1. PHARMACOLOGY OF ANS part 3 General Pharmacology M212
Dr. Laila M. Matalqah
Ph.D. Pharmacology

2. The adrenergic antagonists
also called adrenergic blockers or sympatholytic agents
bind to adrenoceptors but do not trigger the usual receptor- mediated intracellular effects.
α-Adrenergic Blocking Agents
β-Adrenergic Blocking Agents
Drugs affecting Neurotransmitter Release Or Uptake

4. I. α-Adrenergic Blocking Agents
A: Non-selective α- adrenergic blocker
1. Phenoxybenzamine
Link covalently to both α1- and α2-receptors
Irreversible, non-competitive
Action last 24 hours
Action: prevents vasoconstriction of peripheral blood vessels, decreased peripheral resistance, provokes a refl ex tachycardia
this drug is unsuccessful in maintaining lowered blood pressure in hypertension, why?
used in the treatment of pheochromocytoma, a catecholamine- secreting tumor of cells derived from the adrenal medulla.
2. Phentolamine
Furthermore, the ability to
block presynaptic inhibitory α2 receptors in the heart can contribute
to an increased cardiac output. [Note: These receptors, when
blocked, will result in more norepinephrine release, which stimulates
β receptors on the heart, increasing cardiac output.]

5. I. α-Adrenergic Blocking Agents
B: selective α- adrenergic blocker:
are selective competitive blockers of the α1 receptor.
prevents vasoconstriction of peripheral blood vessels and decreased peripheral resistance
1.Prazosin, Terazosin, Doxazosin (for hypertension and congestive heart failure)
By dilating both arteries and veins, these agents decrease preload and afterload, leading to an increase in cardiac output
2. Tamsulosin, and Alfuzosin
Used for benign prostatic hypertrophy (BPH)
Blockade of the α1- receptors decreases tone in the smooth muscle of the bladder neck and prostate and improves urine flow.

7. I. α-Adrenergic Blocking Agents
Side effects

8. II. β-adrenergic blocking agents
nonselective β antagonist
Propranolol
Antagonist both β1 and β2 receptors
Action:
Negative inotropic effect : reduced cardiac output
Negative chronotropic effects: depresses sinoatrial and atrioventricular activity cause Bradycardia
Peripheral vasoconstriction (prevents β2-mediated vasodilation)
Bronchoconstriction: contraindicated in patients with COPD or asthma
decreased glycogenolysis and decreased glucagon secretion.— Hypoglycemia

9. II. β-adrenergic blocking agents
nonselective β antagonist
Propranolol
Therapeutic Uses
Hypertension??? mechanism?
Migraine
Angina pectoris? decrease in heart rate, Cardiac output, work, and oxygen consumption
Myocardial infarction
Hyperthyrodism
Decreased cardiac output is the primary mechanism, but
inhibition of renin release from the kidney, decrease in total
peripheral resistance with long term use, and decreased sympathetic
outflow from the CNS also contribute to propranolol’s antihypertensive
effects

10. II. β-adrenergic blocking agents
nonselective β antagonist
Propranolol
Pharmacokinetics
oral administration
completely absorbed
highly lipophilic.
It is subject to first-pass effect,

11. Side effects of propranolol

12. Remember
Treatment with β blockers must never be stopped quickly because of the risk of precipitating cardiac arrhythmias,
The β blockers must be tapered off gradually for at least a few weeks.
Long-term treatment with a β antagonist leads to up- regulation of the β receptor.

13. Side effects of propranolol
Bronchoconstriction: so it must never be used in treating any individual with COPD or asthma (C/I)
Arrhythmias ? HOW? Up-regulation of receptor? Tapered dose?
Sexual impairment
Metabolic disturbances: Fasting hypoglycemia
CNS effects: depression, dizziness, lethargy, fatigue, weakness, visual disturbances, hallucinations, and others

14. II. β-adrenergic blocking agents
nonselective β antagonist
2. Timolol and nadolol:
They are more potent than propranolol
Block β1- and β2-adrenoceptors
Nadolol has a very long duration of action
Timolol reduces the production of aqueous humor in the eye.
It is used topically in the treatment of chronic open-angle glaucoma

15. II. β-adrenergic blocking agents
Selective β1 antagonists
Metoprolol, Atenolol, Bisoprolol, Betaxolol, Esmolol
They are cardioselective β1 blockers
Cardioselective at low doses and is lost at high doses
Therapeutic use:
hypertension
useful in hypertensive patients with Asthma and COPD.
diabetic hypertensive patients who are receiving insulin or oral hypoglycemic agents.

16. II. β-adrenergic blocking agents
Antagonists of both α and β
Labetalol and carvedilol:
α1-blocking actions that produce peripheral vasodilation, thereby reducing blood pressure
They do not alter serum lipid or blood glucose levels
Therapeutic use in hypertension in elderly and heart failure?
I.V Labetalol as an alternative to methyldopa in the treatment of pregnancy-induced hypertension.

18. III. Drugs affecting neurotransmitter release or uptake
A. Reserpine
blocks the transport of norepinephrine, dopamine, and serotonin from the cytoplasm into storage vesicles in the adrenergic nerves of all body tissues
B. Guanethidine
blocks the release of stored norepinephrine from storage vesicles

21. QA Choose the correct β-blocker???
The best treatment for hypertensive patients with Asthma is
The best treatment for hypertensive patients with hyperlipidemia is
The best treatment for hypertensive elderly patients is
The best treatment for hypertensive patients with Diabetes is
The best treatment for hypertensive patients with angina
The best treatment for hypertensive pregnant lady is------

22. THE END of ANS