In two previous blogs we discussed alpha adrenergic and beta adrenergic blockers, medications that inhibit various actions of the sympathetic nervous system. In this blog, we’ll take a look at adrenergic agonists known as sympathomimetic agents that have the opposite effect. Let’s review how they work.

Basic Review

Adrenergic drugs are substances that can either simulate or impede the actions of the sympathetic nervous system. They accomplish this by influencing the release or activity of the hormones norepinephrine (noradrenaline) and epinephrine (adrenaline) (Brittanica, 2018). These hormones, which are secreted by the adrenal gland, are responsible for the body’s “fight-or-flight” response, causing a constriction of blood vessels, a rise in blood pressure, and an increase in heart rate and force of cardiac contractions. Sympathomimetic agents simulate the action of the sympathetic nervous system and enhance these effects.

Mechanism of Action

In normal sympathetic nervous system physiology, impulses travel down the pre-synaptic neuron where cellular changes occur. Neurotransmitters are released at the synapse and trigger adrenoreceptors located on the post-synaptic nerve. Adrenergic agonists have three mechanisms of action: direct-acting, indirect-acting, or dual-acting. Direct-acting sympathomimetics imitate normal physiology and directly activate the adrenergic receptors. They are classified based on their activity on specific adrenoreceptors: alpha-1, alpha-2, beta-1, and beta-2.

• Alpha-1 (α₁) agonists contract most vascular smooth muscle
• Alpha-2 (α₂) agonists contract mixed smooth muscle
• Beta-1 (β₁) agonists increase heart rate
• Beta-2 (β₂) agonists relax respiratory and uterine smooth muscle

Indirect-acting adrenergic agonists work in three different ways. They can 1. stimulate and increase the release of neurotransmitters such as norepinephrine from the nerve endings into the synapses; 2. decrease the re-uptake of neurotransmitters into the pre-synaptic nerve; and 3. decrease the enzymatic metabolism of neurotransmitters. Indirect-acting sympathomimetics include drugs such as amphetamines and cocaine (Farzam, Kidron & Lakhkar, 2022).
 
Dual-acting or mixed-action adrenergics stimulate both adrenergic receptor sites and the release of norepinephrine from nerve endings. Dual-acting medications include ephedrine and pseudoephedrine.


 

Examples of Direct-Acting Adrenergic Agonists
Drug Name	Receptor	Indication
Phenylephrine	α1	Decongestant, vasopressor
Oxymetazoline	α1, α2	Decongestant, rosacea
Methyldopa	α2	Hypertension, gestational hypertension
Clonidine	α2	Hypertention, attention deficit hyperactivity disorder (ADHD)
Dexmedetomidine	α2	Sedation
Dobutamine	β1	Cardiogenic shock and heart failure
Bronchodilators (i.e. Albuterol)	β2	Obstructive lung disease, asthma
Mirabegron	β3 receptors in the bladder	Overactive bladder (urinary incontinence and frequency)
Norepinephrine	Non-selective (α1, α2, β1)	Shock, hypotension
Epinephrine	Non-selective (α1, α2,  β1, β2)	Cardiac arrest, anaphylaxis, croup
Dopamine	Non-selective (α1, β1)	Hypotension, bradycardia, cardiac arrest
Isoproterenol	Non-selective (β1, β2)	Bradycardia, heart block

Nursing Considerations

When administering adrendergic agonists, be sure to monitor for adverse effects such as hypertension and reflex bradycardia (α₁); hypotension, dry mouth, and sedation (α₂); tachycardia, palpitations, tachyarrhythmias, and anxiety (β₁); tremors and tachycardia (β₂). Patients taking alpha-2 agonists are at risk for substance abuse while those taking beta-2 agonists should be monitored for paradoxical bronchospasm.
 
For complete information, please consult the drug’s specific package insert or the Nursing2022 Drug Handbook® + Drug Updates.
 

References
 
Britannica, T. Editors of Encyclopaedia (2018, July 13). adrenergic drug. Encyclopedia Britannica. https://www.britannica.com/science/adrenergic-drug
 
Farzam, K., Kidron, A. & Lakhkar, A.D. (2022, July 3). Adrenergic Drugs. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK534230/#:~:text=Adrenergic%20drugs%20are%20a%20broad,to%20induce%20various%20physiologic%20effects.