Betabloqueantes

Francisco Jos de la Prada Alvarez Servicio de Nefrologa

Receptores

1: (msculo cardaco)

Incrementa la frecuencia cardaca. Incrementa la contractilidad cardaca. Incrementa la conduccin AV. Disminuye la refractariedad del nodulo AV.

2: (msculo bronquial y musculo liso vascular, y menos en msculo cardaco):

Vasodilatacin. Broncodilatcin. Termognesis. Reduce la contractilidad cardaca.

3 (tejido adiposo y msculo cardaco):

Dollery, CT, Frishman, WH, Cruickshank, JM. Current cardiovascular drugs, 1st ed, Current Science, London, 1993, p. 83. Koch-Weser, J, Frishman, WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305:500. Opie, LH. Drugs and the heart. Part 1. Beta blocking agents. Lancet 1980; 1:693.
2

Caractersticas

Cardioselectividad. Actividad simpaticomimtica intrnseca. Actividad bloqueante alfa adrenrgica.

Caractersticas

Cardioselectividad.

Capacidad del frmaco para bloquear preferentemente los receptores cardacos. La cardioselectividad es una propiedad relativa. A altas dosis se produce el bloqueo 2

Propanolol: no selectivo (igual afinidad por receptores 1 y 2). Acebutolol, Atenolol, betaxolol, Bisoprolol, Celiprolol y Metoprolol: selectivos (principal afinidad por receptores 1, y menos por 2 que median brocodilatacin y vasodilatacin perifrica).

Son preferibles en pacientes asmticos y diabticos.

Koch-Weser, J. Drug therapy: metoprolol. N Engl J Med 1979; 301:698. Frishman, W. Acebutolol. Cardiovasc Rev Rep 1985; 6:979. Frishman, WH. Drug therapy: atenolol and timolol, two new systemic betaadrenoceptor antagonists. N Engl J Med 1982; 306:1456.

Caractersticas

Actividad simpaticomimtica intrnseca.

Actividad agonista parcial por el receptor. Producen menor reduccin en la frecuencia cardaca en reposo (pero impiden la taquicardia con el ejercicio), menor depresin de la conduccin AV y menos inotropismo negativo que los -bloqueantes sin activida ISA. No deberan usarse nen hipertiroidismo, estenosis subartica hipertrfica, diseccin artica, fase post-IAM y angina. Oxprenolol Celiprolol Acebutolol Carteolol Penbutolol
Frishman, WH, Charlap, S. The alpha- and beta-adrenergic blocking drugs. In: Cardiology, Parmley, WW (Ed), JB Lippincott, Philadelphia, 1990, p.1. Frishman, WH. Drug therapy. Pindolol: a new beta-adrenoceptor antagonist with partial agonist activity. N Engl J Med 1983; 308:940. Magder, S, Sami, M, Ripley, R, et al. Comparison of the effect of pindolol and propranolol on exercise performance in patients with angina pectoris. Am J Cardiol 1987; 59:1289. 5

Caractersticas

Actividad bloqueante alfa adrenrgica.

Labetalol:

Bloqueante /Bloqueante : 3/1 a 7/1 (sobre todo por via IV. Por via oral este efecto se reduce con el tratamiento a largo plazo) bloqueante: bradicardia, inotropismo negativo. bloqueante:

Bloquea la vasoconstriccin refleja por el bloqueo Disminuye las resistencias vasculares coronarias y perifricas, mejorando el flujo sanguneo. Mejora la sensibiliad insulnica en diabticos y no diabticos. Mejoran el perfil lipdico.

Carvedilol:

Los 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)adrenoceptor blockade during long-term treatment of heart failure with carvedilol. J Am Coll Cardiol 2001; 38:1463. Hryniewicz, K, Androne, AS, Hudaihed, A, Katz, SD. Comparative effects of carvedilol and metoprolol on regional vascular responses to adrenergic stimuli in normal subjects and patients with chronic heart failure. Circulation 2003; 108:971.

Caractersticas

Actividad bloqueante alfa adrenrgica.

La actividad bloqueante alfa asociada al bloqueo beta tiene un impacto positivo sobre la diabetes y la aterosclerosis, mejorando el control glucmico, reduciendo la hiperinsulinemia compensadora y reduciendo los cambios proaterognicos sobre los lpidos plasmticos.

Giugliano D, Acampora R, Marfella R et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulindependent diabetes mellitus and hypertension. A randomized, controlled trial. Ann Intern Med 1997; 126: 955959. Jacob S, Rett K, Wicklmayr M et al. Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study. J Hypertens 1996; 14: 489494.
7

Caractersticas farmacocinticas

Metabolismo heptico. Eliminacin inalterada por rin.

Frishman, W. Clinical pharmacology of the new beta adrenergic blocking drugs. Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 1979; 97:663. Frishman, WH, Lazar, EJ, Gorodokin, G. Pharmacokinetic optimization of therapy with beta-adrenergic blocking agents. Clin Pharmacokinet 1991; 20:311.

Caractersticas farmacocinticas

Metabolismo heptico:

Liposolubles, absorcin completa en intestino delgado y metabolismo heptico. Biodisponibilidad variable. Corta vida media. Atraviesan la BHE aumentando la incidencia de efectos secundarios.

Revisin de estudios randomizados con mas de 35.000 pacientes. La lipofilia no afecta la aparicin de efectos adversos.

Ko, DT, Hebert, PR, Coffey, CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 2002; 288:351.

Propanolol Metoprolol Oxprenolol

Caractersticas farmacocinticas

Eliminacin inalterada por rin:

Hidrosolubles. No penetran en el SNC Menos biodisponibilidad. Larga vida media en plasma. (pueden administrarse 1 2 veces al da). Requieren ajuste en ERC.
Acebutolol Atenolol Nadolol Sotalol
10

Efectos secundarios

Bradicardia. (Enfermedad del ndulo sinusal) Inotropismo negativo. (Insuficiencia cardaca 6%) Dromotropismo negativo. (Bloqueo AV) Broncoconstriccin.

No selectivos (Propanolol) contraindicados en asma y EPOC. (usar con precaucin los cardioselectivos (atenolol o metoprolol), los que tienen ISA (pindolol y acebutolol) o los bloqueantes (labetalol y carvedilol). No selectivos (Propanolol) pueden empeorar enfermedad vascular perifrica severa o el fenmeno de Raynaud. (usar cardioselectivos Atenolol o metoprolol si la enfermedad es leve o moderada).
Koch-Weser, J, Frishman, WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305:500. Wassertheil-Smoller, S, Oberman, A, Blaufox, MD, et al. The trial of antihypertensive interventions and management (TAIM) study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992; 5:37.

Vasoconstriccin perifrica:

11

Efectos secundarios

Efectos sobre el SNC:

Fatiga (pequeos incrementos en su incidencia 18/1000; 1 de cada 57 pacientes tratados/ao) Impotencia. (pequeos incrementos en su incidencia 5/1000; 1 de cada 199 pacientes tratados/ao) Depresin. (no mayor frecuencia) van Melle, J. Beta-blockers and depression after myocardial infarction. J Am Coll Cardiol 2006; 48:2209. Insomnio. (no mayor frecuencia) Alucinaciones. (no mayor frecuencia)

Ko, DT, Hebert, PR, Coffey, CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 2002; 288:351. Koch-Weser, J, Frishman, WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305:500. Wassertheil-Smoller, S, Oberman, A, Blaufox, MD, et al. The trial of antihypertensive interventions and management (TAIM) study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992; 5:37.
12

Efectos secundarios

Enmascaran los sntomas simpticos mediados por la hipoglucemia y retrasan la recuperacin de la glucemia plasmtica. No selectivos (Propanolol y Labetalol). Hiperpotasemia tras sobrecarga de K (impiden la entrada de K en la clula tras el ejercicio) Ms frecuente con los no selectivos (Propanolol) y Labetalol). Pocos efectos sobre el K de los cardioselectivos (atenolol). El bloqueo alfa protege frente a la elevacin del K (Carvedilol)

Koch-Weser, J, Frishman, WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305:500. Wassertheil-Smoller, S, Oberman, A, Blaufox, MD, et al. The trial of antihypertensive interventions and management (TAIM) study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992; 5:37.

13

Efectos secundarios

Retirada brusca de bloqueantes.

Angina acelerada, IAM y muerte incluso en pacientes sin enfermedad coronaria conocida previamente, posiblemente por up-regulation de receptores tras el bloqueo . Ms frecuente con atenolol (menor vida media)

Koch-Weser, J, Frishman, WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305:500. Wassertheil-Smoller, S, Oberman, A, Blaufox, MD, et al. The trial of antihypertensive interventions and management (TAIM) study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992; 5:37.

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Efectos secundarios

Efectos sobre los lpidos:

Depende de las caractersticas farmacolgicas: Ms importantes en fumadores. No selectivos y 1 bloqueantes: Poco efecto sobre los niveles de colesterol total. Reducen un 10% el HDL colesterol. Aumentan un 20-40% los TG.

Labetalol y bloqueates con ISA (acebutolol y pindolol):

No efecto sobre los lpidos. Previene la peroxidacin de los lpidos. Reduce el colesterol total y eleva menos los TG que metoprolol. Aumenta el HDL-C
15

Carvedilol:

Bloqueo
Acebutolol Atenolol Bexaxolol Bisoprolol Carteolol Carvedilol Celiprolol Si

Cardioselectividad
+ ++ + + + +

ISA

MSA
++ +

Lipofilia
Baja Baja Moderada Moderada Baja

+ + +

Alta

Esmolol
Labetalol Metoprolol Nadolol Si

++
+ ++ +

Baja
Moderada Moderada Baja

Oxprenolol
Pindolol Propanolol Sotalol Timolol

+
++

+
++

Moderada
Moderada Alta Baja Moderada
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Comercial

Asociaciones
Blokium Diu, Normopresil, Tenoretic (100 mg/25 Clortalidona) Kalten (Amiloride 2,5 mg( Hidroclorotiazida 25 mg/Atenolol 50 mg) Emcoretic (5 10 mg / 12,5 25 mg hidroclorotiazida)

Dosis usual en HTA

50 100 mg/24 h

Dosis mxima
200 mg

Atenolol
Bisoprolol Carteolol Carvedilol Celiprolol Esmolol Labetalol Metoprolol

Tenormin, Blokium, Genricos 50,100

Emconco Cor 22,5 y 10. Emconcor, Genricos 5, 10 mg Arteolol 5 mg Coropres 25 mg, Genricos 25 mg Cardem 200 mg Brevibloc 2,5 mg/10 ml Brevibloc 100 mg/10 ml Trandate 100, 200 mg Beloken 100 mg Lopresor 100 mg

2,5 10 mg/24 h 2,5 10 mg/ 24 h 6,25 25 mg/12 h 200 mg/24 h Bolus. 1 mg/kg. Perfusion 150-300 mcg/kg/min 100 mg 400 mg/12 h

20 mg 40 mg/ 24 h

400 mg

1200 mg/12 h

Logimax (Metoprolol 50 mg/ Felodipino 5 mg)

100-400 mg/24 h

Nadolol
Nebivolol Oxprenolol Propanolol Sotalol

Solgol 40, 80 mg
Lobivon 5 mg. Silostar 5 mg Trasicor 80, Trasicor Retard 160 mg Sunial 5, 10, 40 mg. Sumial Retard 160 mg Sotapor 80 y 160 mg Trasitensin (retard 160 mg/ 20 mg Clortalidona)

80 mg en 3-4 dosis/24 h
5 mg/24 h 40-80 mg/12 h Retard 160 mg/24 h 40 mg/12 h 80 mg/ 24 h inicial. 320 640 mg/24 h

320 mg en 3-4 dosis /24 h

480 mg/24 h 160-320 mg/24 h en 3 4 dosis 960 mg/24 h 17

Eliminacin
Acebutolol Atenolol Bexaxolol Bisoprolol Carteolol Carvedilol Celiprolol Esmolol Labetalol Metoprolol Nadolol
RyH R R RyH R H RyH Esterasas H R R

ClCr > 50
100%

ClCr 10-50
50% /24 h 100%/48 h

ClCr < 10
25%/24 h 100%/56 h

Evitar Evitar 50%/24 h Evitar Evitar 100% 100% 100%

Nebivolol
Oxprenolol Pindolol
H RyH H R R

100%
100%

100%
100%

100%
100%

Propanolol
Sotalol Timolol

100% 100%/ 24 h

100% 100%/ 36-48 h

100% Segn respuesta

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Indicaciones

No tienen un efecto especfico cardioprotector en pacientes con HTA. No reducen la Presin arterial central. (no reducen la incidencia de AVC)

Indicaciones:

Pacientes con taquicardia en reposo. Insuficiencia cardaca por disfuncin diastlica y en algunos casos de disfuncin sistlica. Migraas. Glaucoma. Cardiopata isqumica previa.
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Contraindicaciones

Asma. EPOC. Enfermedad vascular periferica severa. Fenmeno de Raynaud. Bradicardia. BAV 2 o 3er grado.

20

Beta blockers in the management of chronic kidney disease

Kidney International (2006) 70, 19051913.

L Bakris, P Hart and E Ritz

21

Sympathetic overactivity in kidney disease is involved in the genesis of hypertension, in the progression of kidney disease, and in the cardiac complications of kidney failure.

22

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

Salplachta J, Bartosikova L, Necas J. Effects of carvedilol and BL-443 on kidney of rats with cyclosporine nephropathy. Gen Physiol Biophys 2002; 21: 189195.

Similar observations concerning kidney disease progression were noted with the central sympathicoplegic agent moxonidine.

Amann K, Nichols C, Tornig J et al. Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure. Nephrol Dial Transplant 1996; 11: 10031011.

Additionally, moxonidine also reduced albumin excretion in patients with type I diabetes, despite causing no change in ambulatory blood pressure.

Strojek K, Grzeszczak W, Gorska J et al. Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy? J Am Soc Nephrol 2001; 12: 602605. Vonend O, Marsalek P, Russ H et al. Moxonidine treatment of hypertensive patients with advanced renal failure. J Hypertens 2003; 21: 17091717.

23

In a separate model of kidney disease (spontaneously hypertensive rats with adriamycin nephropathy), -/-blocker carvedilol decreased systolic blood pressure, decreased renal vascular resistance (RVR), and significantly increased renal blood flow (RBF). Moreover, it significantly decreased interstitial infiltration in the early phase of the study, slowed development of interstitial fibrosis and tubular atrophy, and decreased blood vessel changes. These changes strongly correlated with slowed nephropathy progression as well as decreases in proteinuria.

Jovanovic D, Jovovic D, Mihailovic-Stanojevic N et al. Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy. Clin Nephrol 2005; 63: 446453.

In subtotally nephrectomized rats with known microangiopathy, -blockers increased the capillary density in the heart. This is an important observation, as -blockers clearly improve cardiac function and reduce cardiovascular events in hemodialyzed patients.

Amann K, Ritz E. Microvascular disease the Cinderella of uraemic heart disease. Nephrol Dial Transplant 2000; 15: 14931503. 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. 24

The use of -blockers in CKD patients

As there is overwhelming evidence for sympathetic overactivity in patients with kidney disease, coronary heart disease and heart failure (HF) are the most common causes of death in these patients.

Eknoyan G. On the epidemic of cardiovascular disease in patients with chronic renal disease and progressive renal failure: a first step to improve the outcomes. Am J Kidney Dis 1998; 32: S1S4.

This may be due to inadequate treatment, as demonstrated by a recent study in which -adrenergic blockade was used in fewer than 30% of patients on hemodialysis.

Abbott KC, Trespalacios FC, Agodoa LY et al. Beta-blocker use in long-term dialysis patients: association with hospitalized heart failure and mortality. Arch Intern Med 2004; 164: 24652471.
25

The use of -blockers in CKD patients

This is surprising, as -blockers interfere with the deleterious actions of the SNS on cardiac end points, and are well-established, evidence-based therapy for reducing cardiovascular risk in hypertension and after myocardial infarction.

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. Zuanetti G, Maggioni AP, Keane W et al. Nephrologists neglect administration of betablockers to dialysed diabetic patients. Nephrol Dial Transplant 1997; 12: 2497 2500. Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 25602572. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110: 588636.

26

Observational studies suggest definite survival benefits derived from the use of -blockers in patients with severe renal disease. Furthermore, in a prospective, randomized study in hemodialyzed patients with HF, Cice et al. documented an impressive and significant decrease in death and hospitalization rates attributable to cardiovascular causes in patients on carvedilol compared to placebo .
27

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.

The United States Renal Data System Dialysis Morbidity and Mortality Study found that only 20% of chronic dialysis patients were receiving -blocker therapy.

Abbott KC, Trespalacios FC, Agodoa LY et al. Beta-blocker use in long-term dialysis patients: association with hospitalized heart failure and mortality. Arch Intern Med 2004; 164: 24652471.

In another study, only 24% of patients with established coronary heart disease were treated with -blockers. A similar trend occurs in the predialysis patients.

Trespalacios FC, Taylor AJ, Agodoa LY et al. Incident acute coronary syndromes in chronic dialysis patients in the United States. Kidney Int 2002; 62: 17991805. Wright RS, Reeder GS, Herzog CA et al. Acute myocardial infarction and renal dysfunction: a high-risk combination. Ann Intern Med 2002; 137: 563570.
28

Propanolol

Metoprolol

Atenolol

Labetalol

Carvedilol

Lipofilico
No selectivo

Si
SI

Si
No SI No Dism Aument Dism No Dism No modif No modif

No
No Si No Dism Aument Dism No

Si
Si No Si No modif No modif No modif Si

Si
Si No Si Aument Dism Aument No Dism Aument Aument
29

CardioNo selectividad bloqueo No Sensibilidad Dism insulinica TG HDL HiperK RVR FPR FG Aument Dism SI Aument Dism Dism

No modif No modif No modif No modif No modi No modif

EFFECTS ON KIDNEY FUNCTION

Increased sympathetic activity has been reported consistently in patients with moderate renal failure as well as in those with ESRD undergoing renal dialysis. The level of sympathetic activity is an independent predictor of total as well as cardiovascular mortality in patients with ESRD.

Converse Jr RL, Jacobsen TN, Toto RD et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992; 327: 19121918. Parving HH, Andersen AR, Smidt UM et al. Effect of antihypertensive treatment on kidney function in diabetic nephropathy. BMJ (Clin Res Ed) 1987; 294: 14431447.

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EFFECTS ON KIDNEY FUNCTION

Bloqueantes no slectivos:

Disminuyen la tasa de FG y el Flujo sanguneo renal (FSR), al disminuir el gasto cardaco en pacientes con ERC. En pacientes con funcin renal normal no efectan el FG ni el FSR.

Epstein M, Oster JR, Hollenberg NK. -Blockers and the kidney: implications for renal function and renin release. The Physiologist 1985; 28: 5363. Epstein M, Oster JR. Beta blockers and renal function: a reappraisal. J Clin Hypertens 1985; 1: 8599. Abbott KC, Bakris G. Renal effects of antihypertensive medications: an overview. J Clin Pharmacol 1993; 33: 392399. Zech P, Pozet N, Labeeuw M et al. Acute renal effects of betablockers. Am J Nephrol 1986; 6(Suppl 2): 1519.

31

EFFECTS ON KIDNEY FUNCTION

Bloqueantes cardioselectivos:

No disminuyen el FG y el FSR. Pueden incrementar las Resistencias Vasculares Renales (RVR). Metoprolol disminuyen la actividad de renina plasmtica. Atenolol disminuye la progresin a proteinuria en pacientes con microalbuminuria (pero menos que con el bloqueo del SRAA). Atenolol y Metoprolol en pacientes con ERC no producen efectos adversos en la hemodinmica renal. En pacientes en HD con miocardiopata dilatada, el tratamiento con metoprolol mejor el tamao ventricular, la funcin cardaca, los niveles de Peptido Auricular Natriurtico y Peptido Cerebral Natriuretico.
32

EFFECTS ON KIDNEY FUNCTION

The African American Study of Kidney Disease and Hypertension compared the long acting, once daily formulation of metoprolol, the ACE inhibitor, ramipril, and the calcium channel blocker, amlodipine in 1094 Black subjects with hypertensive nephropathy (GFR 2065 ml/min per 1.73 m2) followed for a mean of 4 years. The primary analysis of the GFR slope did not establish a definitive difference among the three agents. Significant benefits were seen, however, with ramipril compared to metoprolol and amlodipine on the clinical composite outcome of decline of GFR, ESRD, and death. The results of the secondary analyses indicated that ramipril treatment slowed the progression of hypertensive kidney disease to a greater extent than either once daily metoprolol or amlodipine. The once daily metoprolol-treated patients had a significantly lower rate of ESRD or death than those treated with amlodipine.

Wright JT, Bakris G, Greene T. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease. Results from the AASK trial. JAMA 2002; 288: 24212431.

33

EFFECTS ON KIDNEY FUNCTION

Vasodilatadores Labetalol:

Pequeos estudios y con resultados contradictorios En general, no efectos significativoss sobre FG, FSR ni volumen de agua corporal. Aumenta los niveles de glucosa plasmtica sin efectos sobre la insulinemia. Leve descenso de HDL-C. Se elimina con la dilisis, pero no aumenta su aclaramiento corporal total Hay que vigilar la aparicin de hiperK sobre todo en pacientes en HD o tras transplante renal.
34

EFFECTS ON KIDNEY FUNCTION

Vasodilatadores Carvedilol:
Tiene actividad antioxidante. No altera la creatinina ni urea plasmticas. No favorece la hiperK en pacientes con ERC.

Aumenta los niveles de CsA en un 20%. Reduce el estress oxidativo, pudiendo prevenir el aumento de las citoquinas profibrticas que ocurre en pacientes trasplantados que toman CsA.

35

EFFECTS ON KIDNEY FUNCTION

Vasodilatadores Carvedilol:

Mejora el FSR y el FG en pacientes con IC y ERC. En pacientes en HD y con miocardiopata mejoran la FE, reduce los volumnes sistlicos y diastlicos ventriculares, mejorando la supervivencia.
Reduce la albuminuria en pacientes con HTA, DM y noDM, y es capaz de hacer desaparecer la misma hast en un 48-52%.

Carvedilol mejora la sensibilidad a la insulina y el control glucmico. Tiene pocos efectos proaterognicos al no alterar el colesterol y los TG.
36

EFFECTS ON KIDNEY FUNCTION

Vasodilatadores Nevibolol:

Lipoflico. ISA. MSA. Presenta efectos vasodilatadores mediados por el NO. No afecta el metabolismo de glucosa y el perfil lipdico. Tiene efectos protectores sobre la funcin VI. Incrementa el FSR y el FG, a traves de la via del NO. Aumenta la excrecin renal de Na y K.

37

CONCLUSION

CKD, with the frequently associated conditions of hypertension, diabetes, and HF, is a state of overactivity of the SNS. Antiadrenergic drugs play an important role in its management. Antihypertensive regimens including -blockers slow the deterioration of renal function as assessed by decreasing GFR and worsening albuminuria. It is therefore deplorable that -blockers are still underutilized out of fear of adversely affecting renal function and glycemic control.

Beta blockers in the management of chronic kidney disease. Kidney International (2006) 70, 19051913. L Bakris, P Hart and E Ritz

38