Vasopressor · Alpha agonist

Ephedrine

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

Indications

Hypotension in the setting of anesthesia (label), especially after induction or neuraxial block
Hypotension with bradycardia, where its β1 effect helps and phenylephrine's reflex slowing would not
Spinal hypotension at cesarean delivery when the mother is bradycardic; otherwise phenylephrine is preferred
Brief hypotension in the ED or ICU while an infusion is prepared (off-label outside anesthesia)

Dosing

Where	Dose
Blood pressure boluses	Ephedrine: 5–10 mg IV every 5–10 min (anesthesia)

Mechanism of action

Ephedrine is a mixed-acting sympathomimetic. Most of its effect is indirect: it enters sympathetic nerve terminals through the norepinephrine transporter, displaces norepinephrine from storage vesicles and releases it onto α1 and β1 receptors. It is also a weaker direct agonist at α and β receptors. Because the indirect effect depends on releasable stores, repeated doses deplete them and each dose does less (tachyphylaxis).

Pharmacology

Cardiovascular: raises heart rate, contractility and cardiac output, with a smaller rise in SVR, like a weak, long-acting epinephrine
CNS: crosses the blood–brain barrier: alertness, restlessness, insomnia
Respiratory: mild β2 bronchodilation
Other: crosses the placenta (umbilical vein to maternal ratio 1.13) and raises fetal metabolism, lowering fetal pH (Ngan Kee 2009)
Other: urinary retention from α1 tone at the bladder neck

Pharmacokinetics

Onset	Within about 1 min IV
Duration	Pressor effect up to about 1 h after an IV bolus, depending on dose
Half-life	About 3 h in acidic urine to 6 h in alkaline urine (UK SmPC); US labels cite about 6 h
Distribution	Crosses the blood–brain barrier and placenta; present in breast milk
Metabolism	Little; a small fraction becomes active norephedrine
Elimination	About 77% unchanged in urine: 73–99% in acidic and 22–35% in alkaline urine (UK SmPC)

Chemistry

A phenylethylamine with no ring hydroxyls, plus β-hydroxyl, α-methyl and N-methyl groups: without a catechol COMT cannot act, and the α-methyl blocks MAO, so it works orally and lasts far longer than catecholamines
Two chiral centers and four stereoisomers; the drug is (1R,2S)-(−)-ephedrine, and pseudoephedrine is its (1S,2S) diastereomer
Originally from the plant Ephedra sinica (ma huang); now made synthetically
Amine pKa about 9.6 (PubChem): ionized at pH 7.4, but lipophilic enough without ring hydroxyls to enter the brain
Salt matters: ephedrine sulfate 50 mg equals 38 mg base; 50 mg/mL vials must be diluted; ready-to-use 5 mg/mL vials and syringes, pH 4.5–7.0, preservative-free (labels)

Adverse effects and cautions

In the one-pagers

Mental Health: Meds and CommunicationAntidepressants in the ICU and serotonin toxicity: With an MAOI, meperidine can be fatal (NARDIL label) and indirect pressors such as ephedrine can trigger a crisis. Anesthesia texts allow reduced-dose direct-acting pressors; the PARNATE label restricts even epinephrine to emergencies.

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Sources

FDA label: Emerphed (2021)
UK SmPC: ephedrine hydrochloride (2024)
Ngan Kee 2009 (placental transfer)
PubChem: ephedrine

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.