β blockers

β receptor actions

• Dilatation of arterioles and veins → fall in BP (β2)• Cardiac stimulation (β1), ↑ rate, force and

conduction velocity• Bronchodilatation (β2)• Enhanced aqueous secretion

β receptor actions

• Liver—glycogenolysis (β2) → hyperglycaemia

β receptor actions

• Fat—lipolysis (β1 + β2 + β3) → increased blood FFA, calorigenesis.

β receptor actions

• Renin release from kidney (β1)

Β Receptor locationReceptor Locationβ1 Heart, JG cells in kidneyβ2 Bronchi, blood vessels, liver, skeletal muscle

β3 Adipose tissue

TISSUE RECEPTORTYPE

ACTION

Heart • Sinus and AV • Conduction pathway • Myocardial fibrils

β1β1β1

AutomaticityConduction velocity, automaticityContractility, automaticity

Vascular smooth muscle β2 Vasodilation

Bronchial smooth muscle β2 Bronchodilation

Kidneys β1 Renin release

Liver β2 Glycogenolysis and gluconeogenesis

Adipose tissue β3 Lipolysis

Skeletal muscle β2 Tremor

Comparison of agonists and antagonists at β Receptor

Classification of β-blockers• Nonselective (β1 and β2)• a. Without intrinsic sympathomimetic activity• Propranolol, Sotalol, Timolol.• b. With intrinsic sympathomimetic activity• Pindolol• c. With additional α blocking property• Labetalol, Carvedilol

• Cardioselective (β1)• Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol, Betaxolol,

Celiprolol, Nebivolol

Propranolol: A nonselective β antagonist

• Prototype β-adrenergic antagonist• Blocks both β1 and β2 receptors with equal affinity.

Cardiovascular effects of Propranolol

• Negative inotropic and chronotropic effects .• Directly depresses sinoatrial and atrioventricular

nodal activity. • Cardiac output, workload, and oxygen consumption

are decreased by blockade of β1 receptors.

Vascular effects of Propranolol

• Peripheral vasoconstriction• Nonselective blockade of β receptors prevents β2-

mediated vasodilation in skeletal muscles, increasing peripheral vascular resistance.

Effects of Propranolol on bronchial smooth muscle

• Bronchoconstriction• Blocking β2 receptors in the lungs causes contraction

of the bronchiolar smooth muscle.• β-blockers, particularly, nonselective ones, are

contraindicated in patients with COPD or asthma.

Effects of Propranolol on glucose metabolism

• Disturbances in glucose metabolism• β blockade leads to decreased glycogenolysis and

decreased glucagon secretion.• Therefore, if propranolol is given to a diabetic patient

receiving insulin, careful monitoring of blood glucose is essential, because pronounced hypoglycemia may occur after insulin injection.

• β-blockers also attenuate the normal physiologic response to hypoglycemia.

Therapeutic uses of Propranolol

• Hypertension: • Decreased cardiac output is the primary mechanism • Inhibition of renin release from the kidney.• Decrease in total peripheral resistance with long-

term use.

Therapeutic uses of Propranolol

• Angina pectoris: • Propranolol decreases the oxygen requirement of

heart muscle and, therefore, is effective in reducing chest pain on exertion that is common in angina.

Therapeutic uses of Propranolol

• Myocardial infarction: • Propranolol acts by decreasing oxygen requirment to

heart muscle.

Therapeutic uses of Propranolol

• Migraine: mechanism of action unknown.

Therapeutic uses of Propranolol

• Hyperthyroidism: • Propranol acts by blunting the widespread

sympathetic stimulation that occurs in hyperthyroidism.

Adverse effects of Propranolol

• Tiredness and reduced exercise capacity: • Due to blunting of β2 mediated increase in blood

flow to the exercising muscles as well as attenuation of glycogenolysis and lipolysis.

Adverse effects of Propranolol

• Bronchoconstriction: • Due to blockade of β2 receptors on smooth muscles

of bronchi. • Therefore, propranolol is contraindicated in patients

with COPD or asthma.

Adverse effects of Propranolol

• Arrhythmias:• Treatment with β-blockers must never be stopped

abruptly because of the risk of precipitating cardiac arrhythmias, which may be severe.

Adverse effects of Propranolol

• Sexual impairment:• The reasons for this are not clear and may be

independent of β receptor blockade.

Adverse effects of Propranolol

• Metabolic disturbances:• β Blockade leads to decreased glycogenolysis and

decreased glucagon secretion. • Fasting hypoglycemia may occur. • The perception of symptoms of hypoglycemia such

as tremor, tachycardia, and nervousness are blunted by β-blockers.

Adverse effects of Propranolol

• Metabolic disturbances:• Increased low density lipoprotein (“bad”cholesterol), • increased triglycerides, • reduced high-density lipoprotein (“good”cholesterol).

Elimination half-lives for some β-blockers

Nonselective β antagonists

• Timolol • Treatment of glaucoma• Topically applied timolol is effective in diminishing

intraocular pressure in glaucoma. • This occurs by decreasing the secretion of aqueous

humor by the ciliary body.

Selective β1 antagonists

• Acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, and nebivolol.

• In contrast to propranolol, the cardioselective β-blockers have fewer effects on pulmonary function, peripheral resistance, and carbohydrate metabolism.

Therapeutic uses: The cardioselective β-blockers

• Useful in hypertensive patients with impaired pulmonary function.

Antagonists of both α and β adrenoceptors

• Labetalol and carvedilol:• Nonselective β-blockers with concurrent α1-blocking

actions that produce peripheral vasodilation, thereby reducing blood pressure.

• Uses:• Hypertensive emergencies, because it can rapidly

lower blood pressure.• Pregnancy-induced hypertension.

Thank You

Question 1• A β-blocker was prescribed for hypertension in a female

asthma patient. After about a week of treatment, the asthma attacks got worse, and the patient was asked to stop taking the β-blocker. Which of the following β-blockers would you suggest as an alternative in this patient that is less likely to worsen her asthma?

• A. Propranolol.• B. Metoprolol.• C. Labetalol.• D. Carvedilol.

Question 1• Correct answer = B. • The patient was most likely given a nonselective β-blocker

(antagonizes both β1 and β2 receptors) that made her asthma worse due to β2 antagonism.

• An alternative is to prescribe a cardioselective (antagonizes only β1) β-blocker that does not antagonize β2 receptors in the bronchioles.

• Metoprolol is a cardioselective β-blocker. • Propranolol, labetalol, and carvedilol are nonselective β-

blockers and could worsen the asthma.

Question 2

• Which of the following is correct regarding β-blockers?

• A. Treatment with β-blockers should not be stopped abruptly.

• B. Propranolol is a cardioselective β-blocker.• C. β-Blockers may cause orthostatic hypotension.• D. Cardioselective β-blockers worsen asthma.• E. β-Blockers decrease peripheral resistance by

causing vasorelaxation.

Question 2

• Correct answer = A. • If β-blocker therapy is stopped abruptly, that could

cause angina and rebound hypertension.

Question 3

• The therapeutic actions of β blockers such as propranolol in angina pectoris is believed to be primarily a result of

• A) reduced production of catecolamines• B) dilation of coronary vasculature• C) decreased requirment for myocardial oxygen• D) Increased peripheral resistance

Question 3

• Correct answer C• β blockers slows heart rate, reduce cardiac

contractility. • These hemodynamic actions decrease the

requirment of the heart for oxygen.