copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 17 adrenergic agonists
TRANSCRIPT
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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