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Historic perspective of beta adrenergic blockers


  • adrenergic responses classified as “alpha” & “beta” in 1948
  • in late 1950's it was proposed that blockade of beta actions may be of benefit in Rx of angina & hypertension
  • the 1st beta blockers, dichloroisoprenaline & pronethalol were limited in clinical usefulness because of partial agonist activity & tumorigenesis respectively.
  • in the early 1960's, Sir James Black, at ICI in England, began the search for a beta blocker without such side effects and in 1963, propranolol entered clinical trials. It was non-selective without intrinsic sympathomimetic activity, but being the 1st beta blocker available for clinical use has become the prototype beta blocking agent with which others are compared.
  • beta blockers with intrinsic sympathomimetic activity (ISA) (eg. pindolol) introduced which do not have the usual metabolic adverse effects such as increased serum triglyceride levels and thus found use in Rx of hypertension but the reduced efficacy in heart rate reduction has meant that they have not been shown to be of benefit in Rx of angina, tachyarrhythmias or to reduce mortality after AMI's.
  • beta 1 selectivity introduced with metoprolol and atenolol (Tenormin) but asthma still a relative C/I to their use
  • the longer acting atenolol (Tenormin) shown to have no withdrawal reaction at 1 week (ISIS-1), the earlier shorter acting agents produced rebound phenomenon if suddenly stopped producing worsening angina, etc.
  • labetalol introduced which has a relatively high ratio of alpha to beta blockade, but its clinical use was limited by postural hypotension
  • beta blockers without ISA shown to reduce mortality after AMI's
  • ultra short acting beta blocker esmolol introduced
  • beta 3 receptor discovered on adipose tissue - ? role in obesity
  • beta blockers with direct vasodilating actions (milder than labetalol) introduced (eg. Carvedilol, bucindolol & celiprolol) and found use in Rx of systolic hypertension (previously systolic heart failure was thought to C/I beta blocker Rx due to their negative inotropic activity, but the vasodilatation helps overcome this problem).
  • TAIM study in 1992 showed beta blockers effectively lowered BP with a low incidence of adverse effects
  • in 1992, beta blockers shown not to reverse LVH to the same extent as ACEI's.
  • 1997: long term Rx with carvedilol was shown to reduce mortality in systolic heart failure as well as reducing symptoms & improving well-being. Carvedilol also has anti-oxidant, antiproliferative & anti-endothelin properties.
  • HANE study in 1997 showed that BP responses were as good, if not better, with atenolol than with either hydrochlorothiazide, nitrendipine or enalapril.
  • 1998: bisoprolol in pts with NYHA class III or IV CCF Rx with diuretics & ACEI's:
    • reduced all mortality by 34% and sudden death by 44%, reduced hospital admissions by 20%
h_betablockers.txt · Last modified: 2008/09/14 23:31 (external edit)