2. INDEX
• Adrenergic system and receptors and its
function
• Classification of beta-blocker
• Pharmacokinetic
• Clinically usage of beta-blocker
• Sideeffects
• Doses
• Overdose of beta-blocker
7. Beta-Blocking Drugs
Classification:
All of the β blockers used clinically are
competitive pharmacologic antagonists.
Propranolol {Inderal® 10-40mg tab ; 2mg} is the
prototype.
Drugs in this group are usually classified into
subgroups on the basis of β1 selectivity, partial
agonist activity, local anesthetic action, and lipid
solubility.
8. Selective types usually occur in first
letters of alphabetic with exception
nebivolol
Q/ There is no selective B2- blockers, explain
why?
Nebivolol
9. Since blocking B2 receptors leaves alpha1 in
blood vessels functioning this leads to
peripheral vasoconstriction , so this group
introduce to treat this problem
e.g : labetalol & Carvedilol
In addition some of these drugs have direct vasodilator effect through
release NO from endothelium of blood vessels { Celiprolol &
Nebivolol}
10. 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
11.
12. 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
13. 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.
15. blocking B2 will prevent B2 mediated vasodilatation {
this causes vasoconstriction is due to alpha effect }
16. c. Blood pressure :
BP will reduced by the following mechanisms:
1) Decrease COP
2) Decrease rennin from kidney
3) Reduce central sympathetic outflow
4) Some of BB can causes vasodilator action through alpha
blocking activity or generation of NO
17.
18. 3) Eye :
contain B1 &B2 in ciliary body that mediate production of
aqueous humor , so beta blockers reduces IOP
4) 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
5) Sk m: B2 Receptors mediate vasodilatation and tremor ,
so BB causes fatigue and reduces tremor.
19. 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.
20. 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
26. 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.
27. ECG
A number of electrocardiographic findings
associated with mitral valve prolapse (MVP)
have been reported. The most frequent finding
is inversion of T waves in the inferior leads
28. 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.
29. 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.
30. 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 preferred use nonselective type in
hyperthyroidism , why?
31.
32.
33. Timolol and betaxolol most commonly used eye drops in
the treatment of glaucoma , why ? Because they are most
lipophilic beta blockers
34.
35.
36. 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
37. 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
38.
39. 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
40. 8) Treatment of bruxism
Bruxism, which is characterized as the unnecessary
grinding or clenching of teeth, is a problem that affects
8% to 21% of the U.S. population.
Symptoms such as moderate to severe headache,
muscle pain, temporomandibular joint dysfunction, and
permanent tooth damage may persist if bruxism is left
untreated.
Propranolol can be prescribed for these patient even
with normal tension patient.
41. Side effects
1) Fatigue ( because reducing COP (B1), blood flow into
muscles (B2).
2) Bronchoconstriction ( due to blocking B2 in lung ; even
selective type is contraindication in asthmatic patient ).
3) Bradycardia ( so it is contraindication in heart block).
4) Decreases blood flow (due to blocking B2 in sk. m ) that may
causes peripheral vascular disease such as claudication and
Raynaud's phenomena . This condition can be avoid by
prescribing selective B1 blocker such as nebivolol or mixed
alpha and beta blockers such as labetalol
5) Central : Depression and night mires , sexual dysfunction { B2
blocking).
6) Beta blockers are angiogentic agent so it is
contraindicated in psoriatic patients
42. Hyperkalemia ( dangerous in renal failure)
-Hyperlipidemia through reducing hepatic blood flow causing
reduce their metabolism (not preferred in patient with
43. 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 .
44. 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)
45. Relative contraindication of BB (caution )
1) Acute heart failure
2) Raynaud's phenomena and claudication.
3) DM type 1
4) Athlete patient
46.
47.
48. 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
49. 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
