Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 18 Adrenergic Antagonists

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adrenergic Antagonists  Cause direct blockade of adrenergic receptors  With one exception, all produce reversible (competitive) blockade  Most adrenergic antagonists are more selective than the adrenergic agonists.  Two major groups  Alpha-adrenergic blocking agents  Beta-adrenergic blocking agents

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adrenergic Antagonists  Alpha-adrenergic antagonists I: therapeutic and adverse response to alpha blockade  Alpha-adrenergic antagonists II: properties of individual alpha blockers  Beta-adrenergic antagonists I: therapeutic and adverse responses to beta blockade  Beta-adrenergic antagonists II: properties of individual beta blockers

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications of Alpha Blockade  Essential hypertension  Lowers blood pressure by blocking alpha 1 receptors on arterioles and veins, causing vasodilation  Reversal of toxicity from alpha 1 agonists  Benign prostatic hyperplasia  Reduced contraction of smooth muscle in the bladder neck and prostatic capsule

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications of Alpha Blockade  Pheochromocytoma  Catecholamine-secreting tumor  Usually located in adrenal medulla  Principal cause of hypertension is usually activation of alpha 1 receptors, but beta 1 receptors can also contribute  Treatment: best option is surgery Inoperable tumor: alpha 1 antagonists suppress hypertension Inoperable tumor: alpha 1 antagonists suppress hypertension Surgery: before surgery, manipulation of tumor can cause massive catecholamine release Surgery: before surgery, manipulation of tumor can cause massive catecholamine release

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.  Raynaud’s disease  Peripheral vascular disorder  Vasospasms in the toes and fingers  Suppress symptoms by preventing alpha- mediated vasoconstriction  Ineffective against other peripheral vascular disorders that involve inappropriate vasoconstriction Therapeutic Applications of Alpha Blockade

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adverse Effects of Alpha 1 Blockade  Detrimental effects result from blockade of alpha 1 receptors  Effects from alpha 2 receptors are minor  Orthostatic hypotension  Blockade of alpha receptors on veins  Reduced muscle tone in the venous wall  Upon standing, blood pools in the veins  Return of blood to the heart reduced  Cardiac output decreased: blood pressure drops

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adverse Effects of Alpha 1 Blockade  Reflex tachycardia  Reflex to increase heart rate via the autonomic nervous system (ANS)  Nasal congestion  Dilates the blood vessels of the nasal mucosa  Inhibition of ejaculation  Alpha 1 activation required for ejaculation  Impotence is reversible; resolves when drug is discontinued  Sodium retention and increased blood volume  Reduced BP promotes renal retention of sodium and water  Usually combined with diuretic when used for hypertension

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adverse Effects of Alpha 2 Blockade  The most significant adverse effect associated with alpha 2 blockade— potentiation of the reflex tachycardia

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alpha-Adrenergic Antagonists II  Prazosin  Terazosin  Doxazosin  Tamsulosin  Alfuzosin  Phentolamine  Phenoxybenzamine

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Prazosin  Actions and uses  Pharmacokinetics  Adverse effects  Preparations, dosage, and administration

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Terazosin  Actions and uses  Pharmacokinetics  Adverse effects  Preparations, dosage, and administration

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Doxazosin  Actions and uses  Pharmacokinetics  Adverse effects  Preparations, dosage, and administration

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Tamsulosin  Actions and uses  Pharmacokinetics  Adverse effects  Drug interactions  Preparations, dosage, and administration

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alfuzosin  Actions and uses  Pharmacokinetics  Adverse effects  Drug interactions  Preparations, dosage, and administration

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phentolamine  Actions and uses  Adverse effects  Preparations, dosage, and administration

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenoxybenzamine  Actions and uses  Adverse effects  Preparations, dosage, and administration

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists I  Therapeutic applications of beta blockade  Angina pectoris  Hypertension  Cardiac dysrhythmias  Myocardial infarction  Heart failure  Hyperthyroidism  Migraine  Stage fright  Pheochromocytoma  Glaucoma

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists I  Adverse effects of beta blockade  Adverse effects involve both beta 1 and beta 2 blockade.

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists I  Adverse effects of beta 1 blockade  Bradycardia  Reduced cardiac output  Precipitation of heart failure  AV heart block  Rebound cardiac excitation

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists I  Adverse effects of beta 2 blockade  Bronchoconstriction  Inhibition of glycogenolysis

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists II: Propranolol  Pharmacologic effects  Pharmacokinetics  Therapeutic uses  Adverse effects  Bradycardia  AV heart block  Heart failure  Rebound cardiac excitation

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists II: Propranolol  Adverse effects (cont’d)  Bronchoconstriction  Inhibition of glycogenolysis  CNS effects  Precautions, warnings, and contraindications  Severe allergy  Diabetes  Cardiac, respiratory, and psychiatric disorders

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists II: Propranolol  Drug interactions  Calcium channel blockers  Insulin  Preparations, dosage, and administration  General dosing considerations  Preparations  Dosage

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists II: Metoprolol  Pharmacologic effects  Pharmacokinetics  Therapeutic uses  Adverse effects  Precautions, warnings, and contraindications  Preparations, dosage, and administration

26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta-Adrenergic Antagonists II: Other Beta-Adrenergic Blockers  Receptor specificity: selective blockade  Pharmacokinetics  Therapeutic uses  Adverse effects  Intrinsic sympathomimetic activity (partial agonist activity)  Dosage and administration