1. Adrenergic Antagonist
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-20
April 03, 2012

2. Adrenergic Antagonists
Bind to adrenoceptors but do not trigger the usual receptor-mediated intracellular effects
Act by either reversibly or irreversibly attaching to the receptor
Classified according to their relative affinities for α or β receptors in the PNS
Types of adrenergic antagonists:
α-Adrenergic antagonists
β-Adrenergic antagonists
Drugs affecting neurotransmitter release and uptake

3. Adrenergic Antagonists
Types of adrenergic antagonists:
α-Adrenergic antagonists
β-Adrenergic antagonists
Drugs affecting neurotransmitter release and uptake

4. α-Adrenergic Antagonists
Drugs that block α-adrenoceptors profoundly affect blood pressure
Few α-adrenergic antagonists:
Phenoxybenzamine
Phentolamine
Prazosin
Terazosin
Doxazosin

5. Phenoxybenzamine
Nonselective, linking covalently to both α1-postsynaptic and α2-presynaptic receptors
Block is irreversible and noncompetitive, and the only mechanism the body has for overcoming the block is to synthesize new adrenoceptors
Actions last about 24 hrs after a single administration
After the drug is injected, a delay of a few hrs occurs before a blockade develops, because the molecule must undergo biotransformation to the active form

6. Phenoxybenzamine: Therapeutic Use
By blocking α receptors, it prevents vasoconstriction of peripheral blood vessels
Used in the treatment of pheochromocytoma, a catecholamine-secreting tumor of cells derived from the adrenal medulla
Sometimes effective in treating Raynaud's disease
Pheochromocytoma-Neuroendocrine tumor of adrenal gland
Raynaud’s disease-discoloration of finger, toe or other part of the body
Phenoxybenzamine: Adverse Effects
Can cause postural hypotension, nasal stuffiness, nausea, and vomiting

7. Phentolamine Produces a competitive block of α1 and α2 receptors
Action lasts for 4 hrs after a single administration
Therapeutic use: Short-term management of pheochromocytoma
Adverse Effects: Postural hypotension, induces reflex cardiac stimulation and tachycardia, trigger arrhythmias and anginal pain
Pheochromocytoma-Neuroendocrine tumor of adrenal gland
Arrythmias-Heart rate is too fast or too low or irregular
Anginal pain-chest pain

8. Adrenergic Antagonists
Types of adrenergic antagonists:
α-Adrenergic antagonists
β-Adrenergic antagonists
Drugs affecting neurotransmitter release and uptake

9. β-Adrenergic Blocking Agents
β-Blockers are competitive antagonists
All β-blockers lower blood pressure in hypertension
β-Blockers are effective in treating angina, cardiac arrhythmias, myocardial infarction, congestive heart failure, hyperthyroidism, and glaucoma
Myocardial infraction: A heart attack occurs when blood flow to a part of your heart is blocked for a long enough time
Glaucoma refers to a group of eye conditions that lead to damage to the optic nerve

10. Names of β-Adrenergic Antagonists
Propranolol
Acebutolol
Atenolol
Metoprolol

11. Propranolol
A nonselective β antagonist and blocks both β1 and β2 receptors
Sustained-release preparations for once-a-day dosing are available

12. Propranolol: Therapeutic Use
Hypertension:
Lowers blood pressure in hypertension
Glaucoma:
Effective in diminishing intraocular pressure in glaucoma
Migraine:
Effective in reducing migraine
Angina pectoris
Useful in the chronic management of angina
Myocardial infarction:
Protective effect on the myocardium
Myocardium: Muscular tissue of heart

13. Propranolol: Adverse Effects
Bronchoconstriction:
Has a serious and potentially lethal side effect when administered to an asthmatic
An immediate contraction of the bronchiolar smooth muscle prevents air from entering the lungs
Arrhythmias:
Treatment with β-blockers must never be stopped quickly because of the risk of precipitating cardiac arrhythmias
Disturbances in metabolism:
β-Blockade leads to decreased glycogenolysis and decreased glucagon secretion

14. Propranolol: Drug Interactions
Drugs that interfere with the metabolism of propranolol, such as cimetidine, fluoxetine, and paroxetine may potentiate its antihypertensive effects.
Conversely, those that stimulate its metabolism, such as barbiturates, and phenytoin can decrease its effects

15. Acebutolol, Atenolol, Metoprolol
Selective β1 antagonists
Therapeutic use in hypertension:
Useful in hypertensive patients with impaired pulmonary function
Useful in diabetic hypertensive patients who are receiving insulin or oral hypoglycemic agents

16. Adrenergic Antagonists
Types of adrenergic antagonists:
α-Adrenergic antagonists
β-Adrenergic antagonists
Drugs affecting neurotransmitter release and uptake

17. Drugs Affecting Neurotransmitter Release or Uptake
These drugs act on the adrenergic neuron, either to interfere with neurotransmitter release or to alter the uptake of the neurotransmitter into the adrenergic nerve
Few names
Reserpine
Guanethidine

18. Reserpine Guanethidine
Blocks the transport of biogenic amines, norepinephrine, dopamine, and serotonin from the cytoplasm into storage vesicles
Causes the ultimate depletion of biogenic amines
The drug has a slow onset, a long duration of action, and effects that persist for many days after discontinuation
Guanethidine
Blocks the release of stored NE
Leads to gradual depletion of NE in nerve endings
Causes orthostatic hypotension