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

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

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.]

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.

I. α-Adrenergic Blocking Agents Side effects

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

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

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

Side effects of propranolol

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.

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

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

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.

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.

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

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------

THE END of ANS