1. MODE OF ACTION
• Block the action of endogenous
catecholamines (Adrenaline) & (NA) in
particular,
• On B-adrenergic receptros, part of
sympathetic nervous system
• There are three known types of beta
receptor, B1, B2, & B3 receptors
BETA BLOCKERS

2. β-ADRENERGIC RECEPTORS
• β1-adrenergic receptors are located mainly in
the heart & in the kidney
• β2-adrenergic receptors are located mainly in
the lungs, GIT, liver, uterus, vascular smooth
muscle, & skeletal muscle
• β3-adrenergic receptors are located in fat cells

3. β STIMULATION
• Stimulation of β1 receptors at HEART induces a
positive chronotropic & inotropic effect on the
heart and increases cardiac conduction velocity &
automaticity.
• Stimulation of β1 receptors in the kidney causes
renin release
• Stimulation of β2 receptors induces smooth
muscle relaxation, induces tremor in skeletal
muscle, and increases glycogenolysis in the liver
and skeletal muscle
• Stimulation of β3 receptor induces lipolysis.

4. • Differ in intrinsic sympathomimetic activity, in
CNS effects, and in pharmacokinetics
• Beta 1 selective (Cardioselective) – Acebutalol,
Atenolol, Bisoprolol, Esmolol, Metoprolol
• Non-selective ( Beta 1 & 2) – Nadolol,
Penbutolol, Pindolol, Propranolol, Timolol
BETA ANTAGONISTS

5. SELECTIVE BETA 1 ANTAGONISTS
• Acebutalol
• Atenolol
• Metoprolol
• Esmolol (short half life)
– Selectively block beta 1 (Cardioselective)
– To lower B.P. in hypertension
– Increase exercise tolerance in angina
– Also useful for patient with diabetic hypertensive
patients who are receiving insulin/oral hypoglycemic
agents

6. INTRINSIC SYMPATHOMIMETIC
ACTIVITY (ISA)
• Some beta blockers (e.g.
oxprenolol, pindolol, penbutolol, and
acebutolol) exhibit intrinsic sympathomimetic
activity (ISA)
• These agents are capable of exerting low level
agonist activity at the β-adrenergic receptor
while simultaneously acting as a receptor site
antagonist.

7. INTRINSIC SYMPATHOMIMETIC
ACTIVITY (ISA)
• Also referred to as intrinsic sympathomimetic
effect, this term is used particularly with beta
blockers that can show both agonism and
antagonism at a given beta
receptor, depending on the concentration of
the agent (beta blocker) and the
concentration of the antagonized agent
(usually an endogenous compound such
norepinephrine)

8. ANTAGONISTS WITH PARTIAL AGONIST
ACTIONS
• Pindolol
• Acebutalol
• Not pure blockers, weakly stimulate both beta
1 & 2 (intrinsic sympathomimetic activity)
• Decreased metabolic effects
• Uses : hypertension with moderate
bradycardia/ diabetic patients

9. BETA ANTAGONISTS WITH ADDITIONAL CVS
EFFECTS – (3rd GENERATION BETA BLOCKERS)
1. Alpha 1 blockade :
Labetalol, Carvedilol, Bucindolol, Bevantolol, Nip
radilol
2. Increased production of NO :
Celiprolol, Nebivolol, Carteolol, Bopindolol, Nipr
adolol
3. Beta 2 agonist properties :
Celiprolol, Carteolol, Bopindolol
4. Calcium entry blockade :
Carvedilol, Betaxolol, Bevantolol
5. Opening of K channels : Tilisolol
6. Antioxidant action : Carvedilol

10. PHARMACOLOGICAL DIFFERENCES
• Agents with intrinsic sympathomimetic action
(ISA)
– Acebutolol, carteolol, celiprolol, mepindolol, oxprenol
ol, pindolol, labetalol
• Agents with greater aqueous solubility
– Atenolol, celiprolol, nadolol, sotalol
• Agents with membrane stabilizing effect
– Acebutolol, betaxolol, pindolol, propranolol
• Agents with antioxidant effect
– Carvedilol, nebivolol

11. INDICATION DIFFERENCES
• Agents specifically indicated for cardiac arrhythmia
– Esmolol, sotalol, landiolol
• Agents specifically indicated for congestive heart
failure
– Bisoprolol, carvedilol, sustained-release metoprolol,
nebivolol
• Agents specifically indicated for glaucoma
– Betaxolol, carteolol, levobunolol, metipranolol, timolol
• Agents specifically indiciated for myocardial infarction
– Atenolol, metoprolol, propranolol
• Agents specifically indicated for migraine prophylaxis
– Timolol, propranolol

13. BETA BLOCKERS IN CVS
1. Angina pectoris
2. Myocardial infarction
3. Arrhythmias
4. Hypertension
5. Heart failure

14. HYPERTENSION
• The primary antihypertensive mechanism of beta
blockers is unclear but it may involve reduction in
cardiac output (due to negative chronotropic and
inotropic effects)
• It may also be due to reduction in renin release from
the kidneys, and
• A central nervous system effect to reduce sympathetic
activity (for those β-blockers that do cross the blood-
brain barrier, e.g. Propranolol)
• Blockade of the sympathetic nervous system on renin
release leads to reduced aldosterone via the renin
angiotensin aldosterone system with a resultant
decrease in blood pressure due to decreased sodium
and water retention
Reduced C.O.
Decrease sympathetic outflow
Reduce renin

15. ANGINA
• Antianginal effects result from negative
chronotropic and inotropic effects, which
decrease cardiac workload and oxygen
demand
Reduced workload
Decrease C.O.

16. ARRHYTHMIAS
• The antiarrhythmic effects of beta blockers arise
from sympathetic nervous system blockade –
resulting in depression of sinus node function and
atrioventricular node conduction, and prolonged
atrial refraction periods
• Sotalol, in particular, has additional
antiarrhythmic properties and prolongs action
potential duration through potassium channel
blockade

17. ADVERSE EFFECTS
1. Bronchoconstriction (contraindicated in bronchial
asthma)
2. Arrhythmias (beta blockers should be stopped
gradually), bradycardia, cardiac depression
3. Cold
extremities, Insomnia, depression, fatigue, Sexual
impairment
4. Disturbance in metabolism (care in diabetics)
5. Drug interactions –
Cimetidine, Furosemide, Chlorpromazine may
potentiate anti-hypertensive effects
- Barbiturates, Phenytoin, Rifampin can reduce its effects

18. DRUG INTERACTIONS WITH BETA
BLOCKERS
• Antidiabetic medications: beta blockers may mask signs and symptoms of
hypoglycemia
• Calcium channel blockers: (verapamil or diltiazem) has resulted in rare
conduction disturbances
• Cimetidine: Cimetidine may increase plasma concentration by 30% in
patients receiving beta blocker
• ClonidineL potentiates the blood pressure and heart-rate lowering effects
of beta blockers. If combination therapy with clonidine and a beta blocker
is terminated, the beta blocker should be discontinued first
• Digoxin: The concentration of digoxin is increased by 15% when used in
combination with beta blockers
• Rifampin: Rifampin causes a reduction in the plasma concentration by
770% in patients receiving beta blocker
• Other inhibitors of cytochrome P450 2D6 isoenzyme
(fluoxetine, paroxetine, quinidine) May increase plasma concentration in
patients receiving beta blocker.

19. B BLOCKERS AGENT
• Non-selective :
Propranolol
• Partial agonist :
Acebutalol,
Pindolol
• Selective :
Acebutalol,
Atenolol,
Metoprolol
• Both Antagonist
a & B :
Labetolol,
Carvidelol

20. PROPRANOLOL
• Non selective
• It has little intrinsic sympathomimetics action
(ISA) but has strong membrane stabilizing activity
• Pharmacological Actions:
1. CVS – diminishes C.O. (negative inotropic
chronotropic effects). Directly depress SA & AV
nodes
• Beta 1 blockade – reduced C.O., world load,
oxygen consumption (useful for treatment of
angina)

22. PROPRANOLOL
2. Periphrical vasoconstriction – blockade of beta 2
mediated vasodilation
– Reduced C.O. – decreased B.P. reflex peripheral
vasoconstriction
3. Bronchoconstriction – blocking beta 2 receptors ( can
precipitate respiratory crisis in asthma/COPD patients)
4. Disturbances in glucose metabolism – beta blockade –
decreased glycogenolysis and decrease glucagon
secretion. (care in diabetic patient, beta blockers may
also attenuate normal physiological responses to
hypoglycemia)
5. Increased Na+ retention-due low perfusion to
kidney, result Na+ and water retention, leads to
increased BP

23. PHARMACOKINETICS
• Well absorbed, high lipid
solubility.
• Propranolol – first pass
effect; 25% reached
systemic circulation
• CNS effects – present with
propranolol, less with
Nadolol, Atenolol

24. THERAPEUTIC USES
1. Hypertension – lowers B.P. by decreasing
C.O., reduction in renin release, central – reduce
sympathetic action
2. Glaucoma – effective in diminishing intraocular
pressure – decrease secretion of aqueous humor from
ciliary body
3. Migraine prophylaxis – blockade of catecholamine-
induced vasodilation in brain vasculature. Reduced
incidence and severity of migraine
4. Hyperthyroidism-effective in blunting the sympathetic
stimulation and also useful for the storm (prevent
cardiac arrhythmias)

25. THERAPEUTIC USES
5. Angina Pectoris – decreases oxygen requirement
of heart muscle – reduced chest pain on
exertion (useful in chronic stable angina)
6. Myocardial Infarction-protective effect on
myocardium, reduces infarct size, and hastens
recovery
7. Arrhythmias – depress automaticity, prolong AV
conduction, decrease HR and contractility
8. Congestive heart failure (worsen in acute heart
failure but improve life quality in chronic cases)
9. Anxiety-to control somatic symptoms

26. ADVERSE EFFECTS
1. Bronchoconstriction – CI for asthma
2. Arrythmias – never stopped abruptly.
Tappered down in 1 week slowly. Long term
treatment upregulated receptors
3. Nightmares – cross BBB

27. ATENOLOL
• Is a selective β1 receptor antagonist
• Introduced in 1976, atenolol was developed as
a replacement for propranolol in the
treatment of hypertension
• Unlike propranolol, atenolol does not pass
through the blood-brain barrier thus avoiding
various central nervous system side effects

28. ATENOLOL
• Is one of the most widely used β -blockers in the
United Kingdom and was once the first-line
treatment for hypertension
• The role for β -blockers in hypertension was
downgraded in June 2006 in the United Kingdom
to fourth-line, as they perform less appropriately
or effectively than newer drugs, particularly in
the elderly
• Some evidence suggests that even in normal
doses that most frequently used B-blockers carry
an unacceptable risk of provoking type 2 DM

29. ATENOLOL-PHARMACOKINETICS
• The mean elimination half life is 6 hours.
However the action of the usual oral dose of 25
to 100 mg lasts over a period of 24 hours. OD
Dose
• Atenolol is a hydrophilic drug. The concentration
found in brain tissue is approximately 15% of the
plasma concentration only. The drug crosses the
placenta barrier freely. In the milk of
breastfeeding mothers.
• Is almost exclusively eliminated renally and is well
removable by dialysis

30. METOPROLOL
• The active substance metoprolol is employed
either as metoprolol succinate or metoprolol
tartrate (where 100mg metoprolol tartrate
corresponds to 95mg metoprolol succinate)
• The tartrate is an immediate-release and the
succinate is an extended-release
• Genetic Polymorphism CYP2D6 variants

31. METOPROLOL
• Beta 1 Selective
• Moderately lipophilic
• With weak membrane stabilizing activity
• Short half life, therefore must be taken at least
twice daily or as a slow-release preparation
• Decrease heart rate, contractility and cardiac
output, therefore decreasing blood pressure

32. CARVIDELOL
• Non-selective beta blocker/ alpha-1 blocker
indicated in the treatment of mild to
moderate congestive heart failure (CHF)
• As an adjunct to conventional treatments (ACE
inhibitors and diuretics)
• The use of carvedilol has been shown to
provide additional morbidity and mortality
benefits in HEART FAILURE

33. LABETALOL
• Both alpha and beta blocker
• Actions: reduce B.P. esp. pregnancy induced
hypertension (PIH) and Pre Eclampsia
• Used in hypertensive emergency
• Does not alter serum lipid/ blood glucose
level, does not cause reflex tachycardia
• Adverse effects: orthostatic
hypotension, dizziness

34. BETA BLOCKERS REVIEW
• For more than 3 decades, beta-blockers have been
widely used in the treatment of hypertension and are
still recommended as first-line agents by national and
international guidelines
• Recent meta-analyses indicate that, in patients with
uncomplicated hypertension, compared with other
antihypertensive agents, first-line therapy with beta-
blockers was associated with an increased risk of stroke
especially in the elderly
• With no benefit for the end points of all-cause
mortality, cardiovascular morbidity, and mortality.

35. BETA BLOCKERS REVIEW
• Beta blockers (sometimes written as B-blockers) are a
class of drugs used for various indications, but
particularly for the management of cardiac arrhytmias
and cardioprotection after myocardial infarction
• Whilst once 1st line treatment for hypertension, their
role was downgraded in June 2006 in the UK to 4th line
as they perform less well than other drugs
• Particularly in the elderly, and there is increasing
evidence that the most frequently used beta-blockers
at usual dose carry an unacceptable risk of provoking
type 2 diabetes.

36. • It is worthwhile to note that the British
Hypertension Society has withdrawn its
endorsement of beta-blockers as first-line
treatment for patients with uncomplicated
hypertension.