Established uses of beta blockers

1. BETA BLOCKERS
DR. VIKAS MEDEP
DEPT.OF CARDIOLOGY
NIMS

2. TOPIC LAYOUT
INTRODUCTIONINTRODUCTION
PHYSIOLOGYPHYSIOLOGY
CLASSIFICATIONCLASSIFICATION
MECHANISM OF ACTIONMECHANISM OF ACTION
INDICATIONSINDICATIONS
HEART DISEASESHEART DISEASES
CONTRA-INDICATIONS.CONTRA-INDICATIONS.

3. HISTORY AND IMPORTANCE
Beta-blockers were first developed by Sir James black in Beta-blockers were first developed by Sir James black in
the UK in 1962 was awarded the Nobel prize in 1988.the UK in 1962 was awarded the Nobel prize in 1988.
Beta-blockers are one of the 4 oral medications proven Beta-blockers are one of the 4 oral medications proven
to decrease CV morbidity and mortality. to decrease CV morbidity and mortality.
The other three agents being AcE-inhibitors, antiplatelets The other three agents being AcE-inhibitors, antiplatelets
and statins.and statins.
The approximate life-saving potential of these agentsThe approximate life-saving potential of these agents
Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and
Statins 15%.Statins 15%.
More than 100 beta-blockers have been developed, only More than 100 beta-blockers have been developed, only
about 30 are available for clinical useabout 30 are available for clinical use

6. SOLUABILITY
Water-soluble beta-blockers (Atenolol, Nadolol) tend to Water-soluble beta-blockers (Atenolol, Nadolol) tend to
have longer half-lives and are eliminated via the kidney. have longer half-lives and are eliminated via the kidney.
Lipid-soluble beta-blockers (metoprolol, propranolol) are Lipid-soluble beta-blockers (metoprolol, propranolol) are
metabolized mainly in the liver and have shorter half-metabolized mainly in the liver and have shorter half-
lives.lives.
DURATION OF ACTION
Short action – eg EsmololShort action – eg Esmolol
Long acting – eg PropranololLong acting – eg Propranolol

7. GENERATIONS

9. INDICATIONS

11. HEART FAILURE
Beta-blockers are now the cornerstone of systolic heart Beta-blockers are now the cornerstone of systolic heart
failure therapy.failure therapy.
Beta-blocker use is associated with a 30% reduction in Beta-blocker use is associated with a 30% reduction in
mortality, 40% reduction in hospitalizations and 38% mortality, 40% reduction in hospitalizations and 38%
reduction in sudden death in patients with chronic heart reduction in sudden death in patients with chronic heart
failure.*failure.*
Carvedilol, Metoprolol succinate XL, Bisoprolol and Carvedilol, Metoprolol succinate XL, Bisoprolol and
Nebivolol.Nebivolol.
Brophy JM, Joseph L, Rouleau
JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 2001; 134:550.

13. EuropeanHeartJournal(1996 )1 7(SupplementB),17-20

16. ACUTE MYOCARDIAL INFARCTION
Beta blockers significantly reduce morbidity and mortality Beta blockers significantly reduce morbidity and mortality
in patients with acute MIin patients with acute MI
Upto 40% reduction in mortality, beta-blockers reduce Upto 40% reduction in mortality, beta-blockers reduce
the odds of death by 23%.*the odds of death by 23%.*
Current recommendations are to avoid early (<24 hr) Current recommendations are to avoid early (<24 hr)
beta-blocker use in patients with hemodynamic beta-blocker use in patients with hemodynamic
instability, or risk of cardiogenic shock (age > 70 yrs, instability, or risk of cardiogenic shock (age > 70 yrs,
systolic blood pressure <120 mmHg, heart rate >110 systolic blood pressure <120 mmHg, heart rate >110
bpm, killip class III on presentation). bpm, killip class III on presentation).
*( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)*( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)

17. MECHANISM
Decreased oxygen demand due to the reductions in Decreased oxygen demand due to the reductions in
heart rate, blood pressure, and contractility, and the heart rate, blood pressure, and contractility, and the
consequent relief of ischemic chest pain.consequent relief of ischemic chest pain.
Decreased risk of VF ,a relative risk reduction in sudden Decreased risk of VF ,a relative risk reduction in sudden
cardiac deathcardiac death
Decreased automaticity, increased electrophysiologic Decreased automaticity, increased electrophysiologic
threshold for activation, and slowing of conductionthreshold for activation, and slowing of conduction..

18. Bradycardia prolongs diastole and therefore improves Bradycardia prolongs diastole and therefore improves
coronary diastolic perfusion and reduces coronary diastolic perfusion and reduces
afterdepolarizations and triggered activity.afterdepolarizations and triggered activity.
Reduction in remodeling and improvement in left Reduction in remodeling and improvement in left
ventricular hemodynamic functionventricular hemodynamic function,,

22. POST MYOCARDIAL INFARCTION
PROTECTION
Beta-blocker use in Post MI patients reduces CV events Beta-blocker use in Post MI patients reduces CV events
by 23% in prospective studies and upto 40% in by 23% in prospective studies and upto 40% in
observational studies.*observational studies.*
The benefits are greatest in patients at high risk The benefits are greatest in patients at high risk
(advanced age, LV dysfunction, large anterior infarction, (advanced age, LV dysfunction, large anterior infarction,
complex ventricular ectopy). complex ventricular ectopy).
In fact, the only medications proven to reduce SCD in In fact, the only medications proven to reduce SCD in
Post MI patients are beta blockers.Post MI patients are beta blockers.
*( Freemantle et al 1999; Worcester Heart Attack Study 2003)*( Freemantle et al 1999; Worcester Heart Attack Study 2003)

23. β-Blockers in the Post−Myocardial Infarction Patient, Mihai Gheorghiade and
Sidney Goldstein, Circulation. 2002;106:394-398

25. Anti-arrhythmic Effects
Mechanisms: beta-blockers negate the arrhythmogenic : beta-blockers negate the arrhythmogenic
influence of excessive catecholamine states. influence of excessive catecholamine states.
I cal and I f ionic currents are inhibited at the level of I cal and I f ionic currents are inhibited at the level of
action potentials. (class II effect). action potentials. (class II effect).
Sotalol, specifically, prolongs APd (class III anti-Sotalol, specifically, prolongs APd (class III anti-
arrhythmic effect). arrhythmic effect).
Membrane stabilization effect (class I effect) is usually Membrane stabilization effect (class I effect) is usually
not seen at the therapeutic dosages of beta blockers not seen at the therapeutic dosages of beta blockers
employedemployed

26. Efficacy & clinical use: :
In post-MI patients, beta-blockers are superior to
other anti-arrhythmics for ventricular
tachyarrhythmias and reduce arrhythmic cardiac
deaths..
The ESVEM study showed that sotalol was more The ESVEM study showed that sotalol was more
effective than a variety of class I anti-arrhythmics for effective than a variety of class I anti-arrhythmics for
ventricular tachyarrhythmias in post MI patients. ventricular tachyarrhythmias in post MI patients.
Beta-blockers can slow, terminate or prevent Beta-blockers can slow, terminate or prevent
supraventricular tachycardias (SVTs)supraventricular tachycardias (SVTs)

27. Inherited Arrhythmogenic disorders
Beta-blockers are recommended for patients with a Beta-blockers are recommended for patients with a
clinical diagnosis of Long QT syndrome 1 (LQTS 1). clinical diagnosis of Long QT syndrome 1 (LQTS 1).
ICD+ beta blockers are recommended for patients with ICD+ beta blockers are recommended for patients with
LQTS and h/o resuscitated cardiac arrest LQTS and h/o resuscitated cardiac arrest
Beta-blockers are also the drugs of choice for patients Beta-blockers are also the drugs of choice for patients
with catecholaminergic Polymorphic VT (CPVT ). with catecholaminergic Polymorphic VT (CPVT ).
Mutation carriers of CPVT should also receive beta Mutation carriers of CPVT should also receive beta
blockers even in the absence of documented VTblockers even in the absence of documented VT

30. SUDDEN CARDIAC DEATH

32. TAKE HOME POINTS
1.1.BB are strongly indicated in BB are strongly indicated in
2.2.HEART FAILURE, HEART FAILURE,
3.3.ACUTE MYOCARDIAL INFARCTION, ACUTE MYOCARDIAL INFARCTION,
4.4.POST MI CARDIAC PROTECTION, POST MI CARDIAC PROTECTION,
5.5.PREVENTION OF SCD,PREVENTION OF SCD, . .