3. 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
6. 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
7.
8. 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
9. 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.
12. 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
13. 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.
14. 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
16. 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} .
20. 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
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21.
22. 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,
23. 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.
24. 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.
25. 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?
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27.
28. Timolol and betaxolol most commonly used eye drops in
the treatment of glaucoma , why ? Because they are most
lipophilic beta blockers
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31. 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 may
rapture due to stress or cough or even heavy meals leading
hematemesis
32. 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
33. Migraine prophylaxis
Propranolol or Metoprolol
Mechanism not understood
It has been found to be effective as preventive
medications , reducing the frequency of
migraines.
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35. 7)sweat glands
we have 2 types of sweat glands:
1) Eccrine { 99% water & 1% NaCl }
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
2) Apocrine Sweat gland: It is more viscous that
encourage bacterial growth
It is located in frontal , armpit , groin , scalp
It is stimulated by adrenaline so it is blocked by
B Blockers
37. 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
c. In DM , Beta Blockers block glycogenolysis that
mediated through B2 stimulation in liver during
hypoglycemia caused by drugs or to insulin therapy .
38. 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)
39. Relative contraindication of BB (caution )
1) Acute heart failure
2) Raynaud's phenomena and claudication.
3) DM type 1
4) Athlete patient
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41.
42. Clinical applications of β blockers
1)Hypertension :
Atenolol, nebivolol and metoprolol.
2)Angina pectoris :
Propranolol, metoprolol
3) Prophylaxis against MI
Propranolol, metoprolol
4)Arrhythmia : SVT and vent tachycardia ,
Propranolol, metoprolol ,esmolol
5) ventricular ectopic beat , esp if precipitated by
catecholamine
Bisoprolol , Propranolol, metoprolol
6) In cirrhosis,
Propranolol may decrease the incidence of bleeding
esophageal varices
7) Heart failure:
Carvedilol, labetetol, metoprolol succinate
43. 8)Hypertrophic cardiomyopathy:
Propranolol
9)Familial tremor, other types of tremor, "stage fright"
Propranolol
10)Thyroid storm and thyrotoxicosis :
Propranolol, esmolol
11) Treatment of anxiety
Metoprolol ,Propranolol
12) Prophylaxis of migraine
Propranolol
13) Glaucoma :Timolol (topical)
Timolol , betaxolol
