this ppt is a basic one on the pharmacology of betablockers with illustration,,,

2. BETABLOCKERS
DR. V. SATHYANARAYANAN
M.D
PROFESSOR OF
PHARMACOLOGY

3. Overview
Introduction
Classification
Pharmacological actions
Mechanism of action
Pharmacokinetics
Therapeutic uses
Adverse effects & Contraindications
Recent advances
Summary

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

5. Sympathetic Responses
heart rate increases
blood pressure increases
blood is shunted to skeletal muscles
blood glucose increase
bronchioles dilate
pupils dilate

6. ADRENERGIC RECEPTORS
α1
α2
β1
β2
 β3

7. Beta receptors
β -1 β -2 β - 3

8. Distribution and responses of
Adrenergic receptors
Tissue Response
Predominantly beta
receptors
a.Heart : ( β1)
S-A node – β1
Atria -β1
A-v node – β1
Ventricles –β1
b. Bronchial muscle –β2
c. Skeletal muscle changes
– β2
d. Skeletal muscle blood
vessels –β2
Increased heart rate (positive chronotropic action)
Increased contraction(positive inotropic action)
Faster conduction
Increased contractility and conductivity
Increased automaticity
Relaxation
Changes in contractility
Dilatation

18. Classification of β-blockers
1st Generation Non-selective Propranolol
2nd Generation β1-selective
Atenolol
Metoprolol
Betaxolol
Bisoprolol
3rd Generation Additional properties, for
example vasodilation
Carvedilol
Nebivolol

19. CLASSIFICATION

21. PROTOTYPE–PROPARANOLOL
PHARMACOLOGICAL ACTIONS
Heart
 ↓ Automaticity, ↓ Heart rate
 ↓ A.V Conduction
↓Force of contraction, ↓ Cardiac output ↓ BP
( Particularly in stress )
 ↓ Cardiac work, ↓ O2 Consumption

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

25. BLOOD VESSELS
Re-reversal of DALE
 Acute increased Total p → eripheral resistance
 Chronic → ↓ Total peripheral resistance
Decreased Peripheral flow
No Postural Hypotension

27. EYE
 decreases Aqueous humor secretion
 decreases intraocular tension
No action on pupil size

28. Respiratory tract
 Beta -2 receptors bronchi bronchodilatation
Beta blockers bronchoconstriction
 Asthmatics - severe attack may
be precipitated
Contraindicated
in Asthma

29. CNS - Nightmares , increased Dreaming

31. METABOLISM
 Lipid  Inhibits lipolysis
increases LDL, ↓ HDL
Carbohydrate  Mask Hypoglycemic
symptoms
 Inhibit Glycogenolysis  delays recovery from
hypoglycemia

34. SKELETAL MUSCLE
RELAXATION  decreases tremor
Decreases exercise capacity ( Beta 2)
Local anesthetic action

37. PHARMACO KINETICS
 oral absorption  good
Metabolism  high 1st pass effect
Distribution  enters brain (lipid soluble)
Elimination  Plasma  1st order kinetics
 receptor zero Order kinetics
Plasma Protein Binding : 90 %
Excreted In urine

39. ADVERSE EFFECTS
Bronchoconstriction (even eye drops)
Bradycardia, Heart block
Cold extremities
Heart failure
Impaired carbohydrate tolerance
Altered lipid profile (increases risk of CAD)

45. ADVERSE EFFECTS
ABRUPT WITHDRAWAL  rebound
hypertension , worsening of angina
Oculomucocutaneus syndrome (practolol)
Depression
Constipation
Increased Frequency of anaphylaxis
Cold hands and feet
Tiredness and reduced exercise capacity

53. CONTRAINDICATIONS
CHF
Heart block
Bronchial asthma
Peripheral vascular disease

59. DRUG INTERACTIONS
Calcium channel blockers (verapamil)
Cardiac arrest, CHF
NSAIDS Attenuate antihypertensive effect
Cold remedies ( phenylephrine) increases BP
Anti diabetic drugs Delay in recovery from
hypoglycemia

61. THERAPEUTIC USES
CARDIO VASCULAR USES
Angina pectoris
Hypertension
Arrhythmias
Myocardial infarction (cardio protective effects)
Early use
Delayed use
Fallot’s tetrology
Hypertrophic obstructive cardiomyopathy
Dissecting aneurysm
Portal hypertension

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

66. 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

70. ENDOCRINE USES
Hyperthyroidism ( decreases adrenergic activity,
peripheral conversion of T4 TO T3)
Pheochromocytoma (given along with alpha
blockers)

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

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

75. CNS USES
Anxiety , palpitation before examination , stage
appearance
Migraine prophylaxis (nonselective better)
Essential tremor
Alcohol withdrawal state
Opioid withdrawal state
Eyes  Glaucoma (timolol)

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

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

84. SOTALOL
Non selective beta-blocker
Decreased lipid solubility
Blocks potassium channels
Useful in arrhythmias

85. CARDIOSELECTIVE BETA BLOCKERS
Relatively Selective Beta-1 Blockers
In High doses  selectivity lost

86. Beta 1 VS Beta 2 Selectivity

87. ADVANTAGES
Safer in diabetes
Safer in Bronchial asthma (better)
Does not Alter lipid profile
Does not cause Peripheral vascular diseases
No impairment of exercise capacity

88. ATENOLOL
Low lipid solubility – incomplete absorption, no CNS
effects
Low Ist pass effect
 long acting
Narrow range
Preferred in hypertension, angina

90. METOPROLOL
Beta1 Selective blocker like atenolol
Less 1st pass metabolism
Orally, I.V.
Side effects  mild

91. TIMOLOL
Topical –as eye drops indicated in Glaucoma
Oral – like atenolol
used in MI,
angina,
hypertension

93. PINDOLOL
Beta blocker with intrinsic sympathomimetic
activity
Advantageous in bradycardia
Less incidence of rebound hypertension on
withdrawal

95. ACEBUTOLOL
Has intrinsic sympathomimetic activity
Membrane stabilizer (useful in arrhythmias)
Longer t1/2  single daily dose
Less effect on resting heart rate

97. BISOPROLOL
Cardio selective beta-blocker without intrinsic
sympathomimetic activity
Used in angina, hypertension once daily

98. ESMOLOL
Ultra short acting beta-blocker
T½ < 10 min
Has membrane stabilizing activity
Used to terminate SVT, AF, A.FIB
Early treatment of M.I
 during & after cardiac surgery decrease BP,
HR

100. CELIPROLOL
Selective beta1 blocker
Beta2 agonist
 safer in asthma
Also cause vasodilatation

102. NEBIVOLOL
Highly selective B1 blocker
Also acts as NO donor
Improve endothelial function and delay
atherosclerosis
Rapid onset of hypotensive effect

103. LABETALOL
Alpha & and β blocker
Low dose – actions like propranolol given
alone
High dose – like propranolol + phenoxy
benzamine
Orally effective
Used in pheochromocytoma
ADR postural hypotension, failure of
ejaculation

104. CARVEDILOL
Βeta-1, Βeta-2 & alpha-1 blocker
Vasodilator
Antioxidant
Cardio protective in Congestive heart failure
Also used in hypertension

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

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

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

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