Beta adrenergic receptor blockers

1.Review the effects of stimulation and blockade of beta receptors

1.Adrenoreceptors
Location

Postsynaptic,Excitatory

Agonist

Epinephrine,Norepinephrine,Isoprenaline,Dobutamine

Antagonist

Propanolol,Atenolol
Effects of beta receptor block

Heart

Negative inotropic Decrease in FOC

Negative chronotropic Decrease in HR,COP and BP
Decrease in AV conduction,Decrease automatically
Decrease in oxygen consumption of heart

Other actions

Decrease in secretion of Renin

Decrease in glycogenolysis,decrease in gluconeogenesis which
results in delayed recovery from hypoglycemia

2.Adrenoreceptors
Location

Postsynaptic,Inhibitory

Agonist

Epinephrine,Isoprenaline,Salbutamol

Antagonist

Butoxamine
Effects of beta receptor block

Eye

Decrease in IOT by decrease in aqueous humor formation

Lungs

Bronchospasm(in asthmatics)

BV of skeletal
muscle

Unopposed alpha action

Vasoconstriction , Increase in PR

Uterus

No significant effect

2. Classify beta blockers with suitable example. To discuss

the pharmacology of various beta blockers.
Classification of -blockers

Nonselective -blockers

Propranolol (LA) (high lipid solubility)

Oxprenolol (ISA), Acebutolol (ISA), Timolol

Nonselective blockers with 1 blockade

Carvedilol

Labetolol (ISA + LA)

Selective 1-blockers

Metoprolol, Atenolol, Esmolol (short acting)

Selective 1-blocker with 2 agonist activity

Celiprolol

Cardiovascular effects of Beta Blockers

Heart:
FOC, HR, O2 consumption
AV conduction, Automaticity
Pure antagonists produce

At rest little or no change in HR, COP & BP

During exercise or excitement minimise or reduce the effect on CV
system (HR, COP & BP).

-blockers with ISA - HR at rest but during exercise.

-blockers Protect against arrhythmias.

Coronary vasoconstriction occurs. But, overall, ischaemia of
myocardium decreases as oxygen requirement is decreased. Increase

exercise tolerance. Hence, useful in angina pectoris & for

cardioprotective effect following MI.

Peripheral resistance increases.

In Hypertension - there is a gradual fall in BP over a period of few days

due to

in COP

in renin release from kidney

Central sympathetic activity

Advantages: No postural hypotension

Pulmonary effects of Beta Blockers

Healthy people only slight increase in bronchial resistance without

any effect on pulmonary function.

Asthmatics nonselective betablockers can cause life threatening

bronchoconstriction.
Beta1 selective (cardioselective) blockers are less likely to cause
respiratory problems in asthmatics. But, at higher doses even selective
beta blockers may cause bronchoconstriction. so caution is to be
exercised even with cardioselective beta blockers.
Renal: decrease renal blood flow (RBF) & may cause sodium and water
retention.
Eye: decrease tension by decreasing the production of aqueous humor.
Timolol is used topically in glaucoma treatment as it does not have
local anaesthetic action.
Advantages over parasympathomimetics in the treatment of
glaucoma: No significant action on pupil or accommodation.
Diabetes mellitus:

Mask symptoms of hypoglycemia such as palpitation, tremor, sweating

etc.

Non-selective Beta blockers delay recovery from hypoglycemia in

insulin dependent diabetics by inhibiting compensatory
neoglucogenesis & glycogenolysis.

Caution the patient about possible hypoglycemia & delayed recovery

from it. Cardioselective beta blockers are preferable if required.
Plasma lipids: May increase LDL & decrease HDL.

Absorption: orally absorbed.

Bioavailability: most of them, especially propranolol undergo extensive
first pass metabolism & have low bioavailability.

Hence, parenteral doses are relatively lower than oral doses.

Liver disease decreases first pass metabolism

Atenolol is longer acting.
Esmolol is fast & short acting.
Propranolol crosses BBB.
Adverse effect
CVS: Bradycardia, Heart block,
Congestive heart failure may be by removing the sympathetic drive
required to maintain COP. (Drugs with ISA may overcome this ADR).

CNS: sedation, fatigue, depression, bad dreams (propranolol cross into

CNS), sleep alterations

Sudden withdrawal can lead to rebound sensitivity to sympathetic

stimulation resulting in angina or MI.
ADR related to 2 blockade (1 selective drugs may be preferable)
RS: In asthmatics an attack may be precipitated by nonselective drugs.
Respiratory distress is seen in chronic bronchitis and emphysema.

Diabetes mellitus: Severe hypoglycemia & delayed recovery from

hypoglycemia.

Cold extremities
Contraindications: Bradycardia, unstable CHF, Bronchial asthma ,
depression
Uses

Hypertension Mild hypertension,

Synergistic with other antihypertensives

Ishaemic heart disease

Angina pectoris
Myocardial infarction

To limit the area of damage

To prevent cardiac rupture

In secondary prophylaxis by preventing arrhythmias & recurrent

infarction.

Clinically stable Congestive Heart Failure (CHF):

treatment with certain blockers with vasodilatory (1 block) action

eg. Carvedilol or those with ISA eg. Acebutolol to maintain a certain
degree of sympathetic drive to the heart prolongs survival .

Arrhythmias:

Ischaemia induced arrhythmias

Atrial arrhythmias (by increasing AV block)

Glaucoma - aqueous humor formation Timolol is used topically.

Why not propranolol?

Prophylaxis of Migraine

Benign essential tremor - tremor of peripheral origin (by 2- adrenergic

receptor block in skeletal muscle)

Hyperthyroidism immediate relief from signs & symptoms caused by

receptor over activity.

Anxiety states to control peripheral somatic symptoms of

sympathetic over activity such as palpitation & tremor
Prevention of stage fright
receptor blockers
Propranolol: Nonselective -blocker with local anaesthetic activity.
Undergoes extensive first pass metabolism. Crosses into CNS. ADR due
to 2 blockade are present.
Metoprolol: cardioselective beta blocker.
Atenolol: cardioselective, long acting beta blocker.
Esmolol: cardioselective and very short acting beta blocker
Mixed alpha and receptor blockers
Labetalol & Carvedilol

Competitive antagonist at both & -receptors

1 = 2 blockade > 1 blockade

Uses

Pheochromocytoma
hypertensive emergencies

1 blockade promotes vasodilation & hypotension

1 blockade reduces reflex & direct tachycardia.