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BETA BLOCKERS
   DR. VIKAS MEDEP
 DEPT.OF CARDIOLOGY
         NIMS
TOPIC LAYOUT
 INTRODUCTION
 PHYSIOLOGY
 CLASSIFICATION
 MECHANISM  OF ACTION
 INDICATIONS
 HEART DISEASES
 CONTRA-INDICATIONS.
HISTORY AND IMPORTANCE

   Beta-blockers were first developed by Sir James black in
    the UK in 1962 was awarded the Nobel prize in 1988.
   Beta-blockers are one of the 4 oral medications proven
    to decrease CV morbidity and mortality.
   The other three agents being AcE-inhibitors, antiplatelets
    and statins.
   The approximate life-saving potential of these agents
   Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and
    Statins 15%.
   More than 100 beta-blockers have been developed, only
    about 30 are available for clinical use
   SOLUABILITY
   Water-soluble beta-blockers (Atenolol, Nadolol) tend to
    have longer half-lives and are eliminated via the kidney.
   Lipid-soluble beta-blockers (metoprolol, propranolol) are
    metabolized mainly in the liver and have shorter half-
    lives.

   DURATION OF ACTION
   Short action – eg Esmolol
   Long acting – eg Propranolol
GENERATIONS
INDICATIONS
HEART FAILURE

   Beta-blockers are now the cornerstone of systolic heart
    failure therapy.
   Beta-blocker use is associated with a 30% reduction in
    mortality, 40% reduction in hospitalizations and 38%
    reduction in sudden death in patients with chronic heart
    failure.*
   Carvedilol, Metoprolol succinate XL, Bisoprolol and
    Nebivolol.


   Brophy JM, Joseph L, Rouleau
    JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 2001; 134:550.
EuropeanHeartJournal(1996 )1 7(SupplementB),17-20
ACUTE MYOCARDIAL INFARCTION

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


   *( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)
   MECHANISM
   Decreased oxygen demand due to the reductions in
    heart rate, blood pressure, and contractility, and the
    consequent relief of ischemic chest pain.
   Decreased risk of VF ,a relative risk reduction in sudden
    cardiac death
   Decreased automaticity, increased electrophysiologic
    threshold for activation, and slowing of conduction.
   Bradycardia prolongs diastole and therefore improves
    coronary diastolic perfusion and reduces
    afterdepolarizations and triggered activity.
   Reduction in remodeling and improvement in left
    ventricular hemodynamic function,
POST MYOCARDIAL INFARCTION
               PROTECTION
   Beta-blocker use in Post MI patients reduces CV events
     by 23% in prospective studies and upto 40% in
    observational studies.*
   The benefits are greatest in patients at high risk
    (advanced age, LV dysfunction, large anterior infarction,
    complex ventricular ectopy).
   In fact, the only medications proven to reduce SCD in
    Post MI patients are beta blockers.



   *( Freemantle et al 1999; Worcester Heart Attack Study 2003)
β-Blockers in the Post−Myocardial Infarction Patient, Mihai Gheorghiade and
Sidney Goldstein, Circulation. 2002;106:394-398
Anti-arrhythmic Effects
   Mechanisms: beta-blockers negate the arrhythmogenic
    influence of excessive catecholamine states.
   I cal and I f ionic currents are inhibited at the level of
    action potentials. (class II effect).
   Sotalol, specifically, prolongs APd (class III anti-
    arrhythmic effect).
   Membrane stabilization effect (class I effect) is usually
    not seen at the therapeutic dosages of beta blockers
    employed
   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
    effective than a variety of class I anti-arrhythmics for
    ventricular tachyarrhythmias in post MI patients.
   Beta-blockers can slow, terminate or prevent
    supraventricular tachycardias (SVTs)
Inherited Arrhythmogenic disorders

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

1.   BB are strongly indicated in
2.   HEART FAILURE,
3.   ACUTE MYOCARDIAL INFARCTION,
4.   POST MI CARDIAC PROTECTION,
5.   PREVENTION OF SCD, .

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Established uses of beta blockers

  • 1. BETA BLOCKERS DR. VIKAS MEDEP DEPT.OF CARDIOLOGY NIMS
  • 2. TOPIC LAYOUT  INTRODUCTION  PHYSIOLOGY  CLASSIFICATION  MECHANISM OF ACTION  INDICATIONS  HEART DISEASES  CONTRA-INDICATIONS.
  • 3. HISTORY AND IMPORTANCE  Beta-blockers were first developed by Sir James black in the UK in 1962 was awarded the Nobel prize in 1988.  Beta-blockers are one of the 4 oral medications proven to decrease CV morbidity and mortality.  The other three agents being AcE-inhibitors, antiplatelets and statins.  The approximate life-saving potential of these agents  Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and Statins 15%.  More than 100 beta-blockers have been developed, only about 30 are available for clinical use
  • 4.
  • 5.
  • 6. SOLUABILITY  Water-soluble beta-blockers (Atenolol, Nadolol) tend to have longer half-lives and are eliminated via the kidney.  Lipid-soluble beta-blockers (metoprolol, propranolol) are metabolized mainly in the liver and have shorter half- lives.  DURATION OF ACTION  Short action – eg Esmolol  Long acting – eg Propranolol
  • 8.
  • 10.
  • 11. HEART FAILURE  Beta-blockers are now the cornerstone of systolic heart failure therapy.  Beta-blocker use is associated with a 30% reduction in mortality, 40% reduction in hospitalizations and 38% reduction in sudden death in patients with chronic heart failure.*  Carvedilol, Metoprolol succinate XL, Bisoprolol and Nebivolol.  Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 2001; 134:550.
  • 12.
  • 14.
  • 15.
  • 16. ACUTE MYOCARDIAL INFARCTION  Beta blockers significantly reduce morbidity and mortality in patients with acute MI  Upto 40% reduction in mortality, beta-blockers reduce the odds of death by 23%.*  Current recommendations are to avoid early (<24 hr) beta-blocker use in patients with hemodynamic instability, or risk of cardiogenic shock (age > 70 yrs, systolic blood pressure <120 mmHg, heart rate >110 bpm, killip class III on presentation).  *( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)
  • 17. MECHANISM  Decreased oxygen demand due to the reductions in heart rate, blood pressure, and contractility, and the consequent relief of ischemic chest pain.  Decreased risk of VF ,a relative risk reduction in sudden cardiac death  Decreased automaticity, increased electrophysiologic threshold for activation, and slowing of conduction.
  • 18. Bradycardia prolongs diastole and therefore improves coronary diastolic perfusion and reduces afterdepolarizations and triggered activity.  Reduction in remodeling and improvement in left ventricular hemodynamic function,
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  • 22. POST MYOCARDIAL INFARCTION PROTECTION  Beta-blocker use in Post MI patients reduces CV events by 23% in prospective studies and upto 40% in observational studies.*  The benefits are greatest in patients at high risk (advanced age, LV dysfunction, large anterior infarction, complex ventricular ectopy).  In fact, the only medications proven to reduce SCD in Post MI patients are beta blockers.  *( 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
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  • 25. Anti-arrhythmic Effects  Mechanisms: beta-blockers negate the arrhythmogenic influence of excessive catecholamine states.  I cal and I f ionic currents are inhibited at the level of action potentials. (class II effect).  Sotalol, specifically, prolongs APd (class III anti- arrhythmic effect).  Membrane stabilization effect (class I effect) is usually not seen at the therapeutic dosages of beta blockers employed
  • 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 effective than a variety of class I anti-arrhythmics for ventricular tachyarrhythmias in post MI patients.  Beta-blockers can slow, terminate or prevent supraventricular tachycardias (SVTs)
  • 27. Inherited Arrhythmogenic disorders  Beta-blockers are recommended for patients with a clinical diagnosis of Long QT syndrome 1 (LQTS 1).  ICD+ beta blockers are recommended for patients with LQTS and h/o resuscitated cardiac arrest  Beta-blockers are also the drugs of choice for patients with catecholaminergic Polymorphic VT (CPVT ).  Mutation carriers of CPVT should also receive beta blockers even in the absence of documented VT
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  • 32. TAKE HOME POINTS 1. BB are strongly indicated in 2. HEART FAILURE, 3. ACUTE MYOCARDIAL INFARCTION, 4. POST MI CARDIAC PROTECTION, 5. PREVENTION OF SCD, .