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BetabloqueantesBetabloqueantesDr. Francisco Jos de la PradaDr. Francisco Jos de la Prada AlvarezAlvarez

Universidad XochicalcoUniversidad XochicalcoFacultad Modular de MedicinaFacultad Modular de Medicina

Ensenada BC,Ensenada BC, MexicoMexico


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ReceptoresReceptores

1: (msculo cardaco)1: (msculo cardaco) Incrementa la frecuencia cardaca.Incrementa la frecuencia cardaca.

Incrementa la contractilidad cardaca.Incrementa la contractilidad cardaca.

Incrementa la conduccin AV.Incrementa la conduccin AV.

Disminuye la refractariedad del nodulo AV.Disminuye la refractariedad del nodulo AV.

2: (msculo bronquial y musculo liso vascular, y menos en2: (msculo bronquial y musculo liso vascular, y menos enmsculo cardaco):msculo cardaco): Vasodilatacin.Vasodilatacin.

BrBrooncodilatcin.ncodilatcin.

3 (tejido adiposo y msculo cardaco):3 (tejido adiposo y msculo cardaco): T

ermognesis.T

ermognesis. Reduce la contractilidad cardaca.Reduce la contractilidad cardaca.

Dollery, CT, Frishman, WH, Cruickshank, JM. Current cardiovascular drugs, 1stDollery, CT, Frishman, WH, Cruickshank, JM. Current cardiovascular drugs, 1sted, Current Science, London, 1993, p. 83.ed, Current Science, London, 1993, p. 83.

KochKoch--Weser, J, Frishman, WH. betaWeser, J, Frishman, WH. beta--Adrenoceptor antagonists: new drugs andAdrenoceptor antagonists: new drugs andnew indications. N Engl J Med 1981;305:500.new indications. N Engl J Med 1981;305:500.

Opie, LH. Drugs and the heart. Part 1. Beta blocking agents. Lancet 1980;1:693.Opie, LH. Drugs and the heart. Part 1. Beta blocking agents. Lancet 1980;1:693.


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CaracterCaractersticassticas

Cardioselectividad.Cardioselectividad.

Actividad simpaticomimtica intrnseca.Actividad simpaticomimtica intrnseca.

Actividad bloqueante alfa adrenrgica.Actividad bloqueante alfa adrenrgica.


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CaractersticasCaractersticas

Cardioselectividad.Cardioselectividad. Capacidad del frmaco para bloquear preferentementeCapacidad del frmaco para bloquear preferentementelos receptores cardacos.los receptores cardacos.

La cardioselectividad es unaLa cardioselectividad es unapropiedad relativapropiedad relativa. A altas. A altasdosis se produce el bloqueodosis se produce el bloqueo 22 Propanolol:Propanolol: no selectivono selectivo (igual afinidad por receptores(igual afinidad por receptores 1 y1 y 2).2).

Acebutolol, Atenolol, betaxolol, Bisoprolol, Celiprolol yAcebutolol, Atenolol, betaxolol, Bisoprolol, Celiprolol yMetoprololMetoprolol:: selectivosselectivos (principal afinidad por receptores(principal afinidad por receptores 11,, yymenos pormenos por 2 que median brocodilatacin y vasodilatacin2 que median brocodilatacin y vasodilatacinperifrica).perifrica).

Son preferibles en pacientes asmticos y diabticos.Son preferibles en pacientes asmticos y diabticos.

KochKoch--Weser, J. Drug therapy: metoprolol. N Engl J Med 1979;301:698.Weser, J. Drug therapy: metoprolol. N Engl J Med 1979;301:698.

Frishman, W. Acebutolol. Cardiovasc Rev Rep 1985;6:979.Frishman, W. Acebutolol. Cardiovasc Rev Rep 1985;6:979.

Frishman, WH. Drug therapy: atenolol and timolol, two new systemic betaFrishman, WH. Drug therapy: atenolol and timolol, two new systemic beta--adrenoceptor antagonists. N Engl J Med 1982;306:1456.adrenoceptor antagonists. N Engl J Med 1982;306:1456.


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Actividad simpaticomimtica intrnseca.Actividad simpaticomimtica intrnseca. Actividad agonista parcial por el receptor.Actividad agonista parcial por el receptor. ProducenProducen menor reduccinmenor reduccin en la frecuencia cardaca en reposo (pero impiden laen la frecuencia cardaca en reposo (pero impiden la

taquicardia con el ejercicio), menor depresin de la conduccin AV y menostaquicardia con el ejercicio), menor depresin de la conduccin AV y menosinotropismo negativo que losinotropismo negativo que los --bloqueantes sin activida ISA.bloqueantes sin activida ISA.

No deberan usarse nen hipertiroidismo, estenosis subartica hipertrfica,No deberan usarse nen hipertiroidismo, estenosis subartica hipertrfica,diseccin artica, fase postdiseccin artica, fase post--IAM y angina.IAM y angina.

OxprenololOxprenolol

CeliprololCeliprolol AcebutololAcebutolol

CarteololCarteolol PenbutololPenbutolol

Frishman, WH, Charlap, S. The alphaFrishman, WH, Charlap, S. The alpha-- and betaand beta--adrenergic blocking drugs. In: Cardiology, Parmley,adrenergic blocking drugs. In: Cardiology, Parmley,WW (Ed), JB Lippincott, Philadelphia, 1990, p.1.WW (Ed), JB Lippincott, Philadelphia, 1990, p.1.

Frishman, WH. Drug therapy. Pindolol: a new betaFrishman, WH. Drug therapy. Pindolol: a new beta--adrenoceptor antagonist with partial agonistadrenoceptor antagonist with partial agonistactivity. N Engl J Med 1983;308:940.activity. N Engl J Med 1983;308:940.

Magder, S, Sami, M, Ripley, R, et al. Comparison of the effect of pindolol and propranolol onMagder, S, Sami, M, Ripley, R, et al. Comparison of the effect of pindolol and propranolol onexercise performance in patients with angina pectoris. Am J Cardiol 1987;59:1289.exercise performance in patients with angina pectoris. Am J Cardiol 1987;59:1289.


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CaractersticasCaractersticas Actividad bloqueante alfa adrenrgicaActividad bloqueante alfa adrenrgica..

Labetalol:Labetalol: BloqueanteBloqueante /Bloqueante/Bloqueante :3/1 a 7/1 (sobre todo por via IV. Por via oral:3/1 a 7/1 (sobre todo por via IV. Por via oral

este efecto se reduce con el tratamiento a largo plazo)este efecto se reduce con el tratamiento a largo plazo)

bloqueante: bradicardia, inotropismo negativo.bloqueante: bradicardia, inotropismo negativo.

bloqueantebloqueante:: Bloquea la vasoconstriccin refleja por el bloqueoBloquea la vasoconstriccin refleja por el bloqueo

Disminuye las resistencias vasculares coronarias y perifricas, mejorandoDisminuye las resistencias vasculares coronarias y perifricas, mejorandoel flujo sanguneo.el flujo sanguneo.

Mejora la sensibiliad insulnica en diabticos y no diabticos.Mejora la sensibiliad insulnica en diabticos y no diabticos.

Mejoran el perfil lipdico.Mejoran el perfil lipdico.

Carvedilol:Carvedilol: Los beneficios en insuficiencia cardaca no estn relacionados con el bloqueoLos beneficios en insuficiencia cardaca no estn relacionados con el bloqueo

..

Kubo,T, Azevedo, ER, Newton, GE, et al. Lack of evidence for peripheral alpha(1)Kubo,T, Azevedo, ER, Newton, GE, et al. Lack of evidence for peripheral alpha(1)--adrenoceptor blockade during longadrenoceptor blockade during long--term treatment of heart failure with carvedilol. Jterm treatment of heart failure with carvedilol. J

Am Coll Cardiol 2001;38:1463.Am Coll Cardiol 2001;38:1463.

Hryniewicz, K, Androne, AS, Hudaihed, A, Katz, SD. Comparative effects ofHryniewicz, K, Androne, AS, Hudaihed, A, Katz, SD. Comparative effects ofcarvedilol and metoprolol on regional vascular responses to adrenergic stimuli incarvedilol and metoprolol on regional vascular responses to adrenergic stimuli innormal subjects and patients with chronic heart failure. Circulation 2003;108:971.normal subjects and patients with chronic heart failure. Circulation 2003;108:971.


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Actividad bloqueante alfa adrenrgicaActividad bloqueante alfa adrenrgica.. La actividad bloqueante alfa asociada al bloqueoLa actividad bloqueante alfa asociada al bloqueo

beta tiene un impacto positivo sobre la diabetes ybeta tiene un impacto positivo sobre la diabetes yla aterosclerosis, mejorando el control glucmico,la aterosclerosis, mejorando el control glucmico,

reduciendo la hiperinsulinemia compensadora yreduciendo la hiperinsulinemia compensadora yreduciendo los cambios proaterognicos sobre losreduciendo los cambios proaterognicos sobre loslpidos plasmticos.lpidos plasmticos.

Giugliano D, Acampora R, Marfella RGiugliano D, Acampora R, Marfella Ret alet al.. Metabolic andMetabolic andcardiovascular effects of carvedilol and atenolol in noncardiovascular effects of carvedilol and atenolol in non--insulininsulin--

dependent diabetes mellitus and hypertension. A randomized,dependent diabetes mellitus and hypertension. A randomized,controlled trial. Ann Intern Med 1997;126:955controlled trial. Ann Intern Med 1997;126:955959.959.

Jacob S, Rett K, Wicklmayr MJacob S, Rett K, Wicklmayr M et alet al. Differential effect of. Differential effect ofchronic treatment with two betachronic treatment with two beta--blocking agents on insulinblocking agents on insulinsensitivity: the carvedilolsensitivity: the carvedilol--metoprolol study. J Hypertens 1996;metoprolol study. J Hypertens 1996;14:48914:489494.494.


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Caractersticas farmacocinticasCaractersticas farmacocinticas

Metabolismo heptico.Metabolismo heptico.

Eliminacin inalterada por rin.Eliminacin inalterada por rin.

Frishman, W. Clinical pharmacology of the new beta adrenergic blocking drugs.Frishman, W. Clinical pharmacology of the new beta adrenergic blocking drugs.

Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 1979;Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 1979;

97:663.97:663.

Frishman, WH, Lazar, EJ, Gorodokin, G. Pharmacokinetic optimization ofFrishman, WH, Lazar, EJ, Gorodokin, G. Pharmacokinetic optimization of

therapy with betatherapy with beta--adrenergic blocking agents. Clin Pharmacokinet 1991;20:311.adrenergic blocking agents. Clin Pharmacokinet 1991;20:311.


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Metabolismo hepticoMetabolismo heptico:: Liposolubles, absorcin completa en intestino delgado y metabolismoLiposolubles, absorcin completa en intestino delgado y metabolismo

heptico.heptico.

Biodisponibilidad variable.Biodisponibilidad variable.

Corta vida media.Corta vida media. Atraviesan la BHEAtraviesan la BHE aumentando la incidencia de efectos secundariosaumentando la incidencia de efectos secundarios..

Revisin de estudios randomRevisin de estudios randomiizados con mas de 35.000 pacientes.zados con mas de 35.000 pacientes.

La lipofilia no afecta la aparicin de efectos adversos.La lipofilia no afecta la aparicin de efectos adversos. Ko, DT, Hebert, PR, Coffey, CS, et al. BetaKo, DT, Hebert, PR, Coffey, CS, et al. Beta--blocker therapy and symptoms ofblocker therapy and symptoms of

depression, fatigue, and sexual dysfunction. JAMA 2002;288:351.depression, fatigue, and sexual dysfunction. JAMA 2002;288:351.

PropanololPropanolol

MetoprololMetoprolol

OxprenololOxprenolol


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Eliminacin inalterada por rin:Eliminacin inalterada por rin: Hidrosolubles.Hidrosolubles.

No penetran en el SNCNo penetran en el SNC

Menos biodisponibilidad.Menos biodisponibilidad.

Larga vida media en plasma. (pueden administrarse 1 2Larga vida media en plasma. (pueden administrarse 1 2veces al da).veces al da).

Requieren ajuste en ERC.Requieren ajuste en ERC.

AcebutololAcebutolol AtenololAtenolol

NadololNadolol

SotalolSotalol


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Efectos secundariosEfectos secundarios

Efectos sobre el SNC:Efectos sobre el SNC: FatigaFatiga (pequeos incrementos en su incidencia 18/1000;(pequeos incrementos en su incidencia 18/1000;1 de cada 571 de cada 57

pacientes tratados/ao)pacientes tratados/ao)

Impotencia.Impotencia. (pequeos incrementos en su incidencia 5/1000;(pequeos incrementos en su incidencia 5/1000;1 de cada1 de cada199 pacientes tratados/ao)199 pacientes tratados/ao)

Depresin. (no mayor frecuencia)Depresin. (no mayor frecuencia)

van Melle, J. Betavan Melle, J. Beta--blockers and depression after myocardialblockers and depression after myocardialinfarction. J Am Coll Cardiol 2006;48:2209.infarction. J Am Coll Cardiol 2006;48:2209.

Insomnio. (no mayor frecuencia)Insomnio. (no mayor frecuencia)

Alucinaciones. (no mayor frecuencia)Alucinaciones. (no mayor frecuencia) Ko, DT, Hebert, PR, Coffey, CS, et al. BetaKo, DT, Hebert, PR, Coffey, CS, et al. Beta--blocker therapy and symptoms ofblocker therapy and symptoms of

depression, fatigue, and sexual dysfunction. JAMA 2002;288:351.depression, fatigue, and sexual dysfunction. JAMA 2002;288:351.


WassertheilWassertheil--Smoller, S, Oberman, A, Blaufox, MD, et al. The trial ofSmoller, S, Oberman, A, Blaufox, MD, et al. The trial ofantihypertensive interventions and management (TAIM) study. Final results withantihypertensive interventions and management (TAIM) study. Final results withregard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertensregard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens1992;5:37.1992;5:37.


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Enmascaran los sntomas simpticos mediados por laEnmascaran los sntomas simpticos mediados por lahipoglucemia y retrasan la recuperacin de la glucemiahipoglucemia y retrasan la recuperacin de la glucemia

plasmtica.plasmtica. No selectivosNo selectivos (Propanolol(Propanolol y Labetalol).y Labetalol).

Hiperpotasemia tras sobrecarga de K (impiden la entradaHiperpotasemia tras sobrecarga de K (impiden la entrada

de K en la clula tras el ejercicio) Ms frecuente con los node K en la clula tras el ejercicio) Ms frecuente con los noselectivosselectivos (Propanolol(Propanolol)) yy Labetalol)Labetalol).. Pocos efectos sobre elPocos efectos sobre elK de los cardioselectivos (atenolol).K de los cardioselectivos (atenolol). El bloqueo alfa protegeEl bloqueo alfa protegefrente a la elevacin del K (Carvedilol)frente a la elevacin del K (Carvedilol)


WassertheilWassertheil--Smoller, S, Oberman, A, Blaufox, MD, et al. The trial ofSmoller, S, Oberman, A, Blaufox, MD, et al. The trial ofantihypertensive interventions and management (TAIM) study. Final results withantihypertensive interventions and management (TAIM) study. Final results withregard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertensregard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens1992;5:37.1992;5:37.


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Retirada brusca deRetirada brusca de bloqueantes.bloqueantes. Angina acelerada, IAM y muerte incluso en pacientesAngina acelerada, IAM y muerte incluso en pacientes

sin enfermedad coronaria conocida previamente,sin enfermedad coronaria conocida previamente,

posiblemente por upposiblemente por up--regulation de receptoresregulation de receptores tras eltras el

bloqueobloqueo .. Ms frecuente con atenolol (menor vida media)Ms frecuente con atenolol (menor vida media)

KochKoch--Weser, J, Frishman, WH. betaWeser, J, Frishman, WH. beta--Adrenoceptor antagonists: new drugs andAdrenoceptor antagonists: new drugs and

new indications. N Engl J Med 1981;305:500.new indications. N Engl J Med 1981;305:500.

WassertheilWassertheil--Smoller, S, Oberman, A, Blaufox, MD, et al. The trial ofSmoller, S, Oberman, A, Blaufox, MD, et al. The trial of

antihypertensive interventions and management (TAIM) study. Final results withantihypertensive interventions and management (TAIM) study. Final results with

regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertensregard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens

1992;5:37.1992;5:37.


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Efectos sobre los lpidos:Efectos sobre los lpidos: Depende de las caractersticas farmacolgicas:Depende de las caractersticas farmacolgicas:

Ms importantes en fumadores.Ms importantes en fumadores.

No selectivos yNo selectivos y 1 bloqueantes:1 bloqueantes:

Poco efecto sobre los niveles de colesterol total.Poco efecto sobre los niveles de colesterol total.

Reducen un 10% el HDL colesterol.Reducen un 10% el HDL colesterol.

Aumentan un 20Aumentan un 20--40% losTG.40% losTG.

Labetalol yLabetalol y bloqueates con ISAbloqueates con ISA (acebutolol y pindolol):(acebutolol y pindolol): No efecto sobre los lpidos.No efecto sobre los lpidos.

Carvedilol:Carvedilol: Previene la peroxidacin de los lpidos.Previene la peroxidacin de los lpidos.

Reduce el colesterol total y eleva menos los TG que metoprolol.Reduce el colesterol total y eleva menos los TG que metoprolol.

Aumenta el HDLAumenta el HDL--CC


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BloqueoBloqueo

CardioCardio--

selectividadselectividad

ISAISA MSAMSA LipofiliaLipofilia

AcebutololAcebutolol ++ ++ ++++ BajaBaja

AtenololAtenolol ++++ BajaBaja

BexaxololBexaxolol ++ ++ ModeradaModerada

BisoprololBisoprolol ++ ModeradaModerada

CarteololCarteolol ++ BajaBaja

CarvedilolCarvedilol SiSi ++ AltaAlta

CeliprololCeliprolol ++ ++

EsmololEsmolol ++++ BajaBaja

LabetalolLabetalol SiSi ++ ModeradaModerada

MetoprololMetoprolol ++++ ++ ModeradaModerada

NadololNadolol BajaBaja

OxprenololOxprenolol ++ ++ ModeradaModerada

PindololPindolol ++++ ModeradaModerada

PropanololPropanolol ++++ AltaAlta

SotalolSotalol BajaBaja

TimololTimolol ModeradaModerada


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ComercialComercial AsociacionesAsociaciones Dosis usualDosis usual

en HTAen HTA

DosisDosis

mximamxima

AtenololAtenolol Tenormin, Blokium,Tenormin, Blokium,Genricos 50,100Genricos 50,100

Blokium Diu, Normopresil, TenoreticBlokium Diu, Normopresil, Tenoretic

(100 mg/25 Clortalidona)(100 mg/25 Clortalidona)

Kalten (Amiloride 2,5 mg(Kalten (Amiloride 2,5 mg(Hidroclorotiazida 25 mg/Atenolol 50 mg)Hidroclorotiazida 25 mg/Atenolol 50 mg)

5050 100 mg/24 h100 mg/24 h 200 mg200 mg

BisoprololBisoprolol Emconco Cor 2Emconco Cor 22,5 y 10.2,5 y 10.Emconcor, Genricos 5, 10 mgEmconcor, Genricos 5, 10 mg

Emcoretic (5Emcoretic (5 10 mg / 12,510 mg / 12,5 25 mg25 mg

hidroclorotiazida)hidroclorotiazida)

2,52,5 10 mg/24 h10 mg/24 h 20 mg20 mg

CarteololCarteolol Arteolol 5 mgArteolol 5 mg 2,52,5 10 mg/ 24 h10 mg/ 24 h 40 mg/ 24 h40 mg/ 24 h

CarvedilolCarvedilol Coropres 25 mg, Genricos 25Coropres 25 mg, Genricos 25mgmg

6,256,25 25 mg/12 h25 mg/12 h

CeliprololCeliprolol

Cardem 200 mgCardem 200 mg 200 mg/24 h200 mg/24 h 400 mg400 mg

EsmololEsmolol Brevibloc 2,5 mg/10 mlBrevibloc 2,5 mg/10 mlBrevibloc 100 mg/10 mlBrevibloc 100 mg/10 ml

Bolus. 1 mg/kg.Bolus. 1 mg/kg.

Perfusion 150Perfusion 150--300300

mcg/kg/minmcg/kg/min

LabetalolLabetalol Trandate 100, 200 mgTrandate 100, 200 mg 100 mg100 mg 400 mg/12 h400 mg/12 h 1200 mg/12 h1200 mg/12 h

MetoprololMetoprolol Beloken 100 mgBeloken 100 mgLopresor 100 mgLopresor 100 mg

Logimax (Metoprolol 50 mg/ FelodipinoLogimax (Metoprolol 50 mg/ Felodipino

5 mg)5 mg)

100100--400 mg/24 h400 mg/24 h

NadololNadolol

Solgol 40, 80 mgSolgol 40, 80 mg 80 mg en 380 mg en 3--4 dosis/24 h4 dosis/24 h 320 mg en 3320 mg en 3--44

dosis /24 hdosis /24 h

NebivololNebivolol Lobivon 5 mg.Lobivon 5 mg.Silostar 5 mgSilostar 5 mg

5 mg/24 h5 mg/24 h

OxprenololOxprenolol Trasicor 80,Trasicor 80,Trasicor Retard 160 mgTrasicor Retard 160 mg

Trasitensin (retard 160 mg/ 20 mgTrasitensin (retard 160 mg/ 20 mg

Clortalidona)Clortalidona)

4040--80 mg/12 h80 mg/12 h

Retard 160 mg/24 hRetard 160 mg/24 h

480 mg/24 h480 mg/24 h

PropanololPropanolol Sunial 5, 10, 40 mg.Sunial 5, 10, 40 mg.Sumial Retard 160 mgSumial Retard 160 mg

40 mg/12 h40 mg/12 h 160160--320 mg/24 h320 mg/24 hen 3en 3 4 dosis4 dosis

SotalolSotalolS

otapor 80 y 160 mgS

otapor 80 y 160 mg 80 mg/24

h inicial.80 mg/24

h inicial.320320 640 mg/24 h640 mg/24 h 960 mg/24 h960 mg/24 h


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EliminacinEliminacin ClCr > 50ClCr > 50 ClCr 10ClCr 10--5050 ClCr < 10ClCr < 10

AcebutololAcebutolol R y HR y H

AtenololAtenolol RR 100%100% 50%/24 h50%/24 h

100%/48 h

100%/48 h

25%/24 h25%/24 h

100%/56h

100%/56h

BexaxololBexaxolol RR

BisoprololBisoprolol R y HR y H

CarteololCarteolol RR EvitarEvitar

CarvedilolCarvedilol HH EvitarEvitar

CeliprololCeliprolol R y HR y H 50%/24 h50%/24 h

EsmololEsmolol EsterasasEsterasas EvitarEvitar

LabetalolLabetalol HH EvitarEvitar

MetoprololMetoprolol RR 100%100% 100%100% 100%100%

NadololNadolol RR

NebivololNebivolol 100%100% 100%100% 100%100%

OxprenololOxprenolol HH 100%100% 100%100% 100%100%

PindololPindolol R y HR y H

PropanololPropanolol HH 100%100% 100%100% 100%100%

SotalolSotalol RR 100%/24 h100%/24 h 100%/36100%/36--48 h48 h Segn respuestaSegn respuesta

TimololTimolol RR


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ContraindicacionesContraindicaciones

Asma.Asma.

EPOC.EPOC.

Enfermedad vascular periferica severa.Enfermedad vascular periferica severa. Fenmeno de Raynaud.Fenmeno de Raynaud.

Bradicardia. BAV2 o 3er grado.Bradicardia. BAV2 o 3er grado.


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Beta blockers in theBeta blockers in themanagement of chronic kidneymanagement of chronic kidney

diseasedisease

Kidney InternationalKidney International(2006)(2006) 70,70, 190519051913.1913.

LL Bakris, PBakris, P Hart and EHart and E RitzRitz


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Sympathetic overactivitySympathetic overactivity in kidney disease isin kidney disease is

involved in theinvolved in the genesis of hypertension, in thegenesis of hypertension, in the

progression of kidney disease, and in theprogression of kidney disease, and in the

cardiac complications of kidney failure.cardiac complications of kidney failure.


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In subtotally nephrectomized rats,In subtotally nephrectomized rats, nonhypotensive doses ofnonhypotensive doses of --blockers ameliorated the development ofblockers ameliorated the development ofglomerulosclerotic and cardiac lesions.glomerulosclerotic and cardiac lesions.

Salplachta J, Bartosikova L, Necas J. Effects of carvedilol and BLSalplachta J, Bartosikova L, Necas J. Effects of carvedilol and BL--443 on443 onkidney of rats with cyclosporine nephropathy. Gen Physiol Biophys 2002;kidney of rats with cyclosporine nephropathy. Gen Physiol Biophys 2002;21:18921:189195.195.

Similar observations concerning kidney disease progressionSimilar observations concerning kidney disease progressionwere noted with the central sympathicoplegic agentwere noted with the central sympathicoplegic agentmoxonidine.moxonidine.

Amann K, Nichols C, Tornig JAmann K, Nichols C, Tornig J et alet al. Effect of ramipril, nifedipine, and. Effect of ramipril, nifedipine, andmoxonidine on glomerular morphology and podocyte structure inmoxonidine on glomerular morphology and podocyte structure inexperimental renal failure. Nephrol Dial Transplant 1996;11:1003experimental renal failure. Nephrol Dial Transplant 1996;11:10031011.1011.

Additionally,Additionally, moxonidine also reduced albumin excretionmoxonidine also reduced albumin excretion ininpatients with type I diabetes, despite causing no change inpatients with type I diabetes, despite causing no change inambulatory blood pressure.ambulatory blood pressure.

Strojek K, Grzeszczak W, Gorska JStrojek K, Grzeszczak W, Gorska J et alet al. Lowering of microalbuminuria in. Lowering of microalbuminuria indiabetic patients by a sympathicoplegic agent: novel approach to preventdiabetic patients by a sympathicoplegic agent: novel approach to preventprogression of diabetic nephropathy? J Am Soc Nephrol 2001;12:602progression of diabetic nephropathy? J Am Soc Nephrol 2001;12:602605.605.

Vonend O, Marsalek P, Russ HVonend O, Marsalek P, Russ H et alet al. Moxonidine treatment of hypertensive. Moxonidine treatment of hypertensivepatients with advanced renal failure. J Hypertens 2003;21:1709patients with advanced renal failure. J Hypertens 2003;21:17091717.1717.


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In a separate model of kidney disease (spontaneouslyIn a separate model of kidney disease (spontaneouslyhypertensive rats with adriamycin nephropathy),hypertensive rats with adriamycin nephropathy), --//--blockerblockercarvedilol decreased systolic blood pressure, decreasedcarvedilol decreased systolic blood pressure, decreased

renal vascular resistance (RVR), and significantlyrenal vascular resistance (RVR), and significantlyincreased renal blood flow (RBF).increased renal blood flow (RBF). Moreover, it significantlyMoreover, it significantlydecreased interstitial infiltrationdecreased interstitial infiltration in the early phase of thein the early phase of thestudy,study, slowed development of interstitial fibrosis andslowed development of interstitial fibrosis andtubular atrophy, and decreased blood vessel changes.tubular atrophy, and decreased blood vessel changes.These changes strongly correlated withThese changes strongly correlated with slowed nephropathyslowed nephropathy

progression as well as decreases in proteinuria.progression as well as decreases in proteinuria. Jovanovic D, Jovovic D, MihailovicJovanovic D, Jovovic D, Mihailovic--Stanojevic NStanojevic N et alet al. Influence of carvedilol on chronic renal. Influence of carvedilol on chronic renal

failure progression in spontaneously hypertensive rats with adriamycin nephropathy. Clinfailure progression in spontaneously hypertensive rats with adriamycin nephropathy. ClinNephrol 2005;63:446Nephrol 2005;63:446453.453.

In subtotally nephrectomized rats with knownIn subtotally nephrectomized rats with knownmicroangiopathy,microangiopathy, --blockers increased the capillary densityblockers increased the capillary densityin the heart.in the heart. This is an important observation, asThis is an important observation, as --blockersblockersclearlyclearlyimprove cardiac function and reduceimprove cardiac function and reducecardiovascular events in hemodialyzed patients.cardiovascular events in hemodialyzed patients.

Amann K, Ritz E. Microvascular diseaseAmann K, Ritz E. Microvascular disease the Cinderella of uraemic heart disease. Nephrol Dialthe Cinderella of uraemic heart disease. Nephrol DialTransplant 2000;15:1493Transplant 2000;15:14931503.1503.

Cice G, Ferrara L, D'Andrea ACice G, Ferrara L, D'Andrea A et alet al.. Carvedilol increases twoCarvedilol increases two--year survival in dialysis patientsyear survival in dialysis patientswith dilated cardiomyopathy: a prospective, placebowith dilated cardiomyopathy: a prospective, placebo--controlled trial. J Am Coll Cardiol 2003;41:controlled trial. J Am Coll Cardiol 2003;41:

143814381444.1444.


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The use ofThe use of --blockers in CKD patientsblockers in CKD patients

As there is overwhelming evidence for sympatheticAs there is overwhelming evidence for sympatheticoveractivity in patients with kidney disease,overactivity in patients with kidney disease, coronarycoronaryheart disease and heart failure (HF) are the mostheart disease and heart failure (HF) are the mostcommon causes of death in these patients.common causes of death in these patients.

Eknoyan G. On the epidemic of cardiovascular disease in patientsEknoyan G. On the epidemic of cardiovascular disease in patientswith chronic renal disease and progressive renal failure: a first step towith chronic renal disease and progressive renal failure: a first step toimprove the outcomes. Am J Kidney Dis 1998;32: S1improve the outcomes. Am J Kidney Dis 1998;32: S1S4.S4.

This may be due to inadequate treatment, asThis may be due to inadequate treatment, asdemonstrated by a recent study in whichdemonstrated by a recent study in which --adrenergicadrenergic

blockade was used in fewer than 30% of patientsblockade was used in fewer than 30% of patientson hemodialysis.on hemodialysis. Abbott KC, Trespalacios FC, Agodoa LYAbbott KC, Trespalacios FC, Agodoa LYet alet al.. BetaBeta--blocker use inblocker use in

longlong--term dialysis patients: association with hospitalized heart failureterm dialysis patients: association with hospitalized heart failureand mortality. Arch Intern Med 2004;164:2465and mortality. Arch Intern Med 2004;164:24652471.2471.


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The use ofThe use of --blockers in CKD patientsblockers in CKD patients

This is surprising, asThis is surprising, as --blockersblockers interfere with theinterfere with thedeleterious actions of the SNS on cardiac end points,deleterious actions of the SNS on cardiac end points,and are welland are well--established, evidenceestablished, evidence--based therapy forbased therapy forreducing cardiovascular risk in hypertension andreducing cardiovascular risk in hypertension andafter myocardial infarction.after myocardial infarction.

Cice G, Ferrara L, D'Andrea ACice G, Ferrara L, D'Andrea A et alet al.. Carvedilol increases twoCarvedilol increases two--year survival in dialysisyear survival in dialysispatients with dilated cardiomyopathy: a prospective, placebopatients with dilated cardiomyopathy: a prospective, placebo--controlled trial. J Amcontrolled trial. J AmColl Cardiol 2003;41:1438Coll Cardiol 2003;41:14381444.1444.

Zuanetti G, Maggioni AP, Keane WZuanetti G, Maggioni AP, Keane Wet alet al. Nephrologists neglect administration of. Nephrologists neglect administration ofbetablockers to dialysed diabetic patients. Nephrol Dial Transplant 1997;12:2497betablockers to dialysed diabetic patients. Nephrol Dial Transplant 1997;12:24972500.2500.

Chobanian AV, Bakris GL, Black HRChobanian AV, Bakris GL, Black HRet alet al. The Seventh Report of the Joint National. The Seventh Report of the Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High BloodCommittee on Prevention, Detection, Evaluation, and Treatment of High BloodPressure: the JNC 7 report. JAMA 2003;289:2560Pressure: the JNC 7 report. JAMA 2003;289:25602572.2572.

Antman EM, Anbe DT, Armstrong PWAntman EM, Anbe DT, Armstrong PWet alet al. ACC/AHA guidelines for the. ACC/AHA guidelines for themanagement of patients with STmanagement of patients with ST--elevation myocardial infarctionelevation myocardial infarctionexecutiveexecutivesummary: a report of the American College of Cardiology/American Heartsummary: a report of the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines (Writing Committee to Revise theAssociation Task Force on Practice Guidelines (Writing Committee to Revise the1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).

Circulation 2004;110:588Circulation 2004;110:588636.636.


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Observational studiesObservational studiessuggest definite survivalsuggest definite survivalbenefits derived from thebenefits derived from theuse ofuse of --blockers in patientsblockers in patients

with severe renal disease.with severe renal disease.

Furthermore, in aFurthermore, in aprospective,prospective, randomizedrandomized

study in hemodialyzedstudy in hemodialyzedpatients with HF, Cicepatients with HF, Cice et al.et al.documented an impressivedocumented an impressiveand significant decrease inand significant decrease indeath and hospitalizationdeath and hospitalizationrates attributable torates attributable tocardiovascular causes incardiovascular causes in

patients on carvedilolpatients on carvedilolcompared to placebocompared to placebo ..

Cice G, Ferrara L, D'Andrea A et al.

Carvedilol increases two-year survival in

dialysis patients with dilated cardiomyopathy:

a prospective, placebo-controlled trial. J Am

Coll Cardiol 2003;41:14381444.


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The United States Renal Data System DialysisThe United States Renal Data System DialysisMorbidity and Mortality Study found thatMorbidity and Mortality Study found that only 20% ofonly 20% ofchronic dialysis patients were receivingchronic dialysis patients were receiving --blockerblockertherapy.therapy.

Abbott KC, Trespalacios FC, Agodoa LYAbbott KC, Trespalacios FC, Agodoa LYet alet al.. BetaBeta--blocker use inblocker use inlonglong--term dialysis patients: association with hospitalized heart failureterm dialysis patients: association with hospitalized heart failureand mortality. Arch Intern Med 2004;164:2465and mortality. Arch Intern Med 2004;164:24652471.2471.

In another study,In another study, only 24% of patients withonly 24% of patients withestablished coronary heart disease were treatedestablished coronary heart disease were treatedwithwith --blockersblockers. A similar trend occurs in the. A similar trend occurs in thepredialysis patients.predialysis patients.

Trespalacios FC,Taylor AJ, Agodoa LYTrespalacios FC,Taylor AJ, Agodoa LYet alet al.. Incident acute coronaryIncident acute coronarysyndromes in chronic dialysis patients in the United States. Kidneysyndromes in chronic dialysis patients in the United States. KidneyInt 2002;62:1799Int 2002;62:17991805.1805.

Wright RS, Reeder GS, Herzog CAWright RS, Reeder GS, Herzog CA et alet al. Acute myocardial infarction. Acute myocardial infarctionand renal dysfunction: a highand renal dysfunction: a high--risk combination. Ann Intern Medrisk combination. Ann Intern Med2002;137:5632002;137:563570.570.


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PropanololPropanolol MetoprololMetoprolol AtenololAtenolol LabetalolLabetalol CarvedilolCarvedilol

LipofilicoLipofilico SiSi SiSi NoNo SiSi SiSi

NoNoselectivoselectivo SISI NoNo NoNo SiSi SiSi

CardioCardio--

selectividadselectividad

NoNo SISI SiSi NoNo NoNo

bloqueobloqueo NoNo NoNo NoNo SiSi SiSi

SensibilidadSensibilidadinsulinicainsulinica

DismDism DismDism DismDism No modif No modif AumentAument

TGTG AumentAument AumentAument AumentAument No modif No modif DismDism

HDLHDL DismDism DismDism DismDism No modif No modif AumentAument

HiperKHiperK SISI NoNo NoNo SiSi NoNo

RVRRVR AumentAument DismDism No modif No modif No modifNo modif DismDism

FPRFPR DismDism No modif No modif No modif No modif No modifNo modif AumentAument

FGFG DismDism No modif No modif No modiNo modi No modif No modif AumentAument


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EFFECTSON KIDNEYFUNCTIONEFFECTSON KIDNEYFUNCTION

Increased sympathetic activity has been reportedIncreased sympathetic activity has been reported

consistently in patients with moderate renal failure asconsistently in patients with moderate renal failure as

well as in those with ESRD undergoing renal dialysis.well as in those with ESRD undergoing renal dialysis.

The level of sympathetic activity is an independentThe level of sympathetic activity is an independentpredictor of total as well as cardiovascularpredictor of total as well as cardiovascular

mortality in patients with ESRDmortality in patients with ESRD.. Converse Jr RL, Jacobsen TN, Toto RDConverse Jr RL, Jacobsen TN, Toto RD et alet al. Sympathetic overactivity in. Sympathetic overactivity in

patients with chronic renal failure. N Engl J Med 1992;327:1912patients with chronic renal failure. N Engl J Med 1992;327:19121918.1918.

Parving HH, Andersen AR, Smidt UMParving HH, Andersen AR, Smidt UM et alet al. Effect of antihypertensive. Effect of antihypertensive

treatment on kidney function in diabetic nephropathy. BMJ (Clin Res Ed)treatment on kidney function in diabetic nephropathy. BMJ (Clin Res Ed)

1987;294:14431987;294:14431447.1447.


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Bloqueantes no slectivos:Bloqueantes no slectivos: Disminuyen la tasa de FG y el Flujo sanguneo renalDisminuyen la tasa de FG y el Flujo sanguneo renal (FSR)(FSR),,

al disminuir el gasto cardaco en pacientes con ERC.al disminuir el gasto cardaco en pacientes con ERC.

En pacientes con funcin renal normal no efectan el FG niEn pacientes con funcin renal normal no efectan el FG niel FSR.el FSR. Epstein M, Oster JR, Hollenberg NK.Epstein M, Oster JR, Hollenberg NK. --Blockers and the kidney:Blockers and the kidney:

implications for renal function and renin release. The Physiologistimplications for renal function and renin release. The Physiologist1985;28:531985;28:5363.63.

Epstein M, Oster JR. Beta blockers and renal function: a reappraisal. JEpstein M, Oster JR. Beta blockers and renal function: a reappraisal. J

Clin Hypertens19

85;

1:

85

Clin Hypertens19

85;

1:

8599

.99

. Abbott KC, Bakris G. Renal effects of antihypertensive medications:Abbott KC, Bakris G. Renal effects of antihypertensive medications:

an overview. J Clin Pharmacol 1993;33:392an overview. J Clin Pharmacol 1993;33:392399.399.

Zech P, Pozet N, Labeeuw MZech P, Pozet N, Labeeuw M et alet al. Acute renal effects of beta. Acute renal effects of beta--blockers. Am J Nephrol 1986;6(Suppl 2):15blockers. Am J Nephrol 1986;6(Suppl 2):1519.19.


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Bloqueantes cardioselectivos:Bloqueantes cardioselectivos: No disminuyen el FG y el FSR.No disminuyen el FG y el FSR.

Pueden incrementar las Resistencias Vasculares RenalesPueden incrementar las Resistencias Vasculares Renales(RVR).(RVR).

Metoprolol disminuyen la actividad de renina plasmtica.Metoprolol disminuyen la actividad de renina plasmtica.

Atenolol disminuye la progresin a proteinuria en pacientesAtenolol disminuye la progresin a proteinuria en pacientescon microalbuminuria (pero menos que con el bloqueo delcon microalbuminuria (pero menos que con el bloqueo delSRAA).SRAA).

Atenolol y Metoprolol en pacientes con ERC no producenAtenolol y Metoprolol en pacientes con ERC no producenefectos adversos en la hemodinmica renal.efectos adversos en la hemodinmica renal.

En pacientes en HD conEn pacientes en HD con miocardiopata dilatada, elmiocardiopata dilatada, eltratamiento con metoprolol mejor el tamao ventricular, latratamiento con metoprolol mejor el tamao ventricular, lafuncin cardaca, los niveles de Pfuncin cardaca, los niveles de Peptidoeptido AAuricularuricularNNatriurticoatriurtico y Py Peptidoeptido CCerebralerebral NNatriureticoatriuretico..


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The African American Study of Kidney Disease and Hypertension comparedThe African American Study of Kidney Disease and Hypertension comparedthe long acting, once daily formulation ofthe long acting, once daily formulation ofmetoprololmetoprolol, the ACE inhibitor,, the ACE inhibitor,ramiprilramipril, and the calcium channel blocker,, and the calcium channel blocker, amlodipineamlodipine in 1094 Blackin 1094 Blacksubjects with hypertensive nephropathy (GFR20subjects with hypertensive nephropathy (GFR206565 ml/min per 1.73ml/min per 1.73 m2)m2)followed for a mean of4 years.followed for a mean of4 years.

The primary analysis of the GFR slope didThe primary analysis of the GFR slope did not establish a definitivenot establish a definitivedifference among the three agents.difference among the three agents.

Significant benefitsSignificant benefitswere seen, however, withwere seen, however, with ramiprilramipril compared tocompared tometoprolol and amlodipinemetoprolol and amlodipine on the clinical composite outcome of declineon the clinical composite outcome of declineof GFR, ESRD, and deathof GFR, ESRD, and death..

The results of the secondary analyses indicated thatThe results of the secondary analyses indicated that ramipril treatmentramipril treatmentslowed the progression of hypertensive kidney disease to a greaterslowed the progression of hypertensive kidney disease to a greaterextent than either once daily metoprolol or amlodipineextent than either once daily metoprolol or amlodipine..

The once daily metoprololThe once daily metoprolol--treated patients had a significantly lower rate oftreated patients had a significantly lower rate ofESRD or death than those treated with amlodipine.ESRD or death than those treated with amlodipine.

Wright JT, Bakris G, Greene T. Effect of blood pressure lowering and antihypertensive drugWright JT, Bakris G, Greene T. Effect of blood pressure lowering and antihypertensive drugclass on progression of hypertensive kidney disease. Results from the AASK trial. JAMAclass on progression of hypertensive kidney disease. Results from the AASK trial. JAMA2002;288:24212002;288:24212431.2431.


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VasodilatadoresVasodilatadores

Labetalol:Labetalol: Pequeos estudios y conPequeos estudios y con resultados contradictoriosresultados contradictorios

En general, no efectos significativoss sobre FG, FSR niEn general, no efectos significativoss sobre FG, FSR nivolumen de agua corporal.volumen de agua corporal.

Aumenta los niveles de glucosa plasmtica sin efectos sobreAumenta los niveles de glucosa plasmtica sin efectos sobrela insulinemia.la insulinemia.

Leve descenso de HDLLeve descenso de HDL--C.C.

Se elimina con la dilisis, pero no aumenta su aclaramientoSe elimina con la dilisis, pero no aumenta su aclaramientocorporal totalcorporal total

Hay que vigilar la aparicin deHay que vigilar la aparicin de hiperKhiperKsobre todo ensobre todo enpacientes en HD o tras transplante renal.pacientes en HD o tras transplante renal.


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Carvedilol:Carvedilol:

Tiene actividad antioxidanteTiene actividad antioxidante..

No altera la creatinina ni urea plasmticas.No altera la creatinina ni urea plasmticas.

No favorece la hiperK en pacientes con ERC.No favorece la hiperK en pacientes con ERC.

Aumenta los niveles de CsA en un 20%.Aumenta los niveles de CsA en un 20%.

Reduce el estress oxidativoReduce el estress oxidativo, pudiendo prevenir el, pudiendo prevenir elaumento de las citoquinas profibrticas que ocurreaumento de las citoquinas profibrticas que ocurre

en pacientes trasplantados que toman CsA.en pacientes trasplantados que toman CsA.


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EFFECTSON KIDNEYFUNCTIONEFFECTSON KIDNEYFUNCTION VasodilatadoresVasodilatadores

Carvedilol:Carvedilol: Mejora el FSRy el FG en pacientes con IC y ERC.Mejora el FSRy el FG en pacientes con IC y ERC.

En pacientes en HD y con miocardiopataEn pacientes en HD y con miocardiopata mejoran la FE,mejoran la FE,reduce los volumnes sistlicos y diastlicosreduce los volumnes sistlicos y diastlicos

ventriculares, mejorando la supervivencia.ventriculares, mejorando la supervivencia.

Reduce la albuminuria en pacientes con HTA, DM yReduce la albuminuria en pacientes con HTA, DM ynoDM, y es capaz de hacer desaparecer la misma hastnoDM, y es capaz de hacer desaparecer la misma hasten un 48en un 48--52%.52%.

CarvedilolCarvedilol mejora la sensibilidad a la insulina y el controlmejora la sensibilidad a la insulina y el controlglucmico.glucmico.

Tiene pocos efectos proaterognicos al no alterar elTiene pocos efectos proaterognicos al no alterar elcolesterol y los TGcolesterol y los TG..


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Nevibolol:Nevibolol:

Lipoflico.Lipoflico.

ISA.ISA.

MSA.MSA. PresentaPresenta efectos vasodilatadores mediados por el NOefectos vasodilatadores mediados por el NO..

No afecta el metabolismo de glucosa y el perfil lipdicoNo afecta el metabolismo de glucosa y el perfil lipdico..

Tiene efectos protectores sobre la funcin VITiene efectos protectores sobre la funcin VI..

Incrementa el FSRy el FG, a traves de la via del NOIncrementa el FSRy el FG, a traves de la via del NO.. Aumenta la excrecin renal de Na y KAumenta la excrecin renal de Na y K..


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CONCLUSIONCONCLUSION

CKDCKD, with the frequently associated conditions of hypertension,, with the frequently associated conditions of hypertension,diabetes, and HF, is a state ofdiabetes, and HF, is a state ofoveractivity of the SNS.overactivity of the SNS.

Antiadrenergic drugs play an important role in its management.Antiadrenergic drugs play an important role in its management.Antihypertensive regimens includingAntihypertensive regimens including --blockers slow theblockers slow the

deterioration of renal functiondeterioration of renal function as assessed by decreasing GFRas assessed by decreasing GFRand worsening albuminuria.and worsening albuminuria.

It is therefore deplorable thatIt is therefore deplorable that --blockers are still underutilizedblockers are still underutilizedout of fear of adversely affecting renal function and glycemicout of fear of adversely affecting renal function and glycemiccontrol.control.

Beta blockers in the management of chronic kidney disease.Beta blockers in the management of chronic kidney disease. KidneyKidneyInternational (2006) 70, 1905International (2006) 70, 19051913.1913. LL Bakris, PBakris, PHart and EHart and E RitzRitz

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