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Chapter 17

Adrenergic Agonists

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Adrenergic Agonists Produce their effects by activating adrenergic

receptors Sympathomimetic Broad spectrum of applications

Congestive heart failure (CHF) Asthma Preterm labor

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Mechanisms of Adrenergic Receptor Activation

Direct receptor binding Promotion of norepinephrine (NE) release Inhibition of NE reuptake Inhibition of NE inactivation

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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

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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.

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Fig. 17–1.  Structures of representative catecholamines and noncatecholamines.

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Receptor specificity

• Most drugs in chapter • Peripherally acting

sympathomimetics• Direct receptor activation

• Amphetamine, cocaine• Indirect-acting

sympathomimetics

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Receptor Specificity

• Beta2 onlyAlbuterol

• Beta1 and beta2Isoproterenol

• Alpha1 and alpha2 • Beta1 and beta2

Epinephrine

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Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation

Clinical applications of alpha1 Two responses for therapeutic use

Vasoconstriction (most common use)• Blood vessels• Skin• Viscera• Mucous membranes

Mydriasis

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Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation

Drugs capable of activating alpha1 receptors Epinephrine Norepinephrine Phenylephrine Dopamine

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Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation

Therapeutic applications of alpha1 activation Hemostasis

• Arrests bleeding via vasoconstriction Nasal decongestion

• Mucosal vasoconstriction Adjunct to local anesthesia

• Delays absorption of local anesthetic Elevation of blood pressure

• Vasoconstriction Mydriasis

• Radial muscle of the iris

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Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation

Adverse effects of alpha1 activation Hypertension

• Widespread vasoconstriction Necrosis

• Treatment with alpha1-blocking agent Bradycardia

• Response to vasoconstriction and elevated blood pressure (BP)

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Clinical Consequences of Alpha2 Activation

Alpha2 receptors in periphery Located presynaptic ally Activation inhibits NE release

Alpha2 in CNS Reduction of sympathetic outflow to heart and

blood vessels Relief of severe pain

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Clinical Consequences of Beta1 Activation

Therapeutic applications of beta1 activation Cardiac arrest

• Not preferred drug of choice Heart failure

• Positive inotropic effect Shock

• Positive inotropic effect; increases heart rate Atrioventricular heart block

• Enhances impulse conduction through atrioventricular (AV) node

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Clinical Consequences of Beta1 Activation

Adverse effects of beta1 activation Altered heart rate or rhythm

• Tachycardias or dysrhythmias Angina pectoris

• Increased cardiac oxygen demand

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Clinical Consequences of Beta2 Activation

Therapeutic applications of beta2 activation Asthma Delay of preterm labor

Adverse effects of beta2 activation Hyperglycemia Tremor

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Clinical Consequences of Dopamine Receptor Activation

Activation of peripheral dopamine receptors causes dilation of the vasculature of the kidneys.

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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.

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Adrenergic Agonists Epinephrine Norepinephrine Isoproterenol Dopamine Dobutamine Phenylephrine Albuterol

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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

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Epinephrine Pharmacokinetics

Absorption Inactivation

Adverse effects Hypertensive crisis Dysrhythmias Angina pectoris Necrosis following extravasation Hyperglycemia

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Epinephrine Drug interactions

Monoamine oxidase (MAO) inhibitors Tricyclic antidepressants General anesthetics Alpha-adrenergic blocking agents Beta-adrenergic blocking agents

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Epinephrine Preparations, dosage, and administration

EpiPen IV (monitor closely) IM SubQ Intracardiac—rarely used, only in asystole if IV not

available Intraspinal Inhalation Topical

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Norepinephrine Receptor specificity

Alpha1

Alpha2

Beta1

Chemical classification Catecholamine

Therapeutic uses Hypotensive states Cardiac arrest

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Norepinephrine Differs from epinephrine—does not activate

beta2 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

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Isoproterenol

Receptor specificity: beta1 and beta2 Chemical classification: catecholamine Therapeutic uses

Cardiovascular• AV heart block, arrest

Asthma• Bronchodilation—not used anymore

Bronchospasm• During anesthesia

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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

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Dopamine Receptor specificity

Low therapeutic dose: dopamine Moderate therapeutic dose: dopamine and beta1 Very high dose: apha1, beta1, and dopamine

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Dopamine Therapeutic uses

Shock• Increases cardiac output• Increases renal perfusion

Heart failure• Increases myocardial contractility

Acute renal failure (ARF)• Was used to preserve renal function with ARF• Early ARF—failed to protect renal function, shorten

stays, or reduce need for renal transplant

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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

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Dobutamine

Receptor specificity: beta1 Chemical classification: catecholamine Actions and uses

CHF Adverse effects

Tachycardia Drug interactions

MAOIs, TCAs, certain general anesthetics Preparations, dosage, and administration

Continuous IV infusion

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Phenylephrine Receptor specificity

Alpha1

Chemical classification Noncatecholamine

Therapeutic uses Reduces nasal congestion (locally) Elevates blood pressure (parenterally) Dilates pupils (eye drops) Local anesthetic (delays absorption)

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Albuterol

Receptor specificity: beta2 Chemical classification: noncatecholamine Therapeutic uses

Asthma (selective for beta2)• Replaced isoproterenol in treatment

Adverse effects Minimal at therapeutic doses Will activate beta1 receptors at higher doses Tremor most common; also tachycardia