.
Camuso,
Circulation. 2007;116:1555-1562
Phosphodiesterase 5 inhibition with sildenafil improves exercise
capacity and quality of life in patients with systolic HF with
secondary PH.
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Gregory D. Lewis et al. Circulation. 2007;116:1555-1562
Copyright © American Heart Association, Inc. All rights reserved.
Phosphodiesterase 5 inhibition with sildenafil improves
exercise capacity and quality of life in patients with
systolic HF with secondary PH.
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CILOSTAZOL
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Cuatro tipos de
vasodilatadores • GMP c o AMP c dependientes
• Inhibidores ALFA
• Inhibidores directos del Ca
citoplasmático
• Inhibidores directos dela Fosforilacíon
cadena liviana de la miosina
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Cuatro tipos de
vasodilatadores • GMP c o AMP c dependientes
• Inhibidores ALFA
• Inhibidores directos del Ca
citoplasmático
• Inhibidores directos dela Fosforilacíon
cadena liviana de la miosina
![Page 116: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/116.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
Endotelina
E1
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Vasopresina
HistaminaAngiotensina II
IP3
RhoKinasa
Angiotensina II
Tromboxano A2
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
![Page 118: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/118.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
Bloqueador Uso
Nombre
comercial
común
Doxazosin
Hipertensión
e hiperplasia
benigna de
próstata
(HBP)
(Cardura)
Silodosin
Hiperplasia
benigna de
próstata
(Rapaflo)
Prazosin Hipertensión (Minipress)
Tamsulosina
Benign
prostatic
hyperplasia
(Flomax)
Alfuzosina
Benign
prostatic
hyperplasia
(Uroxatral)
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
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Calcio
Fosforilación
Catalítica cadena
liviana miosina
![Page 121: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/121.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
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![Page 123: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/123.jpg)
Efecto
alfabloquenate
de los
betabloqueantes
![Page 124: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/124.jpg)
Efectos vasodilatadores de
los betabloqueantes
![Page 125: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/125.jpg)
Efectos vasodilatadores de los
betabloqueantes
![Page 126: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/126.jpg)
Tres tipos de vasodilatadores
• GMP c o AMP c dependientes
• Inhibidores directos del Ca
citoplasmático
• Inhibidores directos dela Fosforilacíon
cadena liviana de la miosina
![Page 127: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/127.jpg)
Calcio
Fosforilación
Catalítica cadena
liviana miosina
Pg1/Prostaciclinas
Endotelina
E1
GMPc
AMP c
Fosfodiesterasa
2
Oxido Nítrico
BNP
Vasopresina
HistaminaAngiotensina II
IP3
RhoKinasa
Angiotensina II
Tromboxano A2
![Page 128: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/128.jpg)
Calcio
![Page 129: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/129.jpg)
Calcio
![Page 130: Mecanismos Vaso activos II - WordPress.com · 2017-06-15 · •Alpha-adrenoceptor antagonistas (alpha-blockers) •Angiotensina converting enzyme (ACE) inhibitors •Angiotensin](https://reader034.vdocumento.com/reader034/viewer/2022050111/5f48c523a0f8cc35686873ee/html5/thumbnails/130.jpg)
Calcio