SlideShare une entreprise Scribd logo
1  sur  68
Télécharger pour lire hors ligne
CURRENT STATUS OF BETA
BLOCKER USE IN
CARDIOVASCULAR DISEASES
History
• Beta-blockers were first developed by Sir James
Black at the imperial chemical industries in the
United Kingdom in 1962.
• They are considered one of the most important
contributions to clinical medicine and
pharmacology in the 20th century.
• Sir James Black was awarded the Nobel prize in
1988 for advances in medicine.
Today’s talk will include
• The pertinent clinical
pharmacology of beta-blockers
• Their clinical use in cardiovascular
medicine.
CLASSIFICATION
Actions of beta receptor stimulation
Beta 1 VS Beta 2 Selectivity
30 0:1
1:35 1:35
1:75
increasing
ß 1
-selectivity
increasing
ß 2
-selectivity
ICI
11 8.55 1
1 .8 :1
Propranolol
Atenolol Betaxolol
Bisoprolol
no
selectivity
Ratio of constants of inhibition
1:20
M etoprolol
1-selectivity of various -blockers
Wellstein A et al. J Cardiovasc Pharmacol 1986; 8 (Suppl. 11): 36-40
Wellstein A et al. Eur Heart J 1987; 8 (Suppl. M): 3–8
Summary of use of beta blockers in
cardiovascular diseases
ACTIONS OF BETA BLOCKERS
Mechanism of β-blocker benefits
in ischemic heart disease
• Reduction in myocardial oxygen
requirements via a decrease in
heart rate, blood pressure and
ventricular contractility.
• Slowing of the heart rate
prolongs coronary diastolic
filling period.
• Redistribution of coronary
Mechanism of β-blocker benefits
in ischemic heart disease
• Increases threshold to
ventricular fibrillation.
• Reduction in infarct size and
reduction in the risk of cardiac
rupture.
• Reduction in the rate of
reinfarction.
• Regression of the atheromatous
β-Blockers and atheromatous plaque
regression/progression/vulnerabilit
y stability
Decrease in coronary atheromatous plaque
volume by BB
(as assessed by intracoronary ultrasound) over 1 year
(independent of statins, ACE inhibitors, other drugs, low-
density lipoprotein concentration, and heart rate). ns, not
significant; sig, significant.
Sipahi I, Tuzcu EM, Woski KE, et al. Ann Intern Med 2007;147:10–18
Beta-blockers in cardiovascular diseases
Beta-blockers in cardiovascular diseases
MECHANISM OF BETA BLOCKERS IN
HEART FAILURE
• Upregulation of β receptors and improved β adrenergic
signaling.
• Reducing the hyperphosphorylation of calcium release
channels of sarcoplasmic reticulum and normalizing their
function
• Bradycardia (↑ coronary blood flow and decreased
myocardial oxygen demand).
• Protection from catecholamine myocyte toxicity.
• Suppression of ventricular arrhythmias.
• Anti-apoptosis. β2 receptors, which are relatively increased,
are coupled to inhibitory G protein & block apoptosis.
• Inhibition of RAAS. When added to prior ACE-I or ARB,
metoprolol augments RAAS inhibitors
β-Blockers and the
inflammatory process
The effect of monotherapy
antihypertensive treatments upon plasma
C-reactive protein levels. ACE/ARB,
angiotensin-converting enzyme/ ACE
receptor blocker; CCB, calcium channel
blocker.
Palmas W, Ma S, Psaty B, et al. Am J Hypertens 2007;20:233–41
Reduction
in Vascular
markers
with BB
JNC 7 recommendations
Beta blockers for hypertension
• In the 1980s, beta-adrenergic receptor blockers
(beta blockers) became the most popular form of
antihypertensive therapy after diuretics,
reflecting their relative effectiveness and freedom
from many bothersome side effects
• Because beta blockers reduce mortality in
patients post–myocardial infarction or heart
failure (i.e., secondary prevention), it was
assumed they would also provide special
protection against initial cardiac events (i.e.,
primary prevention).
Beta blockers for hypertension….any
benefit in primary prevention??? NO
• In multiple large RCTs, the use of a beta blocker
(particularly atenolol) provided no more
protection against the first myocardial infarction
(MI) than other drugs and was associated with a
statistically significant 16% increase in the
incidence of stroke.
• rationale—beta blockers lower brachial systolic
BP equally but do not lower aortic pressure as
well as other drugs. They reduce heart rate and
increase peripheral resistance, so that the arterial
wave reflection from the periphery returns during
systole rather than during diastole.
This is how braunwald’s textbook summarizes
the use of betablockers in hypertension
• “Beta blockers are specifically recommended for
hypertensive patients with concomitant coronary
disease, particularly after a myocardial infarction,
congestive heart failure, or tachyarrhythmias.”
• “If a beta blocker is chosen, the agents that are more
cardioselective offer the likelihood of fewer
perturbations of lipid and carbohydrate metabolism
and, because of fewer side effects (except for
bradycardia), better adherence to therapy.”
• “Long-acting formulations are better for once-daily
dosing.”
Page 945 braunwald’s textbook of medicine 9th edition
Copyright © The American College of Cardiology.
All rights reserved.
From: Cardiovascular Protection Using Beta-Blockers: A Critical Review of the Evidence
J Am Coll Cardiol. 2007;50(7):563-572. doi:10.1016/j.jacc.2007.04.060
Proposed Use of Beta-Blockers for Hypertension
In patients with uncomplicated hypertension, beta-blockers should not be used as first-line
agents. However, in patients with uncontrolled hypertension on various other antihypertensive
agents and in those with complicated hypertension, beta-blockers should be considered in the
armamentarium of treatment. CHF = chronic heart failure; MI = myocardial infarction.
Figure Legend:
Changing patterns of betablocker use
BISOPROLOL…. THE MOST
CARDIOSELECTIVE BETA BLOCKER
Bisoprolol experience in
Indian patients
Mar
2012
Objectives:
This study was aimed to evaluate the
efficacy and tolerability of
bisoprolol, in Indian patients
diagnosed with stage I essential
hypertension as first line drug.
Primary and secondary outcomes
measures:
• The primary outcome measure was
percentage of patients achieving
blood pressure (BP) <140/90 mm Hg at
Bisoprolol in hypertension
Channaraya V, Marya RK, Somasundaram M, et al. BMJ Open 2012;2:e000683
• Results:
– 2131 (96.44%) patients achieved
BP control.
– There was significant
reduction in systolic blood
pressure (25.29; SD: 13.22 mm
Hg), diastolic blood pressure
(14.14; SD: 7.67 mm Hg) and
heart rate (12/min; SD: 6.15)
compared with baseline (all
p values <0.05).
– The median dose of
bisoprolol and average
period required for the
response were 5 mg/day and
33 days,
0
20
40
60
80
100
120
140
160
180
Baseline 2 4 8 12
SBP
DBP
66
68
70
72
74
76
78
80
82
84
86
88
HR
HR
Channaraya V, Marya RK, Somasundaram M, et al. BMJ Open
Bisoprolol: Pharmacology
• Pharmacology
–Bisoprolol is a highly potent ß1
adrenoceptor blocking agent
–No ISA
–No pronounced negative inotropic
effects
–Low affinity for ß2-receptors
involved with metabolic
regulation
• does not influence airways
resistance
Modified from: Wellstein A et al. J Cardiovasc Pharmacol 1986;8(Su
Wellstein A et al. Eur Heart J 1987;8(Suppl. M):3–8
Highly β1-selective
1:35
1:75
Increasing β1-
selectivity
Increasing β2-selectivity
1.8:1Propranolol
Atenolol
Bisoprolol
No
selecti
vity
Ratio of constants of inhibition
1:20
Metoprolol
ß1-selectivity of bisoprolol compared with other
ß-blockers
Selectivity at clinical dose
β1-adrenoceptor occupancy, as achieved in a dosage interval of 24 h equivalent to a
single dose
ß1- and ß2-receptor occupancy in relation to plasma
concentrations
Wellstein A et al. J Cardiovasc Pharmacol 1986;8(Suppl. 11):41–54
Wellstein A et al. Eur Heart J 1987;8(Suppl. M):3–8
Atenolol
Occupancy Ration = 80% : 20%
Bisoprolol
Occupancy Ration = 100% : 0%
Bisoprolol in HTN with COPD 2013
•Cardioselective beta-1 blockers such as
metoprolol, bisoprolol, or nebivolol may be
beneficial in COPD.
•Atenolol does not reduce cardiovascular
events in patients with hypertension.
•Nonselective beta blockers such as
propranolol may induce bronchospasm and
should not be used in patients with COPD
Dipak Chandy1, Wilbert S Aronow2, Maciej Banach3, 1Division of
Pulmonary, Critical Care and Sleep, 2Division of Cardiology, Department of
Medicine, New York Medical College, Valhalla, NY, USA; 3Department of
Comparison of PK properties of
BB
Metabolic Disturbance
Change in plasma triglyceride and high-density
lipoprotein (HDL) levels in
normocholesterolemic hypertensive patients
after long-term therapy with propranolol
(nonselective), atenolol (moderately β1-
selective), mepindolol (nonselective with
ISA), and bisoprolol (highly β1-selective).
Fogari R, Zoppi A. Rev Contemp Pharmacother 1997;8:45–54.
** **
** **
**
**
** **
**
*
6 12 18 24 30 36 months
Bisoprolol 10 mg/day (n=17)
Propranolol 160 mg/day (n=15)
Atenolol 100 mg/day (n=22)
vs baseline
*p<0.05
**p<0.01
%HDL-cholesterol
+10
0
-10
-20
-30
-40
Difference in
effect on
lipid profile
– Beta-1
selectivity is
the key.
Different beta blockers and sexual
dysfunction versus placebo
Elimination routes of various beta
blockers from body
Product Information for Bisoprolol
Product Information for Bisoprolol
Use in Pregnancy: not labeled; though used by many
COMPARISONS
Atenolol Bisoprolol
Moderately β1-selective Highly β1-selective
No first-pass effect Little first-pass effect (10%)
Bioavailability: 40-50% Bioavailability: 90%
Unchanged renal elimination
=> dose reduction in renal
impairment
Balanced clearance: no dose
adjustment in mild-to-moderate renal
impairment. Do not exceed 10 mg in
severe cases
Once-daily administration (SPC!)
BUT: twice daily necessary
Once-daily administration sufficient and
clinically proven
24 h Peak-trough BP control ratio 31% 24 h Peak-trough BP control ratio 78%
No CHF indication CHF indication
Competitor ß-blocker Pharmacology:
atenolol
Bisoprolol Vs Atenolol: ABPM
study results
• Multi-centric, double-
blind, randomized ABPM study.
• Bisoprolol (10 – 20 mg/OD) Vs
Atenolol (50 – 100mg/OD) for 8
weeks.
• N = 659.
• Efficacy Variables –
–Average 24 hour fall in BP
–Night time 4 hour fall in BP
Neutal J et al. Am J Med,1993;94(2):181-187
Bisoprolol Vs Atenolol: Change
in night time BP
Neutal J et al. Am J Med,1993;94(2):181-187
Bisoprolol Vs Atenolol:
Conclusion
• Conventional BP measurement
fails to detect difference
between bisoprolol and
atenolol.
• Bisoprolol –
–Greater fall in DBP from
baseline than atenolol.
–Greater fall in SBP and DBP in
night time BP than atenolol.Neutal J et al. Am J Med,1993;94(2):181-187
Competitor ß-blocker Pharmacology:
metoprolol succinate
Metoprolol (succinate) Bisoprolol
β1-selective (due to ZOK formulation) Highly β1-selective
50% bioavailability due to first-pass
elimination (CYP2D6)
High bioavailability, small first-pass-
effect
Dose-reduction in hepatic
impairment required
Balanced clearance: no dose
adjustment in mild-to-moderate
hepatic impairment. Do not exceed
10 mg in severe cases
Once-daily administration (due to ZOK
formulation)
Once-daily administration
CHF indication proven (MERIT-HF) CHF indication proven (CIBIS II)
Competitor ß-blocker Pharmacology:
metoprolol tartrate
Metoprolol (tartrate) Bisoprolol
Moderately β1-selective, reliable
selectivity only in lower dose range
Highly β1-selective
Bioavailability: 50% High bioavailability, small first-pass-
effect
Predominantly hepatic clearance:
Dose-reduction in hepatic
impairment required (CYP2D6)
Balanced clearance: no dose
adjustment in mild-to-moderate
hepatic impairment. 10 mg in severe
cases not to be exceeded
Short half-life of 3–4 h, no once daily
administration
Once-daily administration
No CHF indication proven CHF indication proven
180
160
140
120
100
80
90
80
70
60
50
mm Hg SBP
n.s.
DBP
2-4 weeks
0 + 2 + 4 weeks
placebo ß-blocker
p < 0.01
p < 0.05
HRbeats/min
Bisoprolol (n = 44)
Metoprolol (n = 43)
B vs. M
n.s.= not significant
*
** **
* **
**
*
Haasis R et al. Eur Heart J 1987; 8 (Suppl M): 103–113
± SDx
_
Bisoprolol Vs Metoprolol :
Change in
BP & HR (at rest)
0
20
40
60
80
100
%
90%
SBP
Bisoprolol 10 mg
Metoprolol100 mg
HR RPP
66%
93%
54%
92%
60%
n = 87
Haasis R et al. Eur Heart J 1987; 8 (Suppl M): 103–113
Bisoprolol Vs Metoprolol : 24
hr Efficacy
Competitor ß-blocker Pharmacology:
nebivolol (1)
Nebivolol Bisoprolol
Highly β1-selective Highly β1-selective
No adverse effects on lipid/glucose
metabolism
No adverse effects on lipid/glucose
metabolism
Vasodilatation via L-arginine/NO
pathway
Enhanced NO release due to ISA at
β2 or β3-receptors: stimulation β3=>
negative inotropic effects
No ancillary properties
Bioavailability: 90% (poor metabolisers)
Bioavailability: 12% (fast metabolisers)
Bioavailability: 90%
t½: 8 h (fast metabolisers) to 27 h (poor
metabolisers)
t½: 10–12 h
Figure 12: Bisoprolol compared with nebivolol (part 1 of 2)
Competitor ß-blocker Pharmacology:
nebivolol (2)
Nebivolol Bisoprolol
Increase in plasma concentration of
nebivolol and active metabolites in
patients with renal dysfunction
Balanced clearance: 2 independent
and equally effective routes
of clearance
High protein binding: ~98% Low plasma-protein binding: 30%
CHF indication (based on a composite
endpoint of all-cause mortality & CV
hospital admission)
No significant mortality reduction
Indication limited to elderly (70 years)
CHF indication with proven
signifcant mortality reduction
No CAD indication CAD indication approved
Figure 12: Bisoprolol compared with nebivolol (part 2 of 2)
BISOPROLOL
Vs
NEBIVOLOL
BISOPROLOL
Vs
NEBIVOLOL
BISOPROLOL
Vs
NEBIVOLOL
Indirect comparison 2013
STUDY BISOPROLOL NEBIOLOL
MAIN CHF II
At half dose, LVEF
increases
----
SENIORS ---- No significance on LVEF
Also,
NEBIVOLOL
Competitor ß-blocker Pharmacology:
carvedilol
Carvedilol Bisoprolol
Not β1-selective Highly β1-selective
Vasodilatation due to α1-blockade
(but may cause orthostatic disorders)
No α1-blocking activity
Metabolic effects (in some studies):
• No influence on carbohydrate
metabolism
• Positive effect on lipids (HDL  and
LDL)
• Negative lipid effect (cholesterol, TG,
VLDL )
No relevant influence on carbohydrate
metabolism
Lipid profile (almost) not affected
Antioxidative effect? No studies available
Antiproliferative effect? No studies available
Figure 13: Bisoprolol compared with carvedilol (part 1 of 2)
Competitor ß-blocker Pharmacology:
carvedilol
Carvedilol Bisoprolol
Bioavailability: 25% Bioavailability: 90%
Protein binding: >98% Protein binding: 30%
Oral bioavailability of digoxin increased No interaction with other CV drugs
known
Extensive metabolism in the liver
(CYP2D6)
Dose adjustment in patients with
hepatic impairment
Balanced clearance: 2 independent
and equally effective routes of clearance
No dose adjustment required (10 mg not
to be exceeded in terminal insufficiency)
Sensitive to liver enzyme induction Almost insensitive to liver enzyme
induction
t½ 610 h => b.i.d. administration
(extended release formulation available)
t½: 1012 h, once-daily administration
Figure 13: Bisoprolol compared with carvedilol (part 2 of 2)
6. CIBIS–ELD
2011
CIBIS–ELD
2011
CIBIS–ELD
2011
CIBIS–ELD
2011
CIBIS–ELD
2011
• More pulmonary adverse events occurred
with Carvedilol.
7. Bisoprolol
Vs
Carvedilol
in
CHF and COPD
2011
Bisoprolol
Vs
Carvedilol
Bisoprolol
Vs
Carvedilol
THANKYOU!
Beta-blockers in cardiovascular diseases
Beta-blockers in cardiovascular diseases
Cardiovascular contraindications
Classification of β-blockers
1st Generation Non-selective Propranolol
2nd Generation β1-selective
Atenolol
Metoprolol
Betaxolol
Bisoprolol
3rd Generation
Additional
properties, for
example
vasodilation
Carvedilol
Nebivolol
Table 6: Classification of ß-blockers

Contenu connexe

Tendances

SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
 
Beta blockers in cardiology practice
Beta blockers in cardiology practiceBeta blockers in cardiology practice
Beta blockers in cardiology practicescsinha
 
Sodium glucose co transporter( SGLT2) Inhibitors
Sodium glucose co transporter( SGLT2) Inhibitors Sodium glucose co transporter( SGLT2) Inhibitors
Sodium glucose co transporter( SGLT2) Inhibitors Philip Vaidyan
 
Beta blockers all are not same
Beta blockers   all are not sameBeta blockers   all are not same
Beta blockers all are not samePraveen Nagula
 
Angiotensin-II Receptor Blocker Update --dr shanjida
Angiotensin-II Receptor Blocker Update --dr shanjidaAngiotensin-II Receptor Blocker Update --dr shanjida
Angiotensin-II Receptor Blocker Update --dr shanjidaFerdous Rafy
 
Beta blockers: Role in Hypertension
Beta blockers: Role in HypertensionBeta blockers: Role in Hypertension
Beta blockers: Role in HypertensionSujay Iyer
 
Beta adrenergic blockers
Beta adrenergic blockersBeta adrenergic blockers
Beta adrenergic blockersKarun Kumar
 
Strategies for the use of cardioselective beta blockers in cv continuum
Strategies for the use of cardioselective beta blockers in cv continuum Strategies for the use of cardioselective beta blockers in cv continuum
Strategies for the use of cardioselective beta blockers in cv continuum scsinha
 
Oral anticoagulants ppt
Oral anticoagulants ppt Oral anticoagulants ppt
Oral anticoagulants ppt Shalini Garg
 
Sacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart diseaseSacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart diseasepankaj bhosale
 
NOACS.Newer Anticoagulant.
NOACS.Newer Anticoagulant.NOACS.Newer Anticoagulant.
NOACS.Newer Anticoagulant.Dr.Hasan Mahmud
 

Tendances (20)

Antiplatelet drugs (antithrombotics)
Antiplatelet drugs (antithrombotics)Antiplatelet drugs (antithrombotics)
Antiplatelet drugs (antithrombotics)
 
Telmisartan
TelmisartanTelmisartan
Telmisartan
 
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:
 
Are all arbs the same?
Are all arbs the same?Are all arbs the same?
Are all arbs the same?
 
ARB in the management of Hypertension
ARB in the management of HypertensionARB in the management of Hypertension
ARB in the management of Hypertension
 
Beta blockers for heart failure
Beta blockers for heart failureBeta blockers for heart failure
Beta blockers for heart failure
 
Beta blockers in cardiology practice
Beta blockers in cardiology practiceBeta blockers in cardiology practice
Beta blockers in cardiology practice
 
Sodium glucose co transporter( SGLT2) Inhibitors
Sodium glucose co transporter( SGLT2) Inhibitors Sodium glucose co transporter( SGLT2) Inhibitors
Sodium glucose co transporter( SGLT2) Inhibitors
 
Telmisartan
TelmisartanTelmisartan
Telmisartan
 
Anticoagulants
AnticoagulantsAnticoagulants
Anticoagulants
 
Beta blockers all are not same
Beta blockers   all are not sameBeta blockers   all are not same
Beta blockers all are not same
 
Dapagliflozin- a novel SGLT2 inhibitor
Dapagliflozin- a novel SGLT2 inhibitorDapagliflozin- a novel SGLT2 inhibitor
Dapagliflozin- a novel SGLT2 inhibitor
 
Angiotensin-II Receptor Blocker Update --dr shanjida
Angiotensin-II Receptor Blocker Update --dr shanjidaAngiotensin-II Receptor Blocker Update --dr shanjida
Angiotensin-II Receptor Blocker Update --dr shanjida
 
Beta blockers: Role in Hypertension
Beta blockers: Role in HypertensionBeta blockers: Role in Hypertension
Beta blockers: Role in Hypertension
 
Statin
StatinStatin
Statin
 
Beta adrenergic blockers
Beta adrenergic blockersBeta adrenergic blockers
Beta adrenergic blockers
 
Strategies for the use of cardioselective beta blockers in cv continuum
Strategies for the use of cardioselective beta blockers in cv continuum Strategies for the use of cardioselective beta blockers in cv continuum
Strategies for the use of cardioselective beta blockers in cv continuum
 
Oral anticoagulants ppt
Oral anticoagulants ppt Oral anticoagulants ppt
Oral anticoagulants ppt
 
Sacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart diseaseSacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart disease
 
NOACS.Newer Anticoagulant.
NOACS.Newer Anticoagulant.NOACS.Newer Anticoagulant.
NOACS.Newer Anticoagulant.
 

En vedette (20)

Beta blockers
Beta blockersBeta blockers
Beta blockers
 
Beta blockers
Beta blockers Beta blockers
Beta blockers
 
Beta blockers
Beta blockers Beta blockers
Beta blockers
 
ADRENERGIC BLOCKERS
ADRENERGIC BLOCKERSADRENERGIC BLOCKERS
ADRENERGIC BLOCKERS
 
Adrenergic antagonists alpha and beta blockers
Adrenergic antagonists   alpha and beta blockersAdrenergic antagonists   alpha and beta blockers
Adrenergic antagonists alpha and beta blockers
 
Nebivolol Hcl
Nebivolol Hcl Nebivolol Hcl
Nebivolol Hcl
 
Bystolic
BystolicBystolic
Bystolic
 
Beta Blockers in HTN
Beta Blockers in HTNBeta Blockers in HTN
Beta Blockers in HTN
 
Beta blockers dr wan azizi
Beta blockers dr wan aziziBeta blockers dr wan azizi
Beta blockers dr wan azizi
 
Nebil
NebilNebil
Nebil
 
Beta Blocker Toxicity and Safety
Beta Blocker Toxicity and SafetyBeta Blocker Toxicity and Safety
Beta Blocker Toxicity and Safety
 
Alpha adrenergic blockers
Alpha adrenergic blockersAlpha adrenergic blockers
Alpha adrenergic blockers
 
Nebivolol
NebivololNebivolol
Nebivolol
 
Nebivolol 99200-09-6-api
Nebivolol 99200-09-6-apiNebivolol 99200-09-6-api
Nebivolol 99200-09-6-api
 
Beta blockers in hypertension
Beta blockers in hypertensionBeta blockers in hypertension
Beta blockers in hypertension
 
Dr. onn akbar ali heart specialist kpj kajang heart failure and beta blocker
Dr. onn akbar ali heart specialist kpj kajang   heart failure and beta blockerDr. onn akbar ali heart specialist kpj kajang   heart failure and beta blocker
Dr. onn akbar ali heart specialist kpj kajang heart failure and beta blocker
 
Adrenergic blockers
Adrenergic blockersAdrenergic blockers
Adrenergic blockers
 
The Pharmacology of Beta-Blockers
The Pharmacology of Beta-BlockersThe Pharmacology of Beta-Blockers
The Pharmacology of Beta-Blockers
 
Bisoprolol
BisoprololBisoprolol
Bisoprolol
 
Launching Simposium PIT IDI Kota Bogor 2013
Launching Simposium PIT IDI Kota Bogor 2013Launching Simposium PIT IDI Kota Bogor 2013
Launching Simposium PIT IDI Kota Bogor 2013
 

Similaire à Beta-blockers in cardiovascular diseases

not all beta blockers are same powerpoint.pptx
not all beta blockers are same powerpoint.pptxnot all beta blockers are same powerpoint.pptx
not all beta blockers are same powerpoint.pptxdkapila2002
 
Beta blockers in cardiology
Beta blockers in cardiologyBeta blockers in cardiology
Beta blockers in cardiologySaikumar Dunga
 
FINAL.. beta blockers in cardiovascular disease.pptx
FINAL.. beta blockers in cardiovascular disease.pptxFINAL.. beta blockers in cardiovascular disease.pptx
FINAL.. beta blockers in cardiovascular disease.pptxdkapila2002
 
Beta_Blockers.ppt
Beta_Blockers.pptBeta_Blockers.ppt
Beta_Blockers.pptBabu427058
 
Sujay iyer beta blockers
Sujay iyer beta blockersSujay iyer beta blockers
Sujay iyer beta blockerssekarkt
 
Sujay iyer beta blockers
Sujay iyer beta blockersSujay iyer beta blockers
Sujay iyer beta blockerssekarkt
 
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.ppt
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.pptPDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.ppt
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.pptenfermeriaucicoronar
 
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...cacao83
 
Combination Therapy In Hypertension - Dr Vivek Baliga Presentation
Combination Therapy In Hypertension - Dr Vivek Baliga PresentationCombination Therapy In Hypertension - Dr Vivek Baliga Presentation
Combination Therapy In Hypertension - Dr Vivek Baliga PresentationDr Vivek Baliga
 
combinatintherapyhypertension-baliga.pdf
combinatintherapyhypertension-baliga.pdfcombinatintherapyhypertension-baliga.pdf
combinatintherapyhypertension-baliga.pdfAshutoshChaturvedi36
 
Established uses of beta blockers
Established uses of beta blockersEstablished uses of beta blockers
Established uses of beta blockersRamachandra Barik
 
Servier Slideshow Material - Cosyrel.pptx
Servier Slideshow Material - Cosyrel.pptxServier Slideshow Material - Cosyrel.pptx
Servier Slideshow Material - Cosyrel.pptxHartantoSantoso2
 
Betaadrenergicblockers 150412052808-conversion-gate01
Betaadrenergicblockers 150412052808-conversion-gate01Betaadrenergicblockers 150412052808-conversion-gate01
Betaadrenergicblockers 150412052808-conversion-gate01Dr Ramesh Krishnan
 
lipid effects of antihypertensive medications
   lipid effects of antihypertensive medications   lipid effects of antihypertensive medications
lipid effects of antihypertensive medicationsSoM
 

Similaire à Beta-blockers in cardiovascular diseases (20)

not all beta blockers are same powerpoint.pptx
not all beta blockers are same powerpoint.pptxnot all beta blockers are same powerpoint.pptx
not all beta blockers are same powerpoint.pptx
 
Beta blockers
Beta blockers Beta blockers
Beta blockers
 
Beta blockers in cardiology
Beta blockers in cardiologyBeta blockers in cardiology
Beta blockers in cardiology
 
FINAL.. beta blockers in cardiovascular disease.pptx
FINAL.. beta blockers in cardiovascular disease.pptxFINAL.. beta blockers in cardiovascular disease.pptx
FINAL.. beta blockers in cardiovascular disease.pptx
 
Lekcia antyhiper
Lekcia antyhiperLekcia antyhiper
Lekcia antyhiper
 
beta blockers
beta blockersbeta blockers
beta blockers
 
Beta_Blockers.ppt
Beta_Blockers.pptBeta_Blockers.ppt
Beta_Blockers.ppt
 
Role of beta blocker and statin in primary prevention of cardiovascular disease
Role of beta blocker and statin in primary prevention of cardiovascular diseaseRole of beta blocker and statin in primary prevention of cardiovascular disease
Role of beta blocker and statin in primary prevention of cardiovascular disease
 
Sujay iyer beta blockers
Sujay iyer beta blockersSujay iyer beta blockers
Sujay iyer beta blockers
 
Sujay iyer beta blockers
Sujay iyer beta blockersSujay iyer beta blockers
Sujay iyer beta blockers
 
Sujay iyer beta blockers
Sujay iyer beta blockersSujay iyer beta blockers
Sujay iyer beta blockers
 
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.ppt
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.pptPDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.ppt
PDC_HUSD_Curso10_Betabloqueantes_FdelaPrada.ppt
 
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
 
Combination Therapy In Hypertension - Dr Vivek Baliga Presentation
Combination Therapy In Hypertension - Dr Vivek Baliga PresentationCombination Therapy In Hypertension - Dr Vivek Baliga Presentation
Combination Therapy In Hypertension - Dr Vivek Baliga Presentation
 
combinatintherapyhypertension-baliga.pdf
combinatintherapyhypertension-baliga.pdfcombinatintherapyhypertension-baliga.pdf
combinatintherapyhypertension-baliga.pdf
 
Established uses of beta blockers
Established uses of beta blockersEstablished uses of beta blockers
Established uses of beta blockers
 
CARVEDILOL MORE THAN MERE A BETA-BLOCKER
CARVEDILOL MORE THAN MERE A BETA-BLOCKERCARVEDILOL MORE THAN MERE A BETA-BLOCKER
CARVEDILOL MORE THAN MERE A BETA-BLOCKER
 
Servier Slideshow Material - Cosyrel.pptx
Servier Slideshow Material - Cosyrel.pptxServier Slideshow Material - Cosyrel.pptx
Servier Slideshow Material - Cosyrel.pptx
 
Betaadrenergicblockers 150412052808-conversion-gate01
Betaadrenergicblockers 150412052808-conversion-gate01Betaadrenergicblockers 150412052808-conversion-gate01
Betaadrenergicblockers 150412052808-conversion-gate01
 
lipid effects of antihypertensive medications
   lipid effects of antihypertensive medications   lipid effects of antihypertensive medications
lipid effects of antihypertensive medications
 

Plus de Kunal Mahajan

Journal club drug eluting balloon for cad
Journal club   drug eluting balloon for cadJournal club   drug eluting balloon for cad
Journal club drug eluting balloon for cadKunal Mahajan
 
Journal club april 2015
Journal club april 2015Journal club april 2015
Journal club april 2015Kunal Mahajan
 
Left main disease pci vs cabg excel trial 2016
Left main disease   pci vs cabg excel trial 2016Left main disease   pci vs cabg excel trial 2016
Left main disease pci vs cabg excel trial 2016Kunal Mahajan
 
In stent neoatherosclerosis
In stent neoatherosclerosis In stent neoatherosclerosis
In stent neoatherosclerosis Kunal Mahajan
 
The vascular biology of atherosclerosis
The vascular biology of atherosclerosisThe vascular biology of atherosclerosis
The vascular biology of atherosclerosisKunal Mahajan
 
Journal club may 2016
Journal club may 2016Journal club may 2016
Journal club may 2016Kunal Mahajan
 
Noncompaction cardiomyopathy
Noncompaction cardiomyopathyNoncompaction cardiomyopathy
Noncompaction cardiomyopathyKunal Mahajan
 
Journal club-bioresorbable scaffolds
Journal club-bioresorbable scaffoldsJournal club-bioresorbable scaffolds
Journal club-bioresorbable scaffoldsKunal Mahajan
 
Natural history and treatment of aortic stenosis
Natural history and treatment of aortic stenosisNatural history and treatment of aortic stenosis
Natural history and treatment of aortic stenosisKunal Mahajan
 
Journal club 19 08-2015
Journal club 19 08-2015Journal club 19 08-2015
Journal club 19 08-2015Kunal Mahajan
 
current status of GP2B3A inhibitors in PCI
current status of GP2B3A inhibitors in PCIcurrent status of GP2B3A inhibitors in PCI
current status of GP2B3A inhibitors in PCIKunal Mahajan
 
Atrial septal defects
Atrial septal defectsAtrial septal defects
Atrial septal defectsKunal Mahajan
 
Journal club cad in women
Journal club cad in womenJournal club cad in women
Journal club cad in womenKunal Mahajan
 
Primary prevention of cardiovascular
Primary prevention of cardiovascularPrimary prevention of cardiovascular
Primary prevention of cardiovascularKunal Mahajan
 
Brainstem stroke syndromes ppt
Brainstem stroke syndromes pptBrainstem stroke syndromes ppt
Brainstem stroke syndromes pptKunal Mahajan
 

Plus de Kunal Mahajan (19)

Journal club drug eluting balloon for cad
Journal club   drug eluting balloon for cadJournal club   drug eluting balloon for cad
Journal club drug eluting balloon for cad
 
Journal club april 2015
Journal club april 2015Journal club april 2015
Journal club april 2015
 
Left main disease pci vs cabg excel trial 2016
Left main disease   pci vs cabg excel trial 2016Left main disease   pci vs cabg excel trial 2016
Left main disease pci vs cabg excel trial 2016
 
Levosimendan in acs
Levosimendan in acsLevosimendan in acs
Levosimendan in acs
 
In stent neoatherosclerosis
In stent neoatherosclerosis In stent neoatherosclerosis
In stent neoatherosclerosis
 
The vascular biology of atherosclerosis
The vascular biology of atherosclerosisThe vascular biology of atherosclerosis
The vascular biology of atherosclerosis
 
Journal club may 2016
Journal club may 2016Journal club may 2016
Journal club may 2016
 
Noncompaction cardiomyopathy
Noncompaction cardiomyopathyNoncompaction cardiomyopathy
Noncompaction cardiomyopathy
 
Journal club-bioresorbable scaffolds
Journal club-bioresorbable scaffoldsJournal club-bioresorbable scaffolds
Journal club-bioresorbable scaffolds
 
Natural history and treatment of aortic stenosis
Natural history and treatment of aortic stenosisNatural history and treatment of aortic stenosis
Natural history and treatment of aortic stenosis
 
Takayasu arteritis
Takayasu arteritis Takayasu arteritis
Takayasu arteritis
 
Journal club 19 08-2015
Journal club 19 08-2015Journal club 19 08-2015
Journal club 19 08-2015
 
current status of GP2B3A inhibitors in PCI
current status of GP2B3A inhibitors in PCIcurrent status of GP2B3A inhibitors in PCI
current status of GP2B3A inhibitors in PCI
 
Atrial septal defects
Atrial septal defectsAtrial septal defects
Atrial septal defects
 
Journal club cad in women
Journal club cad in womenJournal club cad in women
Journal club cad in women
 
Primary prevention of cardiovascular
Primary prevention of cardiovascularPrimary prevention of cardiovascular
Primary prevention of cardiovascular
 
Glucose triad
Glucose triadGlucose triad
Glucose triad
 
Brainstem stroke syndromes ppt
Brainstem stroke syndromes pptBrainstem stroke syndromes ppt
Brainstem stroke syndromes ppt
 
BASICS of CT Head
BASICS of CT HeadBASICS of CT Head
BASICS of CT Head
 

Dernier

Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfHongBiThi1
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologyDeepakDaniel9
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.pptRamDBawankar1
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 

Dernier (20)

Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacology
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 

Beta-blockers in cardiovascular diseases

  • 1. CURRENT STATUS OF BETA BLOCKER USE IN CARDIOVASCULAR DISEASES
  • 2. History • Beta-blockers were first developed by Sir James Black at the imperial chemical industries in the United Kingdom in 1962. • They are considered one of the most important contributions to clinical medicine and pharmacology in the 20th century. • Sir James Black was awarded the Nobel prize in 1988 for advances in medicine.
  • 3. Today’s talk will include • The pertinent clinical pharmacology of beta-blockers • Their clinical use in cardiovascular medicine.
  • 5. Actions of beta receptor stimulation
  • 6. Beta 1 VS Beta 2 Selectivity
  • 7. 30 0:1 1:35 1:35 1:75 increasing ß 1 -selectivity increasing ß 2 -selectivity ICI 11 8.55 1 1 .8 :1 Propranolol Atenolol Betaxolol Bisoprolol no selectivity Ratio of constants of inhibition 1:20 M etoprolol 1-selectivity of various -blockers Wellstein A et al. J Cardiovasc Pharmacol 1986; 8 (Suppl. 11): 36-40 Wellstein A et al. Eur Heart J 1987; 8 (Suppl. M): 3–8
  • 8. Summary of use of beta blockers in cardiovascular diseases
  • 9. ACTIONS OF BETA BLOCKERS
  • 10. Mechanism of β-blocker benefits in ischemic heart disease • Reduction in myocardial oxygen requirements via a decrease in heart rate, blood pressure and ventricular contractility. • Slowing of the heart rate prolongs coronary diastolic filling period. • Redistribution of coronary
  • 11. Mechanism of β-blocker benefits in ischemic heart disease • Increases threshold to ventricular fibrillation. • Reduction in infarct size and reduction in the risk of cardiac rupture. • Reduction in the rate of reinfarction. • Regression of the atheromatous
  • 12. β-Blockers and atheromatous plaque regression/progression/vulnerabilit y stability Decrease in coronary atheromatous plaque volume by BB (as assessed by intracoronary ultrasound) over 1 year (independent of statins, ACE inhibitors, other drugs, low- density lipoprotein concentration, and heart rate). ns, not significant; sig, significant. Sipahi I, Tuzcu EM, Woski KE, et al. Ann Intern Med 2007;147:10–18
  • 15. MECHANISM OF BETA BLOCKERS IN HEART FAILURE • Upregulation of β receptors and improved β adrenergic signaling. • Reducing the hyperphosphorylation of calcium release channels of sarcoplasmic reticulum and normalizing their function • Bradycardia (↑ coronary blood flow and decreased myocardial oxygen demand). • Protection from catecholamine myocyte toxicity. • Suppression of ventricular arrhythmias. • Anti-apoptosis. β2 receptors, which are relatively increased, are coupled to inhibitory G protein & block apoptosis. • Inhibition of RAAS. When added to prior ACE-I or ARB, metoprolol augments RAAS inhibitors
  • 16. β-Blockers and the inflammatory process The effect of monotherapy antihypertensive treatments upon plasma C-reactive protein levels. ACE/ARB, angiotensin-converting enzyme/ ACE receptor blocker; CCB, calcium channel blocker. Palmas W, Ma S, Psaty B, et al. Am J Hypertens 2007;20:233–41 Reduction in Vascular markers with BB
  • 18. Beta blockers for hypertension • In the 1980s, beta-adrenergic receptor blockers (beta blockers) became the most popular form of antihypertensive therapy after diuretics, reflecting their relative effectiveness and freedom from many bothersome side effects • Because beta blockers reduce mortality in patients post–myocardial infarction or heart failure (i.e., secondary prevention), it was assumed they would also provide special protection against initial cardiac events (i.e., primary prevention).
  • 19. Beta blockers for hypertension….any benefit in primary prevention??? NO • In multiple large RCTs, the use of a beta blocker (particularly atenolol) provided no more protection against the first myocardial infarction (MI) than other drugs and was associated with a statistically significant 16% increase in the incidence of stroke. • rationale—beta blockers lower brachial systolic BP equally but do not lower aortic pressure as well as other drugs. They reduce heart rate and increase peripheral resistance, so that the arterial wave reflection from the periphery returns during systole rather than during diastole.
  • 20. This is how braunwald’s textbook summarizes the use of betablockers in hypertension • “Beta blockers are specifically recommended for hypertensive patients with concomitant coronary disease, particularly after a myocardial infarction, congestive heart failure, or tachyarrhythmias.” • “If a beta blocker is chosen, the agents that are more cardioselective offer the likelihood of fewer perturbations of lipid and carbohydrate metabolism and, because of fewer side effects (except for bradycardia), better adherence to therapy.” • “Long-acting formulations are better for once-daily dosing.” Page 945 braunwald’s textbook of medicine 9th edition
  • 21. Copyright © The American College of Cardiology. All rights reserved. From: Cardiovascular Protection Using Beta-Blockers: A Critical Review of the Evidence J Am Coll Cardiol. 2007;50(7):563-572. doi:10.1016/j.jacc.2007.04.060 Proposed Use of Beta-Blockers for Hypertension In patients with uncomplicated hypertension, beta-blockers should not be used as first-line agents. However, in patients with uncontrolled hypertension on various other antihypertensive agents and in those with complicated hypertension, beta-blockers should be considered in the armamentarium of treatment. CHF = chronic heart failure; MI = myocardial infarction. Figure Legend:
  • 22. Changing patterns of betablocker use
  • 24. Bisoprolol experience in Indian patients Mar 2012
  • 25. Objectives: This study was aimed to evaluate the efficacy and tolerability of bisoprolol, in Indian patients diagnosed with stage I essential hypertension as first line drug. Primary and secondary outcomes measures: • The primary outcome measure was percentage of patients achieving blood pressure (BP) <140/90 mm Hg at Bisoprolol in hypertension Channaraya V, Marya RK, Somasundaram M, et al. BMJ Open 2012;2:e000683
  • 26. • Results: – 2131 (96.44%) patients achieved BP control. – There was significant reduction in systolic blood pressure (25.29; SD: 13.22 mm Hg), diastolic blood pressure (14.14; SD: 7.67 mm Hg) and heart rate (12/min; SD: 6.15) compared with baseline (all p values <0.05). – The median dose of bisoprolol and average period required for the response were 5 mg/day and 33 days, 0 20 40 60 80 100 120 140 160 180 Baseline 2 4 8 12 SBP DBP 66 68 70 72 74 76 78 80 82 84 86 88 HR HR Channaraya V, Marya RK, Somasundaram M, et al. BMJ Open
  • 27. Bisoprolol: Pharmacology • Pharmacology –Bisoprolol is a highly potent ß1 adrenoceptor blocking agent –No ISA –No pronounced negative inotropic effects –Low affinity for ß2-receptors involved with metabolic regulation • does not influence airways resistance
  • 28. Modified from: Wellstein A et al. J Cardiovasc Pharmacol 1986;8(Su Wellstein A et al. Eur Heart J 1987;8(Suppl. M):3–8 Highly β1-selective 1:35 1:75 Increasing β1- selectivity Increasing β2-selectivity 1.8:1Propranolol Atenolol Bisoprolol No selecti vity Ratio of constants of inhibition 1:20 Metoprolol ß1-selectivity of bisoprolol compared with other ß-blockers
  • 29. Selectivity at clinical dose β1-adrenoceptor occupancy, as achieved in a dosage interval of 24 h equivalent to a single dose ß1- and ß2-receptor occupancy in relation to plasma concentrations Wellstein A et al. J Cardiovasc Pharmacol 1986;8(Suppl. 11):41–54 Wellstein A et al. Eur Heart J 1987;8(Suppl. M):3–8 Atenolol Occupancy Ration = 80% : 20% Bisoprolol Occupancy Ration = 100% : 0%
  • 30. Bisoprolol in HTN with COPD 2013 •Cardioselective beta-1 blockers such as metoprolol, bisoprolol, or nebivolol may be beneficial in COPD. •Atenolol does not reduce cardiovascular events in patients with hypertension. •Nonselective beta blockers such as propranolol may induce bronchospasm and should not be used in patients with COPD Dipak Chandy1, Wilbert S Aronow2, Maciej Banach3, 1Division of Pulmonary, Critical Care and Sleep, 2Division of Cardiology, Department of Medicine, New York Medical College, Valhalla, NY, USA; 3Department of
  • 31. Comparison of PK properties of BB
  • 32. Metabolic Disturbance Change in plasma triglyceride and high-density lipoprotein (HDL) levels in normocholesterolemic hypertensive patients after long-term therapy with propranolol (nonselective), atenolol (moderately β1- selective), mepindolol (nonselective with ISA), and bisoprolol (highly β1-selective). Fogari R, Zoppi A. Rev Contemp Pharmacother 1997;8:45–54. ** ** ** ** ** ** ** ** ** * 6 12 18 24 30 36 months Bisoprolol 10 mg/day (n=17) Propranolol 160 mg/day (n=15) Atenolol 100 mg/day (n=22) vs baseline *p<0.05 **p<0.01 %HDL-cholesterol +10 0 -10 -20 -30 -40 Difference in effect on lipid profile – Beta-1 selectivity is the key.
  • 33. Different beta blockers and sexual dysfunction versus placebo
  • 34. Elimination routes of various beta blockers from body
  • 36. Product Information for Bisoprolol Use in Pregnancy: not labeled; though used by many
  • 38. Atenolol Bisoprolol Moderately β1-selective Highly β1-selective No first-pass effect Little first-pass effect (10%) Bioavailability: 40-50% Bioavailability: 90% Unchanged renal elimination => dose reduction in renal impairment Balanced clearance: no dose adjustment in mild-to-moderate renal impairment. Do not exceed 10 mg in severe cases Once-daily administration (SPC!) BUT: twice daily necessary Once-daily administration sufficient and clinically proven 24 h Peak-trough BP control ratio 31% 24 h Peak-trough BP control ratio 78% No CHF indication CHF indication Competitor ß-blocker Pharmacology: atenolol
  • 39. Bisoprolol Vs Atenolol: ABPM study results • Multi-centric, double- blind, randomized ABPM study. • Bisoprolol (10 – 20 mg/OD) Vs Atenolol (50 – 100mg/OD) for 8 weeks. • N = 659. • Efficacy Variables – –Average 24 hour fall in BP –Night time 4 hour fall in BP Neutal J et al. Am J Med,1993;94(2):181-187
  • 40. Bisoprolol Vs Atenolol: Change in night time BP Neutal J et al. Am J Med,1993;94(2):181-187
  • 41. Bisoprolol Vs Atenolol: Conclusion • Conventional BP measurement fails to detect difference between bisoprolol and atenolol. • Bisoprolol – –Greater fall in DBP from baseline than atenolol. –Greater fall in SBP and DBP in night time BP than atenolol.Neutal J et al. Am J Med,1993;94(2):181-187
  • 42. Competitor ß-blocker Pharmacology: metoprolol succinate Metoprolol (succinate) Bisoprolol β1-selective (due to ZOK formulation) Highly β1-selective 50% bioavailability due to first-pass elimination (CYP2D6) High bioavailability, small first-pass- effect Dose-reduction in hepatic impairment required Balanced clearance: no dose adjustment in mild-to-moderate hepatic impairment. Do not exceed 10 mg in severe cases Once-daily administration (due to ZOK formulation) Once-daily administration CHF indication proven (MERIT-HF) CHF indication proven (CIBIS II)
  • 43. Competitor ß-blocker Pharmacology: metoprolol tartrate Metoprolol (tartrate) Bisoprolol Moderately β1-selective, reliable selectivity only in lower dose range Highly β1-selective Bioavailability: 50% High bioavailability, small first-pass- effect Predominantly hepatic clearance: Dose-reduction in hepatic impairment required (CYP2D6) Balanced clearance: no dose adjustment in mild-to-moderate hepatic impairment. 10 mg in severe cases not to be exceeded Short half-life of 3–4 h, no once daily administration Once-daily administration No CHF indication proven CHF indication proven
  • 44. 180 160 140 120 100 80 90 80 70 60 50 mm Hg SBP n.s. DBP 2-4 weeks 0 + 2 + 4 weeks placebo ß-blocker p < 0.01 p < 0.05 HRbeats/min Bisoprolol (n = 44) Metoprolol (n = 43) B vs. M n.s.= not significant * ** ** * ** ** * Haasis R et al. Eur Heart J 1987; 8 (Suppl M): 103–113 ± SDx _ Bisoprolol Vs Metoprolol : Change in BP & HR (at rest)
  • 45. 0 20 40 60 80 100 % 90% SBP Bisoprolol 10 mg Metoprolol100 mg HR RPP 66% 93% 54% 92% 60% n = 87 Haasis R et al. Eur Heart J 1987; 8 (Suppl M): 103–113 Bisoprolol Vs Metoprolol : 24 hr Efficacy
  • 46. Competitor ß-blocker Pharmacology: nebivolol (1) Nebivolol Bisoprolol Highly β1-selective Highly β1-selective No adverse effects on lipid/glucose metabolism No adverse effects on lipid/glucose metabolism Vasodilatation via L-arginine/NO pathway Enhanced NO release due to ISA at β2 or β3-receptors: stimulation β3=> negative inotropic effects No ancillary properties Bioavailability: 90% (poor metabolisers) Bioavailability: 12% (fast metabolisers) Bioavailability: 90% t½: 8 h (fast metabolisers) to 27 h (poor metabolisers) t½: 10–12 h Figure 12: Bisoprolol compared with nebivolol (part 1 of 2)
  • 47. Competitor ß-blocker Pharmacology: nebivolol (2) Nebivolol Bisoprolol Increase in plasma concentration of nebivolol and active metabolites in patients with renal dysfunction Balanced clearance: 2 independent and equally effective routes of clearance High protein binding: ~98% Low plasma-protein binding: 30% CHF indication (based on a composite endpoint of all-cause mortality & CV hospital admission) No significant mortality reduction Indication limited to elderly (70 years) CHF indication with proven signifcant mortality reduction No CAD indication CAD indication approved Figure 12: Bisoprolol compared with nebivolol (part 2 of 2)
  • 51. Indirect comparison 2013 STUDY BISOPROLOL NEBIOLOL MAIN CHF II At half dose, LVEF increases ---- SENIORS ---- No significance on LVEF
  • 52. Also,
  • 54. Competitor ß-blocker Pharmacology: carvedilol Carvedilol Bisoprolol Not β1-selective Highly β1-selective Vasodilatation due to α1-blockade (but may cause orthostatic disorders) No α1-blocking activity Metabolic effects (in some studies): • No influence on carbohydrate metabolism • Positive effect on lipids (HDL  and LDL) • Negative lipid effect (cholesterol, TG, VLDL ) No relevant influence on carbohydrate metabolism Lipid profile (almost) not affected Antioxidative effect? No studies available Antiproliferative effect? No studies available Figure 13: Bisoprolol compared with carvedilol (part 1 of 2)
  • 55. Competitor ß-blocker Pharmacology: carvedilol Carvedilol Bisoprolol Bioavailability: 25% Bioavailability: 90% Protein binding: >98% Protein binding: 30% Oral bioavailability of digoxin increased No interaction with other CV drugs known Extensive metabolism in the liver (CYP2D6) Dose adjustment in patients with hepatic impairment Balanced clearance: 2 independent and equally effective routes of clearance No dose adjustment required (10 mg not to be exceeded in terminal insufficiency) Sensitive to liver enzyme induction Almost insensitive to liver enzyme induction t½ 610 h => b.i.d. administration (extended release formulation available) t½: 1012 h, once-daily administration Figure 13: Bisoprolol compared with carvedilol (part 2 of 2)
  • 60. CIBIS–ELD 2011 • More pulmonary adverse events occurred with Carvedilol.
  • 68. Classification of β-blockers 1st Generation Non-selective Propranolol 2nd Generation β1-selective Atenolol Metoprolol Betaxolol Bisoprolol 3rd Generation Additional properties, for example vasodilation Carvedilol Nebivolol Table 6: Classification of ß-blockers

Notes de l'éditeur

  1. Coronary plaque disruption was closely related to a high heart rate, which was reversed by the presence of β-blockade; β-blockadealso reduces coronary artery wall stress. Thus, β-blockers appear to stabilize the vulnerable plaque. β-Blockers can also decrease the coronary artery atheromatous plaque volume as assessed directly by intravascular ultra sonography. In patients with known coronary artery disease (80% of whom had hypertension) followed up for 1 year, those on β-blockers (n = 1154, nonrandomized) experienced a signifi cant regression ofplaque volume compared with those who were not on β-blockers (n = 361); the effect of statins is included for comparison.
  2. Many factors underlie the infl ammatory process, a major component being high sympathetic nerve (β1) activity/noradrenaline levels. Thus, in patients with ischemic heart disease and hypertensives, β-blockers were more effective than diuretics, calcium blockers, ACEinhibitors, and angiotensin receptor I blockers in reducing CRP levels.
  3. Bisoprolol 5-10 mg will have little, or no, effect on metabolic parameters such as lipids, blood sugar/haemoglobin A1c (HbA1c),23 and post-insulin blood sugar and lactate changes.
  4. ABPM: BP Control beyond traditional BP control. Superior 24 hour BP control as compared to atenolol. Ensures more than 82% of patients with Stage II HTn achieve BP goals.