Adrenergic blockers work by binding to adrenergic receptors and preventing the action of adrenergic drugs. They can block alpha receptors, beta receptors, or both. Alpha blockers are classified as non-selective or selective. Prazosin is a highly selective alpha-1 blocker used to treat hypertension and benign prostatic hypertrophy. Beta blockers decrease heart rate, contraction force and blood pressure. They are used to treat hypertension, angina, arrhythmias and other conditions. Labetalol blocks both alpha-1 and beta receptors and is used to treat hypertension and hypertensive emergencies.

1. Anti-Adrenergic Drugs
By
Prof. Saba Shaikh

2. Adrenergic Blockers
• Adrenergic blockers bind to the adrenergic receptors and
prevent the action of adrenergic drugs. They may block alpha or
beta receptors or both.
• Alpha receptor antagonists block the adrenergic responses
mediated through alpha adrenergic receptors.
• Some of them have selectivity for a1 or a2 receptors.

3. Classification of Alpha blocker
1. Non-selective
a. Non-competitive blocker: Phenoxybenzamine
b. Competitive blockers: Ergot alkaloids (ergotamine), tolazoline, phentolamine,
chlorpromazine
2. Selective
a. a1-blockers: Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin
b. a2-blocker: Yohimbine

4. Phenoxybenzamine
• Phenoxybenzamine binds covalently to alpha receptors causing irreversible
blockade.
• Given IV, blood pressure gradually falls and is associated with tachycardia and
increased CO.
• The action lasts for 3-4 days.
• It also blocks histamine, 5-HT and cholinergic receptors.
• Phenoxybenzamine can be used orally in the treatment of pheochromocytoma.

5. Ergot alkaloids Ergotamine, ergotoxine and their derivatives are
competitive antagonists and the blockade is of short duration.
Some of them have a direct stimulant effect on smooth muscles—cause
contraction of the uterus and ↑ BP due to vasoconstriction.
Prolonged use of these can cause gangrene of the toes and fingers.
Phentolamine and tolazoline are competitive α- blockers.
 In addition they also block 5-HT receptors, stimulate gut motility and ↑
gastric secretion. Hence they can cause vomiting and diarrhea.

6. Selective α1 Blockers
Prazosin is a potent, highly selective, α1- blocker with 1000 times greater
affinity for α1 receptors.
 Arterioles and venules are dilated resulting in decreased peripheral
vascular resistance and cardiac output.
There is no significant tachycardia
Prazosin also inhibits phosphodiesterase, the enzyme that degrades cAMP
resulting in ↑ cAMP which also contributes to vasodilation.

7. • Other actions of Prazosin
• Prazosin and its congeners are found to ↓ LDL and triglycerides and ↑ HDL
cholesterol.
• They are useful in prostatic hypertrophy.
• Prazosin is orally effective, extensively bound to plasma proteins and is
metabolized in the liver. Its duration of action is 8-10 hrs.
• Adverse effects: First dose phenomenon– one hour after the initial dose, marked
postural hypotension occurs which may lead to fainting. To avoid this, prazosin
should be started with a low dose and taken at bed time. Other side effects
include headache an dizziness. Tamsulosin can cause abnormal ejaculation.

8. Congeners of Prazosin
• Congeners of Prazosin-include terazosin, doxazosin, alfuzosin and tamsulosin.
Others are indoramin and urapidil.
These congeners are longer acting and can be given once daily.
highly selective for α1 receptors.
Postural hypotension is milder than with prazosin.
No significant effect on cardiac function.
↓LDL and ↑HDL cholesterol

9. • Yohimbine is a relatively selective α2-blocker which increases BP and
heart rate.
• It causes congestion of genitals because of which it is used to treat
psychogenic impotence.
• It is also claimed to be an aphrodisiac though the effect is only
psychological.

10. Uses of α-blockers
• Hypertension
• Pheochromocytoma
• Peripheral vascular diseases
• Congestive cardiac failure
• Benign prostatic hypertrophy

12. Pharmacological action of Beta-blockers
• CVS :β-blockers decrease heart rate, force of contraction and cardiac output. Blood
pressure falls.
• Respiratory tract: Blockade of β2 receptors in the bronchial smooth muscle causes
increase in airway resistance—may precipitate acute attack in asthmatics.
• Eye: Many β-blockers reduce intraocular pressure by decreased secretion of
aqueous humor.
• Metabolic : β-antagonists block lipolysis and glycogenolysis.

13. Pharmacokinetics
• Though well absorbed on oral administration, some β-blockers like
propranolol undergo extensive first pass metabolism. Most of them have
short t½ and are metabolized in the liver.
• Adverse effects:
• Bradycardia, Cold extremities, β-blockers can precipitate acute asthmatic
attack, Insomnia, depression and rarely hallucinations, fatigue, and can also
cause dizziness.

14. Contraindications of beta-blockers
• Beta blockers are contraindicated in bradycardia, heart block,
asthmatics and chronic obstructive pulmonary disease (COPD).

15. Some important drug interactions
• 1. Propranolol + insulin—when diabetics on insulin also receive propranolol:
• i. β-blockade masks tachycardia which is the first warning signal of hypoglycaemia.
• ii. β-blockade delays the recovery from hypoglycaemia by preventing glycogenolysis
• 2. Propranolol + verapamil—Because both these cause myocardiac depression, profound
depression may result if both are used together. Hence the combination should be avoided.
• 3. β-blockers + catecholamines—intense vasoconstriction is possible from even small doses
of adrenaline that is used with LAs. Hence it is safer to use plain local anaesthesia in such
patients.

16. Cardioselective β-blockers e.g. Atenolol, metoprolol, esmolol.
These drugs:
• Selectively block β1 receptors; β2 -blockade is weak
• Bronchospasm is less/negligible
• Inhibition of glycogenolysis is lower— hence safer in diabetics
• Exercise performance is impaired to a lesser degree
• Lesser chances of peripheral vascular disease.

17. Some individual drugs
Atenolol
• Selective β1-blocker
• Longer acting-given once daily
• Less lipid soluble-does not cross BBBhence no CNS side effects
• No side effects on lipid profile.
Hence very commonly used (25-100 mg daily)
Esmolol
• Selective β1 -blocker
• Ultra short-acting– t½–8 minutes.
• Used IV
• Safer in critically ill patients and in emergencies when immediate β-blockade is
needed.

18. Metoprolol
• Selective β1 blocker
• Well absorbed but undergoes significant first-pass metabolism
• Given twice daily (50-200 mg)
• Used in hypertension and angina pectoris
Acebutolol
• β1 selective with some partial agonistic effects
• May be used in hypertension and arrhythmias.
Celiprolol
• β1 blocker and β2 agonistic effects
• Safer in asthmatics
• Used in hypertension.

19. Uses of beta-blockers
• Hypertension
• Angina pectoris
• Cardiac arrhythmia
• CCF
• MI
• Thyrotoxicosis
• Glaucoma
• Prophylaxis of migraine
• Anxiety

20. Alpha and Beta-adrenergic Blockers
• Labetalol blocks both α1 and β (β1 and β2 ) receptors.
• It is a competitive antagonist.
• Heart rate, contractility, AV conduction and BP fall. Vasodilation (α1 and β blockade) and
reduced CO contribute to antihypertensive effect. Blood flow to the limbs increases.
• Side effects include postural hypotension, GI disturbances and other effects of alpha and
beta blockade.
• Uses : Labetalol is used in hypertensive emergencies and pheochromocytoma.. It is used
in the treatment of hypertension and congestive cardiac failure.