BETA-BLOCANTELE

2007 - 2008
Definiie
ageni care se leag selectiv de -adrenoreceptori

Antagonizeaz competitiv i reversibil stimulii
-adrenergici la nivelul diverselor sisteme i organe

Principalele proprieti
Antiischemic

Antiaritmic

Antihipertensiv

Benefic n insuficiena cardiac
Efecte mediate de receptorii
1
i
2

esut Receptor Efect
Inim
NSA
NAV
Atriu
Ventriculi

Artere
Vene
Muchi scheletici

Ficat
Pancreas (celule )
Adipocite
Bronhii
Rinichi
Uter
Terminaiuni nervoase
Paratiroide
Tiroid

1
,
2

1
,
2

1
,
2

1
,
2

2

1

2


1
,
2

2


FC
viteza de conducere
contractilitatea
contractilitatea, viteza de conducere i
automatismul c. idioventriculari
vasodilataie
vasodilataie
vasodilataie, contractilitatea, influx
de K
+
, glicogenoliz
glicogenoliz, gluconeogenez
secreia de insulin i glucagon
lipoliz
bronhodilataie
eliberarea de renin
relaxare
eliberarea de noradrenalin
secreia de PTH
conversia T
4
T
3

CLASIFICAREA BETA-BLOCANTELOR
BB ASI Liposolub. Vd periferic i.v. D medie/zi p.o.
I. Neselective
Carteolol
Nadolol
Penbutolol
Pindolol
Propranolol
Sotalol
Timolol

+
0
+
++
0
0
0



Moderat









+
+

2,5-20 mg
40-320 mg
20-80 mg
10-40 mg
40-180 mg

5-40 mg
II.
1
-selective
Acebutolol
Atenolol
Betaxolol
Bisoprolol
Celiprolol
Esmolol
Metoprolol
Nebivolol

+
0
0
0
+
0
0
0

moderat

moderat
moderat
moderat








+


+


+



+
+


200-800 mg
25-100 mg
5-20 mg
2,5-10 mg
200-600 mg
Doar i.v.!!!
50-100 mg
2,5-5 mg
III. Antag
1
i
Bucindolol
Carvedilol
Labetalol

+
0
+

Moderat
moderat


+
+
+

25-100 mg
3,125-50 mg
200-800 mg
Efecte cardiovasculare
Antihipertensiv:
- DC / inhib eliberarea de renin i producerea de
angiotensina II / activitatea vasomotorie central
Antiischemic:
- VO
2
prin FC, contractilitii, TAS
- diastolei perfuzia miocardic
Ameliorarea structurii i funciei VS:
- dimensiunea VS
- FE VS
Antiaritmic
Inhibarea agregrii plachetare
Efect benefic asupra endoteliului vascular ( stresul
mecanic asupra plcii de aterom / Antioxidant i
proliferrii celulelor musculare netede (unele BB) /
Antiapoptotic)
Efecte secundare
CARDIOVASCULARE:
- bradicardie, BAV
- extremiti reci, fenomen Raynaud
- tonus vasomotor coronarian (vc alpha-mediat)

METABOLICE:
- mascarea semnelor de hipoglicemie (tremor, tahicardie)

PULMONARE:
- rezistenei n cile aeriene

CENTRALE: (BB lipofile)
- fatigabilitate / cefalee / insomnie / depresie

libidoului, impoten
Contraindicaii
Contraindicaii absolute:
Astm bronic
Hipotensiune arterial simptomatic
IC decompensat sever

Contraindicaii relative:
- BPOC n absena bronhospasmului
- Boal vascular periferic / claudicaie intermitent
- Diabet zaharat
Inima normal
este un organ
1
care
funcioneaz
ntr-un mediu
1
1
1
1
Normal
1
1
1
1
1
1
1
1
2 2
Normal
1
1
1
1
1
1
1
1
2 2
1
1
1
Insuficiena cardiac: modificarea mediului

1
in unul
1
/
2
/
1
Insuficien cardiac
1
2
2
2
2
1
1 1
1
1
1
1
2
2
1
1
Activarea sistemului nervos simpatic n
insuficiena cardiac
Disfuncie cardiac
Activare simpatic

1

receptori

2

receptori

1

receptori
PROGRESIA BOLII
Efectele diferitelor - blocante
Activare simpatic
Diferene farmacologice

1

receptori

2

receptori

1

receptori
Cardiotoxicitate
Bisoprolol
Carvedilol
Metoprolol
Diferene farmacologice ntre
-blocantele aprobate pentru ICC

1

2

1
Efecte
blocada blocada blocada ASI adiionale*

Carvedilol +++ +++ +++ - +++
Metoprolol +++ - - - -
Bisoprolol +++ - - - -
*anti-oxidant, anti-proliferativ
ASI Activitate Simpatomimetic Intrinsec
COMET
Sever
COPERNICUS
(carvedilol)
MERIT-HF
(metoprolol)
(carvedilol vs metoprolol)
US Carvedilol Program
(carvedilol)
CAPRICORN
(carvedilol)
Uoar Medie spre moderat
(NYHA I-II) (NYHA I) (NYHA II-III) (NYHA IV)
CARMEN
(carvedilol)
CIBIS II
(bisoprolol)
Trialurile cu -blocante - n ICC
Ce diferene poteniale pot fi luate n
considerare cnd tratm pacieni cu IC
cu -blocante
Efectul asupra supravieuirii

Efectul asupra funciei ventriculare

Eficacitatea i sigurana n subgrupe importante
sau boli asociate

Tolerabilitate, probleme de dozaj
-blocada n IC medie
i moderat:
reducerea mortalitii
de toate cauzele
-blocada n IC sever
COPERNICUS mortalitatea de toat cauzele
Meta-analiza trialurilor de comparare direct
a metoprololului i carvedilolului n IC
Packer et al. Am Heart J 2001
Impactul carvedilol-ului asupra fluxului
sanguin renal n IC
Efectul -blocadei asupra mortalitii de
toate cauzele n funcie de statusul diabetic
Efectele -blocantelor asupra lipidelor plasmatice
Adaptat dup Jacob et al. Am J Hypertension 1998
I I I
IIa IIa IIa
IIb IIb IIb
III III III
I I I
IIa IIa IIa
IIb IIb IIb
III III III
I I I
IIa IIa IIa
IIb IIb IIb
III III III
IIa IIa IIa
IIb IIb IIb
III III III
Se initiaza si se continua nelimitat totdeauna post infarct
miocardic, sindrom coronarian acut, disfunctie VS cu/fara
simptome de decompensare cardiaca, daca nu exista
contraindicatii.

Terapie cronica pentru celelalte categorii de pacienti cu boala
coronariana sau alta BCV sau diabet zaharat, daca nu exista
contraindicatii.
-blocante - Recomandari
I I I IIa IIa IIa
IIb IIb IIb
III III III
I I I IIa IIa IIa
IIb IIb IIb
III III III
I I I IIa IIa IIa
IIb IIb IIb
III III III
IIa IIa IIa
IIb IIb IIb
III III III
Faza de
tratament
Tratament acut
Preventie secundara
Total
Nr. total de
pacienti
28,970
24,298
53,268
0.5 1.0 2.0
RR de deces
-blocker
favorabil
RR (95% CI)
Placebo
favorabil
0.87 (0.77-0.98)
0.77 (0.70-0.84)
0.81 (0.75-0.87)
Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart
Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.
Trailuri de preventie secundara cu -blocante
CI=Confidence interval, RR=Relative risk
-blocante - Recomandari
-blocante Beneficii in insuficienta cardiaca si
disfunctie sistolica de VS

Studiu

Medicament
IC
Severitate
Pacienti
(n)
Follow-up
(ani)
Doza medie Rezultate
CIBIS Bisoprolol* Moderata-
Severa
641 1.9 3.8
mg/zi
Mortalitate de toate
cauzele 22% (p=NS)
CIBIS-II Bisoprolol* Moderata-
Severa
2,647 1.3 7.5
mg/zi
Mortalitate de toate
cauzele 34%
(P<0.0001)
BEST Bucindolol* Moderata-
Severa
2,708 2.0 152
mg/zi
Mortalitate de toate
cauzele 10% (p=NS)
MERIT-HF Metoprolol
succinate
#
Usoara-
Moderata
3,991 1.0 159
mg/zi
Mortalitate de toate
cauzele
34% (P=0.0062)
MDC Metprolol
tartrate*
Usoara-
Moderata
383 1.0 108
mg/zi
Deces sau necesitate
de Tx 30% (P=NS)
CAPRICORN Carvedilol Usoara 1,989 1.3 40
mg/zi
Mortalitate de toate
cauzele 23% (P
=0.03)
US Carvedilol Carvedilol Usoara-
Moderata
1,094 0.5 45
mg/zi
Mortalitate de toate
cauzele
65% (P=.0001)
COPERNICUS Carvedilol Severa 2,289 0.9 37
mg/zi
Mortalitate de toate
cauzele
35% (P =0.0014)
Vaccinarea antigripala

Pacientii cu BCV trebuie sa fie vaccinati
antigripal
I I I
IIa IIa IIa
IIb IIb IIb
III III III
I I I
IIa IIa IIa
IIb IIb IIb
III III III
I I I
IIa IIa IIa
IIb IIb IIb
III III III
IIa IIa IIa
IIb IIb IIb
III III III
Vaccinare antigripala - Evidente
Community cohort of 140,055 subjects in the 19981999 season of which 55.5 % were immunized.
Nichol et al. N Engl J Med 2003;348:1322-32.


Spitalizare
Subiecti
vaccinati
(N=77,738)
Subiecti
neimunizati
(N=62,317)
Odds Ratio
ajustata
P
Pneumonie sau gripa 495 (0.6) 581 (0.9)
0.68
(0.600.78)
<0.001
Boala cardiaca 888 (1.1) 1026 (1.6)
0.81
(0.730.89)
<0.001
Boala coronariana
ischemica
457 (0.6) 535 (0.9)
0.80
(0.700.91)
0.001
Insuficienta cardiaca 466 (0.6) 538 (0.9)
0.81
(0.700.92)
0.002
Boala cerebrovasculara 398 (0.5) 427 (0.7)
0.84
(0.720.97)
0.018
Deces 943 (1.2) 1361 (2.2)
0.52
(0.470.57)
<0.001
Spitalizare sau deces 2387 (3.1) 2910 (4.7)
0.65
(0.620.70)
<0.001
Eficienta vaccinarii antigripale in perioadele endemice