Beta blockers

By Dr. Bharath R. Kuna

Department of pharmacology
MGM Medical College, Kamothe
BETA RECEPTORS
 BETA BLOCKERS
Beta blockers competitively block the beta-mediated actions of
catecholamines and other adrenergic agonists.

Also called :
1.Beta adrenergic antagonists.
2. Beta receptor blockers.
3. Sympatholytic agents.

Drugs in this group are usually classified into subgroups on

the basis of β1 selectivity, partial agonist activity, local
anesthetic action, and lipid solubility
CLASSIFICATION
 Beta blockers with special effect
1)Beta blockers with membrane stabilizing action =
local anesthetic effect OR ( quinidine like action )
This action causes decreases in action potential and
tissue excitability (through decrease sodium rash into
cells with subsequent reduces depolarization)
e.g.: propranolol
This feature is useful in treatment of arrhythmia
2) Beta blockers with partial agonist activity :
e.g. Pindolol and acebutolol = in overdose not cause
bradycardia
 Continue
3) Beta blockers with very short duration of action:
Esmolol :10 min . It is used IV infusion for 30min in surgical
operation to treat arrhythmia
4) Beta blockers with alpha and beta Blocking activity :
e.g. Labetalol Has direct vasodilator effect and also can be
used for RX pheochromocytoma
5) Beta blockers with anti-oxidant action ;
-Free radical (reactive oxygen species ) like O , OH causes
damage the tissue and promote aging process of cells , so
this drug protect the cells from these free radicals.
e.g. Carvedilol
6) Beta blockers with NO releasing activity
e.g. Nebivolol : the most selective drug
 Pharmacokinetics
-All beta blockers well absorbed from GIT.
-They undergo first pass effect in liver { decreases
their levels} which may account 90% in lipid soluble
types (i.e 10% reach to systemic circulation)
-Also beta blockers can be classified into
1)Lipophilic BB ( Propranolol) : good absorption and
have CNS effect but undergo extensive first pass
effect so shorter duration of action
2)Hydrophilic ( Atenolol ) less absorption and less
CNS effect ; less first pass effect , so it had long
duration of action.
PHARMACOLOGICAL ACTIONS
RESPIRATORY SYSTEM
EYE
contain B1 &B2 in ciliary body that mediate production of aqueous
humor , so beta blockers reduces IOP

CNS : In Brain, NE responsible for alertness and act as

antidepressant , so lipid soluble BB decreases NE that leads to
sedation , apathy and depression, and night mares and vivid dreams

SKELETAL MUSCLES: On chronic use, B2 blockers may skeletal

muscle weakness & tiredness due to blockade of B2-Receptors of the
skeletal muscle and blood vessels supplying it.
Also reduces stress induced tremor.
DOC in hyperthyroidism
 Uses of B blockers
1) HT: by 5 mechanism
- All BB are effective in treatment of HT.
2) IHD :
A. Classic angina:
Physiology :
The heart receives its own supply of blood from the coronary
arteries.
The two major coronary arteries branch off from the aorta
near the point where the aorta and the left ventricle meet.
These arteries and their branches supply all parts of the heart
muscle with blood.
All body arteries fill during systole with exception
coronary arteries fill during diastole.
 Role of BB in classic angina
In classical angina there is atherosclerosis {due to high lipid diet } that
occur in these arteries causes narrowing lumen with subsequent
reduced blood flow so this patient suffer chest pain esp. during
exercise .
Using BB in this patient is very useful because:
1)BB reduces cardiac work
2)BB reduces O2 demand
3)BB causes bradycardia so it prolongs time of diastole ( give better
chance to coronary artery to fill blood) {increases diastolic filling time}
4)BB blocks B2 in coronary arteries so prevent vasodilatation in
normal arteries which steals blood from atherosclerotic artery
( prevent coronary steal) so this BB causes redistribution of blood .
5)BB normally myocardium take energy from oxidation FFA 60% and
40% oxidation of glucose ; fatty acid oxidation required high O2 , BB
causes metabolic switch to glucose away from FFA oxidation so less
oxygen is required
A Treatment of angina
 Question ?
Why it is unsuitable to give vasodilator in classic
angina?
Because in this patient has both normal and
atherosclerotic artery , so when we give him a
vasodilator this will act (dilates) only on normal
arteries that receive full blood while atherosclerotic
one will be deprive from blood thus more ischemia
will be { this condition is called coronary steal} .
B
Beta blockers and heart failure
Some, but not all, β-blockers can reduce morbidity and
. mortality when used properly in heart failure
Labetalol, Carvedilol, and metoprolol succinate appear
.to be beneficial in this application

Metoprolol succinate vs metoprolol tartrate

.
 4) Treatment of Mitral valve prolapse
Also called MVP, is a condition in which the two valve
flaps of the mitral valve don't close smoothly or evenly,
but bulge (prolapse) upward into the left atrium.
When the heart pumps , part of one or both flaps
collapse backward into the left atrium.
In some cases, the prolapsed valve lets a small amount
of blood leak backward through the valve, called
regurgitation, which may cause a heart murmur
•Beta blockers. prevent irregular
heartbeats by making heart beat more
slowly and with less force, which
reduces blood pressure.
5) Supra ventricular tachycardia (SVT)
It is origin in atria , send high amplitude impulses
So that BB causes :
a. decrease AV node conduction so decreases HR ,
b. BB prolongs refractory period { i.e. make SA node
response slow to stimulation= decrease firing rate}
c. some BB like propranolol has membrane
stabilizing effect that mean has the ability to reduce
depolarization (decreases Na inward)
d. Some patient with SVT caused by hyperthyroidism
so that thyroxine stimulate B1 causing tachycardia
and SVT ; BB inhibit this effect.
6) Hypertrophic obstructive cardiomyopathy:
-cardiac anomaly
-incidence 1 per 1000
-Occur in pediatric group
-Feature : thickening of inter-ventricular septum ( normal thickness is
max. 12mm ) while in this condition may reaches 17mm , by this
defect the aorta will be affected ( physically narrowed ) so by effort
situation contraction is increased however blood ejection is
interrupted by this narrow lumen .
-Symptoms : may be asymptomatic or many pediatric loss the ability
to physical performance and may be associated with cyanosis
-Prognosis : is not treated may causes sudden death especially in
athletes
Treatment : BB because it produce bradycardia so blood ejection
.through aorta not congested
.It is also known as a leading cause of sudden cardiac death in young athletes
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some
.suggest routinely screening certain populations for this disease
Non-cardiac uses of beta blockers
1) Hyperthyroidism
In hyperthyroidism , T3 & T4 stimulates cardiac B1
(causing palpitation ) and B2 in periphery causing
(tremor) and central effect causing sleep
disorders.
Role of BB :
1) Reduces sympathetic over activity
2) BB decrease peripheral conversion of T4 to active
form T3
Note : we prefer to use nonselective type in
hyperthyroidism , why?
 2

Timolol and betaxolol most commonly used eye drops in

the treatment of glaucoma , why ? Because they are most
lipophilic beta blockers
3

4
4) Esophageal varicocele
Esophageal varices are abnormal, enlarged veins in
esophagus.
This condition occurs most often in people with
serious liver diseases.
Esophageal varices develop when normal blood
flow to the liver is blocked by a clot or scar tissue
in the liver , so blood flows into smaller blood
vessels that aren't designed to carry large volumes
of blood. The vessels can leak blood or even
rupture, causing life-threatening bleeding.
Normally Portal vein take about 1/3 of blood from
GIT into liver ; patient with liver cirrhosis blood
cannot push through portal vein so blood shunt to
small blood vessels that can not tolerates this high
quantity of blood so this may causes tortuosity that
 Causes of esophageal varices include:
•Severe liver scarring (cirrhosis).
•Blood clot (thrombosis).
•Parasitic infection. Schistosomiasis is a parasitic infection.
The parasite can damage the liver, as well as the lungs,
intestine, bladder and other organs.
Treatment of esophageal varicocele
Rx
liver transplantation and can be
symptomatically improved by B blockers
that reduces COP so intestinal blood will
decrease so that reduce blood shunt and
congestion , also BB blocks B2 in intestine
so that useful vasoconstriction will be occur
decreasing intestinal blood flow
Migraine prophylaxis
Propranolol or Metoprolol
Mechanism not understood
It has been found to be effective as preventive
medications , reducing the frequency of
.migraines
.
6
7)sweat glands
:we have 2 types of sweat glands
Eccrine { 99% water & 1% NaCl } )1

It is present in soles and palms and all over the

body except the vermilion of lips & nail beds
It is stimulated by Ach and blocked by BOTOX

Apocrine Sweat gland: It is more viscous that )2

encourage bacterial growth
It is located in frontal , armpit , groin , scalp
It is stimulated by adrenaline so it is blocked by
B Blockers
ADR
 Diabetic complication :
a. In DM : diabetic angiopathy occur (less blood flow ) , BB
increases peripheral ischemia through blocking B2 receptor
so aggravates this condition
b. in DM , beta blockers mask symptoms of hypoglycemia
such as tremor , sweating , and tachycardia
•In DM , Beta Blockers block glycogenolysis that mediated
through B2 stimulation in liver during hypoglycemia caused
by drugs or to insulin therapy .
Absolute Contraindication of b- Blockers
1) Bronchial asthma
2) Heart block
3) Prinzmetal's angina { in some population inherits
in coronary arty alpha receptors more than B2 ;
in those patient during sympathetic stimulation
vasoconstriction occur so this type called
vasospastic or alpha mediated angina } using BB
in those patient is dangerous because it block the
little B2 in coronary artery leading to complete
vasoconstriction)
4) Sudden withdrawals of BB ( may causes angina)
Relative contraindication of BB (caution )
1) Acute heart failure
2) Raynaud's phenomena and claudication.
3) DM type 1
4) Athlete patient
 Clinical applications of β blockers
: Hypertension)1
.Atenolol, nebivolol and metoprolol
: Angina pectoris)2
Propranolol, metoprolol
Prophylaxis against MI )3
Propranolol, metoprolol
, Arrhythmia : SVT and vent tachycardia)4
Propranolol, metoprolol ,esmolol
ventricular ectopic beat , esp if precipitated by )5
catecholamine
Bisoprolol , Propranolol, metoprolol
,In cirrhosis )6
Propranolol may decrease the incidence of bleeding
esophageal varices
:Heart failure )7
Carvedilol, labetetol, metoprolol succinate
Hypertrophic cardiomyopathy: )8
Propranolol
Familial tremor, other types of tremor, "stage fright" )9
Propranolol

: Thyroid storm and thyrotoxicosis )10

Propranolol, esmolol

Treatment of anxiety )11

Metoprolol ,Propranolol
Prophylaxis of migraine )12
Propranolol
Glaucoma :Timolol (topical) )13
Timolol , betaxolol
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