In this session, Drugs that antagonise the effect of sympathomimetics are discussed briefly.

1. Sympatholytics
Dr Ibanda H

2. prerequisites
• Synthesis, storage, release and reuptake of catecholamines
• Signaling mechanisms at alpha and beta receptors
• Distribution of the different subtypes of alpha and beta receptors
• Effects of agonists on the different alpha and beta receptors

3. Lesson objectives
By the end of this lecture, we should be knowing:
 Classification of sympatholytic agents
 Mechanism of action of the different classes of Sympatholytics
 Clinical applications, adverse effects, and contraindications of the different sympatholytic agents

4. Classification of sympatholytic agents

5. Alpha adrenoceptor blockers
Irreversible alpha antagonists:
 phenoxybenzamine
Mechanism of action these bind irreversibly to alpha receptors, the blockade
is only reversed by synthesis of new receptors
Clinical use. Pheocromocytoma
Adverse effect: Orthostatic hypotension, reflux tachycardia

6. Reversible alpha antagonists:
 phentolamine
 Prazosin
 Doxazosin
 Alphuzosin
 Tamsulosin and others
Mechanism of Action: Reversible α adrenoceptor blockers bind to α receptors reversibly, in
that, the blockade can be overcome by increasing the dosage of the α agonists. They vary in
their affinity for the different subtypes of α receptors
Clinical applications: BPH, hypertension, Raynaud phenomenon, reversing local anesthesia
Adverse effects. Orthostatic hypotension, nasal congestion

7. Classification of Beta Adrenoceptor Blockers
• Non specific beta blockers
• Beta 1 Specific blockers
• Beta blockers with intrinsic sympathomimetic activity
• Third generation Beta blockers (β1-non selective)
• Third generation beta blockers (β1-selective)

8. Non specific beta blockers
 adolol
 Penbutolol
 Propranolol
 Timolol
β1 Selective blockers
 Atenolol
 Metoprolol
 Bisoprolol
 Esmolol
 Acebutolol
Beta blockers with intrinsic sympathomimetic
activity
Third generation Beta blockers (β1-non
selective)
 Carteolol,
 Carvedilol
 Bucindolol
 Labetalol
Third generation beta blockers (β1-
selective)
 Betaxolol
 Celiprolol
 Nebivolol

9. Third generation β blocker
• Third generation β blocker have other cardiovascular effects than just βl receptors blockade.
Vasodilation is one of those other effects, which make them useful in the treatment of
hypertension, heart failure and myocardial infarction.
• The mechanism by which this vasodilation comes about include:
 Blockade of α1 receptors
 Inducing production of Nitric oxide
 Being agonists at β2 receptors
 Blockade of Ca2+ entrance
 K+ channel opening
 Antioxidants activity

10. A table showing how third generation beta blocker exert their
addition cardiovascular action, especially vasodilation

13. Clinical applications of β blockers
Myocardial infarction
Congestive Heart failure
Hypertrophic obstructive cardiomyopathy (HOCM)
Tachyarrhythmia
Relief of catecholamine induced cardiomyopathy in Pheocromocytoma
Glaucoma
Hyperthyroidism
Students are required to get at least 10 more uses of β blockers

14. Adverse effects of beta blockers
• Bradycardia
• Bronchoconstriction if we block β2
• Fatigue, sleep & disturbances
• These drugs may blunt the body’s
ability to recognise hypoglycemia.
This can occur in DM patient
receiving insulin and/or oral
hypoglycemic

15. • References
Brunton, L., Parker, K., Blumenthal, D., & Buxton, I. (2008). Goodman &
Gilman’s Manual of pharmacology and Therapeutics. New York. McGraw-Hill
Katzung, B. G., Masters, B. S., & Trevor, J. A. (2012). Basic & Clinical
Pharmacology. New York. McGraw-Hill.