Download Epinephrine

Adrenergic Agonists
Adrenergic Agonists
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Produce their effects by activating adrenergic
receptors
Sympathomimetic
Broad spectrum of applications
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Congestive heart failure (CHF)
Asthma
Preterm labor
Mechanisms of Adrenergic
Receptor Activation
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Direct receptor binding
Promotion of norepinephrine (NE) release
Inhibition of NE reuptake
Inhibition of NE inactivation
Overview of Adrenergic Agonists
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Therapeutic applications and adverse effects
of adrenergic receptor activation
Properties of representative adrenergic
agonists
Discussion of adrenergic agonists in other
chapters
Overview of the
Adrenergic Agonists
Catecholamines
• Cannot be used orally (MAO and
COMT)
• Brief duration of action
• Cannot cross the blood-brain barrier
(polar molecules)
Noncatecholamines
• Can be given orally
• Metabolized slowly by MAO—longer
half-life
• More able to cross the blood-brain
barrier
COMT = catechol-O-methyltransferase, MAO = monoamine oxidase.
Fig. 17–1.
Structures of representative catecholamines and noncatecholamines.
• Most drugs in chapter
• Peripherally acting
sympathomimetics
• Direct receptor activation
Receptor
specificity
• Amphetamine, cocaine
• Indirect-acting
sympathomimetics
Receptor Specificity
Albuterol
Isoproterenol
Epinephrine
• Beta2 only
• Beta1 and beta2
• Alpha1 and alpha2
• Beta1 and beta2
Therapeutic Applications and Adverse
Effects of Adrenergic Receptor Activation
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Clinical applications of alpha1
Two responses for therapeutic use
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Vasoconstriction (most common use)
• Blood vessels
• Skin
• Viscera
• Mucous membranes
Mydriasis
Therapeutic Applications and Adverse
Effects of Adrenergic Receptor Activation
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Drugs capable of activating alpha1 receptors
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Epinephrine
Norepinephrine
Phenylephrine
Dopamine
Therapeutic Applications and Adverse
Effects of Adrenergic Receptor Activation
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Therapeutic applications of alpha1 activation
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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
Therapeutic Applications and Adverse
Effects of Adrenergic Receptor Activation
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Adverse effects of alpha1 activation
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Hypertension
• Widespread vasoconstriction
 Necrosis
• Treatment with alpha1-blocking agent
 Bradycardia
• Response to vasoconstriction and elevated blood
pressure (BP)
Clinical Consequences of
Alpha2 Activation
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Alpha2 receptors in periphery
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Located presynaptic ally
Activation inhibits NE release
Alpha2 in CNS
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Reduction of sympathetic outflow to heart and
blood vessels
Relief of severe pain
Clinical Consequences of
Beta1 Activation
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Therapeutic applications of beta1 activation
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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
Clinical Consequences of
Beta1 Activation
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Adverse effects of beta1 activation
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Altered heart rate or rhythm
• Tachycardias or dysrhythmias
Angina pectoris
• Increased cardiac oxygen demand
Clinical Consequences of
Beta2 Activation
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Therapeutic applications of beta2 activation
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Asthma
Delay of preterm labor
Adverse effects of beta2 activation
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Hyperglycemia
Tremor
Clinical Consequences of
Dopamine Receptor Activation
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Activation of peripheral dopamine receptors
causes dilation of the vasculature of the
kidneys.
Multiple Receptor Activation:
Treatment of Anaphylactic Shock
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Pathophysiology of anaphylaxis
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Severe allergic response
Hypotension, bronchoconstriction, edema of the
glottis
Treatment
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Epinephrine, injected IM, is the treatment of
choice for anaphylactic shock.
Adrenergic Agonists
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Epinephrine
Norepinephrine
Isoproterenol
Dopamine
Dobutamine
Phenylephrine
Albuterol
Epinephrine
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Therapeutic uses
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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
Epinephrine
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Pharmacokinetics
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Absorption
Inactivation
Adverse effects
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Hypertensive crisis
Dysrhythmias
Angina pectoris
Necrosis following extravasation
Hyperglycemia
Epinephrine
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Drug interactions
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Monoamine oxidase (MAO) inhibitors
Tricyclic antidepressants
General anesthetics
Alpha-adrenergic blocking agents
Beta-adrenergic blocking agents
Epinephrine
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Preparations, dosage, and administration
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EpiPen
IV (monitor closely)
IM
SubQ
 Intracardiac—rarely used, only in asystole if IV not
available
 Intraspinal
 Inhalation
 Topical
Norepinephrine
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Receptor specificity
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Chemical classification
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Alpha1
Alpha2
Beta1
Catecholamine
Therapeutic uses
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Hypotensive states
Cardiac arrest
Norepinephrine
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Differs from epinephrine—does not activate
beta2 receptors
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Does not promote hyperglycemia
Cannot be given orally (MAO and COMT)
Necrosis with extravasation
Drug interactions
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MAO inhibitors (MAOIs), tricyclic antidepressants
(TCAs), general anesthetics, adrenergic blocking
agents
Isoproterenol
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Receptor specificity: beta1 and beta2
Chemical classification: catecholamine
Therapeutic uses
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Cardiovascular
• AV heart block, arrest
Asthma
• Bronchodilation—not used anymore
Bronchospasm
• During anesthesia
Isoproterenol
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Adverse effects
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Drug interactions
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Fewer than those of NE or epinephrine (does not
activate alpha-adrenergic receptors)
Tachydysrhythmias and angina pectoris
Hyperglycemia in diabetes patients
MAOIs, TCAs, beta-adrenergic blockers
Preparations and administration
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IV, IM, and intracardiac injections
Dopamine
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Receptor specificity
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Low therapeutic dose: dopamine
Moderate therapeutic dose: dopamine and beta1
Very high dose: apha1, beta1, and dopamine
Dopamine
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Therapeutic uses
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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
Dopamine
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Adverse effects
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Drug interactions
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Tachycardia, dysrhythmias, anginal pain
Necrosis with extravasation
MAOIs, TCAs, certain general anesthetics,
diuretics
Preparations, dosage, and administration
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Preparations: dispensed in aqueous solutions
Dosage: must be diluted
Administration: administered by IV
Dobutamine
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Receptor specificity: beta1
Chemical classification: catecholamine
Actions and uses
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Adverse effects
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Tachycardia
Drug interactions
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CHF
MAOIs, TCAs, certain general anesthetics
Preparations, dosage, and administration
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Continuous IV infusion
Phenylephrine
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Receptor specificity
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Chemical classification
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Alpha1
Noncatecholamine
Therapeutic uses
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Reduces nasal congestion (locally)
Elevates blood pressure (parenterally)
Dilates pupils (eye drops)
Local anesthetic (delays absorption)
Albuterol
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Receptor specificity: beta2
Chemical classification: noncatecholamine
Therapeutic uses
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Asthma (selective for beta2)
• Replaced isoproterenol in treatment
Adverse effects
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Minimal at therapeutic doses
Will activate beta1 receptors at higher doses
Tremor most common; also tachycardia