PH 1.

13:BETA
BLOCKERS
Dr. Lavakumar S
Professor
Dept of Pharmacology
SSSMCRI
 SLO
• Define beta blockers
• Classify beta receptors
• Classify beta blockers
• Discuss the pharmacological actions of Propranolol
• Enumerate the uses of Beta blockers
• Enlist the ADRs
• Briefly discuss individual drugs
• Highlight the important drug interactions
 Introduction
• Beta blockers are drugs that block the beta 1
and beta 2 receptors
• Antagonism
• Beta 1- Cardioselective
• Both beta 1 and beta 2- Non selective
•Bronchodilatation
•Intestinal relaxation
•Uterine relaxation
•Detrusor relaxation
•Enhanced secretory of
ciliary epithelium
• Beta adrenergic blocking drugs
• Classification
• Non-selective – Propranolol, nadolol, timolol,
sotalol.
• Cardioselective – metoprolol, atenolol,
acebutolol, esmolol, betaxolol, bisoprolol.
• Partial agonists – pindolol, oxprenolol, carteolol,
bopindolol, penbutalol
• Additonal alpha blocking property – labetolol,
carvedilol
• β1blocker β2 agonist - celiprolol.
• Pharmacological actions
• CVS – decrease heart rate, force of contraction
and cardiac output. Blood pressure falls.
• A-V conduction is delayed.
• Myocardial oxygen requirement is reduced.
• Also improve exercise tolerance in angina
patients.
• High doses produce membrane stabilising
effect like quinidine.
• Blood vessels – on long term use, β-blockers
reduce peripheral vascular resistance in
hypertensive patients. They reduce renin
release, decrease central sympathetic outflow,
reduce cardiac output.
• Respiratory tract: Non selective beta blockers
worsens COPD by causing broncho-constriction
• Eye – decrease secretion of aqueous humour.
• Metabolic – block lipolysis and glycogenolysis.
Plasma triglycerides may increase and HDL
levels decrease
• In higher doses block sodium channels
• Pharmacokinetics
• Have short half life and are metabolised in the
liver.
• Adverse reactions
• Bradycardia
• CCF – sympathetic activity supports the heart.
β-blockade eliminates this and may
precipitate CCF and acute pulmonary oedema.
• Cold extremities – peripheral vascular disease.
• Precipitate acute asthmatic attack, can worsen
COPD.
• CNS – insomnia, depression, and rarely
hallucinations
• Fatigue due to decreased blood flow to the
muscles during exercise and reduced cardiac
output.
• Metabolic effects – carbohydrate tolerance
may be impaired in diabetics. Plasma levels of
triglycerides and LDL cholesterol may rise
while HDL cholesterol may decrease.
• Abrupt withdrawal – rebound hypertension,
precipitate anginal attacks due to up
regulation of β-receptors.
• β-blockers should be gradually tapered.
• β-blockers can cause dizziness.
• Topical – burning and dryness of the eye.
• Important drug interactions
• Propranolol + insulin - masks tachycardia
– Prevents glycogenolysis
Propranolol + verapamil – profound depression
β-blockers + catecholamines
β-blockers, digitalis and verapamil – depression of
A-V conduction.
Enzyme inducers like rifampicin reduce the plasma
levels of propranolol.
NSAIDs counter the antihypertensive effect of β-
blockers .
• Cardio selective β-blockers
• Selectively block β1 receptors
• Bronchospasm is less.
• Inhibition of glycogenolysis is lower.
• Exercise performance is impaired to a lesser
degree.
• Lesser chances of peripheral vascular disease.
• Partial agonists(Beta blockers with ISA-
Pindolol oxprenolol)
• Preferred in patients with low cardiac reserve
or those who are likely to have severe
bradycardia.
• Individual β-antagonists
• Atenolol
– Selectively block β1 receptors
– Longer acting
– Less lipid soluble
– no side effects on lipid profile
– Very commonly used in hypertension and angina.
• Esmolol
– Selectively block β1 receptors
– Ultra short acting-half life 8 minutes
– Rapid acting
– Used IV
– Safer in critically ill patients and useful in
emergencies
– used in supraventricular and other arrhythmias,
perioperative hypertension.
• Metoprolol
– Selectively block β1 receptors
– Well absorbed but undergoes significant first-pass
metabolism
– Given twice daily
– Used in hypertension and angina
• Acebutolol
• β1 selective with partial agonistic effect
• Less likely to cause bradycardia
• Converted to active metabolite
• May be used in hypertension and arrhythmias
• Nebivolol
– Highly selective
– Causes vasodilatation through NO production
– No myocardial depression
– Reduce BP by reducing vascular resistance
Bisoprolol
highly selective
Used in hypertension, heart failure.
• Timolol
– Nonselective, short-acting
– Used in glaucoma
– Used orally in hypertension, angina and MI.
Pindolol and oxprenolol
non selective
partial agonist at β1, β2 receptors.
• Probable advantages
– Milder bradycardia
– Milder myocardiac depression
– Better tolerated in asthmatics
– Milder effect on lipid profile
– Less chances of rebound hypertension on
withdrawal.
Probable disadvantages
Not suitable for prophylaxis of migraine and
myocardial infarction.
• Celiprolol
– β1 blocker, β2 agonist effects
– Additional vasodilator activity through NO
production.
– Safer in asthmatics
– Used in hypertension, angina.
• Uses of β blockers
• Hypertension
• Angina pectoris
• Cardiac arrhythmias
• Myocardial infarction
• Congestive cardiac failure
• Obstuctive cardiomyopathy
• Pheochromocytoma
• Dissecting aneurysm of the aorta
• Thyrotoxicosis
• Glaucoma
• Prophylaxis of migraine
• Anxiety
• Cirrhosis
• Esophageal varices
• Alcohol withdrawal
• Contraindications
• May be dangerous in patients with CCF
• Avoided in patients with bradycardia
• With heart block
• Avoided in patients with bronchial asthma and
COPD
• Avoided in diabetics
 Drug Interactions
• Aluminium salts decrease absorbtion
• Phenytoin, rifampicin, smoking induce hepatic
microsomal enzyme – decrease concentration of beta
blocker
• Cimetidine, hydralazine - increase bioavailability of beta
blockers.
• Decrease renal clearance of lignocaine
• Additive effect with CCB and other hypertensives
• NSAID – blunts anti hypertensive action of betablocker
• Alpha and beta adrenergic blockers
• Labetalol
• Competitive antagonist
• Vasodilation and CO contribute to
antihypertensive effect
• Blood flow to the limbs increases.
• Side effects
• Postural hypotension, gastrointestinal
disturbances
• Uses
• Hypertensive emergencies and
pheochromocytoma
• Carvedilol
• Antioxidant and antiproliferative properties
• Used in the treatment of hypertension, CCF
and myocardial infarction.
 SUMMARY
• Non selective and cardio selective beta
blockers
• Beta blockers are important agents in cardio
vascular therapeutics- SHT, CCF, Angina,
Arrhythmias
• CI: Bradycardia conditions, Heart blocks,
Prinzmetal angina, Asthma
• Alpha + Beta blockers = Carvedilol, Labetalol
• Thank u
Thank you