1. Beta Receptor Blockers
Dr. Ritu Budania
MBBS, MD

2. Overview
• Introduction
• Classification
• Pharmacological actions
• Pharmacokinetics
• Therapeutic uses
• Adverse effects & Contraindications
• Recent advances
• Summary

3. Introduction
Sympathetic Nervous System- Fight, Fear , Flight

4. Beta receptors
β -1 β -2 β - 3

7. Beta Receptor
Blockers

8. Classification:
First Generation ( non-selective)
• Propranolol
• Timolol
• Sotalol
• Pindolol
• Nadolol
Second generation (Beta 1 selective)
• Metoprolol
• Atenolol
• Acebutolol
• Bisoprolol
• Esmolol

9. Third Generation ( additional alpha blocking/
vasodilator property)
• Labetalol
• Carvedilol
• Celiprolol
• Nebivolol

10. Pharmacological Actions:
1. Heart:
Sympathetic Stimulation
Beta -1 receptors on myocardium
Myocardial contractility
Heart Rate
Cardiac output
Cardiac work
Oxygen consumption
Beta Blockers

11. • Increase refractory period
• A-V conduction is delayed
• Decreases automaticity

12. 2.Blood vessels
Vasoconstriction Vasodilatation
Alpha -1 receptors Beta -2 receptors

13. With continued treatment, resistance vessels
gradually adapt to chronically reduced cardiac
output so that t.p.r. decreases ,BP falls
Total peripheral resistance (t.p r.) is
increased
initially (due to blockade of β
mediated
vasodilatation)
Cardiac output is reduced
Little change in BP
β blockers

14. Other mechanisms for Anti- hypertensive action:
(i) Reduced NA release from sympathetic terminals
due to blockade of pre- synaptic β receptor
mediated facilitation of the release process.
(ii) Decreased renin release from kidney
(iii) Decrease in Central sympathetic outflow

15. 3.Respiratory tract
• Beta -2 receptors bronchi bronchodilation
• Beta blockers broncho constriction
• Asthmatics - severe attack may
be precipitated
Contraindicated
in Asthma

16. 4.Metabolic Effects:
 Hypoglycemia
Adrenaline
β- 2 receptors in liver
glycogenolysis
 Masks sympathetic manifestations of hypoglycemia
 Plasma triglyceride levels increase
 LDL/HDL ratio is increased
Propranolol

17. 5.Eye
 Ciliary epithelium – β -2 receptors
-increases aqueous secretion
Their blockade reduces Aqueous
secretion
Reduces Intra- ocular pressure

18. Pharmacokinetics
• Well absorbed after oral administration
• Propranolol- extensive first-pass metabolism-
low oral bioavailability
• Chronic use of propranolol - itself decreases
hepatic blood flow- bioavailability of
propranolol is increased

19. • Longest acting- Nadolol- 14-24 hrs
• Shortest- Esmolol
Ultra short acting blocker
 inactivated by esterases in
blood
 plasma t1/2 < 10 min
 Rapid onset, short lasting
effect
 Intravenous in emergency

20. Lipid insoluble( Atenolol, Sotalol)
• Less CNS side effects
• Less first pass metabolism
• Long t ½- 6- 20 hrs

21. Drugs with partial agonistic activity
• intrinsic sympathomimetic action
• Pindolol, Acebutolol
1. Less Bradycardia
preferred in those prone to severe bradycardia
2. Withdrawal is less likely to exacerbate hypertension or
angina
3. Plasma lipid profile is not worsened

22. Advantages of Cardio selective Beta
blockers over non -selective blockers:
1. safer in asthmatics
2. safer in diabetics
3 .Peripheral vascular disease
4. less deleterious effect on lipid profile
5. Less liable to impair exercise capacity

23. Therapeutic uses
Cardiovascular uses Non-cardiovascular uses

24. Cardiovascular
Uses

25. 1.Hypertension:
• Past- recommended as first-line therapy
• Present status - benefits have been
overshadowed by their side-effect profile
•sexual dysfunction
•fatigue
• depression
• metabolic abnormalities

26. Consider Beta blocker if:
 intolerance or contraindication to ACE
inhibitors/angiotensin II receptor antagonists
With increased sympathetic drive- HTN with
tachycardia
Tense young patient
Post MI

27. • Atenolol 25–100 mg
• Metoprolol 25–100 mg
• Propranolol 40–160 mg
• Labetalol 200–800 mg
• Carvedilol 12.5–50 mg
• Combined with Calcium channel blockers-
check reflex tachycardia

28.  Atenolol
-Most commonly used
- Selective β-1 blocker
- Low lipid solubility.
-Does not cross BBB- CNS ADR are less
-Longer duration of action, OD dosing
 Metoprolol
-Cardioselective Beta 1 blocker
-Can be used in Diabetics with HTN, CHF

29. Hypertensive Emergency:
Systolic BP >180 mm of Hg
Diastolic BP > 120 mm of Hg
Treatment:
1.Sodium nitroprusside- DOC
2.Glyceryl trinitrate
3. Esmolol
0.25-0.5 mg/kg IV over 1 min, then 0.05-0.1
mg/kg/min IV for 4 min
4.Labetalol

30. Labetolol
• 3rd generation
• Alpha -1 blocker
• β -1 blocker
• Partial agonist β -2
(Vasodilation,Bronchodilation)
Uses:
• Hypertensive emergencies
• Pheochromocytoma
• Pregnancy induced hypertension

31. 2.Congestive Heart Failure:
Heart Failure
Decreased Cardiac output
Sympathetic activation
Beta-1 receptors
Myocardium
myocyte
hypertrophy,
myocyte apoptosis
detrimental
remodelling
JG cells kidney
Renin release

32. β blocker in CHF -proper patient selection :
 mild to moderate (NYHA class II, III ) cases of
dilated cardiomyopathy with systolic
dysfunction
No place in decompensated patients.
 Stopped during an episode of acute heart
failure
Starting dose -very low -then titrated
upward

33. Drug Initial dose Maximum dose
Carvedilol 3.125 mg BD 25-50 mg BD
Bisoprolol 1.25 mg QID 10 mg QID
Metoprolol 12.5–25 mg QID 200 mg QID

34. Carvedilol
• Alpha 1, β1, β2 blocker
• Anti oxidant property
• Inhibits free radical induced lipid
peroxidation, vascular smooth muscle
mitogenesis
• Use: cardioprotective in CHF
Hypertension

35. 3. Angina Pectoris

36. Beta blockers Decrease cardiac work load
Decrease myocardial oxygen demand
 Angina of effort (Classical Angina)

37. Combined with nitrates for chronic prophylaxis
Cardioselective-
Metoprolol 25- 100 mg
Atenolol 25- 100 mg
Abrupt withdrawal- precipitate Angina / MI- up
regulation of beta receptors
Contraindicated in Prinzmetals angina

38. 4.Myocardial Infarction
a. Myocardial salvage during evolution of MI
β blockers-
(i) limit infarct size by reducing oxygen consumption, prevents
re- infarction
(ii) prevent arrhythmias including ventricular fibrillation
• Not given if-
- Heart rate < 60/min
- Systolic BP < 90 mm Hg
- PR interval > 0.24 sec
- LVF
• Within 4-6 hrs Metoprolol- 5 mg i.v every 5 mins – 3 doses
• Metoprolol 25–50 mg orally every 6 h

39. b. Secondary prophylaxis of MI :
Decrease subsequent mortality by 20%.
(i) By preventing re-infarction
(ii) By preventing sudden ventricular fibrillation
at the second attack of MI
• β- 1 selective antagonist –Atenolol ,
Carvedilol
• Atleast for 2 years

40. 5. Cardiac Arrhythmias
SA node - Decrease slope of phase - 4
depolarisation
Decrease automacity in SA node, purkinje
fibres
Prolong ERP of AV node – impedes A-V
conduction

41. Esmolol
Intravenous
It has been used to terminate:
 Paroxysmal supraventricular tachycardia
 episodic atrial fibrillation or flutter
Adrenergically mediated arrhythmia
Pheochromocytoma
arrhythmia during anaesthesia
intra operative, post operative hypertension
 in early treatment of myocardial infarction

42.  Sotalol
• Additional K channel blocking
• Class III anti-arrhythmic
Acebutolol- 20- 40mg
Propranolol - 40 – 80 mg

43. 6.Dissecting aortic aneurysm
• Intravenous Propranolol, Metoprolol-
maintain heart rate of approximately 60
beats/min

44. 7.Hypertrophic obstructive cardiomyopathy
 Subaortic region is hypertrophic
 Forceful contraction of this region under
sympathetic stimulation (exercise, emotion)
increases outflow resistance
8. Mitral valve prolapse

45. Non- cardiovascular
uses

46. 1.Hyperthyroidism
• Thyroxine
Up regulation of β-1 receptors in myocardium
Tachycardia, palpitations
• T 4 T 3

47. β blockers given -
(i) with carbimazole or radioiodine
(ii) with iodide preoperatively
(iii) Thyroid storm (thyrotoxic crisis): emergency
Propranolol- 1-2 mg slow i.v. 40-80 mg
orally

48. 2.Glaucoma
• Decrease aqueous secretion
• chronic simple (wide angle) glaucoma

49. Advantages of topical β- blockers over
Miotics
No
change in pupil size
 myopia
 headache
fluctuations in i.o.t
 convenient OD / BD dosing

50. Timolol
• Non-selective
• Action is smooth , well sustained
• Effect on i.o.t. persists for 2-3 weeks following
discontinuation
• Dose – O.25% drops BD
Levobunolol- Long duration, OD

51. Side effects
• Redness and dryness of eye
• Allergic blepharoconjunctivitis
• Corneal hypoesthesia
• Systemic side effects- threatening
bronchospasm- asthmatics, bradycardia

52. Betaxolol
• β- 1 selective blocker
• Systemic side effects less
• Protective effect in retinal neurones -
reducing Na/Ca influx.
• O.5 % 1 drop BD

53. 3. Pheochromocytoma:
• Adrenal gland tumour
Excess catecholamines
hypertension, tachycardia
• First alpha blocker is given then Beta blocker
otherwise dangerous rise in BP can occur

54. 4. Migraine
• Prophylaxis
• severe migraine
• Propranolol
- most effective drug
- reduces frequency, severity of attacks- in 70%
patients
- Effect seen in 4 weeks
-Dose- 40 mg BD to 160 mg BD
• Others- timolol, metoprolol,atenolol

55. 5.Anxiety
- Stage fright, Nervousness, panic
- Propranolol- 10- 20 mg BD

56. 6. Alcohol Withdrawal
7.Oesophageal variceal bleeding and
portal hypertension
-Nadolol + isosorbide mononitrate

57. Contraindications
1. Asthma, COPD
2. Prinzmetals angina
3. Bradycardia
Heart Block
Acute decompensated heart failure
4. Peripheral Vascular disease

58. Adverse Effects
1 . Adverse Lipid profile-
total TG and LDL- cholesterol increase
 HDL- cholesterol falls.
Cardioselective β blockers - little/no
deleterious effect on blood lipids
2.Fatigue and reduced exercise capacity

59. 3.CNS side effects
sleep disturbance, bad dreams, sexual dysfunction
4.Hypoglycemia
-Masks sympathetic symptoms of hypoglycemia
5.Rebound Hypertension
-Chronic therapy up regulation of Beta receptors
-sudden withdrawal rebound hypertension
-Gradually tapered and Withdrawn
6. Miscellaneous:
Labetalol- postural hypotension, Hepatoxicity

60. Beta blocker Overdose
• Glucagon
- specific antidote
-positive inotropic action on the heart
• Cardiac pacing
• If bronchospasm occurs- Ipratopium
• Other antidotes –Salbutamol
and Isoprenaline

61. Celiprolol
• Selective β1 blocker
• Weak β2 agonistic activity
• Nitric oxide release ,vasodilatation
• No deleterious effects on lipid profile
• Safe in asthmatics
• Hypertension, Angina
• Dose:200mg OD -400mg OD

62. Nebivolol
• highly selective β1 blocker
• Nitric oxide release, vasodilatation
• Use: Hypertension
• Dose - 2.5 mg OD

63. Newer uses:
• Post traumatic stress disorder
• Agoraphobia
Uses under study:
• Propranolol -for orbital , periorbital hemangiomas in infants
• Breast cancer
• Pindolol- depression

64. New β blockers:
• Nipradilol (nonselective β-receptor and
selective α1-receptor blocking properties,
glaucoma)
• Dilevalol ( stereoisomer of Labetalol)- HTN
• Bopindolol

65. • Butoxamine
-Selective β 2 blocker
- Experimental drug

66. Summary
• Therapeutically important class of drugs
To summarise:
• Heart failure- Carvedilol
• Hypertension- Atenolol
• Emergency - Esmolol
• Migraine - Propranolol
• Glaucoma - Timolol

67. References
1.T. Westfall, D. Westfall, Adrenergic agonists & antagonists, Goodman &
Gilman’s The Pharmacological basis of Therapeutics, 12 th edition,
2006, Pg 237-296
2.HL, KK Sharma. Principles of Pharmacology. 2nd ed. Pg 185- 190
3.K. D. Tripathi, Adrenergic and Antiadrenergic drugs, Essentials of Medical
Pharmacology,6th edition, 2008, Pg 134-148
4.Longo, Fausi, Kasper. Harrisons principles of Internal Medicine, 18TH ed.
5.NICE clinical guideline 127.Developed by the Newcastle Guideline
Development and Research Unit and updated by the National Clinical
Guideline Centre and the British Hypertension Society. Hypertension
Clinical management of primary hypertension in adult

68. 6.Kenji Inoue,Kei Noguchi, Masato Wakakura,Goji Tomita .Effect of five years of
treatment with nipradilol eye drops in patients with normal tension
glaucoma
7.Lalonde RL, Tenero DM, Kazierad .Dilevalol: an overview of its clinical
pharmacology and therapeutic use in hypertension