Sympathomimetic drugs

Last updated: September 19, 2023

Summary

Sympathomimetics are substances that mimic or modify the actions of endogenous catecholamines of the sympathetic nervous system. Direct agonists directly activate adrenergic receptors while indirect agonists enhance the actions of endogenous catecholamines. Sympathomimetics stimulate alpha-1 adrenergic receptors, beta-adrenergic receptors, and dopamine (D) receptors in various target tissues, such as the eyes, heart, and vascular smooth muscle. The clinical indications for sympathomimetics are broad and include asthma, heart failure, shock, and anaphylaxis. Side effects include hypertension, sinus tachycardia, and skeletal muscle tremor.

Overview

Sympathomimetic drugs mimic or enhance the actions of endogenous catecholamines of the sympathetic nervous system (fight-or-flight reaction).

Direct sympathomimetic drugs

Direct sympathomimetics stimulate adrenergic and dopaminergic receptors directly.

Beta-adrenergic agonists: predominantly act on the adrenergic beta-receptors (e.g., isoproterenol)
Alpha-adrenergic agonists: predominantly act on the adrenergic alpha-receptors (e.g., phenylephrine)
Dopaminergic agonists: predominantly act on the D1 receptor (e.g., fenoldopam)

Overview of direct sympathomimetics ^[1]^[2]
Drugs	Action	Cardiovascular effects	Indications
Albuterol, salmeterol, formoterol, terbutaline	β₂ > β₁	Mild increase in heart rate (HR)	Asthma Acute exacerbation: short-acting selective β₂-agonists (e.g., albuterol) Prophylaxis (in chronic disease): long-acting selective β₂-agonists (e.g., salmeterol) COPD Preterm labor: Terbutaline is a tocolytic used to delay preterm labor for up to 48 hours. Hyperkalemia
Clonidine, guanfacine	α₂	Lowers blood pressure (BP)	HTN ADHD Tourette syndrome Drug withdrawal
Dobutamine	β₁ > β₂, α Inotropic effects > chronotropic effects	No change or mild decrease in BP Raises HR, cardiac output (CO)	Heart failure Cardiogenic shock Cardiac stress testing
Dopamine	D₁ = D₂ > β > α Chronotropic effects at lower doses (β effect) Vasoconstriction at high doses (α effect)	Raises BP (at high doses), HR, CO	Heart failure Cardiogenic shock Unstable bradycardia
Epinephrine	β > α (at high doses the α effect is predominant) Stronger β₂-receptor effect than norepinephrine	Raises BP (at high doses), HR, CO	Anaphylaxis Cardiac arrest Septic shock Postbypass hypotension Asthma Open-angle glaucoma
Fenoldopam	D₁ Vasodilates coronary and peripheral vessels Promotes natriuresis	Raises CO, HR Lowers BP (through vasodilatation)	Hypertensive crisis Postoperative hypertension
Isoproterenol	β₁ = β₂ Marginal α effect	Raises CO, HR Lowers BP (through vasodilatation)	Bradycardia or heart block It may worsen ischemia. Cardiac arrest from heart block when pacemaker therapy is unavailable
Methyldopa	α₂	Lowers BP	HTN, especially in pregnancy
Midodrine	α₁	Raises BP (through vasoconstriction) Lowers HR No change or decrease in CO	Autonomic insufficiency and symptomatic orthostatic hypotension Possible side effect: worsening of supine hypertension
Mirabegron	β₃	Raises BP	Urinary urge incontinence or overactive bladder
Norepinephrine	α₁ > α₂ > β₁	Raises BP (through vasoconstriction) Lowers HR (reflex bradycardia) as a response to the increased mean arterial pressure (MAP), which counteracts chronotropic effects No change or increase in CO	Septic shock Neurogenic shock Hypotension
Oxymetazoline	α₁ > α₂	May raise BP	Epistaxis Rhinitis, sinusitis (topical decongestant) Rosacea
Phenylephrine	α₁ > α₂	Raises BP (through vasoconstriction) Lowers HR No change or decrease in CO	Hypotension Rhinitis, obstructed Eustachian tubes Phenylephrine acts as a nasal decongestant by reducing hyperemia and mucosal edema Allergic conjunctivitis Open-angle glaucoma Ischemic priapism (high-dose intracavernosal phenylephrine injection)

“DINED” is the acronym for examples of direct sympathomimetic drugs: Dopamine, Isoproterenol, Norepinephrine, Epinephrine, Dobutamine.

Examples of direct sympathomimetic drugs

Indirect sympathomimetic drugs

Indirect sympathomimetics increase the synaptic activity of endogenous catecholamines by increasing presynaptic release or inhibiting reuptake.

Overview of indirect sympathomimetics ^[1]^[3]
Drugs	Action			Indications
Drugs	Indirect general agonist	Reuptake inhibitor	Releases catecholamines	Indications
Amphetamines	Yes	Yes	Yes	ADHD ^[4] Narcolepsy Obesity
Cocaine	Yes	Yes	No	Local anesthesia Vasoconstriction
Ephedrine	Yes	No	Yes	Anesthesia-induced hypotension Urinary incontinence Nasal congestion (pseudoephedrine) Reduces hyperemia and edema Opens nasal meatus and Eustachian tubes

Pharmacodynamics

Overview of sympathomimetic effects ^[1]^[3]
Organ system	Receptor	Sympathomimetic effect
Eye	α₁	Mydriasis (↑ pupillary dilator muscle contraction) Distant accommodation (↑ ciliary body contraction)
	α₂	↓ Aqueous humor production
	β₂	↑ Aqueous humor production
Blood vessels	α₁	↑ Vascular smooth muscle contraction of arterioles → ↑ peripheral resistance → ↑ afterload Venoconstriction → ↑ venous return → ↑ preload
	α₂	↑ Platelet aggregation
	β₂	Peripheral vasodilation → ↓ peripheral resistance → ↓ afterload
Heart	β₁	↑ HR ↑ Contractility ↑ Automaticity and conduction velocity
Bronchi	β₂	Bronchodilation
Gastrointestinal tract	α₁	Sphincter contraction
Gastrointestinal tract	β₂	↓ Peristalsis
Liver	α₁	↑ Glycogenolysis ↑ Gluconeogenesis (β2 activation)
Liver	β₂	↑ Glycogenolysis ↑ Gluconeogenesis (β2 activation)
Pancreas	α₂	↓ Insulin release
Pancreas	β₂	↑ Insulin release
Kidneys	β₁	↑ Release of renin
Bladder	α₁	Sphincter contraction → urinary retention
	β₂	Detrusor relaxation
	β₃	Detrusor relaxation
Female reproductive organs	β₂	↓ Uterine tone (tocolysis)
Male reproductive organs	α₁	Ejaculation from vas deferens
Skeletal muscle	β₂	↑ Contraction ↑ Glycogenolysis
Skeletal muscle	β₃	↑ Thermogenesis in skeletal muscle
Adipose tissue	α₂	↓ Lipolysis
Adipose tissue	β_1–3	↑ Lipolysis

Both alpha-adrenergic and beta-adrenergic agonists are not fully selective at high doses.

Adverse effects

See also “Stimulant intoxication and withdrawal.”

Direct sympathomimetics

Side effects of direct sympathomimetics ^[1]
Drugs	Side effects
α₁-agonists ^[5]	Hypertension (due to peripheral vasoconstriction) and reflex bradycardia Urinary retention Ischemia and necrosis, especially of the fingers or toes Rebound congestion (with nasal decongestants used > 4–6 days) Piloerection
α₂-agonists	The side effects of α₂-agonists are mainly due to their sympatholytic effects. ^[2] CNS depression (e.g., sedation) Respiratory depression Bradycardia and hypotension Miosis Rebound hypertension after sudden interruption Dry mouth α-Methyldopa Autoimmune hemolytic anemia with positive direct Coombs test SLE-like syndrome Hyperprolactinemia
β₁-agonists	Tachycardia and arrhythmias Can precipitate angina or myocardial infarction in patients with coronary artery disease
β₂-agonists	Tremor (most common side effect), agitation, insomnia, diaphoresis Hypotension (due to peripheral vasodilation) and reflex tachycardia Metabolic disturbances: hyperglycemia, hypokalemia

Catecholamines (e.g., epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine) should only be administered if monitored by an experienced physician! High-dose catecholamine administration requires intra-arterial blood pressure monitoring.

Indirect sympathomimetics

Side effects of indirect sympathomimetics ^[1]
Drugs	Side effects
Amphetamines	See “Amphetamine intoxication”.
Cocaine	See “Cocaine intoxication”.
Ephedrine	Hypertension Reflex bradycardia (due to hypertension) or tachycardia Dizziness Nausea, vomiting Pseudoephedrine Rebound congestion (when used > 4–6 days) Anxiety and/or ↑ CNS stimulation (e.g., alertness, nervousness, insomnia) Tachyphylaxis

In case of cocaine intoxication, the concurrent administration of beta-blockers can induce extreme hypertension and coronary vasospasm due to unopposed alpha-1 activation.

We list the most important adverse effects. The selection is not exhaustive.

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