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59-291 Section 2, Lecture 4
Adrenergic Receptor Agonists
• Termed sympathomimetic drugs
• Divided into three groups
• Direct-acting agonists
– Catecholamines
– Noncatecholamines
• Indirect-acting agonists
• Mixed acting agonists
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Catecholamines
• Naturally occurring:
– NE: endogenous sympathetic neurotransmitter
– EP: The principle hormone of adrenal medulla
– Dopamine: Precursor to EP and NE
• Synthetic: Isoproterenol, dobutamine
• Structure: catechol moiety, ethylamine side chain
• Inactivation: COMT, MAO; found in the gut, liver
and other tissues
• Low oral bioavailability, short plasma half-lives
• Must be administered parenterally for systemic
actions; Anaphylactic shock
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Mechanisms and Effects
• Cathecolamines differ in their affinities and
specificities for receptors
• Size of alkyl substitution on the amine
nitrogen determines the relative affinity for
a and b receptors
• Larger alkyl group, higher affinity for breceptors; Isoproterenol
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Ethylamine
NE: Constricts all blood vessels
EP: Constricts some blood
vessels but dilates the others
Dopamine: stimulates release of
NE from sympathetic nerves
(Direct and indirect agonist)
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Drug
Pharmacologic Effect (and Receptor)
Direct-acting catecholamines
Dobutamine
Cardiac stimulation (β1) and vasodilation (β2)
Dopamine*
Renal vasodilation (D1), cardiac stimulation
(β1), and increased blood pressure (β1 and α1)
Epinephrine
Vasoconstriction and increased blood pressure
(α1), cardiac stimulation (β1), and
bronchodilation (β2)
Isoproterenol
Cardiac stimulation (β1) and bronchodilation
(β2)
Norepinephrine
Vasoconstriction and increased blood pressure
(α1)
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Drug
Clinical Use
Direct-acting catecholamines
Dobutamine
Cardiogenic shock, acute heart failure, and cardiac stimulation during
heart surgery
Dopamine*
Cardiogenic shock, septic shock, heart failure, and adjunct to fluid
administration in hypovolemic shock
Epinephrine
Anaphylactic shock, cardiac arrest, ventricular fibrillation, reduction in
bleeding during surgery, and prolongation of the action of local
anesthetics
Isoproterenol
Asthma, refractory atrioventricular block, and refractory bradycardia
Norepinephrine
Hypotension and shock
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Sys, Dias., MeanArt. P
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Adverse effects: -excessive vasoconstriction leading to ischemia
-reduces blood flow to vital organs such as
kidneys; cause excessive cardiac stimulation
leading to myocardial ischemia or arrythmias
-b-adrenergic agonists: hyperglycemia
undesirable in diabetics
Indirect-Acting
Amphetamine- induces the
release of NE
Cocaine-prevents reuptake of NE
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Mixed-Acting: the name says it all! Direct and Indirect acting
adrenergic agonists
activate both α and b receptors Ephedrine and
Pseudoephedrine vasoconstriction via a1 receptors; useful as
nasal decongestants; via b bronchodilate
Adverse effects: tachycardia, hypertension, urinary retention
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Practice Questions
• Which of the following drugs does
stimulate mainly b receptors
–
–
–
–
NE
EP
Isoproterenol
Dopamine
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• Which of the following catecolamines may
cause reflex bradycardia due to stimulation
of a1 receptors?
–
–
–
–
NE
EP
Dopamine
Isoproterenol
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• What is the treatment of choice for
anaphylactic shock
–
–
–
–
NE
EP
Isoproterenol
Dobutamine
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