see also:

• beta blocker overdose
• history of beta blockers
• cardiology
• pharmacology main index
• sympathomimetics
• propranolol
• metoprolol
• atenolol (Tenormin)
• esmolol
• sotalol

• beta blockers are used for many therapeutic effects including lowering blood pressure, slowing the heart rate, reducing mortality after acute myocardial infarction (AMI/STEMI/NSTEMI), preventing migraine, symptomatic Mx of hyperthyroidism, etc.
• they generally have the following potential adverse effects:
  • reduced exercise tolerance
  • worsening cardiac failure in those with poor cardiac function
  • risk of heart block in those at risk or with concurrent medications which block A-V conduction such as calcium channel blockers
  • risk of bronchospasm in those with asthma
  • exacerbation of peripheral vascular disease symptoms
  • metabolic effects including altered lipid profiles, glucose metabolism, and a mild increased risk of gout
  • obscuring the clinical features of hypoglycaemia which increases risk of unrecognised episodes in diabetics.
  • in addition, some, such as sotalol prolong QTc interval and may increase risk of torsades ventricular tachycardia (VT)
• beta adrenergic blocker overdose can be fatal and difficult to Rx

• bradycardia & negative inotropic effect ⇒ decreased cardiac output;
• decreased BP if hypertension but full response may take several weeks:
  • (initial increase in peripheral resistance (beta2 block) which later normalises, then falls)
• suppress exercise-induced tachycardia if therapeutic dose;
• decreased renin secretion;
• block catecholamine-induced tremor;
• class II antiarrhythmic actions:
  • decreases spontaneous rate of depolarisation of ectopic pacemakers;
  • decreases conduction in atria & in AV node;
  • increases functional refractory period of AV node;
    • NB. some membrane-stabilising effect (Class Ia) in high [];
  • decreases angina by decreased HR, decreased contractility ⇒ decreased oxygen needs;
  • increased exercise tolerance if exertional angina;

• bronchospasm
• blockade of skeletal muscle vasodilatation;
• adverse lipid profile?;
• impaired glucose mobilisation & K+ entry into cells;

• May produce less decrease in HR & BP (but still block exertional increase in HR, CO):
  • ⇒ ? better for decreased cardiac reserve or tendency for bradycardia;
  • ⇒ not as good for Rx tachyarrhythmias, angina or post-AMI
• May result in lower peripheral resistance in short term use (normally there is an increase);
• May not effect plasma renin activity but still anti-HT effect;
• May have less frequent adverse lipid profile alteration;
• May have less tendency to bronchospasm;
• eg. pindolol, penbutolol, acebutolol, (labetalol, celiprolol @ B2 only).

• Many beta-blockers have this activity but only had high doses, which may be important in overdose;
• eg. propranolol, acebutolol, labetalol, metoprolol, pindolol;

• May result in lower peripheral resistance in short term use (normally there is an increase);
• May reduce vasoconstriction;
• Eg. labetalol (alpha1);

• Lessen adverse beta2-block effects of:
  • bronchospasm (but still use with great caution in asthmatics);
  • blockage of skeletal muscle vasodilatation;
  • adverse lipid profile?;
  • impaired glucose mobilisation & K+ entry into cells;
  • Eg. metoprolol; atenolol (Tenormin); acebutolol; betaxolol; esmolol; celiprolol; bisoprolol;

• see class III antiarrhythmic
• prolongs action potential duration, increasing refractory period and prolonging QT interval
• eg. sotalol

• less vasodilating than labetalol though
• eg. Carvedilol, bucindolol & celiprolol

• Most are well absorbed orally → peak plasma conc. @ 1-3hrs.
• Most have high 1st pass effect → low bioavailability of 25-40%
  • EXCEPT pindolol, sotalol, betaxolol & penbutolol which are >90%.
• Most are rapidly distributed with high Vd.
• Only propranolol & penbutolol are highly lipid-soluble & penetrate blood-brain-barrier well.
• Most have half lives in range 2-5hrs EXCEPT esmolol 10min, & sotalol 12hrs (& less common)
• Most are extensively metabolised in liver
  • EXCEPT:
    • atenolol (Tenormin) & pindolol less extensive metabolised
    • esmolol is rapidly hydrolysed by RBC esterases
    • nadolol is excreted unchanged in urine → long half life of 14-24hrs

• reduction of cardiac output without reflex increases in periph. vasc. resistance
• reverses HT-related LVH although not as good as ACEI's
• reduces mortality & morbidity
• esp. useful if coexistent IHD or tachyarrhythmias
• phaeochromocytoma:
  • an alpha-blocker usually commenced first to avoid unopposed alpha effects on periph. vasculature

• reduces exertion-induced rise in BP and HR
  • ⇒ longer diastolic filling time ⇒ increased oxygen delivery
  • ⇒ decreased oxygen consumption at a given cardiac workload

• non-ISA beta blockers useful in:
  • reducing rate in sinus tachycardia
  • block AV node conduction in AF thus controlling ventricular rate
  • have little or no proarrythmic activity
• sotalol has additional class III effect and is useful in:
  • suppression of non-sustained and sustained ventricular arrhythmias

• have been shown to reduce mortality post-AMI presumably via:
  • reduced myocardial work
  • increased coronary perfusion via prolonging diastolic filling
  • inhibit catechol-stimulated rise in free fatty acid metabolism ⇒ improved myocardial metabolism
  • reduction of catecholamine-induced arrhythmias at time of AMI
• since thrombolytic Rx introduced, have not been routinely used IV during AMI's although had been shown to be of benefit

• newer direct vasodilating beta blockers reduce systolic BP without negative inotropic activity being such a problem
• eg. Carvedilol

• acting by slowing heart rate & prolonging diastolic filling time
• for pts who remain symptomatic despite standard Rx (ACEI, diuretics & digoxin)
• must start at low doses & increase very carefully
• vasodilating beta blockers may be better tolerated esp. at initiation of Rx

• reduce systolic force generated within vessel

• sympathetic activation is an important triggering factor in this syndrome

• adjunctive Rx in Mx of sympathetic effects

• timolol
• betaxolol
  • A cardioselective B1-blocker used topically to reduce intraocular pressure without producing bronchospasm as may topical timolol.

• is generally of the form (except labetalol which is more like dobutamine):
  • R - benzene ring - O - CH2 - CHOH - CH2 - NH - R1
• compare with:
  • catecholamines: catechol ring - CHOH - CH2 - NH - R
  • non-catechol sympathomimetics: R-benzene - CHOH - CHR1 - NH - R2
  • dobutamine catechol - CH2 - CH2 - NH - R - phenol
  • labetalol R-phenol - CHOH - CH2 - NH- R1- benzene