Beta-blockers are a class of drugs that are used to manage various cardiac conditions by blocking the effects of epinephrine and other stress hormones on beta receptors. They were first developed in the 1950s and revolutionized cardiology. Beta-blockers are indicated for conditions like hypertension, arrhythmias, heart attack, and glaucoma. While they provide important benefits, they can also cause adverse effects like fatigue, dizziness, and bronchospasm. Different beta-blockers have varying levels of selectivity for beta-1 versus beta-2 receptors and some have additional alpha-blocking properties. Guidelines provide recommendations on the appropriate use of specific beta-blockers for different cardiac indications.

1. Beta-blockers
Dr.Md.Toufiqur
Rahman
FCPS, MD, FACC, FESC, FRCPE,
FSCAI, MBBS, FAHA, FSCAI,
FCCP, FRCPG
Associate Professor of cardiology
NICVD, Dhaka

2. Introduction and history
• Beta blockers (sometimes written as β-blockers) or beta-
adrenergic blocking agents, beta-adrenergic antagonists, or beta
antagonists, are a class of drugs used for various indications, but
particularly for the management of cardiac arrhythmias,
cardioprotection after myocardial infarction (heart attack), and
hypertension As beta adrenergic receptor antagonists, they
diminish the effects of epinephrine (adrenaline) and other stress
hormones. In 1958 the first beta blocker, dichloroisoproterenol,
was synthesised by Eli Lilly Laboratories, but it was Sir James W.
Black in 1962, who found the first clinically significant use of
beta blockers with propranolol and pronethalol; it revolutionized
the medical management of angina pectoris and is considered by
many to be one of the most important contributions to clinical
medicine and pharmacology of the 20th century.

3. Introduction
• Beta blockers block the action of endogenous
catecholamines (epinephrine (adrenaline) and
norepinephrine (noradrenaline) in particular), on
β-adrenergic receptors, part of the sympathetic
nervous system which mediates the "fight or
flight" response. There are three known types of
beta receptor, designated β1, β2 and β3 receptors.
β1-adrenergic receptors are located mainly in the
heart and in the kidneys. β2-adrenergic receptors
are located mainly in the lungs, gastrointestinal
tract, liver, uterus, vascular smooth muscle, and
skeletal muscle.β3-adrenergic receptors are
located in fat cells.

4. Indications for beta blockers
• Angina pectoris
• Atrial fibrillation
• Cardiac arrhythmia
• Congestive heart failure
• Essential tremor
• Glaucoma
• Hypertension
• Migraine prophylaxis
• Mitral valve prolapse
• Myocardial infarction
• Phaeochromocytoma, in conjunction with α-blocker
• Symptomatic control (tachycardia, tremor) in anxiety
and hyperthyroidism

5. Beta blockers have also been used in the
following conditions
• Acute aortic dissection
• Hypertrophic obstructive cardiomyopathy
• Marfan syndrome (treatment with propranolol
slows progression of aortic dilation and its
complications)
• Prevention of variceal bleeding in portal
hypertension
• Possible mitigation of hyperhidrosis
 Social anxiety disorder and other anxiety disorders

6. Adverse effects
• Adverse drug reactions(ADRs) associated with the use of beta
blockers include: nausea, diarrhoea, bronchospasm, dyspnea, cold
extremities, exacerbation of Raynaud's syndrome, bradycardia,
hypotension, heart failure, heart block, fatigue, dizziness, alopecia
(hair loss), abnormal vision, hallucinations, insomnia, nightmares,
sexual dysfunction, erectile dysfunction and/or alteration of glucose
and lipid metabolism. Mixed α1/β-antagonist therapy is also
commonly associated with orthostatic hypotension. Carvedilol
therapy is commonly associated with edema.
• Central nervous system (CNS) adverse effects (hallucinations,
insomnia, nightmares) are more common in agents with greater lipid
solubility, which are able to cross the blood-brain barrier into the
CNS. Similarly, CNS adverse effects are less common in agents with
greater aqueous solubility.

7. • Adverse effects associated with β2-adrenergic receptor antagonist
activity (bronchospasm, peripheral vasoconstriction, alteration of
glucose and lipid metabolism) are less common with β1-selective
(often termed "cardioselective") agents, however receptor
selectivity diminishes at higher doses. Beta blockade, especially of
the beta-1 receptor at the macula densa inhibits renin release, thus
decreasing the release of aldosterone. This causes hyponatremia and
hyperkalemia.
• A 2007 study revealed that diuretics and beta-blockers used for
hypertension increase a patient's risk of developing diabetes while
ACE inhibitors and Angiotensin II receptor antagonists
(Angiotensin Receptor Blockers) actually decrease the risk of
diabetes. Clinical guidelines in Great Britain, but not in the United
States, call for avoiding diuretics and beta-blockers as first-line
treatment of hypertension due to the risk of diabetes.
Adverse effects

8. Precautions
• Beta blockers must not be used in the treatment of cocaine,
amphetamine, or other alpha adrenergic stimulant
overdose. The blockade of only beta receptors increases
hypertension, reduces coronary blood flow, left ventricular
function, and cardiac output and tissue perfusion by means
of leaving the alpha adrenergic system stimulation
unopposed. The appropriate antihypertensive drugs to
administer during hypertensive crisis resulting from
stimulant abuse are vasodilators like nitroglycerin,
diuretics like furosemide and alpha blockers like
phentolamine.

9. Toxicity
• Glucagon has been used in the treatment of
overdose. Glucagon has a positive inotropic action
on the heart and decreases renal vascular
resistance. It is therefore useful in patients with
beta-blocker cardiotoxicity. Cardiac pacing should
be reserved for patients unresponsive to
pharmacological therapy.
• Patients who experience bronchospasm due to the
B2 blocking effects of non-selective beta-blockers
may be treated with anticholinergic drugs such as
Ipratropium, which are safer than beta agonists in
patients with cardiovascular disease.

10. β-Receptor antagonism
• Stimulation of β1 receptors by epinephrine induces a positive
chronotropic and inotropic effect on the heart and increases cardiac
conduction velocity and automaticity.Stimulation of β1 receptors on
the kidney causes renin release. Stimulation of β2 receptors induces
smooth muscle relaxation, induces tremor in skeletal muscle, and
increases glycogenolysis in the liver and skeletal muscle. Stimulation
of β3 receptors induces lipolysis.
• Beta blockers inhibit these normal epinephrine-mediated sympathetic
actions,but have minimal effect on resting subjects. That is, they
reduce excitement/physical exertion on heart rate and force of
contraction, and also tremor and breakdown of glycogen, but increase
dilation of blood vessels and constriction of bronchi.
• It is therefore expected that non-selective beta blockers have an
antihypertensive effect. The primary antihypertensive mechanism of
betablockers is unclear but it may involve reduction in cardiac output
(due to negative chronotropic and inotropic effects). It may also be
due to reduction in renin release from the kidneys, and a central
nervous system effect to reduce sympathetic activity (for those β-
blockers that do cross the blood-brain barrier, e.g. Propranolol).

11. β-Receptor antagonism
• Antianginal effects result from negative chronotropic and inotropic
effects, which decrease cardiac workload and oxygen demand.
Negative chronotropic properties of beta blockers allow the lifesaving
property of heart rate control. Beta blockers are readily titrated to
optimal rate control in many pathologic states.
• The antiarrhythmic effects of beta blockers arise from sympathetic
nervous system blockade – resulting in depression of sinus node
function and atrioventricular node conduction, and prolonged atrial
refractory periods. Sotalol, in particular, has additional antiarrhythmic
properties and prolongs action potential duration through potassium
channel blockade.
• Blockade of the sympathetic nervous system on renin release leads to
reduced aldosterone via the renin angiotensin aldosterone system with
a resultant decrease in blood pressure due to decreased sodium and
water retention.

12. Intrinsic sympathomimetic activity
• Also referred to as intrinsic sympathomimetic effect, this term is used
particularly with beta blockers that can show both agonism and
antagonism at a given beta receptor, depending on the concentration
of the agent (beta blocker) and the concentration of the antagonized
agent (usually an endogenous compound such as norepinephrine.
• Some beta blockers (e.g. oxprenolol, pindolol, penbutolol and
acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These
agents are capable of exerting low level agonist activity at the β-
adrenergic receptor while simultaneously acting as a receptor site
antagonist. These agents, therefore, may be useful in individuals
exhibiting excessive bradycardia with sustained beta blocker therapy.
• Agents with ISA are not used in post-myocardial infarction as they
have not been demonstrated to be beneficial. They may also be less
effective than other beta blockers in the management of angina and
tachyarrhythmia.

13. Effects of beta blockers
• α1-Receptor antagonism
• Some beta blockers (e.g. labetalol and carvedilol) exhibit
mixed antagonism of both β- and α1-adrenergic receptors,
which provides additional arteriolar vasodilating action.
Other effects
• Beta blockers decrease nocturnal melatonin release,
perhaps partly accounting for sleep disturbance caused by
some agents.
• They can also be used to treat glaucoma because they
decrease intraocular pressure by lowering aqueous humor
secretion.

14. Non-selective agents
• Alprenolol
• Bucindolol
• Carteolol
• Carvedilol (has additional α-blocking activity)
• Labetalol (has additional α-blocking activity)
• Nadolol
• Penbutolol(has intrinsic sympathomimetic activity)
• Pindolol (has intrinsic sympathomimetic activity)
• Propranolol
• Sotalol
• Timolol
• Eucommia bark (herb)

15. β1-Selective agents
• Acebutolol (has intrinsic sympathomimetic activity)
• Atenolol
• Betaxolol
• Bisoprolol
• Celiprolol
• Esmolol
• Metoprolol
• Nebivolol

16. β2-Selective agents
• Butaxamine (weak α-adrenergic agonist activity) -
No common clinical applications, but used in
experiments.
• ICI-118,551 Highly selective β2-adrenergic
receptor antagonist - No known clinical
applications, but used in experiments due to its
strong receptor specificity.
β3-Selective agents
• SR 59230A (has additional α-blocking activity) -
Used in experiments

17. Indication differences
• Agents specifically indicated for cardiac arrhythmia
– Esmolol, sotalol, landiolol
• Agents specifically indicated for congestive heart failure
– Bisoprolol, carvedilol, sustained-release metoprolol, nebivolol
• Agents specifically indicated for glaucoma
– Betaxolol, carteolol, levobunolol, metipranolol, timolol
• Agents specifically indicated for myocardial infarction
– Atenolol, metoprolol, propranolol
• Agents specifically indicated for migraine prophylaxis
– Timolol, propranolol
• Propranolol is the only agent indicated for control of tremor,
portal hypertension, and esophageal variceal bleeding, and used
in conjunction with α-blocker therapy in phaeochromocytoma.

18. Pharmacological classification of beta-blockers

19. Effects mediated by beta- receptors

20. Intravenous dosing of beta-blockers

21. Use of beta-blockers in AMI

22. Use of beta-blockers in secondary
prevention after myocardial
infarction

23. Use of beta-blockers in non-ST
segment elevation ACS

24. Use of beta-blockers in
chronic,stable ischemic heart disease

25. Use of beta-blockers in chronic heart failure

26. Practical guidance on using b-adrenergic blockers in
heart failure

27. Practical guidance on using b-adrenergic
blockers in heart failure

28. Use of beta-blockers in arrhythmia
Eur Heart J 2001;1852–923. Eur Heart J 2003;24:1857–97.

29. Use of beta-blockers in prevention of sudden cardiac death
Eur Heart J 2003;24:28–66. Eur Heart J 2001;22:1374–450.
Eur Heart J 2003;24:13–5.

30. Use of beta-blockers in hypertension
Eur. Heart J. 1998;19:1434–1503. Circulation 1999;100:1134–46.
Circulation 2001;104:1577–9. J Hypertens 1999;17:151–8.

31. Use of beta-blockers in aortic dissection
Eur Heart J 2001;22:1642–81.

32. Use of beta-blockers in non-cardiac surgery
Circulation 2002;105:1257–67.

33. Classes of Recommendations

34. Levels of Evidence

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