Beta Adrenergic

Blocking
Agents

Dr.Usha V. Nayak
Professor & Head
Department of Pharmacology
 ★ History
★ Comparative & Distinguishing Features

Session ★ Classification

Overview ★ Pharmacological Properties

★ Adverse Effects & Precautions
★ Therapeutic Uses
★ Specific Agents
HISTORY
Raymond Ahlquist
first identified two
Adrenergic types -
Alpha and Beta
Sir James Black and his
co-workers began to develop
agents that selectively
blocked Beta adrenergic
receptors with the resulting
synthesis of Propranolol
DISTINGUISHING FEATURES
 Pharmacodynamic Features
★ Relative Affinity for Beta receptor
subtypes
★ Ability to block Alpha Adrenergic
Distinguishing
Receptors
Parameters
★ Intrinsic sympathomimetic properties
between Beta
(Agonist actions at Adrenergic
Blocking
receptors)
Agents
★ Membrane stabilising property
★ Ability to cause vasodilation
 Pharmacokinetic Features
Distinguishing ★ Differences in Lipid Solubility
Parameters ★ Other Pharmacokinetic parameters
between Beta
Blocking
Agents
CLASSIFICATION
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

FIRST GENERATION:CLASSICAL NON-SELECTIVE BETA BLOCKERS

SECOND GENERATION : BETA 1 SELECTIVE BETA BLOCKERS

THIRD GENERATION :BETA BLOCKERS WITH ADDITIONAL

ACTIONS

NON-SELECTIVE BETA 1 SELECTIVE ADDITIONAL VASODILATOR PROPERTY

 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

FIRST GENERATION:CLASSICAL NON-SELECTIVE BETA BLOCKERS

WITH NO ADDITIONAL ACTIONS WITH ADDITIONAL ACTIONS

- Nadolol - Propranolol (MSA)* (Highly
lipophilic)
- Timolol - Pindolol (IAA)**
- Penbutolol
* MSA - Membrane stabilising activity ** (IAA)Intrinsic Agonist Activity
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

SECOND GENERATION: BETA 1 SELECTIVE BLOCKERS

WITH NO ADDITIONAL ACTIONS WITH ADDITIONAL ACTIONS

- Atenolol - Acebutolol (MSA)*,(IAA)**
- Bisoprolol - Metoprolol (MSA)*
- Esmolol
* MSA - Membrane stabilising activity ** (IAA)Intrinsic Agonist Activity
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

THIRD GENERATION: BETA BLOCKERS WITH ADDITIONAL ACTIONS

NONSELECTIVE THIRD GENERATION BETA BLOCKERS

DRUG MSA IAA
Carteolol 0 ++
Carvedilol ++ 0
Labetalol ++ ++
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

THIRD GENERATION: BETA BLOCKERS WITH ADDITIONAL ACTIONS

BETA 1 SELECTIVE THIRD GENERATION BETA BLOCKERS

DRUG MSA IAA
Betaxolol + 0
Celiprolol 0 +
Nebivolol 0 0
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

THIRD GENERATION : BETA BLOCKERS WITH PUTATIVE ADDITIONAL

MECHANISMS OF VASODILATION

NITRIC OXIDE BETA 2 RECEPTOR ALPHA 1 RECEPTOR

PRODUCTION AGONISM ANTAGONISM
Bopindolol Bopindolol Bevantolol
Carteolol Carteolol Bucindolol
Celiprolol Celiprolol Carvedilol
Nebivolol Labetalol
Nipradilol Nipradilol
 CLASSIFICATION OF BETA ADRENERGIC BLOCKERS

THIRD GENERATION : BETA BLOCKERS WITH PUTATIVE ADDITIONAL

MECHANISMS OF VASODILATION

Ca++ ENTRY K+ CHANNEL ANTIOXIDANT

BLOCKADE OPENING ACTIVITY
Bevantolol Tilisolol Carvedilol
Betaxolol
Carvedilol
PHARMACOLOGICAL
ACTIONS
 General Properties
★ The pharmacological properties of these compounds can be
explained by the knowledge of Beta receptors activated in
various tissues and the activity of sympathetic nerves that
innervate these tissues
★ Hence Beta receptor blockade has little effect on heart of an
individual at rest , but will have profound effects when
sympathetic/adrenergic control of the heart is dominant , as
during exercise or stress
ACTIONS ON THE
CARDIOVASCULAR
SYSTEM
 ACTIONS ON THE
CARDIOVASCULAR SYSTEM :
CARDIAC EFFECTS
❖ The major effects of these agents are on the cardiovascular
system
❖ The effects in normal subjects and those with cardiovascular
disease such as hypertension and myocardial ischemia are
different
❖ Catecholamines have positive chronotropic, inotropic and
dromotropic effects
❖ Hence, Beta adrenergic antagonists produce negative
chronotropic, inotropic and dromotropic effects
❖ They slow the heart rate and decrease myocardial contractility
and conductivity, if there are sympathetic stimuli to antagonise
❖ Hence their effects are modest at rest, but more pronounced
during exercise or stress
The short term effects of these agents on the cardiovascular

system include

❖ Decrease in cardiac output (Beta 1 inotropic effect blocked)

❖ Increased peripheral resistance ( Beta 2 vascular receptors

blocked and activation of compensatory reflexes causing

activation of alpha receptors)

However, long term use leads to
❖ Peripheral resistance returns to normal or falls in hypertensive
patients
❖ Also, with Beta receptor antagonists that are also Alpha 1
receptor antagonists (Labetalol,Carvedilol and Bucindolol ),
cardiac output is maintained with a greater fall in peripheral
resistance
❖ This is also seen with Beta receptor antagonists that are direct
vasodilators
❖ In the presence of Beta receptor blockade, exercise-induced
increases in heart rate and myocardial contractility are
attenuated
❖ Beta blockers tend to decrease work capacity
❖ Exercise performance may be impaired to a lesser extent by
Beta 1 selective agents than by non-selective agents
❖ Since Beta 2 blockade blunts the increase in blood flow to
skeletal muscle during exercise and also attenuates the
activation of glycogenolysis and lipolysis
 ACTIONS ON THE
CARDIOVASCULAR SYSTEM :
EFFECTS ON CORONARY BLOOD
FLOW
❖ Coronary blood flow increases during exercise or stress to meet the
metabolic demands of the body
❖ By increasing heart rate, contractility,systolic pressure
catecholamines increase myocardial oxygen demand
❖ However, in patients with coronary artery disease, fixed narrowing
of the vessels attenuates the expected increase in flow leading to
myocardial ischemia
❖ Beta receptor antagonists decrease the effects of catecholamines

on the determinants of myocardial Oxygen consumption

❖ The net effect of Beta adrenergic blockers is to improve the

relationship between cardiac Oxygen supply and demand

❖ Exercise tolerance is generally improved in patients with angina

 ACTIONS ON THE
CARDIOVASCULAR SYSTEM :
EFFECTS ON CARDIAC RHYTHM &
AUTOMATICITY
❖ The Beta Receptor Antagonists have significant effects on cardiac

rhythm and automaticity

❖ These drugs reduce the sinus rate

❖ Reduce the rate spontaneous rate of depolarisation of ectopic

pacemakers

❖ Slow conduction in the atria

❖ Increase the functional refractory period of the AV node

❖ High concentrations of some Beta Blockers

(Propranolol,Pindolol,Acebutolol,Metoprolol,Carvedilol,Betaxolol))

possess Membrane Stabilising Activity , this may not be significant

at therapeutic doses
 ACTIONS ON THE
CARDIOVASCULAR SYSTEM
:BLOOD PRESSURE
❖ Beta receptor antagonists do not reduce blood pressure in

individuals with normal blood pressure

❖ In the early stages of use in hypertensives, they may have no effect

or sometimes increase blood pressure due to the initial effects on

peripheral resistance

❖ In the long term ,they decrease the blood pressure which could be

due to multiple effects

❖ Blockade of Beta 1 receptor mediated release of renin from the

juxtaglomerular cells

❖ The antihypertensive are usually more marked in individuals with

elevated levels of plasma renin

❖ A delayed fall in peripheral vascular resistance due to a persistently

reduced cardiac output is also thought to be a factor in decreasing

blood pressure
❖ Some Beta receptor antagonists have additional effects that

contribute to the antihypertensive effect

❖ These drugs all produce peripheral vasodilation due to the possible

following mechanisms

Production of NO Activation of Beta 2 receptors

Blockade of Ca++ entry Blockade of Alpha 1 receptors

Opening of K+ channels Antioxidant activity

These mechanisms contribute to the antihypertensive effects by

❖ Enhancing hypotension

❖ Increasing peripheral blood flow

❖ Decreasing afterload

❖ Production of vasodilation , decreasing preload

( Celiprolol,Nebivolol )
In Pheochromocytoma,

❖ Non-selective beta receptor antagonists inhibit the vasodilation caused by

Isoproterenol

❖ They augment the pressor response to Adrenaline

❖ In these patients, Beta receptor antagonists should be used only after

adequate alpha receptor blockade

❖ This prevents uncompensated Alpha receptor mediated vasoconstriction

caused by Adrenaline produced by the tumour

ACTIONS ON
THE
PULMONARY
SYSTEM
❖ Non-selective Beta blockers like propranolol block Beta 2 receptors

in bronchial smooth muscle

❖ This does not produce much effect in normal individuals

❖ However in patients with bronchial asthma , COPD this blockade

can lead to significant bronchoconstriction

❖ Though Beta 1 selective Beta blockers and those with ISA are lessly

to produce these effects they are better avoided in individuals with

bronchospastic disease

❖ Celiprolol that is both selective for Beta 1 receptor and possesses

ISA may prove safer

METABOLIC
EFFECTS
 EFFECTS ON
CARBOHYDRATE
METABOLISM
❖ Non-selective Beta receptor blockers prevent the perception of

hypoglycemia since palpitations and tremors are not experienced

(hypoglycemia unawareness) due to Beta 1 receptor blockade

❖ These agents prevent Beta 2 receptor mediated catecholamine induced

glycogenolysis and mobilisation of glucose during hypoglycemia

(hypoglycemia unresponsiveness)

❖ Hence, Beta 1 receptor selective antagonists are preferred in diabetes

mellitus
 EFFECTS ON
LIPID METABOLISM
❖ Beta Antagonists decrease release of (Free Fatty Acids) FFA from

adipose tissue

❖ Long term use increases LDL cholesterol and triglycerides and

decreases HDL cholesterol

❖ However, selective Beta receptor blockers like celiprolol, carvedilol and

carteolol may improve the lipid profile

 EFFECTS ON
INTRAOCULAR
PRESSURE
❖ Beta Antagonists used topically or orally cause a reduction in IOP due to

a decrease in secretion of aqueous humour

OTHER EFFECTS
❖ Beta Antagonists block catecholamine induced tremor

❖ Propranolol is an approved agent for the treatment of essential tremor

 THERAPEUTIC
IMPLICATIONS OF
SELECTIVE ACTIONS /
ADDITIONAL PROPERTIES
 SELECTIVE BETA 1
RECEPTOR BLOCKADE
❖ Certain Beta Antagonists that show selectivity for blockade of Beta 1

receptors as compared to Beta 2 receptors

❖ Such selectivity is observed at therapeutic doses but may be lost at

higher doses

❖ block catecholamine induced tremor

❖ Propranolol is an approved agent for the treatment of essential tremor

MEMBRANE STABILISING
PROPERTY
❖ Beta Antagonists used topically or orally cause a reduction in IOP due to

a decrease in secretion of aqueous humour

INTRINSIC AGONIST
ACTIVITY
PHARMACOKINETICS
❖ Most Beta receptor blockers are completely and rapidly absorbed

❖ Some of these drugs like propranolol and metoprolol are rapidly

metabolised by the liver (first pass metabolism)

❖ This the oral doses for such agents are high and there is marked

inter-individual variation in plasma levels

❖ Those beta blockers that are largely excreted by the kidney like atenolol,

nadolol tend to accumulate in presence of renal damage

❖ Pindolol,acebutolol,atenolol and timolol are excreted by both routes

❖ Plasma half life of Beta receptor blockers that mainly metabolised by the

liver are short (2-3 hrs), while those which are excreted unchanged have

longer half lives (8-10 hrs)

❖ Duration of effect is dependent on presence of hepatic,renal damage and

by production of active metabolites

❖ The active metabolite 4-hydroxy propranolol makes twice daily dosage

schedule adequate
❖ Their plasma half lives do not correlate with duration of therapeutic effects

❖ This is because Beta receptor blockers may show zero order elimination at

higher doses

❖ Hence, most beta blockers can be orally administered at much longer

intervals than their plasma half lives

ADVERSE EFFECTS &
PRECAUTIONS
CARDIOVASCULAR ADVERSE
EFFECTS
❖ Beta receptor blockers may cause or exacerbate heart failure

❖ Drugs with IAA may prove safer in this setting

❖ Bradycardia is a normal response to these drugs, but in patients with

partial/complete AV conduction defects, Beta blockers can produce

life-threatening arrhythmias

❖ Patients often complain of cold extremities on long term use

❖ Symptoms of peripheral vascular disease may worsen and Raynaud’s

phenomenon may develop

❖ Abrupt discontinuation of Beta blockers after long term use can exacerbate

angina

❖ This occurs because long term use of these antagonists leads to

upregulation of the beta receptors and increased sensitivity to Beta

receptor agonists

❖ Hence gradual tapering is advised prior to discontinuation

❖ Drugs with IAA like Pindolol are safer to discontinue

PULMONARY ADVERSE
EFFECTS
❖ Blockade of Beta 2 receptors in bronchial smooth muscle may produce life

threatening increase in airway resistance in individuals with bronchospastic

disease

❖ Though drugs with IAA (Agonists at beta 2 receptor) may be safer, these

drugs are best avoided in individuals with obstructive airway disease

ADVERSE EFFECTS ON THE
C.N.S.
❖ Beta receptor blockers with higher lipophilicity are more likely to produce

both actions and adverse effect in the CNS

❖ Adverse effects on the CNS include fatigue, sleep disturbances (insomnia

and nightmares) and depression

METABOLIC ADVERSE
EFFECTS
❖ Blunting of recognition of hypoglycemia by patients (Both non-selective and

selective blockers)

❖ Delay of recovery from insulin-induced hypoglycemia ( Non-selective

blockers)

❖ These drugs should be used in caution with individuals prone to episodes

of hypoglycemia

❖ Long term use can affect lipid profile adversely

OTHER ADVERSE EFFECTS
❖ Allergic reactions

❖ Sexual dysfunction

❖ Thrombocytopenia
 DRUG
INTERACTIONS
 DRUGS THAT DECREASE HEPATIC BLOOD FLOW AND INCREASE
BIOAVAILABILITY OF BETA ANTAGONISTS

❖ Cimetidine

❖ Hydralazine
DRUGS THAT DECREASE ABSORPTION OF BETA ANTAGONISTS

❖ Aluminium salts

❖ Cholestyramine

❖ Colestipol
DRUGS / AGENTS THAT INDUCE HEPATIC BIOTRANSFORMATION OF BETA
ANTAGONISTS

❖ Phenytoin

❖ Rifampicin

❖ Phenobarbital

❖ Smoking
DRUGS THAT DECREASE / INCREASE ACTIONS OF BETA ANTAGONISTS

❖ NSAIDs that cause sodium retention can attenuate the

antihypertensive action of Beta blockers

❖ Drugs that produce myocardial depressant actions can

produce dangerous cardiac slowing when used with Beta

blocking drugs ( Verapamil, Amiodarone)

CONTRAINDICATIONS
❖ Diabetes Mellitus

❖ Bronchial asthma, COPD

❖ Peripheral Vascular Disease

❖ AV conduction blocks
THERAPEUTIC USES
CLINICAL SELECTION OF A
BETA RECEPTOR
ANTAGONIST
The various beta receptor antagonists that are used for the

treatment of angina and hypertension appear to have similar

efficacies

Selection of the appropriate agent for an individual patient is made

based on the following factors

❖ Pharmacokinetic and pharmacodynamic differences among

these drugs
❖ Cost

❖ Concurrent medical problems

❖ Beta 1 selective agents are preferred for individuals having

Bronchial asthma, COPD, diabetes mellitus,peripheral vascular

disease or Raynaud’s phenomenon

❖ In patients with bradycardia, drugs with intrinsic

sympathomimetic activity may be preferred

❖ Third generation agents , with additional actions that blocklike

alpha 1 receptors, stimulate beta 2 receptors, enhance NO

production , open K+ channels or possess antioxidant

properties may offer therapeutic advantages

CARDIOVASCULAR USES
❖ Hypertension

❖ Ischemic heart disease

❖ Cardiac arrhythmias

❖ Hypertrophic Obstructive Cardiomyopathy

❖ Dissecting aortic aneurysm

CARDIOVASCULAR USES :
HYPERTENSION
❖ The preferred beta blockers for hypertension are beta 1 receptor blockers with
IAA like atenolol, metoprolol, bisoprolol
❖ Beta receptor antagonists do not reduce blood pressure in individuals with
normal blood pressure
❖ In the early stages of use in hypertension, they may have no effect or
sometimes increase blood pressure due to the initial effects on peripheral
resistance
❖ In the long term ,they decrease the blood pressure which could be due to
multiple effects
❖ Blockade of Beta 1 receptor mediated release of renin from the

juxtaglomerular cells

❖ The antihypertensive are usually more marked in individuals with

elevated levels of plasma renin

❖ A delayed fall in peripheral vascular resistance due to a persistently

reduced cardiac output is also thought to be a factor in decreasing

blood pressure
❖ Some Beta receptor antagonists have additional effects that

contribute to the antihypertensive effect

❖ These drugs all produce peripheral vasodilation due to the possible

following mechanisms

Production of NO Activation of Beta 2 receptors

Blockade of Ca++ entry Blockade of Alpha 1 receptors

Opening of K+ channels Antioxidant activity

These mechanisms contribute to the antihypertensive effects by

❖ Enhancing hypotension

❖ Increasing peripheral blood flow

❖ Decreasing afterload

❖ Production of vasodilation , decreasing preload

( Celiprolol,Nebivolol )
 CARDIOVASCULAR USES :
ISCHEMIC HEART DISEASE -
ANGINA
❖ Reduction in the severity and frequency of attacks of exertional angina

❖ They also improve survival in patients of MI

❖ Hence recommended as first line treatment of patients with stable and

unstable angina/ACS

❖ Beta blockers are not useful for vasospastic angina and may worsen the

condition(unopposed alpha 1 mediated coronary vasoconstriction)

❖ These agents produce a fall in myocardial oxygen consumption at

rest and during exertion

❖ This decrease in oxygen consumption is due to a negative

chronotropic effect ,negative inotropic effect and a reduction

arterial blood pressure during exercise

❖ A decrease in heart rate prolongs the time for myocardial perfusion

during diastole
❖ The phenomenon of "coronary steal," i.e., the shunting of blood

from ischemic to normally perfused areas of myocardium, has

been described as an effect of the administration of several

vasodilating agents

❖ Administration of a coronary constrictor that reduced blood flow

in the normal myocardium can increase the flow to the ischemic

areas, thus producing a "reverse coronary steal”

❖ Beta blockers can increase blood flow towards ischemic regions by

increasing coronary collateral resistance

❖ This prevents blood from being shunted away from the ischemic

myocardium during maximal coronary dilation (reverse steal)

❖ Beta blockers used for the treatment of angina are beta 1 selective

and without intrinsic sympathomimetic activity (Atenolol,

metoprolol,bisoprolol)
 CARDIOVASCULAR USES :
ISCHEMIC HEART DISEASE -
MYOCARDIAL INFARCTION
❖ Beta blockers when used early , can reduce infarct size

(myocardial salvage)

❖ Reduce complications like arrhythmia (esmolol IV)

❖ Decrease mortality

❖ Reduce risk of CHF

❖ Reduce the risk of reinfarction

CARDIOVASCULAR USES :
CARDIAC ARRHYTHMIA
❖ Beta blockers belong to Class II of the antiarrhythmic drugs

❖ They mainly suppress adrenergic mediated ectopic activity

❖ Propranolol is useful in treating sinus tachycardia,Atrial and

nodal extrasystoles.

❖ It can be used for prevention of recurrences of PSVT, which has

been treated with Adenosine or Verapamil

❖ Propranolol can be used to control ventricular rate in patients

with atrial fibrillation and atrial flutter

❖ Esmolol has a rapid onset with a short duration of action

❖ It is used for the emergency control of ventricular rate in Atrial

fibrillation and atrial flutter

❖ It can terminate supraventricular tachycardia

❖ It is used for arrhythmias associated with anesthesia

CARDIOVASCULAR USES :
DISSECTING AORTIC
ANEURYSM
❖ Reduction in the force of myocardial contraction (negative

inotropic action)

❖ Decrease in the rate of development of the cardiac contractile

force

❖ Chronic treatment with Beta antagonists slows the progression of

aortic dilation and its complications

CARDIOVASCULAR USES :
HOCM
❖ Reduction in heart rate leading to increased diastolic filling time
❖ The sympatholytic effects of beta-blockade cause decreased
inotropy, and possibly a reduction in ventricular stiffness
❖ Beta blockers reduce physiologic outflow obstruction, angina,
dyspnea on exertion, and the risk of ventricular arrhythmias in
this condition
❖ Propranolol , nadolol and bisoprolol have shown good efficacy
❖ Non-vasodilating beta-blockers should be favored in these
patients with to avoid exacerbating the outflow gradient
❖ Hypertension

❖ Ischemic heart disease

❖ Cardiac arrhythmias

❖ Hypertrophic Obstructive Cardiomyopathy

❖ Dissecting aortic aneurysm

NON CARDIOVASCULAR
USES : ENDOCRINE
NON CARDIOVASCULAR
USES : ENDOCRINE -
HYPERTHYROIDISM
❖ Many of the signs and symptoms of hyperthyroidism resemble

that of increased sympathetic nervous system activity

❖ Beta blockers control many of the cardiovascular

manifestations of hyperthyroidism

❖ In addition , propranolol inhibits the peripheral conversion of

thyroxine to triiodothyronine , an effect that may be

independent of beta receptor blocking activity

NON CARDIOVASCULAR
USES : ENDOCRINE -
PHEOCHROMOCYTOMA
❖ Tumour of the adrenal gland, where large amounts of

catecholamines are secreted into the circulation

❖ This causes hypertension which is severe and episodic

❖ Usual treatment is surgical

❖ In inoperable and malignant pheochromocytomas, a

conservative medical approach is used

❖ An important aspect of BP control in pheochromocytoma is initial

treatment with α-blockers and after achieving adequate α-blockade,

the patient can be treated with β-blockers to achieve heart rate control

❖ Beta receptor antagonists are also used , but only following the use of

an Alpha adrenergic antagonist

❖ This prevents uncompensated Alpha receptor mediated

vasoconstriction caused by Adrenaline produced by the tumour

NON CARDIOVASCULAR
USES : NON-ENDOCRINE
NON CARDIOVASCULAR
USES : GLAUCOMA
❖ After Prostaglandin analogs, the Beta receptor antagonists are

currently the next most common topical treatment

❖ These include the topical non selective Beta receptor blockers

timolol,levobunolol,metipranolol and carteolol.

❖ Betaxolol a selective Beta 1 receptor antagonist is available for

ophthalmic use but is less efficacious then the non-selective , since

the Beta receptors in the eye are mostly of the Beta 2 subtype
❖ In the eye the target tissues are the ciliary body epithelium and blood

vessels where Beta 2 receptors are predominant in number

❖ Beta blockade leads to decreased aqueous production and fall in IOT

❖ Beta blockade is thought to blunt the adrenergic activation of the cyclic

AMP-PKA pathway which is required for the production of aqueous

humour

❖ They produce no effects on size of the pupil or hamper vision

NON CARDIOVASCULAR
USES : MIGRAINE
❖ Propranolol, timolol and metoprolol are effective for the prophylaxis

of migraine

❖ THey are not useful for treatment for acute attacks of migraine

❖ Agents with ISA are not preferred as given the vascular basis of this

type of headache, the vasodilation produced is not desirable

NON CARDIOVASCULAR
USES :
ANXIETY,STAGE-FRIGHT
❖ Propranolol and other Beta blockers are effective in controlling acute

panic symptoms in individuals who are required to perform in public or

in other anxiety-provoking situations

❖ Tachycardia, muscle tremors and other manifestations of increased

sympathetic activity are reduced

NON CARDIOVASCULAR
USES : ALCOHOL
WITHDRAWAL
❖ Benzodiazepines are the preferred medications used in the treatment
of alcohol withdrawal syndrome
❖ Beta blockers may be helpful adjuncts to benzodiazepines in the
treatment of alcohol withdrawal syndrome ,however, these
medications should not be used as monotherapy.
❖ Adjunctive treatment with a beta blocker should be considered in
patients with coronary artery disease, who may not tolerate the strain
that alcohol withdrawal can place on the cardiovascular system.
 NON CARDIOVASCULAR
USES : ESSENTIAL TREMOR
❖ It is thought that propranolol causes blockade of peripheral noncardiac

beta-2 receptors located in the muscle spindles

❖ Less lipophilic beta blockers are also effective in suppressing ET

further supporting a peripheral target of action

❖ In response to this blockade, epinephrine upregulates the sensitivity of

muscle spindles, leading to increased rhythmic afferent activity and,

higher synchronization of afferent signals

NON CARDIOVASCULAR
USES : PORTAL
HYPERTENSION
❖ Propranolol and nadolol are efficacious in the primary prevention of

variceal bleeding in patients with portal hypertension caused by liver

cirrhosis

❖ By blocking Beta1 receptors and reducing cardiac output

❖ By blocking Beta 2 receptors, producing splanchnic vasoconstriction

and reducing portal flow. Consequently, they reduce portal pressure.

INDIVIDUAL AGENTS
AGENTS THAT BLOCK BOTH
ALPHA & BETA ADRENERGIC
RECEPTORS
LABETALOL
❖ It is a Third generation non-selective beta receptor antagonist

❖ It exhibits different relative affinities for the adrenergic receptors ,

hence its effects are complex, its actions include

❖ Non selective beta 1 and beta 2 receptor blockade

❖ Partial agonistic activity at beta 2 receptor

❖ Selective blockade of alpha 1 receptor

❖ Inhibition of neuronal uptake of Noradrenaline

Pharmacokinetics

❖ The drug undergoes extensive first pass metabolism

❖ It has a t1/2 of 4 hours and administered b.i.d.

Adverse reactions
❖ In the CVS are similar to those of other beta blockers , in addition it
can produce postural hypotension, fluid retention
❖ It can causes GI disturbances and dryness of mouth
❖ Nervousness
❖ Sexual dysfunction
❖ Muscle cramps
❖ Depression
❖ Accumulates in melanin containing tissues, hence a periodic eye
examination is recommended
Therapeutic Uses/Indications

❖ Hypertensive emergencies as an IV infusion

The concurrent alpha 1 blockade causes a rapid onset

CARVEDILOL
❖ It is a Third generation non-selective beta receptor antagonist

❖ Non selective beta 1 and beta 2 receptor blockade

❖ Selective blockade of alpha 1 receptor

❖ Antioxidant activity

❖ Anti-inflammatory activity

❖ Membrane Stabilising Activity

❖ Blockade of Calcium entry

Pharmacokinetics

❖ The drug is rapidly absorbed on oral administration

❖ Highly plasma protein bound

❖ It has an elimination t1/2 of 7-10 hours

Adverse reactions
❖ Orthostatic hypotension and dizziness due to alpha receptor
blockade
❖ Initial exacerbation of heart failure like other beta blockers
❖ Renal failure
Therapeutic Uses/Indications

❖ Hypertension

❖ Heart failure (reduces workload on the heart, decreases lipid

peroxidation and vascular wall thickening)

❖ Ischemic heart disease

BISOPROLOL,NEBIVOLOL
❖ Bisoprolol is a Second generation selective beta 1 receptor antagonist

❖ Nebivolol is a third generation selective beta 1 receptor antagonist

❖ They exhibit NO-mediated vasodilator properties

❖ They are used in Hypertension, CHF and improve left ventricular

function
THANK YOU