Sympathomimetics: Uses, common brands, and safety info

We’ve all been there—watching a scary movie when our heart starts beating fast, we can feel our blood pressure rising and our body gets tense. Stressful situations activate our body’s autonomic nervous system to kick into high gear by a sudden release of certain hormones. This activation stimulates our adrenal glands, part of our sympathetic nervous system, which triggers the release of naturally occurring substances known as catecholamines. Catecholamines include adrenaline (epinephrine), noradrenaline (norepinephrine), and to a lesser extent, dopamine. 

Manipulation of the sympathetic nervous system for therapeutic benefit through medications that mimic the action of epinephrine, norepinephrine, or dopamine are known as sympathomimetics. This broad class of medications can manage many conditions and ailments, including glaucoma, chronic obstructive pulmonary disease, low and high blood pressure, heart failure, nasal congestion, and asthma to name a few. Here we will categorize sympathomimetic medications used clinically based on their specific site of activity, as well as conditions they manage, and important safety information

* Due to the extent of conditions that sympathomimetics can help manage, this list of medications is not all-inclusive. 

What are sympathomimetics?

Sympathomimetics are medications that act as the name implies—they mimic or modify the activity of naturally occurring catecholamines of the sympathetic nervous system. The medications can be either naturally occurring or man-made. This class of medications is generally categorized based on their 1) mode of action (direct or indirect), and 2) their affinity to different receptor types.

Direct versus indirect

Sympathomimetic medications either directly act on one or more adrenoreceptors or may indirectly work to increase the concentration of naturally occurring (endogenous) catecholamine. This indirect increase can occur through several mechanisms. 

Receptor affinity

The body was a wide supply of different adrenoreceptors across many organ systems. Adrenoreceptors throughout the body are classified as alpha (α), beta (β), or dopamine receptors. Subsets of these main categories of receptors are focused on a location-specific pattern; for example, β1 receptors are localized in the heart muscle, whereas β2 receptors are more concentrated in the lungs. Sympathomimetics that act more specifically on β1 receptors are more helpful in managing heart conditions, like issues with blood pressure, whereas those that act more specifically on β2 receptors are more helpful in managing lung conditions, like asthma or chronic obstructive pulmonary disease (COPD). 

The distribution of these receptors is outlined in the list below:

• α1: Vascular smooth muscle and pupillary dilator muscle

• α2: Some vascular smooth muscle

• β1: Heart

• β2: Airways, vascular smooth muscle

• β3: Urinary bladder

• D1*: Renal blood vessels

* A discussion of medications that act upon dopamine adrenoreceptors is outside the scope of this article.

How do sympathomimetics work?

The actions of sympathomimetics can broadly be classified into seven types of responses:

1. Increasing smooth vascular muscle resistance (e.g., contraction)

2. Decreasing smooth vascular muscle (e.g., dilation)

3. Stimulation of the heart, leading to increased heart rate, contraction, and/or conduction

4. Prevent stimulation of the heart, leading to decreased heart rate, contraction, and/or conduction

5. Metabolic actions (e.g., the liver releases more glucose)

6. Endocrine actions (e.g., increasing or decreasing insulin release)

7. Actions in the central nervous system by increasing or decreasing certain chemical production or release 

The response to the use of this class of medications is fairly predictable with knowledge of how selective the medication is to the adrenoreceptor type, and the anticipated type of above response is based upon the location of those adrenoreceptors in specific cells, tissues, or organs. Ultimately, the response to a sympathomimetic drug depends on the concentration and proportion of adrenoceptors it can reach. 

What are sympathomimetics used for?

Due to the wide distribution throughout various tissues in the body on which adrenoceptors exist, sympathomimetics can be used to manage a vast array of medical conditions. 

• Heart conditions: low blood pressure, including that caused by dehydration or infection, high blood pressure, ischemic heart disease, heart attack (myocardial infarction)

• Lung conditions: asthma and COPD

• Allergic rhinitis

• Symptom management of the common cold, including postnasal drip 

• Eye conditions: glaucoma and conjunctivitis

• Neurologic conditions: management of chronic pain

• Psychiatric conditions: attention-deficit hyperactivity disorder (ADHD), narcolepsy

• Metabolic: weight loss

• Genitourinary: urinary incontinence/overactive bladder, benign prostatic hyperplasia (BPH)

Types of sympathomimetics 

Alpha adrenergic agonists

Stimulation of α1 adrenoreceptors generally results in vasoconstriction. Depending on the sympathomimetic used and localization of the adrenoreceptor it acts upon, you can see an increase in blood pressure (midodrine), relief of nasal congestion (Sudafed/pseudoephedrine), dilation of the pupil (Mydriacyl/tropicamide), or urinary retention.

Stimulation of α2 adrenoreceptors generally results in more relaxation of smooth muscle, and these medications can be useful in the management of high blood pressure (Kapvay/ clonidine), in the management of glaucoma by increasing outflow of aqueous humor (Alphagan P/brimonidine), or as a muscle relaxer (Zanaflex/tizanidine).

Alpha adrenergic antagonists

If activity upon α1 receptors is stimulatory and of α2 receptors is inhibitory, blocking or antagonism of these receptors can be expected to result in opposite effects. Alpha adrenergic receptor antagonists are generally nonselective, meaning that most block both α1 and α2 adrenoreceptors.

Medications that selectively block α1 adrenoreceptors prevent smooth muscle contraction, thus resulting in dilation. Their major uses are for high blood pressure (hypertension) and for symptomatic benign prostatic hypertrophy (BPH). Examples of α1 blockers in clinical use for hypertension include Cardura (doxazosin), and those in clinical use for BPH include Uroxatral (alfuzosin). 

Selective antagonism of α2 adrenoreceptors is rare; blockade generally occurs indirectly due to non-selective affinity of sympathomimetics to other receptors. Yohimbine is a supplement that is a selective α2 adrenergic antagonist and has been promoted for the management of erectile dysfunction. 

Beta adrenergic agonists

β1 adrenoreceptors are primarily concentrated in the heart, and so stimulation will lead to increased heart rate and result in increased blood pressure. Dobutamine is the prototypical β1 selective agonist, and is used for short-term management of cardiac decompensation that may occur after cardiac surgery, in patients with congestive heart failure, or in the setting of a heart attack.

β2 adrenoceptors agonists are useful in the management of asthma and COPD due to the concentration of this adrenoreceptor on smooth muscles of the airways. β2 agonists work to relax these smooth muscles, resulting in bronchodilation, or opening up of airways. Examples include the inhaled medications Serevent Diskus (salmeterol) and Brovana (arformoterol). β2 adrenoreceptors are also found on the uterus, and terbutaline has been used successfully to prevent preterm labor. 

β3 adrenoreceptors are localized in the urinary bladder, and action on these receptors by medications has been effective in the management of overactive bladder. Examples of these types of medications include Myrbetriq (mirabegron) and Gemtesa (vibegron). Mirabegron has demonstrated reductions in incontinence episodes per 24-hour period, as well as improvements in overall quality of life due to this condition.

Beta adrenergic antagonists

Like the α adrenergic antagonists resulting in the opposite effects of α adrenergic agonists, the same holds true for β adrenergic antagonists when compared to β adrenergic agonists. Also, like α adrenergic antagonists, β adrenergic antagonists can be either selective or non-selective.

Overall, β adrenergic antagonists are among the most significant class of medications developed because of their efficacy in treating so many conditions, including high blood pressure, heart failure, ischemic heart disease, and certain irregular heart rhythms. 

Due to the concentration of β1 adrenoreceptors on the heart, selective β1 blockers decrease heart rate, which in turn can decrease blood pressure, and can decrease contractility. Examples of selective β1 blockers include Tenormin (atenolol) and Lopressor (metoprolol). β2 blockade occurs due to the non-selective activity of β1 blocking medications, and examples include Inderal XL (propranolol) used in a wide array of cardiac conditions, and Timoptic  (timolol) for managing elevated intraocular pressure in open-angle glaucoma.  

Indirect-acting or mixed-acting sympathomimetics

Examples of this classification of sympathomimetics have powerful central nervous system (CNS) stimulant actions, which explains their use in the management of ADHD and narcolepsy but also have some peripheral α and β actions. Examples include Ritalin (methylphenidate) and Focalin (dexmethylphenidate). These medications work by releasing norepinephrine and other chemicals to result in wakefulness, alertness, and ability to concentrate. They also can increase blood pressure and can directly stimulate the heart due to their peripheral α and β activity.

Who can take sympathomimetics?

Can men and women take sympathomimetics?

Sympathomimetics can be taken by either women or men. Some, such as those used primarily in the management of BPH, are more commonly prescribed in men but have off-label uses that might result in use for women. For example, Uroxatral (alfuzosin) is FDA approved for the management of BPH which inherently would limit its use to men, but can be used off-label to break up kidney stones and therefore might be prescribed in women. 

Can you take sympathomimetics while pregnant or breastfeeding?

As with all medications in pregnancy or when breastfeeding, a discussion should occur with a medical professional to review the specific sympathomimetic and outline risks versus benefits.

Depending on the condition being managed, safer alternatives than sympathomimetics may exist during pregnancy. For example, in the management of high blood pressure in pregnancy, β blockers are not the preferred drug class due to concerns of fetal growth restriction. 

Before discontinuing any sympathomimetic upon finding out you are pregnant, always discuss with a medical professional first since uncontrolled conditions can result in pregnancy complications. 

When breastfeeding, certain sympathomimetics used to manage symptoms of a cold can cross into breast milk. A nursing mother may notice some effects of the medication in her child, but generally, short-term use of these medications is considered safe.   

Can children take sympathomimetics?

The most likely use of sympathomimetics in children would be with the indirect-acting or mixed-acting medications in the management of ADHD. Ideally, medications for the management of ADHD should be avoided in children less than six years of age, and an emphasis should be placed on behavior therapy. 

Can seniors take sympathomimetics?

Aside from increased monitoring and/or some dose adjustments, sympathomimetics are safe for seniors when taken as directed. Because sympathomimetics manage so many conditions that are more common in older adults, it is likely for seniors to be taking some type of a sympathomimetic. Sympathomimetics like β1-blockers are part of treatment algorithms for many conditions, including management of heart attacks as risk reduction strategies. They’re also helpful in symptom management of other chronic conditions usually associated with older age, like glaucoma. 

Are sympathomimetics safe?

Under the guidance of a medical professional and when taken as instructed, sympathomimetics are safe and effective. However, like with many medications, purposeful or accidental excessive ingestions or administrations can come with serious side effects. Toxicity associated with most sympathomimetic use has no specific reversal agents, so these situations depend on symptom management to get the patient through the acute period. 

Several of the sympathomimetic medications carry a black box warning. Midodrine carries a Black Box Warning because it can cause a dramatic increase in blood pressure upon sitting or standing up, so it is recommended to only be used in patients whose lives are considerably impaired due to the condition of orthostatic hypotension despite standard clinical care.  Several β1 blockers, including metoprolol, atenolol, and nadolol carry a black box warning against abruptly stopping therapy since it may result in worsening or new episodes of ischemic heart disease, and in some cases may result in a heart attack. 

The methylphenidate-containing products carry a black box warning given the potential for abuse and dependence. Finally, terbutaline carries a black box warning against use beyond 48 to 72 hours in preventing preterm labor or in an outpatient setting as it may cause serious side effects, such as increased heart rate, hyperglycemia, heart arrhythmias, and heart attack. 

In 2005 the FDA removed phenylpropanolamine, a sympathomimetic which was a common ingredient in many cough and cold remedies as well as diet aids, from all over-the-counter formulations because it was found to be a risk factor for hemorrhagic stroke. 

Recalls

• Phenylephrine [2021] (phenylephrine recall)

• Labetalol [2019] (labetalol recall)

Restrictions

Pseudoephedrine is a sympathomimetic that comes with several restrictions following the Combat Methamphetamine Epidemic Act of 2005. The act prevents over-the-counter sales of cold medicines that contain the ingredient pseudoephedrine, which can be used to make methamphetamine. Cold medications including pseudoephedrine must be sold behind a pharmacy counter, and the amount that can be purchased each month by an individual is limited. 

Are sympathomimetics controlled substances?

Some sympathomimetics are controlled substances but are generally limited to those used to manage psychiatric conditions like ADHD and/or narcolepsy. Other sympathomimetics are not controlled substances. 

Common sympathomimetics side effects

Side effects related to sympathomimetics are generally due to excess activity or blockade at the adrenoreceptor on which they work. Therefore, one might experience extremes of blood pressure (too high or too low), extremes of changes in heart rate (too fast or too slow), heart arrhythmias, insomnia, dizziness, tremor, or difficulty breathing.

How much do sympathomimetics cost?

Many sympathomimetic medications are available in a generic formulation. Therefore, the cost of these medications can range from a few dollars to hundreds of dollars for those that are branded and/or formulated in extended-release formulations. A free SingleCare discount coupon could help you save up to 80% off sympathomimetics and other prescription drugs.