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Betabloqueantes
Francisco José de la Prada Alvarez
Servicio de Nefrología
1
Receptores β

β1: (músculo cardíaco)





β2: (músculo bronquial y musculo liso vascular, y menos en
músculo cardíaco):



Incrementa la frecuencia cardíaca.
Incrementa la contractilidad cardíaca.
Incrementa la conducción AV.
Disminuye la refractariedad del nodulo AV.
Vasodilatación.
Broncodilatción.
β3 (tejido adiposo y músculo cardíaco):


Termogénesis.
Reduce la contractilidad cardíaca.



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
Características



Cardioselectividad.
Actividad simpaticomimética intrínseca.
Actividad bloqueante alfa adrenérgica.
3
Características

Cardioselectividad.


Capacidad del fármaco para bloquear preferentemente
los receptores cardíacos.
La cardioselectividad es una propiedad relativa. A altas
dosis se produce el bloqueo β 2



Propanolol: no selectivo (igual afinidad por receptores β1 y β2).
Acebutolol, Atenolol, betaxolol, Bisoprolol, Celiprolol y
Metoprolol: selectivos (principal afinidad por receptores β1, y
menos por β2 que median brocodilatación y vasodilatación
periférica).
Son preferibles en pacientes asmáticos y diabéticos.



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.
4
Características

Actividad simpaticomimética intrínseca.








Actividad agonista parcial por el receptor.
Producen menor reducción en la frecuencia cardíaca en reposo (pero impiden la
taquicardia con el ejercicio), menor depresión de la conducción AV y menos
inotropismo negativo que los β-bloqueantes sin activida ISA.
No deberían usarse nen hipertiroidismo, estenosis subaórtica hipertrófica,
disección aórtica, 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
Características

Actividad bloqueante alfa adrenérgica.

Labetalol:



Bloqueante β/Bloqueante α: 3/1 a 7/1 (sobre todo por via IV. Por via oral
este efecto se reduce con el tratamiento a largo plazo)
β bloqueante: bradicardia, inotropismo negativo.
α bloqueante:





Bloquea la vasoconstricción refleja por el bloqueo β
Disminuye las resistencias vasculares coronarias y periféricas, mejorando
el flujo sanguíneo.
Mejora la sensibiliad insulínica en diabéticos y no diabéticos.
Mejoran el perfil lipídico.
Carvedilol:

Los beneficios en insuficiencia cardíaca no están relacionados con el bloqueo
α.


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.
6
Características

Actividad bloqueante alfa adrenérgica.

La actividad bloqueante alfa asociada al bloqueo
beta tiene un impacto positivo sobre la diabetes y
la aterosclerosis, mejorando el control glucémico,
reduciendo la hiperinsulinemia compensadora y
reduciendo los cambios proaterogénicos sobre los
lípidos plasmáticos.


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: 955–959.
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: 489–494.
7
Características farmacocinéticas


Metabolismo hepático.
Eliminación inalterada por riñón.


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.
8
Características farmacocinéticas

Metabolismo hepático:




Liposolubles, absorción completa en intestino delgado y metabolismo
hepático.
Biodisponibilidad variable.
Corta vida media.
Atraviesan la BHE aumentando la incidencia de efectos secundarios.


Revisión de estudios randomizados con mas de 35.000 pacientes.
La lipofilia no afecta la aparición 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
9
Características farmacocinéticas

Eliminación inalterada por riñón:









Hidrosolubles.
No penetran en el SNC
Menos biodisponibilidad.
Larga vida media en plasma. (pueden administrarse 1 ó 2
veces al día).
Requieren ajuste en ERC.
Acebutolol
Atenolol
Nadolol
Sotalol
10
Efectos secundarios




Bradicardia. (Enfermedad del nódulo sinusal)
Inotropismo negativo. (Insuficiencia cardíaca 6%)
Dromotropismo negativo. (Bloqueo AV)
Broncoconstricción.


No selectivos (Propanolol) contraindicados en asma y EPOC. (usar
con precaución los cardioselectivos (atenolol o metoprolol), los que
tienen ISA (pindolol y acebutolol) o los α bloqueantes (labetalol y
carvedilol).
Vasoconstricción periférica:

No selectivos (Propanolol) pueden empeorar enfermedad vascular
periférica severa o el fenómeno 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.
11
Efectos secundarios

Efectos sobre el SNC:





Fatiga (pequeños incrementos en su incidencia 18/1000; 1 de cada 57
pacientes tratados/año)
Impotencia. (pequeños incrementos en su incidencia 5/1000; 1 de cada
199 pacientes tratados/año)
Depresión. (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 síntomas simpáticos mediados por la
hipoglucemia y retrasan la recuperación de la glucemia
plasmática. No selectivos (Propanolol y Labetalol).

Hiperpotasemia tras sobrecarga de K (impiden la entrada
de K en la célula tras el ejercicio) Más frecuente con los no
selectivos (Propanolol) y Labetalol). Pocos efectos sobre el K
de los cardioselectivos (atenolol). El bloqueo alfa protege
frente a la elevación 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 β bloqueantes.


Angina acelerada, IAM y muerte incluso en pacientes
sin enfermedad coronaria conocida previamente,
posiblemente por up-regulation de receptores β tras el
bloqueo β.
Más 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.
14
Efectos secundarios

Efectos sobre los lípidos:


Depende de las características farmacológicas:
Más importantes en fumadores.

No selectivos y β1 bloqueantes:
 Poco efecto sobre los niveles de colesterol total.
 Reducen un 10% el HDL colesterol.
 Aumentan un 20-40% los TG.

Labetalol y β bloqueates con ISA (acebutolol y pindolol):


No efecto sobre los lípidos.
Carvedilol:



Previene la peroxidación de los lípidos.
Reduce el colesterol total y eleva menos los TG que metoprolol.
Aumenta el HDL-C
15
Bloqueo
α
Cardioselectividad
Acebutolol
+
Atenolol
++
Bexaxolol
+
Bisoprolol
+
Carteolol
Carvedilol
++
+
++
Moderada
Baja
Alta
+
Baja
Si
++
+
Moderada
+
Moderada
Nadolol
Baja
Oxprenolol
+
Pindolol
++
Propanolol
Baja
Moderada
+
Esmolol
Lipofilia
Baja
Si
+
Metoprolol
+
MSA
+
Celiprolol
Labetalol
ISA
+
Moderada
Moderada
++
Alta
Sotalol
Baja
Timolol
Moderada
16
Comercial
Asociaciones
Dosis usual
en HTA
Dosis
máxima
Atenolol
Tenormin, Blokium,
Genéricos 50,100
Blokium Diu, Normopresil, Tenoretic
(100 mg/25 Clortalidona)
Kalten (Amiloride 2,5 mg(
Hidroclorotiazida 25 mg/Atenolol 50 mg)
50 – 100 mg/24 h
200 mg
Bisoprolol
Emconco Cor 2´2,5 y 10.
Emconcor, Genéricos 5, 10 mg
Emcoretic (5 – 10 mg / 12,5 – 25 mg
hidroclorotiazida)
2,5 – 10 mg/24 h
20 mg
Carteolol
Arteolol 5 mg
2,5 – 10 mg/ 24 h
40 mg/ 24 h
Carvedilol
Coropres 25 mg, Genéricos 25
mg
6,25 – 25 mg/12 h
Celiprolol
Cardem 200 mg
200 mg/24 h
Esmolol
Brevibloc 2,5 mg/10 ml
Brevibloc 100 mg/10 ml
Bolus. 1 mg/kg.
Perfusion 150-300
mcg/kg/min
Labetalol
Trandate 100, 200 mg
100 mg – 400 mg/12 h
Metoprolol
Beloken 100 mg
Lopresor 100 mg
Nadolol
Solgol 40, 80 mg
80 mg en 3-4 dosis/24 h
Nebivolol
Lobivon 5 mg.
Silostar 5 mg
5 mg/24 h
Oxprenolol
Trasicor 80,
Trasicor Retard 160 mg
Propanolol
Sotalol
Logimax (Metoprolol 50 mg/ Felodipino
5 mg)
Trasitensin (retard 160 mg/ 20 mg
Clortalidona)
400 mg
1200 mg/12 h
100-400 mg/24 h
320 mg en 3-4
dosis /24 h
40-80 mg/12 h
Retard 160 mg/24 h
480 mg/24 h
Sunial 5, 10, 40 mg.
Sumial Retard 160 mg
40 mg/12 h
160-320 mg/24 h
en 3 – 4 dosis
Sotapor 80 y 160 mg
80 mg/ 24 h inicial.
320 – 640 mg/24 h
960 mg/24 h
17
Eliminación
ClCr > 50
ClCr 10-50
ClCr < 10
Acebutolol
RyH
Atenolol
R
Bexaxolol
R
Bisoprolol
RyH
Carteolol
R
Evitar
Carvedilol
H
Evitar
Celiprolol
RyH
Esmolol
Esterasas
Evitar
Labetalol
H
Evitar
Metoprolol
R
100%
100%
100%
Nadolol
R
100%
100%
100%
100%
100%
100%
Nebivolol
100%
50% /24 h
100%/48 h
25%/24 h
100%/56 h
50%/24 h
Oxprenolol
H
Pindolol
RyH
Propanolol
H
100%
100%
100%
Sotalol
R
100%/ 24 h
100%/ 36-48 h
Según respuesta
Timolol
R
18
Indicaciones



No tienen un efecto específico cardioprotector en
pacientes con HTA.
No reducen la Presión arterial central. (no reducen la
incidencia de AVC)
Indicaciones:





Pacientes con taquicardia en reposo.
Insuficiencia cardíaca por disfunción diastólica y en algunos
casos de disfunción sistólica.
Migrañas.
Glaucoma.
Cardiopatía isquémica previa.
19
Contraindicaciones





Asma.
EPOC.
Enfermedad vascular periferica severa.
Fenómeno de Raynaud.
Bradicardia. BAV 2º o 3er grado.
20
Beta blockers in the
management of chronic kidney
disease
Kidney International (2006) 70, 1905–1913.
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.


Similar observations concerning kidney disease progression
were noted with the central sympathicoplegic agent
moxonidine.


Salplachta J, Bartosikova L, Necas J. Effects of carvedilol and BL-443 on
kidney of rats with cyclosporine nephropathy. Gen Physiol Biophys 2002;
21: 189–195.
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: 1003–1011.
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: 602–
605.
Vonend O, Marsalek P, Russ H et al. Moxonidine treatment of hypertensive
patients with advanced renal failure. J Hypertens 2003; 21: 1709–1717.
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: 446–453.
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: 1493–1503.
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:
1438–1444.
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: S1–S4.
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: 2465–2471.
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: 1438–1444.
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: 2560–2572.
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: 588–636.
26
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: 1438–1444.

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

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: 2465–2471.
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: 1799–1805.
Wright RS, Reeder GS, Herzog CA et al. Acute myocardial infarction
and renal dysfunction: a high-risk combination. Ann Intern Med
2002; 137: 563–570.
28
Propanolol
Metoprolol
Atenolol
Labetalol
Carvedilol
Lipofilico
Si
Si
No
Si
Si
No
selectivo
SI
No
No
Si
Si
CardioNo
selectividad
SI
Si
No
No
α bloqueo
No
No
Si
Si
Sensibilidad Dism
insulinica
Dism
Dism
No modif
Aument
TG
Aument
Aument
Aument
No modif
Dism
HDL
Dism
Dism
Dism
No modif
Aument
HiperK
SI
No
No
Si
No
RVR
Aument
Dism
No modif No modif
Dism
FPR
Dism
No modif
No modif No modif
Aument
FG
Dism
No modif
No modi
Aument
No
No modif
29
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: 1912–1918.
Parving HH, Andersen AR, Smidt UM et al. Effect of antihypertensive
treatment on kidney function in diabetic nephropathy. BMJ (Clin Res Ed)
1987; 294: 1443–1447.
30
EFFECTS ON KIDNEY FUNCTION

Bloqueantes no slectivos:


Disminuyen la tasa de FG y el Flujo sanguíneo renal (FSR),
al disminuir el gasto cardíaco en pacientes con ERC.
En pacientes con función 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: 53–63.
Epstein M, Oster JR. Beta blockers and renal function: a reappraisal. J
Clin Hypertens 1985; 1: 85–99.
Abbott KC, Bakris G. Renal effects of antihypertensive medications:
an overview. J Clin Pharmacol 1993; 33: 392–399.
Zech P, Pozet N, Labeeuw M et al. Acute renal effects of beta-blockers.
Am J Nephrol 1986; 6(Suppl 2): 15–19.
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 plasmática.
Atenolol disminuye la progresión 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 hemodinámica renal.
En pacientes en HD con miocardiopatía dilatada, el
tratamiento con metoprolol mejoró el tamaño ventricular, la
función cardíaca, los niveles de Peptido Auricular
Natriurético 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 20–65 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: 2421–2431.
33
EFFECTS ON KIDNEY FUNCTION


Vasodilatadores
Labetalol:






Pequeños estudios y con resultados contradictorios
En general, no efectos significativoss sobre FG, FSR ni
volumen de agua corporal.
Aumenta los niveles de glucosa plasmática sin efectos sobre la
insulinemia.
Leve descenso de HDL-C.
Se elimina con la diálisis, pero no aumenta su aclaramiento
corporal total
Hay que vigilar la aparición 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 plasmáticas.
 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 profibróticas 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 miocardiopatía mejoran la FE,
reduce los volumnes sistólicos y diastólicos
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
glucémico.
Tiene pocos efectos proaterogénicos al no alterar el
colesterol y los TG.

36
EFFECTS ON KIDNEY FUNCTION


Vasodilatadores
Nevibolol:








Lipofílico.
ISA.
MSA.
Presenta efectos vasodilatadores mediados por el NO.
No afecta el metabolismo de glucosa y el perfil lipídico.
Tiene efectos protectores sobre la función VI.
Incrementa el FSR y el FG, a traves de la via del NO.
Aumenta la excreción 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, 1905–1913. L Bakris, P Hart and E Ritz
38