1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 17 Adrenergic Agonists

2. 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adrenergic Agonists  Produce their effects by activating adrenergic receptors  Sympathomimetic  Broad spectrum of applications  Congestive heart failure (CHF)  Asthma  Preterm labor

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mechanisms of Adrenergic Receptor Activation  Direct receptor binding  Promotion of norepinephrine (NE) release  Inhibition of NE reuptake  Inhibition of NE inactivation

4. 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Overview of Adrenergic Agonists  Therapeutic applications and adverse effects of adrenergic receptor activation  Properties of representative adrenergic agonists  Discussion of adrenergic agonists in other chapters

5. 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Overview of the Adrenergic Agonists Cannot be used orally (MAO and COMT) Brief duration of action Cannot cross the blood-brain barrier (polar molecules) Catecholamines Can be given orally Metabolized slowly by MAO—longer half-life More able to cross the blood-brain barrier Noncatecholamines COMT = catechol-O-methyltransferase, MAO = monoamine oxidase.

6. 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 17–1. Structures of representative catecholamines and noncatecholamines.

7. 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Receptor specificity Most drugs in chapter Peripherally acting sympathomimetics Direct receptor activation Amphetamine, cocaine Indirect-acting sympathomimetics

8. 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Receptor Specificity Beta2 only Albuterol Beta1 and beta2 Isoproterenol Alpha1 and alpha2 Beta 1 and beta 2 Epinephrine

9. 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Clinical applications of alpha 1  Two responses for therapeutic use  Vasoconstriction (most common use) Blood vessels Blood vessels Skin Skin Viscera Viscera Mucous membranes Mucous membranes  Mydriasis

10. 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Drugs capable of activating alpha 1 receptors  Epinephrine  Norepinephrine  Phenylephrine  Dopamine

11. 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Therapeutic applications of alpha 1 activation  Hemostasis Arrests bleeding via vasoconstriction Arrests bleeding via vasoconstriction  Nasal decongestion Mucosal vasoconstriction Mucosal vasoconstriction  Adjunct to local anesthesia Delays absorption of local anesthetic Delays absorption of local anesthetic  Elevation of blood pressure Vasoconstriction Vasoconstriction  Mydriasis Radial muscle of the iris Radial muscle of the iris

12. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Adverse effects of alpha 1 activation  Hypertension Widespread vasoconstriction Widespread vasoconstriction  Necrosis Treatment with alpha 1 -blocking agent Treatment with alpha 1 -blocking agent  Bradycardia Response to vasoconstriction and elevated blood pressure (BP) Response to vasoconstriction and elevated blood pressure (BP)

13. 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Consequences of Alpha 2 Activation  Alpha 2 receptors in periphery  Located presynaptic ally  Activation inhibits NE release  Alpha 2 in CNS  Reduction of sympathetic outflow to heart and blood vessels  Relief of severe pain

14. 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Consequences of Beta 1 Activation  Therapeutic applications of beta 1 activation  Cardiac arrest Not preferred drug of choice Not preferred drug of choice  Heart failure Positive inotropic effect Positive inotropic effect  Shock Positive inotropic effect; increases heart rate Positive inotropic effect; increases heart rate  Atrioventricular heart block Enhances impulse conduction through atrioventricular (AV) node Enhances impulse conduction through atrioventricular (AV) node

15. 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Consequences of Beta 1 Activation  Adverse effects of beta 1 activation  Altered heart rate or rhythm Tachycardias or dysrhythmias Tachycardias or dysrhythmias  Angina pectoris Increased cardiac oxygen demand Increased cardiac oxygen demand

16. 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Consequences of Beta 2 Activation  Therapeutic applications of beta 2 activation  Asthma  Delay of preterm labor  Adverse effects of beta 2 activation  Hyperglycemia  Tremor

17. 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Consequences of Dopamine Receptor Activation  Activation of peripheral dopamine receptors causes dilation of the vasculature of the kidneys.

18. 18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Multiple Receptor Activation: Treatment of Anaphylactic Shock  Pathophysiology of anaphylaxis  Severe allergic response  Hypotension, bronchoconstriction, edema of the glottis  Treatment  Epinephrine, injected IM, is the treatment of choice for anaphylactic shock.

19. 19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adrenergic Agonists  Epinephrine  Norepinephrine  Isoproterenol  Dopamine  Dobutamine  Phenylephrine  Albuterol

20. 20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epinephrine  Therapeutic uses  Delays absorption of local anesthetic  Controls superficial bleeding  Elevates blood pressure  Mydriasis during ophthalmologic procedures  Overcomes AV block  Restores cardiac function in arrest  Bronchial dilation in asthma  Treatment of choice for anaphylactic shock

21. 21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epinephrine  Pharmacokinetics  Absorption  Inactivation  Adverse effects  Hypertensive crisis  Dysrhythmias  Angina pectoris  Necrosis following extravasation  Hyperglycemia

22. 22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epinephrine  Drug interactions  Monoamine oxidase (MAO) inhibitors  Tricyclic antidepressants  General anesthetics  Alpha-adrenergic blocking agents  Beta-adrenergic blocking agents

23. 23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Epinephrine  Preparations, dosage, and administration  EpiPen  IV (monitor closely)  IM  SubQ  Intracardiac—rarely used, only in asystole if IV not available  Intraspinal  Inhalation  Topical

24. 24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Norepinephrine  Receptor specificity  Alpha 1  Alpha 2  Beta 1  Chemical classification  Catecholamine  Therapeutic uses  Hypotensive states  Cardiac arrest

25. 25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Norepinephrine  Differs from epinephrine—does not activate beta 2 receptors  Does not promote hyperglycemia  Cannot be given orally (MAO and COMT)  Necrosis with extravasation  Drug interactions  MAO inhibitors (MAOIs), tricyclic antidepressants (TCAs), general anesthetics, adrenergic blocking agents

26. 26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Isoproterenol  Receptor specificity: beta 1 and beta 2  Chemical classification: catecholamine  Therapeutic uses  Cardiovascular AV heart block, arrest AV heart block, arrest  Asthma Bronchodilation—not used anymore Bronchodilation—not used anymore  Bronchospasm During anesthesia During anesthesia

27. 27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Isoproterenol  Adverse effects  Fewer than those of NE or epinephrine (does not activate alpha-adrenergic receptors)  Tachydysrhythmias and angina pectoris  Hyperglycemia in diabetes patients  Drug interactions  MAOIs, TCAs, beta-adrenergic blockers  Preparations and administration  IV, IM, and intracardiac injections

28. 28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dopamine  Receptor specificity  Low therapeutic dose: dopamine  Moderate therapeutic dose: dopamine and beta 1  Very high dose: apha 1, beta 1, and dopamine

29. 29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dopamine  Therapeutic uses  Shock Increases cardiac output Increases cardiac output Increases renal perfusion Increases renal perfusion  Heart failure Increases myocardial contractility Increases myocardial contractility  Acute renal failure (ARF) Was used to preserve renal function with ARF Was used to preserve renal function with ARF Early ARF—failed to protect renal function, shorten stays, or reduce need for renal transplant Early ARF—failed to protect renal function, shorten stays, or reduce need for renal transplant

30. 30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dopamine  Adverse effects  Tachycardia, dysrhythmias, anginal pain  Necrosis with extravasation  Drug interactions  MAOIs, TCAs, certain general anesthetics, diuretics  Preparations, dosage, and administration  Preparations: dispensed in aqueous solutions  Dosage: must be diluted  Administration: administered by IV

31. 31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dobutamine  Receptor specificity: beta 1  Chemical classification: catecholamine  Actions and uses  CHF  Adverse effects  Tachycardia  Drug interactions  MAOIs, TCAs, certain general anesthetics  Preparations, dosage, and administration  Continuous IV infusion

32. 32Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Phenylephrine  Receptor specificity  Alpha 1  Chemical classification  Noncatecholamine  Therapeutic uses  Reduces nasal congestion (locally)  Elevates blood pressure (parenterally)  Dilates pupils (eye drops)  Local anesthetic (delays absorption)

33. 33Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Albuterol  Receptor specificity: beta 2  Chemical classification: noncatecholamine  Therapeutic uses  Asthma (selective for beta 2 ) Replaced isoproterenol in treatment Replaced isoproterenol in treatment  Adverse effects  Minimal at therapeutic doses  Will activate beta 1 receptors at higher doses  Tremor most common; also tachycardia