13. ďąWith 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:
ď Hypoglycemia
Adrenaline
β- 2 receptors in liver
glycogenolysis
ď Masks sympathetic manifestations of hypoglycemia
ď Plasma triglyceride levels increase
ď LDL/HDL ratio is increased
Propranolol
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
ďUltra short acting blocker
ď inactivated by esterases in
blood
ď plasma t1/2 < 10 min
ď Rapid onset, short lasting
effect
ď 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
25. 1.Hypertension:
⢠Past- recommended as first-line therapy
⢠Present status - benefits have been
overshadowed by their side-effect profile
â˘sexual dysfunction
â˘fatigue
⢠depression
⢠metabolic abnormalities
26. Consider Beta blocker if:
ď intolerance or contraindication to ACE
inhibitors/angiotensin II receptor antagonists
ďWith increased sympathetic drive- HTN with
tachycardia
ďTense young patient
ďPost MI
28. ď 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
ď 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
32. β blocker in CHF -proper patient selection :
ďą mild to moderate (NYHA class II, III ) cases of
dilated cardiomyopathy with systolic
dysfunction
ďąNo place in decompensated patients.
ďą Stopped during an episode of acute heart
failure
ďąStarting dose -very low -then titrated
upward
36. ďBeta blockers Decrease cardiac work load
Decrease myocardial oxygen demand
ď Angina of effort (Classical Angina)
37. ďCombined with nitrates for chronic prophylaxis
ďCardioselective-
Metoprolol 25- 100 mg
Atenolol 25- 100 mg
ďAbrupt withdrawal- precipitate Angina / MI- up
regulation of beta receptors
ďContraindicated 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 â 3 doses
⢠Metoprolol 25â50 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 âAtenolol ,
Carvedilol
⢠Atleast for 2 years
40. 5. Cardiac Arrhythmias
ďSA node - Decrease slope of phase - 4
depolarisation
ďDecrease automacity in SA node, purkinje
fibres
ďProlong ERP of AV node â impedes A-V
conduction
41. Esmolol
ďIntravenous
ďIt has been used to terminate:
ďą Paroxysmal supraventricular tachycardia
ďą episodic atrial fibrillation or flutter
ďąAdrenergically mediated arrhythmia
Pheochromocytoma
ďąarrhythmia during anaesthesia
ďąintra operative, post operative hypertension
ďą in early treatment of myocardial infarction
42. ď Sotalol
⢠Additional K channel blocking
⢠Class III anti-arrhythmic
ďAcebutolol- 20- 40mg
ďPropranolol - 40 â 80 mg
44. 7.Hypertrophic obstructive cardiomyopathy
ď Subaortic region is hypertrophic
ď Forceful contraction of this region under
sympathetic stimulation (exercise, emotion)
increases outflow resistance
8. Mitral valve prolapse
49. Advantages of topical β- blockers over
Miotics
No
ďchange in pupil size
ď myopia
ď headache
ďfluctuations in i.o.t
ďź convenient OD / BD dosing
50. ďTimolol
⢠Non-selective
⢠Action is smooth , well sustained
⢠Effect on i.o.t. persists for 2-3 weeks following
discontinuation
⢠Dose â O.25% drops BD
ďLevobunolol- 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
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 âSalbutamol
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
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 Îą1-receptor blocking properties,
glaucoma)
⢠Dilevalol ( stereoisomer of Labetalol)- HTN
⢠Bopindolol
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 &
Gilmanâs 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